NOVEL PTP1B INHIBITORS
FIELD OF THE INVENTION:
The present invention is directed to a novel substituted heterocyclic compounds or
pharmaceutically acceptable salts thereof. Present invention also relates to process for their
preparation and pharmaceutically acceptable compositions containing them and their application
as pharmaceuticals for treatment of diseases.
The said compounds by virtue of its inhibitory action on an enzyme protein tyrosine phosphatase
1B (PTP1B) are useful in the treatment of diabetes and obesity.
BACKGROUND OF THE INVENTION:
Type 2 diabetes (T2DM), also known as non-insulin dependent diabetes mellitus (NIDDM)
afflicts about 150 million people worldwide and the numbers continue to grow each year.
Similarly the incidence and prevalence of obesity is also increasing at alarming rate. Obesity is
also associated with heart disease, diabetes, stroke, high blood pressure and some cancers. The
increase in the prevalence of obesity has been identified as a major cause of the projected
increase in diabetes. The increase in type 2 diabetes and obesity was previously observed
primarily in adult population, associated with a sedentary lifestyle, but has now become a
medical problem in children also (Sinha R. et al, NEJM 346; 802-10; 2002 & Rocchini AP.,
NEJM 346; 854-55; 2002) The increased incidence of type 2 diabetes and obesity in the
population has fuelled an intensified search for new therapeutic treatment options.
The relationship of obesity and type 2 diabetes has a phylogenetic component and is associated
with insulin resistance. Type 2 diabetes and obesity are characterised by resistance to hormones,
insulin and leptin, possibly due to attenuated or diminished signaling from the receptors. (Kishor
M. Wasan & Norbert A. Looije ; J Pharm Pharmaceut Sci (www.cspscanada.org) 8(2):259-271,
2005)

In an attempt to maintain glucose homeostasis in the face of progressive insulin resistance, the
pancreas secretes increasingly higher amounts of insulin. However, when the -cells no longer
can secrete adequate amount of insulin, hyperglycemia and type 2 diabetes develop. Insulin
resistance plays an important role in the development of abnormalities such as impaired glucose
tolerance, type 2 diabetes, obesity and hyperlipidemia. Since defective insulin signaling has been
found as one of the root cause of insulin resistance, therapeutic strategies designed to improve
insulin receptor signaling have generated special interest for the researchers.
Presently available therapies for Type 2 Diabetes include acarbose, sulfonylureas, biguinides,
thiazolidinediones and insulin therapy. These therapies address different metabolic defects
present in type 2 diabetic conditions. Unfortunately none of these are capable of addressing
multiple defects. These therapies also have their own limitations. Sulfonylureas risk
hypoglycemia and weight gain, whereas acarbose has G.I. side effects. Biguinides also causes
G.I. side effects and lactic acidosis and according to reports, it has limitation of having effective
in restricted populations. The much sought after thiazolidinediones (TZDs) have multiple
drawbacks like weight gain, edema, nausea, poor responder rate and effectiveness in restricted
populations. The ultimately used insulin therapy poses problems of route of administration,
hypoglycemia and weight gain. Thus, in the presently available therapies for diabetes, none has a
potential to address insulin signaling.
Hence, there is a need for oral therapy for Type 2 Diabetes that will improve insulin signaling
and will also address the commonly present side effects of hypoglycemia and weight gain.
The reversible tyrosine phosphorylation of key proteins by protein tyrosine kinases (PTKs) and
protein tyrosine phosphatases (PTPs) is one of the major processes involved in the regulation of
metabolic and mitogenic signal transduction processes in cells (Moller et al, 2000). The insulin
receptor (IR) is a classical example of this. On binding insulin, the resultant conformational
changes allow the IR to autophosphorylate itself on defined tyrosine residues and thereby initiate
its activation cascade (Hubbard, 1997). PTPs down regulate signal transduction pathways by
dephosphorylating the tyrosine residues on PTKs, including the IR, and other downstream
signaling proteins. Therefore, selective inhibition of critical PTPs has been proposed as a means
whereby signaling pathway activation may be maintained or even initiated and thus such agents

could be useful in the treatment of diseases in which an enhanced or prolonged signaling is
warranted (Taylor and Hill, 2004).
Among the various candidate targets for obtaining insulin sensitizers, protein tyrosine
phosphatases (PTPs) are particularly interesting since they play a key role in modulating the
activity of the insulin signaling cascade. Several candidate PTPs have been identified, including
PTP1B, PTP, leukocyte antigen related (LAR) and T cell protein tyrosine phosphatase
(TCPTP). PTP1B has been of particular interest since it seems to be a key regulator of insulin
receptor activity that acts at the insulin receptor and at downstream signaling components, such
as IRS 1.
PTP1B has been implicated as a negative regulator of the insulin signaling pathway in vitro.
Experimental evidence has also shown that the mice null for this protein have increased glucose
tolerance and insulin sensitivity, together with resistance to diet-induced obesity (Klaman et al,
2000).
Knock out studies have been carried out to understand the importance of PTP1B in the overall
physiology of insulin signaling and glucose metabolism (Klaman et al, 2000, Elchebly et al,
1999). The PTP1B knockout mouse showed many characteristics that are considered desirable
for an antidiabetic treatment. Importantly the knockout mice grew normally. These animals had
lower blood glucose and insulin levels as well as the consequent marked increase in insulin
sensitivity. Moreover, the insulin stimulated tyrosine phosphorylation levels of insulin receptor,
and IRS-1 were increased/prolonged in muscle and liver. This is in contrast to the main target
tissue for the PPARy agonist class of insulin sensitizers, which is adipose tissue. These animals
showed decreased plasma triglycerides too. However, most remarkably, the knockout animals
also exhibited a resistance to weight gain when placed on a high fat diet. They had lower body
fat. Insulin is an anabolic hormone and insulin administration is generally associated with weight
gain rather than weight loss. A number of recent studies have concluded that PTP1B is involved
in the dephosphorylation of JAK2, which is an important second messenger of the leptin
receptor. Hence, resistance to weight gain might be due to improved leptin action (Cheng et al,
2002).

The pharmacological effects of PTP1B inhibition were studied by treatment of genetically
diabetic mice with PTP1B antisense construct. Intraperitoneal administration of highly selective
second generation PTP1B ASO to db/db and ob/ob mice once a week for 4 weeks caused
significant reduction in blood glucose levels to near normal values. Importantly hypoglycemia
was not observed. The decreases in blood glucose were accompanied by attenuation of
hyperinsulinemia in ob/ob mice. These results, along with the improved performance of the
treated diabetic mice on glucose and insulin tolerance tests, suggest that the ASO acts as an
insulin sensitizer. Additionally, in agreement with the studies in the PTP1B knockout mice,
significantly reduced weight gain was seen in fat fed normal mice treated with the PTP1B ASO
(Gum et al, 2003; Rondinone et al, 2002; Zinker et al, 2002).
Thus, the scientific data obtained from PTP1B knockout and PTP1B inhibition studies clearly
indicate that PTP1B inhibition improves insulin sensitivity by enhancing insulin signaling. They
have utility in controlling or treating type 1 or type 2 diabetes, in improving glucose tolerance
and decreasing insulin resistance. These inhibitors can also be of use in treating diet-induced
obesity by improving leptin signaling and function.
Furthermore, there is evidence that suggests inhibition of protein tyrosine phosphatase PTP1B is
therapeutically beneficial for the treatment of diseases such as, autoimmune disease, acute and
chronic inflammation, osteoporosis and various forms of cancer (J. Natl. Cancer Inst. 86: 372-
378 (1994); Mol. Cell. Biol. 14: 6674-6682 (1994); The EMBO J., 12: 1937-1946 (1993); J.
Biol. Chem. 269: 30659-30667 (1994); and Biochemical Pharmacology 54: 703-711(1997)).
Because of the important roles played by upregulated protein tyrosine phosphatase PTP1B in the
disease states of T2DM, obesity, autoimmune disease, acute and chronic inflammation,
osteoporosis and various forms of cancer, agents that inhibit this enzyme specifically may
provide the desired therapeutic benefits without the unwanted side effects derived from
inhibiting the related phosphatases.
Accordingly there is a continuing need to identify novel compounds, which are PTP1B
inhibitors. It has been found that the compounds of the present invention have been categorically

shown to inhibit the enzyme PTP1B and accordingly have value in the treatment of disease
conditions mediated by the PTP IB enzyme.
WO2004047760, WO2005082901 discloses certain thiazolidine compounds and its method for
preparation that are hYAk3 inhibitors, useful for the treatment of diseases associated with
imbalance or inappropriate activity of hYAK3 proteins.
WO2006002829, WO2006040050 and WO2006040052 discloses certain thiazolidine
compounds that are CDK1 inhibitors useful as antiproliferative agents.
WO2006047269 discloses certain thiazolone as estrogen receptors modulators having essentially
1, 4 -disubstituted phenyl ring which has one of the substitution as at least aralkyl or
heteroaralkyl.
SUMMARY OF THE INVENTION:
The present invention provides substituted heterocyclic compounds of the general formula (I), or
their pharmaceutically acceptable salts or prodrugs thereof, which by virtue of its inhibitory
action on an enzyme protein tyrosine phosphatase IB (PTP1B) are useful in the treatment of
disorders mediated by PTP IB, particularly diabetes and obesity.



R1,R2 and R3 are independently selected from the group consisting of:
i) Hydrogen ii) -CH2COOR4 iii) -X(CH2)n -aryl, where n is selected from 0, 1 or 2, and X is
selected from S, NH or O, iv) -S-alkyl, v) -OR4 vi)OCH2cycloalkyl, wherein cycloalkyl is
selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl vii) -
CH2CONH2, viii)-CN, ix) Halo x) alkyl xi) -S02aryl xii) -CF3 xiii) -CO2R4 xiv) -COalkyl xv)
-NH2 xvi) -NO2 xvii) -CH2CONH-PhCH2COO R4 xviii) Tetrazolyl xix) Triazolyl xx) Pyrrolyl
xxi) Benzimidazolyl xxii) Pyrazolyl xxiii) Phthalamoyl xxiv) Phenyl optionally substituted with
one or more group selected from cyano, amino, carboxy, halo, nitro, alkyl, hydroxyl, -O-alkyl
xxv) Biphenyl xxvi) -OCH2CO2R4 xxvii) Pyridyl xxviii) Thienyl xxix) Dimethylamino xxx), -
CH2OH xxxi) -CF2H xxxii) -SO2NHR4 xxxiii) NHCOalkyl xxxiv) -OCF3






administering to said mammal a therapeutically effective amount of a compound of formula (I),
or their pharmaceutically acceptable salt, as defined hereinafter.
According to a further feature of this aspect of the invention there is provided a method for
preventing or treating disease conditions mediated by the PTP IB enzyme, particularly diabetes
mellitus and obesity in a mammal, such as human being, in need of such treatment which
comprises administering to said mammal a therapeutically effective amount of a compound of
formula (I), or their pharmaceutically acceptable salt, as defined hereinafter.
According to a further aspect of the present invention there is provided a compound of the
formula (I) or their pharmaceutically acceptable salt, as defined hereinafter for use in a method
of prophylactic or therapeutic treatment of a mammal, such as human being, and in particular for
use in the treatment of diabetes mellitus and obesity.
According to another feature of the invention there is provided the use of a compound of the
formula (I), or their pharmaceutically acceptable salt, as defined hereinafter in the manufacture
of a medicament for use in the production of a PTP1B inhibitory effect in a mammal, such as
human being.
According to another feature of the invention there is provided the use of a compound of the
formula (I), or their pharmaceutically acceptable salt, as defined hereinafter in the manufacture
of a medicament for use in the treatment of disease conditions mediated by the PTP 1B enzyme,
particularly diabetes mellitus and obesity.
Brief Description of the Drawing:
Figure 1: Effect of Compound no. 28 on fasted and non-fasted blood glucose in high fat fed obese C57BL/6 male
mice
Values are Mean ± SEM
Values are calculated as % change in blood glucose from baseline blood glucose values.
• = P < 0.05 vs. Vehicle
Figure 2: Effect of 4 days treatment with Compound no.28 on AUC blood glucose post insulin tolerance test in high
fat fed obese C57BL/6 male mice.
Values are Mean ± SEM
a = P<0.05






i) Hydrogen ii) -CH2COOR4 iii) -X(CH2)n -aryl, where n is selected from 0, 1 or 2, and X is
selected from S, NH or 0, iv) -S-alkyl, v) -OR4 vi)OCH2cycloalkyl, wherein cycloalkyl is
selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl vii) -
CH2CONH2, viii)-CN, ix) Halo x) alkyl xi) -S02aryl xii) -CF3 xiii) -CO2R4 xiv) -COalkyl xv)
-NH2 xvi) -N02 xvii) -CH2CONH-PhCH2COOR4 xviii) Tetrazolyl xix) Triazolyl xx) Pyrrolyl
xxi) Benzimidazolyl xxii) Pyrazolyl xxiii) Phthalamoyl xxiv) Phenyl optionally substituted with
one or more group selected from cyano, amino, carboxy, halo, nitro, alkyl, hydroxyl, -O-alkyl



R6 is selected from the group consisting of
i) hydrogen,
ii) -OR4,
iii) alkyl,
iv) halo,
v) heterocyclyl,
vi) -S alkyl,
vii) -S-aryl,
viii) -COOR4,
ix) Benzyl,
x) heteroaryl;
R7 is selected from the group consisting of
i) alkyl,
ii) hydrogen,
iii) halo;
or R6 and R7 together may form cycloalkane ring selected from the group of cyclopentane,
cyclohexane, cyclobutane;
R8 and R9 are independently selected from the group consisting of
i) hydrogen,
ii) halo,
iii) -OR4,
iv) alkyl,
v) -CONHR4
vi) -COOR4,
vii) -COalkyl;
R10 is selected from the group consisting of
i) Alkyl, ii)Aryl;

R11 is selected from the group consisting of
i) hydrogen,
ii) alkyl,
iii) aryl;
and with the proviso that:
i) when R5 is -C(O)C(O)OH, then ' Y' is (i), and p is null
ii) when A is phenyl and is substituted by R1 at fourth position then R1 is not -X(CH2)n-
aryl,.





wherein z is selected from aryl or heteroaryl, optionally substituted by a group
independently selected from H, alkyl, Halo, nitro, -OR4, CF3 and CONHR4;
R6 and R7 are independently selected from hydrogen or halogen;
R8 and R9 are independently selected from the group consisting of
i) hydrogen,
ii) halo,
iii) -OR4,
iv) Alkyl,
v) -CONHR4
vi) COOR4,
vii) -COalkyl;

A family of specific compounds of particular interest within the above formula (I) consists of
compound or their pharmaceutically acceptable salts:
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound
no. 1)
{4-[5-(l-Carboxymethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2ylamino]-phenyl}-acetic
acid. (Compound no. 2)
{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 3)
{4-[5-(4-Methylsulfanyl-benzylidene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 4)
[4-(5-Benzylidene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no. 5)
{4-[5-(4-Methoxy-naphthalen-l-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 6)
{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 7)
{4-[5-(lH-Indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 8)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
9)
{4-[5-(3-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 10)
{4-[5-(l-tert-Butoxycarbonylmethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 11)
[4-(4-Oxo-5-quinolin-2-ylmethylene-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
12)
{4-[5-(l-Benzofuran-2-yl-ethylidene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 13)
{3-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 14)
{4-[5-(l-Carbamoylmethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 15)
[3-(5-Naphthalen-2-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound
no. 16)
{4-[5-(2'-Cyano-biphenyl-4-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 17)
{4-[4-Oxo-5- (4-pyrrol-l -yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 18)
(4-{4-Oxo-5- [4-(lH-tetrazol-5-yl)-benzylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no. 19)
(4-{5-[2-Butyl-5-chloro-3-(2'-cyano-biphenyl-4-ylmethyl)-3H-imidazol-4-ylmethylene]-4-oxo-4,5-dihydro-
thiazol-2-ylamino}-phenyl)-acetic acid. (Compound no. 20)
{3-[5-(3-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 21)
(4-{2-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-lamino]-acetyl amino}-
phenyl)-acetic acid. (Compound no. 22)
{3-[5-(l-Carbamoylmethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 23)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-benzyl]-phosphonic acid diethyl
ester. (Compound no. 24)

4-Methyl-N-{2-[4-(5-naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-
benzene sulfonamide. (Compound no. 25)
N-(2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide. (Compound no. 26)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-methyl-
benzenesulfonamide. (Compound no. 27)
N- {2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-methyl-
benzenesulfonamide sodium salt. (Compound no. 28)
(4-{4-Oxo-5-[l-(toluene-4-sulfonyl)-lH-indol-3-ylmethylene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 29)
(3-{4-Oxo-5-[l-(toluene-4-sulfonyl)-lH-indol-3-ylmethylene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 30)
{4-[5-(3,4-Dichloro-benzylidene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 31)
{4-[5-(3-Hydroxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyI}-acetic acid.
(Compound no. 32)
5-(3-Benzyloxy-naphthalen-2-ylmethylene)-2-[4-(lH-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one.
(Compound no. 33)
[4-(N'-{4-Oxo-5-[4-(lH-tetrazol-5-yl)-benzylidene]-4,5-dihydro-thiazol-2-yl}-hydrazino)-phenyl]-acetic
acid. (Compound no. 34)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-N-hydroxy-acetamide.
(Compound no. 35)
(4-{5-t4-(Morpholine-4-carbonyl)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no. 36)
{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 37)
(4-[5-(2-Butyl-5-chloro-3H-imidazol-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 38)
(4-{5-[4-(2-Fluoro-4-nitro-phenoxy)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic
acid. (Compound no. 39)
(4-{4-Oxo-5-[4-(piperazine-l-carbonyl)-benzylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no. 40)
5-(6-Methoxy-naphthalen-2-ylmethylene)-2-[4-(lH-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one.
(Compound no. 41)
3-[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionic acid.
(Compound no. 42)
3-{4-[5-(l-Carboxymethyl-lH-indol-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-lamino]-phenyl}-
propionic acid. (Compound no. 43)
{3-[2-(4-Methylsulfamoylmethyl-phenlamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-indol-l-yl}-acetic acid.
(Compound no. 44)
{4-[4-Oxo-5-(4-tetrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 45)
3-{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-propionic
acid. (Compound no. 46)
{5-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-acetic
acid. (Compound no. 47)
2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-butyric
acid. (Compound no. 48)
3-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-propionic
acid. (Compound no. 49)
(4-{5-[3-(l,3-Dioxo-l,3-dihydro-isoindol-2-yl)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-

phenyl)-acetic acid. (Compound no. 50)
{4-[4-Oxo-5-(3-pyrroI-l-yl-benzyIidene)-4,5-dihydro-thiazoI-2-ylamino]-phenyl}-acetic acid. (Compound
no. 51)
N-Methyl-C-[4-(5-naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-
methanesulfonamide. (Compound no. 52)
2-[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionicacid.
(Compound no. 53)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionic acid.
(Compound no. 54)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-succinic acid. (Compound
no. 55)
{4-[5-(4-Hydroxy-3,5-dimethoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 56)
(4-{5-[l-(6-Methoxy-naphthalen-2-yl)-ethylidene]-4-oxo-4,5-dihydro-thiazol-2-lamino}-phenyl)-acetic
acid. (Compound no. 57)
3-{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-lamino]-phenyl}-propionic
acid. (Compound no. 58)
{4-[4-Oxo-5-(3,4,5-trimethoxy-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 59)
(4-{5-[l-(4-Bromo-phenyl)-lH-pyrrol-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 60)
(4-{4-Oxo-5-[l-(3-pyrrol-l-yl-phenyl)-ethylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no. 61)
(4-[4-Oxo-5-(l-phenyl-lH-pyrrol-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 62)
C-{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-N-methyl-
methanesulfonamide. (Compound no. 63)
C-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-N-ethyl-
methanesulfonamide. (Compound no. 64)
C-{4-[5-(2'-Cyano-biphenyI-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-N-methyl-
methanesulfonamide. (Compound no. 65)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-bromo-acetic acid.
(Compound no. 66)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-benzyl]-malonic acid. (Compound
no. 67)
[4-(5-Biphenyl-4-yImethyIene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyI]-morpholin-4-yl-acetic acid.
(Compound no. 68)
N-(2-{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-lamino]-phenyl}-acetyl)-
4-methyl-benzenesulfonamide sodium salt. (Compound no. 69)
5-Naphthalen-2-ylmethylene-2-[4-(lH-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one. (Compound no.
70)
{4-[4-Oxo-5-(4-oxo-4H-chromen-3-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 71)
{4-[4-Oxo-5-(4-trifluoromethyl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 72)
{4-[5-(6-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 73)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
74)
f4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-bromo-sodium acetate.
(Compound no. 75)

[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-orpholin-4-yl-sodiumacetate.
(Compound no. 76)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionic acid.
(Compound no. 77)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate. (Compound
no. 78)
{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 79)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate.
(Compound no. 80)
{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 81)
{5-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-sodium
acetate. (Compound no. 82)
{4-[4-Oxo-5-(3-pyrrol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 83)
2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
butyrate. (Compound no. 84)
(4-{5-[3-(4-Fluoro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyI)-
acetic acid. (Compound no. 85)
{4-[5-(9,9a-Dihydro-4aH-fluoren-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 86)
{4-[4-Oxo-5-(3-[l,2,4]triazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 87)
{4-[5-(3-Benzoimidazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 88)
3-[4-(5-Naphthalen-2-ylmethyIene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium propionate.
(Compound no. 89)
(4-{4-Oxo-5-[3-(4-pyridin-2-yl-piperazin-l-yl)-benzylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 90)
{4-[4-Oxo-5-(3-pyrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 91)
{4-[4-Oxo-5-(3-tetrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 92)
5-(3-Benzyloxy-naphthalen-2-ylmethylene)-2-[4-(5H-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one
sodium salt. (Compound no. 93)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
94)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate. (Compound
no. 95)
3-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-lamino]-phenyl}-sodium
propionate. (Compound no. 96)
[5-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-indol-l-yl]-sodium acetate.
(Compound no. 97)
5-(6-Methoxy-naphthalen-2-ylmethylene)-2-[4-(5H-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one
sodium salt. (Compound no. 98)
{5-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-sodium
acetate. (Compound no. 99)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-oxazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
100)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-oxazol-2-ylamino)-phenyl]-sodium acetate. (Compound

no.101)
N-(2-{4-[4-Oxo-5-(4-phenyl-cyclohexa-l,5-dienylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-benzenesulfonamide sodium salt. (Compound no. 102)
N-(2-{4-[4-Oxo-5-(4-pyrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide. (Compound no. 103)
N-(2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide sodium salt. (Compound no. 104)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-chloro-
benzenesulfonamide sodium salts. (Compound no. 105)
4-Chloro-N-(2-{4-[5-(6-methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-benzenesulfonamide sodium salt. (Compound no. 106)
4-Chloro-N-(2-{4-[4-oxo-5-(4-pyrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide sodium salt. (Compound no. 107)
N-(2-{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide. (Compound no. 108)
[4-(4-Oxo-5-l,l';4',l"]terphenyl-ylmethylene-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid.
(Compound no. 109)
{4-[5-(6-Bromo-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 110)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-oxo-acetic acid.
(Compoundno. Ill)
4-Methyl-N-{2-[4-(5-naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-
benzenesulfonamide sodium salt. (Compound no. 112)
(4-{5-[3-(4-Fluoro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 113)
C-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-N-
methyl-methanesulfonamide. (Compound no. 114)
{4-[5-(2-Benzyloxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 115)
{4-[5-(3-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 116)
{4-[5-(3-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyI}-sodium
acetate. (Compound no. 117)
N-(2-{4-[5-(2-Benzyloxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-methyl-
benzenesulfonamide sodium salt. (Compound no. 118)
{4-[5-(2-Benzyloxy-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 119)
(4-{5-[2-(2'-Cyano-biphenyl-4-ylmethoxy)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 120)
[4-(5-Benzo[l,3]dioxol-5-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid.
(Compound no. 121)
{4-[5-(2-Benzyloxy-4-tetrazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 122)
{4-[5-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 123)
{4-[4-Oxo-5-(l-phenyl-5-pyrrol-l-yl-lH-pyrazol-3-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 124)
N-(2-{4-[5-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide. (Compound no. 125)
N-(2-{4-[5-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide. (Compound no. 126)

N-(2-{4-[5-(2-Benzyloxy-4-tetrazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide sodium salt. (Compound no. 127)
[2-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-thiazol-4-yl]-sodium acetate.
(Compound no. 128)
{4-[4-Oxo-5-(3-phenethyloxy-naphthalen-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 129)
[2-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-thiazol-4-yl]-acetic acid. (Compound
no. 130)
N-(2-{4-[5-(3-Benzyloxy-4-tetrazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide sodium salt. (Compound no. 131)
{4-[5-(5-Methyl-l-phenyl-lH-pyrazol-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 132)
{2-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-thiazol-4-yl}-acetic
acid. (Compound no. 133)
{2-[5-(5-Methyl-l-phenyl-lH-pyrazol-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-thiazol-4-yl}-
acetic acid. (Compound no. 134)
{4-[5-(3-Cyclopentylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 135)
2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-3-phenyl-
sodium propionate. (Compound no. 136)
{4-[5-(4-Fluoro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound no.
137)
{4-[4-Oxo-5-(3-propoxy-naphthalen-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 138)
{4-[5-(l-Isopropyl-l,2,3,4-tetrahydro-quinolin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 139)
{4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 140)
{4-[5-(l-Methyl-l,2,3,4-tetrahydro-quinolin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 141)
(4-{4-Oxo-5-[3-(tetrahydro-furan-2-ylmethoxy)-naphthalen-2-ylmethylene]-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetic acid. (Compound no. 142)
4-[5-(6-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 143)
{4-[5-(3,5-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 144)
{4-[4-Oxo-5-(2-phenyl-thiazol-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate,
(compound no. 145)
{4-[5-(l-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 146)
{4-[4-Oxo-5-(4-tetrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 147)
{4-[4-Oxo-5-(4-pyrrol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodiumacetate.
(Compound no. 148)
{4-[5-(4-Benzyloxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 149)
{4-[5-(l-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 150)
{4-[5-(l-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 151)
{4-[5-(4'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium

acetate. (Compound no. 152)
[4-(5-[2,2']Bithiophenyl-5-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate.
(Compound no. 153)
3-{4-[5-(l-Hydroxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
propionate. (Compound no. 154)
2-{4-[5-(l-Methoxy-naphthalen-2-yimethylene)-4-oxo-4,5-dihydro-thiazoI-2-ylamino]-phenyl}-sodium
butyroate. (Compound no. 155)
{5-[5-(l-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-
sodiumacetate. (Compound no. 156)
(4-{5-[5-Bromo-2-(2'-cyano-biphenyl-4-ylmethoxy)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 157)
N-(2-{4-[5-(4'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylmethyl]-phenyl}-acetyl)-
4-methyl-benzenesulfonamide sodium salt. (Compound no. 158)
{5-[5-(4'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylmethyl]-indol-l-yl}-sodium
acetate. (Compound no. 159)
{4-[5-(2,3-Dihydro-benzofuran-5-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 160)
4- {4-[2-(4-Carboxymethyl-phenylamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-phenyl} -1 -methyl-
pyridinium; chloride sodium salt. (Compound no. 161)
(4-{5-t3-(4-Nitro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 162)
{4-[5-(6-Carboxymethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyi}-
acetic acid. (Compound no. 163)
{4-[5-(3,7-Dimethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 164)
{4-[5-(6-Fluoro-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 165)
{4-f5-(3,5-Dimethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 166)
(4-{5-[3-(4-Methyl-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 167)
4-Methyl-N-[2-(4-{5-[3-(4-methyl-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide sodium salt. (Compound no. 168)
(4-{4-Oxo-5-[3-(thiophen-2-ylmethoxy)-naphthalen-2-ylmethylene]-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 169)
{4-[5-(lH-Indol-5-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 170)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid ethyl ester.
(Compound no. 171)
3-f4-(5-BiphenyI-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium propionate.
(Compound no. 172)
4-Methyl-N-[2-(4-{4 -oxo-5-[4-(4-pyridin-2-yl-piperazin-l-yl)-benzylidene]-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide sodium salt. (Compound no. 173)
{4-[5-(4'-Methyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 174)
{4-[5-(6-Isopropyl-4-oxo-4H-chromen-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 175)
N-(2-{4-[5-(3-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
4-methyl-benzenesulfonamide sodium salt. (Compound no. 176)
3-{4-[5-(3-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
propionate. (Compound no. 177)

{4-[5-(2-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 178)
{4-[5-(3-Carboxymethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 179)
(4-{5-[3-(2-Methoxy-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 180)
(4-{5-[3-(3-Methoxy-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 181)
(4-{5-[3-(4-Chloro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 182)
3-(4-{5-[3-(4-Methyl-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium propionate. (Compound no. 183)
3-(4-{5-[3-(4-Chloro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium propionate. (Compound no. 184)
{4-[5-(6-Hydroxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 185)
[4-(5-Biphenyl-3-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate. (Compound
no. 186)
N-(2-{4-[5-(2-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide sodium salt. (Compound no. 187)
{4-[5-(3,7-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 188)
{4-[5-(4'-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 189)
{4-[5-(4-Morpholin-4-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 190)
4'-[2-(4-Carboxymethyl-phenylamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-biphenyl-4-carboxylic acid.
(Compound no. 191)
(4-[4-Oxo-5-(5-phenyl-thiophen-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 192)
[4-(5-Benzo[b]thiophen-3-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate.
(Compound no. 193)
{4-[5-(3'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 194)
{4-[5-(4'-Ethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 195)
{4-[4-Oxo-5-(4'-pyrrol-l-yl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 196)
(4-{5-[3-(2-Fluoro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 197)
{4-[5-(4'-Hydroxymethyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 198)
{4-[5-(4'-Hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 199)
5-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-2-carboxymethyl-benzoicacid.
(Compound no. 200)
{4-[5-(4'-Carboxymethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyI}-acetic
acid. (Compound no. 201)
[4-(l-Carboxymethyl-5-naphthalen-2-yl-lH-[l,2,4]triazol-3-ylamino)-phenyl]-acetic acid. (Compound no.
202)
{4-[5-(3,8-Dimethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic

acid. (Compound no. 203)
4-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodiumbutyroate.
(Compound no. 204)
3-{4-[5-(6-Fluoro-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
propionate. (Compound no. 205)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-yIamino)-2-fluoro-phenyl]-sodium acetate.
(Compound no. 206)
{4-[5-(2'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 207)
{4-[5-(4'-Difluoromethyl-biphenyl-4-ylmethylene)-4-oxo-4;5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 208)
{4-[5-(3',5'-Difluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 209)
{4-[4-Oxo-5-(4'-suIfamoyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 210)
{4-[5-(3-Methyl-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 211)
N-(2-{4-[5-(4'-Hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-yIamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide di-sodium salt. (Compound no. 212)
[3-(4-Oxo-2-{4-[2-oxo-2-(toluene-4-su]fonylamino)-ethyl]-phenyIamino}-4H-thiazol-5-ylidenemethyl)-
naphthalen-2-yloxy]-acetic acid. (Compound no. 213)
N-(2-{4-[5-(4'-Ethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide sodium salt. (Compound no. 214)
N-(2-{4-[5-(4'-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide sodium salt. (Compound no. 215)
{4-[5-(3-Fluoro-4'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 216)
{4-[5-(3-Benzyloxy-4-tetrazol-l-yI-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 217)
Fluoro-{2-fluoro-4-[5-(4'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 218)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-
trifluoromethyl-benzenesulfonamide, sodium salt. (Compound no. 219)
{4.[5_(4'.Methylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 220)
{4-[5-(2,,4'-Difluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 221)
{2-Fluoro-4-[4-oxo-5-(4'-pyrrol-l-yl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 222)
Thiophene-2-sulfonic acid {2-[4-(5-biphenyl-4-ylmethylene-4-oxo-4s5-dihydro-thiazol-2-ylamino)-
phenyl]-acetyl}-amide, sodium salt. (Compound no. 223)
N.{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazot-2-ytamino)-phenyl]-acetyl}-4-fluoro-
benzenesulfonamide, sodium salt. (Compound no. 224)
N-{2-t4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-
methanesulfonamide, sodium salt. (Compound no. 225)
N.{2-[4-(5-Biphenyt-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-methoxy-
benzenesulfonamide, sodium salt. (Compound no. 226)
{4-[4-Oxo-5<4'-trifluoromethoxy-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 227)
{4.[5-(3.Fluoro-4'-hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 228)

{4-[5-(3'-Fluoro-4'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 229)
{4-[5-(4'-Acetylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 230)
{4-[4-Oxo-5-(4'-trifluoromethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 231)
{4-[5-(4'-Cyclohexylmethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 232)
{4-[5-(3'-Fluoro-4'-hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid, disodium salt. (Compound no. 233)
{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 234)
4-Methyl-N-(2-{4-[5-(4'-methylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-benzenesulfonamide sodium salt. (Compound no. 235)
{2-Fluoro-4-[5-(6-methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 236)
{4-[4-Oxo-5-(4-pvridin-4-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 237)
{4-[5-(3-Fluoro-4'-methylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-sodium acetate. (Compound no. 238)
N-(2-{4-[5-(3-Fluoro-4'-methylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-trifluoromethyl-benzenesulfonamide sodium salt. (Compound no. 239)
{4-[5-(6-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 240)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-2-fluoro-phenyl]-3-methoxy-but-2-
enoic acid ethyl ester. (Compound no. 241)
{4-[5-(4-Methyl-3-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 242)
{4-[5-(4'-Cyano-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 243)
{4-[5-(l-Biphenyl-4-yl-ethylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 244)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-oxazol-2-ylamino)-phenyl]-acetyl}-4-methyl-
benzenesulfonamide. (Compound no. 245)
{4-[5-(6-Isopropoxy-5-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 246)
{4-[5-(5-Chloro-2-methoxy-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 247)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-3-(4-fluoro-phenyl)-acrylic
acid ethyl ester. (Compound no. 248)
N-(2-{4-[5-(l-Biphenyl-4-yl-ethylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-methyl-
benzenesulfonamide. (Compound no. 249)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-hydroxyimino-acetic acid
ethyl ester. (Compound no. 250)
N-(2-{4-[5-(6-Isopropoxy-5-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-methyl-benzenesulfonamide. (Compound no. 251)
(4-{5-[5-(4-Methoxy-phenyl)-isoxazol-3-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 252)
{4-[5-(2-Fluoro-biphenyl-4-ylmethyl)-4-oxo-4,5-dihydro-oxazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 253)
N-(2-{4-[5-(5-Chloro-2-methoxy-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-

phenyl}-acetyl)-4-methyl-benzenesulfonamide. (Compound no. 254)
{4-[5-(3',5'-Difluoro-4-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 255)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-oxo-acetic acid. (Compound
no. 256)
l-{4-[5-(2-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
cyclopentanecarboxylic acid sodium salt. (Compound no. 257)
N-(2-{4-[5-(6-Hydroxy-5-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-methyl-benzenesulfonamide. (Compound no. 258)
4-Methyl-N-(2-{4-[5-(4-methyl-3-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-benzenesulfonamide, sodium salt. (Compound no. 259)
{4-[5-(3',5'-Difluoro-4-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-acetic acid. (Compound no. 260)
{2-Fluoro-4-[4-oxo-5-(3,2',4',5'-tetrafluoro-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 261)
-{4-[4-Oxo-5-(4'-propoxy-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 262)
{4-[5-(4'-Cyclopropylmethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 263)
{4-[5-(2-Benzyloxy-3,5-diiodo-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 264)
{4-[5-(2,4'-Dimethoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
acetic acid. (Compound no. 265)
3-{4-[5-(6-Ethoxycarbonylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-propionic acid. (Compound no. 266)
Bromo-(2-fluoro-4-{5-[l-(4-nitro-phenyl)-ethylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 267)
{4-[5-(4'-Benzylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
bromo-acetic acid. (Compound no. 268)
{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-oxazol-2-ylamino]-2-fluoro-phenyl}-
acetic acid. (Compound no. 269)
N-(2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methoxy-benzenesulfonamide. (Compound no. 270)
2-{2-Fluoro-4-[4-oxo-5-(4-pyrrol-l-yl-benzyl)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-butyric acid.
(Compound no. 271)
{4-[5-(4'-Amino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid ethyl
ester. (Compound no. 272)
Methoxy-{4-[5-(4'-nitro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thia
zol-2-ylamino]-phenyl}-acetic acid. (Compound no. 273)
4-Methyl-N-[2-(4-{5-[4'-(4-nitro-phenylsulfanyl)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide. (Compound no. 274)
N-[2-(4-{5-[4'-(2-Fluoro-4-nitro-phenylamino)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-4-methyl-benzenesulfonamide. (Compound no. 275)
[4'-(4-Oxo-2-{4-[2-oxo-2-(toluene-4-sulfonylamino)-ethyl]-phenylamino}-4H-thiazol-5-ylidenemethyl)-
biphenyl-4-yl]-acetic acid butyl ester. (Compound no. 276)
4-Methyl-N-[2-(4-{5-[4'-(4-nitro-phenoxy)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide. (Compound no. 277)
4-Methyl-N-(2-{4-[4-oxo-5-(4-tetrazol-l-yl-benzylidene)-4,5-dihydro-oxazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide. (Compound no. 278)
N-(2-{4-[5-(4'-Acetyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide. (Compound no. 279)

Thiophene-2-sulfonic acid(2-{4-[5-(3-ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-acetyl)-amide. (Compound no. 280)
Bromo-{4-[5-(3,5-dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 281)
2-{4-[5-(4'-Amino-3-fluoro-3'-methoxycarbonyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-octanedioic acid. (Compound no. 282)
{2-{4-[5-(3-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-5-
methyl-hexanoic acid. (Compound no. 283)
2-(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-octanedioic acid. (Compound no. 284)
2-{2-Fluoro-4-[5-(5'-fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-butyric acid. (Compound no. 285)
2-(2-Fluoro-4-{5-[l-(4-nitro-phenyl)-ethylidene]-4-oxo-4,5-dihydro-oxazol-2-ylamino}-phenyl)-propionic
acid. (Compound no. 286)
6-(4'-{2-[4-(Bromo-carboxy-methyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-biphenyl-
4-ylsulfanyl)-hexanoic acid. (Compound no. 287)
2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
octanedioic acid. (Compound no. 288)
2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-5-methyl-hexanoic acid. (Compound no. 289)
2-{2-Fluoro-4-[4-oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-butyric acid, (compound no. 290)
3-Methoxy-2-{4-[5-(4'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acrylic acid. (Compound no. 291)
Bromo-{4-[5-(5-bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 292)
2-{2-Fluoro-4-[5-(4'-hydroxy-3'-hydroxymethyl-5'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-
thiazol-2-ylamino]-phenyl}-pentanoic acid. (Compound no. 293)
2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
octanedioic acid. (Compound no. 294)
4-Amino-4'-{2-[4-(l-carboxy-ethyl)-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-fluoro-biphenyl-
3-carboxylic acid methyl ester. (Compound no. 295)
4-Amino-4'-{2-[4-(bromo-carboxy-methyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-
fluoro-biphenyl-3-carboxylic acid methyl ester. (Compound no. 296)
4-Amino-4'-{2-[4-(l-carboxy-butyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-fluoro-
biphenyl-3-carboxylic acid methyl ester. (Compound no. 297)
4-Amino-4'-{2-[4-(carboxy-pyrrol-l-yl-methyl)-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-
fluoro-biphenyl-3-carboxylic acid methyl ester. (Compound no. 298)
N-(2-{4-[5-(3-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
nitro-benzenesulfonamide. (Compound no. 299)
{4-[5-(3-Benzyloxy-naphthalen-2-ylmethyl)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetic
acid. (Compound no. 300)
N-(2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-trifluoromethyl-benzenesulfonamide. (compound no. 301)
{4-[5-(4'-Acetyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 302)
[4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-(l-hydroxy-
ethyl)-phenyl]-acetic acid. (Compound no. 303)
2-{4-[5-(l,4-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
pentanoic acid. (Compound no. 304)
N-(2-{4-[5-(l,4-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-

acetyl)-3-fluoro-4-methyl-benzenesulfonamide. (Compound no. 305)
6-(4'-{2-[4-(l-Carboxy-propyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-fluoro-
biphenyl-4-ylsulfanyl)-hexanoic acid. (Compound no. 306)
2-{4-[4-Oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethyl)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-propionic
acid. (Compound no. 307)
{2-Fluoro-4-[5-(5'-fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-hydroxy-acetic acid. (Compound no. 308)
2-(4-{5-[4'-(5-Carboxy-pentylsulfanyl)-3-fluoro-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-octanedioic acid. (Compound no. 309)
(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-2-
fluoro-phenyl)-bromo-acetic acid. (Compound no. 310)
4-(3-{2-[4-(l-Carboxy-butyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-naphthalen-2-
yloxymethyl)-benzoic acid ethyl ester. (Compound no. 311)
N-(2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-nitro-benzenesulfonamide. (compound no. 312)
2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl }-6-methyl-heptanoic acid. (Compound no. 313)
Ethylsulfanyl-{4-[5-(3-isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl} -acetic acid. (Compound no. 314)
2-{4-[5-(l,4-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
propionic acid. (Compound no. 315)
2-{4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-butyric acid. (Compound no. 316)
6-(4'-{2-[4-(Carboxy-phenylsulfanyl-methyl)-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-biphenyl-
4-ylsulfanyl)-hexanoic acid . (Compound no. 317)
N-(2-{2-Fluoro-4-[4-oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-propyl-benzenesulfonamide. (Compound no. 318)
N-(2-{4-[5-(2,4-Dimethoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetyl)-
4-methyl-benzenesulfonamide. (Compound no. 319)
N-(2-{4-[5-(4-Chloro-3-nitro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-ethyl-
benzenesulfonamide. (Compound no. 320)
N-(2-{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-trifluoromethyl-benzenesulfonamide. (Compounds no. 321)
N-(2-{4-[5-(5-Bromo-2-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide. (Compound no. 322)
2-{4-[5-(3-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-octanedioic
acid. (Compound no. 323)
2-(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-2-
fluoro-phenyl)-butyric acid. (Compound no. 324)
N-[2-(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-acetyl]-4-methoxy-benzenesulfonamide. (Compound no. 325)
4-(3-{2-[4-(Carboxy-hydroxy-methyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-
naphthalen-2-yloxymethyl)-benzoic acid ethyl ester. (Compound no. 326)
4-[3-(2-{4-[2-(4-Fluoro-benzenesulfonylamino)-2-oxo-ethyl]-phenylamino}-4-oxo-4H-thiazol-5-
ylidenemethyl)-naphthalen-2-yloxymethyl]-benzoic acid ethyl ester. (Compound no. 327)
3-Fluoro-N-[2-(4-{5-[3-(4-fluoro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-4-methyl-benzenesulfonamide. (Compound no. 328)
[6-(4-Oxo-2-{4-[2-oxo-2-(thiophene-2-sulfonylamino)-ethyl]-phenylamino}-4H-thiazol-5-ylidenemethyl)-
naphthalen-2-yloxy]-acetic acid tert-butyl ester. (Compound no. 329)
N-(2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-methanesulfonamide. (Compound no. 330)

Bromo-{4-[5-(3,5-dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-acetic acid. (Compound no. 331)
2-{4-[5-(6-tert-Butoxycarbonylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
2-fluoro-phenyl}-butyric acid. (Compound no. 332)
N-(2-{4-[5-(4'-Hydroxy-3'-hydroxymethyl-5'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-
2-ylamino]-phenyl}-acetyl)-methanesulfonamide. (Compound no. 333)
2-{4-[5-(4'-Hydroxy-3'-hydroxymethyl-5'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-6-methyl-heptanoic acid. (Compound no. 334)
{2-Fluoro-4-[4-oxo-5-(3,4,5-trimethoxy-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 335)
4-Methyl-N-(2-{4-[4-oxo-5-(3,4,5-trimethoxy-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-benzenesulfonamide. (Compound no. 336)
2-{4-[5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
octanedioic acid. (Compound no. 337)
2-{4-[5-(2,4-Dimethoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-propionic
acid. (Compound no. 338)
Bromo-{4-[5-(4-chloro-3-nitro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetic
acid, (compound no. 339)
2-{4-[5-(5'-Fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-octanedioic acid. (Compound no. 340)
Bromo-{4-[5-(3,4-dipropoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetic
acid. (Compound no. 341)
2-{4-[5-(3,5-Dibromo-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
propionic acid. (Compound no. 342)
Bromo-{2-fluoro-4-[4-oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 343)
4-Ethyl-N-(2-{4-[5-(2-fluoro-5-nitro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide. (Compound no. 344)
{4-[5-(6-tert-Butoxycarbonylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-
fluoro-phenyl}-acetic acid. (Compound no. 345)
2-{2-Fluoro-4-[4-oxo-5-(4-trifluoromethyl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-pentanoic
acid. (Compound no. 346)
Thiophene-2-sulfonicacid(2-{4-[5-(3,4-dipropoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-
fluoro-phenyl}-acetyl)-amide. (Compound no. 347)
2-{4-[5-(4'-Benzylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-pentanoic acid. (Compound no. 348)
2-(2-Fluoro-4-{5-[4'-(2-fluoro-4-nitro-phenylamino)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-butyric acid, (compound no. 349)
{4-[5-(5'-Fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-(4-methyl-piperazin-l-yl)-acetic acid. (Compound no. 350)
4'-[2-(4-Carboxymethyl-3-fluoro-phenylamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-biphenyl-4-carboxylic
acid butyl ester. (Compound no. 351)
{4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-oxazol-2-ylamino]-2-fluoro-phenyl}-
acetic acid. (Compound no. 352)
Definitions
As used throughout the present specification, the following terms have the meanings indicated.

The term "PTP1B" means protein tyrosine phosphatase enzyme 1B. PTP1B as used herein refers
to the enzyme in its wild-type or natural form, or can refer to any isolated or purified form.
Further, the term PTP1B means either the enzyme in its full-length form or in a truncated form.
The use of the terms "a" and "an" and "the" and similar referents in the context of describing the
invention (especially in the context of the following claims) are to be construed to cover both the
singular and the plural, unless otherwise indicated herein or clearly contradicted by context.
In the claims which follow and in the description of the invention, except where the context
requires otherwise due to express language or necessary implication, the word "comprise" or
variation such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the
presence of the stated features but not to preclude the presence or addition of further features in
various embodiments of the invention.
The term "compound" as used herein refers to any compound encompassed by the generic
formula disclosed herein. The compound described herein may contain one or more double
bonds and therefore, may exist as stereoisomer, such as double-bond isomers (i.e., geometric
isomers). Accordingly, the chemical structures depicted herein encompass all possible
stereoisomer of the illustrated compounds including the stereoisomerically pure form (e.g.,
geometrically pure) and stereoisomeric mixtures. The compounds may also exist in several
tautomeric forms including the enol form, the keto form and mixtures thereof. Accordingly, the
chemical structures depicted herein encompass all possible tautomeric forms of the illustrated
compounds. The compounds may also possess one or more asymmetric centres or planes.
Compounds of the present invention containing an asymmetrically substituted atom may be
isolated in optically active or racemic forms. It is well known in the art how to prepare optically
active forms, such as by resolution of racemic forms (racemates), by asymmetric synthesis, or by
synthesis from optically active starting materials. Resolution of the racemates can be
accomplished, for example, by conventional methods such as crystallization in the presence of a
resolving agent, or chromatography, using, for example a chiral HPLC column. Compounds
may exist in unsolvated forms as well as solvated forms, including hydrated forms. In general,

compounds may be hydrated or solvated. Certain compounds may exist in multiple crystalline or
amorphous forms. In general, all physical forms are equivalent for the uses contemplated herein
and are intended to be within the scope of the present invention. The compound herein described
may also exist in the form ester wherever possible like ester of carboxy group etc. Further, it
should be understood, when partial structures of the compounds are illustrated, a dash (" - ")
indicate the point of attachment of the partial structure to the rest of the molecule.
The term "alkyl" as used herein refers to a monovalent and saturated straight chain (i.e. linear) or
cyclic or a branched chain containing from 1 to 8 carbon atoms, and may be unsubstituted or
optionally substituted and may contain one or two double or triple bonds. Representative
examples of alkyl include, but are not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl,
isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, cyclohexyl, cyclopentyl and the like. The alkyl
groups of the present invention may be substituted with 0, 1, 2, 3 or 4 substituents independently
selected from the group consisting of cyano, halo, nitro, hydroxy, carboxy, amino, alkyl.
The term "aryl" as used herein refers to an aromatic group for example, which is a 6 to 15
membered monocyclic or bicyclic or tricyclic carbon-containing ring system, which may be
unsubstituted or substituted. Aryl groups having an unsaturated or partially saturated ring fused
to an aromatic ring can be attached through the saturated or unsaturated part of the group.
Representative examples of aryl include, but are not limited to phenyl, biphenyl, naphthyl,
dihydronaphthyl, indanyl and the like. The aryl groups of the present invention may be
substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of
cyano, halo, nitro, hydroxy, carboxy, amino, alkyl, Oalkyl, C02alkyl.
The term "heteroaryl" as used herein refers to an aromatic group for example, which is a 5 to 10
membered monocyclic or bicyclic ring system, which has at least one heteroatom and at least one
carbon atom containing ring. The term "heteroatom" as used in the specification and claims
includes oxygen, sulfur and nitrogen. The heteroaryl group may be attached at any available
nitrogen or carbon atom of any ring. Exemplary monocyclic heteroaryl groups include pyrrolyl,
pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl,
furanyl, thienyl, oxadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl and the like.

Exemplary bicyclic heteroaryl groups include indolyl, benzothiazolyl, benzodioxolyl,
benzoxazolyl, benzothienyl, quinolinyl, isoquinolinyl, benzimidazolyl, cinnolinyl, quinoxalinyl,
indazolyl, pyrrolopyridyl, furopyridinyl and the like.
The term "heterocyclyl" refers to a stable, fully saturated or unsaturated nonaromatic cyclic
group, for example, which is a 3 to 10 membered monocyclic or bicyclic ring system, which has
at least one heteroatom in at least one carbon atom containing ring. Each ring of the heterocyclyl
group containing a heteroatom may have 1, 2 or 3 heteroatoms independently selected from
nitrogen, oxygen or sulfur atoms. The heterocyclyl group may be attached at any heteroatom or
carbon atom of the cycle, which results in the creation of a stable structure. Exemplary
monocyclic heterocyclyl groups include aziridinyl, azetidinyl, pyrrolidinyl, pyrazolinyl,
imidazolinyl, imidazolidinyl, oxazolidinyl, isoxazolinyl, thiazolidinyl, isothiazolidinyl,
tetrahydrofuryl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl,
4-piperidonyl, hexahydropyrazine, hexahydropyridazine, hexahydropyrmidine,
tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl
sulfone, isothiazolidinyl and the like. Exemplary bicyclic heterocyclyl groups include
tetrahydroisoquinolinyl, benzopyranyl, indolizinyl, chromonyl, dihydroisoindolyl,
dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), benzothiopyranyl,
dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl
sulfone, dihydrobenzopyranyl, indolinyl, isoindolinyl, tetrahydroquinolinyl, and the like.
The terms "halogen" or "halo" include fluorine, chlorine, bromine, and iodine.
All substituents (Ri, R2, .........) described herein may be attached to the main structure at any
heteroatom or carbon atom which results in creation of stable compounds.
As used herein above and throughout this application, "nitrogen" and "sulfur" include any
oxidized form of nitrogen and sulfur and the quaternized form of any basic nitrogen.
Asymmetric centers exist in the compounds of the present invention. These centers are
designated by the symbols "R" or "S," depending on the configuration of substituents around the
chiral carbon atom. It should be understood that the invention encompasses all stereochemical

isomeric forms, including diastereomeric, enantiomeric, and epimeric forms,as well as d-isomers
and 1-isomers, and mixtures thereof. Individual stereoisomers of compounds can be prepared
synthetically from commercially available starting materials which contain chiral centers or by
preparation of mixtures of enantiomeric products followed by separation such as conversion to a
mixture of diastereomers followed by separation or recrystallization, chromatographic
techniques, direct separation of enantiomers on chiral chromatographic columns, or any other
appropriate method known in the art. Starting compounds of particular stereochemistry are
either commercially available or can be made and resolved by techniques known in the art.
Additionally, the compounds of the present invention may exist as geometric isomers. The
present invention includes all cis. trans, syn, anti, entgegen (E), and zusammen (Z) isomers as
well as the appropriate mixtures thereof. Additionally, compounds may exist as tautomers: all
tautomeric isomers are provided by this invention. Additionally, the compounds of the present
invention can exist in unsolvated as w?ell as solvated forms with pharmaceutieally acceptable
solvents such as water, ethanol, and the like. In general, the solvated forms are considered
equivalent to the unsolvated forms for the purposes of the present invention.
The term "prodrug" refers to a compound that is made more active in vivo. The present
compounds can also exist as prodrugs, as described in Hydrolysis in Drug and Prodrug
Metabolism : Chemistry, Biochemistry, and Enzymology (Testa, Bernard and Mayer, Joachim M.
Wiley-VHCA, Zurich, Switzerland 2003). Prodrugs of the compounds described herein are
structurally modified forms of the compound that readily undergo chemical changes under
physiological conditions to provide the compound. Additionally, prodrugs can be converted to
the compound by chemical or biochemical methods in an ex vivo environment. For example,
prodrugs can be slowly converted to a compound when placed in a transdermal patch reservoir
with a suitable enzyme or chemical reagent. Prodrugs are often useful because, in some
situations, they may be easier to administer than the compound, or parent drug. They may, for
instance, be bioavailable by oral administration whereas the parent drug is not. The prodrug may
also have improved solubility in pharmaceutical compositions over the parent drug. A wide
variety of prodrug derivatives are known in the art, such as those that rely on hydrolytic cleavage
or oxidative activation of the prodrug. An example, without limitation, of a prodrug would be a

compound which is administered as an ester (the "prodrug"), but then is metaboiically
hydrolyzed to the carboxylic acid, the active entity. Additional examples include peptidyl
derivatives of a compound.
The compounds of the present invention can exist as pharmaceutically acceptable salts . The
present invention includes compounds listed above in the form of salts, in particular acid
addition salts. Suitablee salts include those formed with both organic and inorganic acids. Such
acid addition salts will normally be pharmaceutically acceptable. However, salts of non-
pharmaceutically acceptable salts may be of utility in the preparation and purification of the
compound in question. Basic addition salts may also be formed and be pharmaceutically
acceptable. For a more complete discussion of the preparation and selection of salts, refer to
Pharmaceutical Salts: Properties, Selection, and Use (Stahl, P. Heinrich. Wiley-VCHA, Zurich,
Switzerland, 2002).
The term " pharmaceutically acceptable salts " or "therapeutically acceptable salt," as used
herein, represents salts or zwitterionic forms of the compounds of the present invention which
are water or oil-soluble or dispersible and therapeutically acceptable as defined herein. The salts
can be prepared during the final isolation and purification of the compounds or separately by
reacting the appropriate compound in the form of the free base with a suitable acid.
Representative acid addition salts include acetate, adipate, alginate, L-ascorbate, aspartate,
benzoate, benzenesulfonate (besylate), bisulfate, butyrate, camphorate, camphorsulfonate, citrate,
digluconate, formate, fumarate, gentisate, glutarate, glycerophosphate, glycolate, hemisulfate,
heptanoate, hexanoate, hippurate, hydrochloride, hydrobromide, hydroiodide, 2-
hydroxyethansulfonate (isethionate), lactate, maleate, malonate, DL-mandelate,
mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, 2-
naphthalenesulfonate, oxalate, pamoate, pectinate, persulfate, 3-phenylproprionate, phosphonate,
picrate, pivalate, propionate, pyroglutamate, succinate, sulfonate, tartrate, L-tartrate,
trichloroacetate, trifluoroacetate, phosphate, glutamate, bicarbonate, para-toluenesulfonate (p-
tosylate), and undecanoate. Also, basic groups in the compounds of the present invention can be
quaternized with methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dimethyl,
diethyl, dibutyl, and diamyl sulfates; decyl, lauryl, myristyl, and steryl chlorides, bromides, and

iodides; and benzyl and phenethyl bromides. Examples of acids which can be employed to form
therapeutically acceptable addition salts include inorganic acids such as hydrochloric,
hydrobromic, sulfuric, and phosphoric, and organic acids such as oxalic, maleic, succinic, and
citric. Salts can also be formed by coordination of the compounds with an alkali metal or
alkaline earth ion. Hence, the present invention contemplates sodium, potassium, magnesium,
and calcium salts of the compounds of the compounds of the present invention and the like.
Basic addition salts can be prepared during the final isolation and purification of the compounds
by reacting a carboxy group with a suitable base such as the hydroxide, carbonate, or bicarbonate
of a metal cation or with ammonia or an organic primary, secondary, or tertiary amine. The
cations of therapeutically acceptable salts include lithium, sodium, potassium, calcium,
magnesium, and aluminum, as well as nontoxic quaternary amine cations such as ammonium,
tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine,
triethylamine, diethylamine, ethylamine, tributylamine, pyridine, N,N-dimethylaniline, N-
methylpiperidine, AT-methylmorpholine, dicyclohexylamine, procaine, dibenzylamine, N,N-
dibenzylphenethylamine, 1-ephenamine, and N,N-dibenzylethylenediamine. Other representative
organic amines useful for the formation of base addition salts include ethylenediamine,
ethanolamine, diethanolamine, piperidine, and piperazine.
"Treating" or "treatment" of any disease or disorder refers, in one embodiment, to ameliorating
the disease or disorder (i.e., arresting or reducing the development of the disease or at least one
of the clinical symptoms thereof). In another embodiment "treating" or "treatment" refers to
ameliorating at least one physical parameter, which may not be discernible by the patient. In yet
another embodiment, "treating" or "treatment" refers to inhibiting the disease or disorder, either
physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a
physical parameter) or both. In yet another embodiment, "treating" or "treatment" refers to
delaying the onset of the disease or disorder. As used herein, amelioration of the symptoms of a
particular disorder by administration of a particular compound or pharmaceutical composition
refers to any lessening, whether permanent or temporary, lasting or transient that can be
attributed to or associated with administration of the composition.

"therapeutically effective amount" refers to an amount of a compound that confers a therapeutic
effect (e.g., treats, controls, ameliorates, prevents, delays the onset of, or reduces the risk of
developing a disease, disorder, or condition or symptoms thereof) on the treated subject, when
administered to a subject in need thereof. The therapeutic effect may be objective (i.e.,
measurable by some test or marker) or subjective (i.e., subject gives an indication of or feels an
effect). The "therapeutically effective amount" will vary depending on the compound, mode of
administration, the disease and its severity and the age, weight, etc., of the subject to be treated.
Pharmaceutical Compositions
According to another embodiment, the invention is to provide pharmaceutical composition
comprising a compound of formula (I) or their pharmaceutically acceptable salt, as defined
herein in association with a pharmaceutically-acceptable diluent, carrier or excipient.
While it is possible to administer pharmaceutically effective quantity of compound of general
formula (I) either individually or in combination, directly without any formulation, it is common
practice to administer the compounds in the form of pharmaceutical dosage forms comprising
pharmaceutically acceptable excipient(s) with an active ingredient. The compounds of general
formula (I) may be administered orally, parenterally, or by inhalation in dosage unit formulations
containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles.
Oral administration in the form of a tablet, capsule, elixir, syrup, lozenge, troche, or the like is
particularly preferred. The term parenteral as used herein includes subcutaneous injections,
intradermal, intravascular (e.g., intravenous), intramuscular, spinal, intrathecal injection or like
injection or infusion techniques. In addition, there is provided a pharmaceutical formulation
comprising a compound of general Formula (I) and a pharmaceutically acceptable carrier. One or
more compounds of general Formula (I) may be present in association with one or more non-
toxic pharmaceutically acceptable carriers and/or diluents and/or adjuvants and if desired other
active ingredients. The pharmaceutical compositions containing compounds of general Formula
(I) may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or
oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules, or syrups or
elixirs.

Compositions intended for oral use may be prepared according to any method known to the art
for the manufacture of pharmaceutical compositions and such compositions may contain one or
more agents selected from the group consisting of sweetening agents, flavoring agents, coloring
agents and preserving agents in order to provide pharmaceutically elegant and palatable
preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically
acceptable excipients that are suitable for the manufacture of tablets. These excipients may be for
example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate
or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic
acid; binding agents, for example starch, gelatin or acacia, and lubricating agents, for example
magnesium stearate, stearic acid or talc. The tablets may be uncoated or they may be coated by
known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby
provide a sustained action over a longer period. For example, a time delay material such as
glyceryl monostearate or glyceryl distearate may be employed.
Formulations for oral use may also be presented as hard gelatin capsules wherein the active
ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium
phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water
or an oil medium, for example peanut oil, liquid paraffin or olive oil.
Aqueous suspensions contain the active materials in admixture with excipients suitable for the
manufacture of aqueous suspensions. Such excipients are suspending agents, for example sodium
carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate,
polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents may be a
naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene
oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of
ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or
condensation products of ethylene oxide with partial ester derived from fatty acids and a hexitol
such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with
partial ester derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan
monooleate. The aqueous suspensions may also contain one or more preservatives, for example

ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring
agents, and one or more sweetening agents, such as sucrose or saccharin.
Oily suspensions may be formulated by suspending the active ingredients in a vegetable oil, for
example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid
paraffin. The oily suspensions may contain a thickening agent, for example beeswax, hard
paraffin or cetyl alcohol. Sweetening agents such as those set forth above, and flavoring agents
may be added to provide palatable oral preparations. These compositions may be preserved by
the addition of an anti-oxidant such as ascorbic acid.
Dispersible powders and granules suitable for preparation of an aqueous suspension by the
addition of water provide the active ingredient in admixture with a dispersing or wetting agent,
suspending agent and one or more preservatives. Suitable dispersing or wetting agents and
suspending agents are exemplified by those already mentioned above. Additional excipients, for
example sweetening, flavoring and coloring agents, may also be present.
Pharmaceutical compositions of the invention may also be in the form of oil-in-water emulsions.
The oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for
example liquid paraffin or mixtures of these. Suitable emulsifying agents may be naturally-
occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides,
for example soy bean, lecithin, and ester or partial ester derived from fatty acids and hexitol,
anhydrides, for example sorbitan monooleate, and condensation products of the said partial ester
with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also
contain sweetening and flavoring agents.
Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propylene
glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative and
flavoring and coloring agents. The pharmaceutical compositions may be in the form of a sterile
injectable aqueous or oleaginous suspension. This suspension may be formulated according to
the known art using those suitable dispersing or wetting agents and suspending agents which
have been mentioned above. The sterile injectable preparation may also be sterile injectable

solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a
solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed
are water, Ringer's solution and. isotonic sodium chloride solution. In addition, sterile, fixed oils
are conventionally employed as a solvent or suspending medium. For this purpose any bland
fixed oil may be employed including synthetic mono- or diglycerides. In addition, fatty acids
such as oleic acid find use in the preparation of injectables.
The compounds of general formula (I) may also be administered in the form of suppositories,
e.g., for rectal administration of the drug. These compositions can be prepared by mixing the
drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the
rectal temperature and will therefore melt in the rectum to release the drug. Such materials are
cocoa butter and polyethylene glycols.
Compounds of general formula (I) may be administered parenterally in a sterile medium. The
drug, depending on the vehicle and concentration used, can either be suspended or dissolved in
the vehicle. Advantageously, adjuvants such as local anesthetics, preservatives and buffering
agents can be dissolved in the vehicle.
Dose is appropriately decided by its form of preparation, method of administration, purpose of
use and age, body weight and symptom of the patient to be treated and it is not constant.
In another embodiment of the present invention there is provided a process for the preparation of
the compounds of the present invention. Representative methods for synthesizing compounds of
the invention are mentioned below in the following non-limiting scheme. The starting materials
can be obtained from commercial sources or can be prepared by well-established literature
methods known to those of ordinary skill in the art. It is to be understood that the selection of a
particular synthetic method depends on the nature of the substituents required for the desired
final compound. The order of synthetic steps can be altered and known variations of the
conditions and processes of the preparative procedures can be used to prepare these compounds.
Accordingly, compounds of formula (I) of the present invention can be prepared as described in
the schemes below.



As shown in Scheme 1, an appropriate aldehyde or ketone of formula (II) is reacted with a
compound of formula (III) in presence of a base such as alkali metal hydroxide like sodium
hydroxide and potassium hydroxide, piperidine, sodium acetate ,ammonium acetate etc. to
provide compounds of formula (IV). The compounds of formula (IV) can be treated with a base
such as Hunig's base or triethyl amine and alkyl halide preferably methyl iodide to afford
compounds of formula (V). Compounds of formula (V) may be further treated with a suitable
amine of formula (Vl-a), (Vl-b), or (VI-c) and a base such as potassium tertiary butoxide,
triethylamine or hunigs base in solvents such as tertiary butanol, ethanol, n-propanol
,isopropanol etc. under reflux conditions to afford compounds of respective formula (I a-c).
Furthermore, exocyclic double bond of compound of formula (IV) could be reduced to single
bond of compound of formula (IVa), which could subsequently be alkylated to afford compound
of formula (Va). Compounds of formula (Va) may be further treated with a suitable amine of
formula (Vl-a), (Vl-b), or (VI-c) and a base such as potassium tertiary butoxide, triethylamine
and hunigs base in solvents such as tertiary butanol, ethanol, n-propanol ,isopropanol etc. under
reflux conditions to afford compounds of respective formula (I d-f). The bases that can be used
for the conversion of compound (V) and (Va) to compounds of formula (I a-f) can be selected
from the group comprising of alkali metal alkoxides such as sodium or potassium alkoxide,
alkali metal hydroxides such as sodium or potassium hydroxide, alkali metal hydrides such as
sodium hydride, triethylamine, Hunig's base and the like. In an alternate embodiment, the
conversion of compound (V) and (Va) to (I a-f) can also be effected by microwave irradiation.
The other compounds of formula I having different L other than stated above can also be
prepared by reacting formula (V) or V (a) with appropriate compound of formula (VI).
Compounds of formula (III) where X = S, (i.e. Rhodanine ) used in the above scheme can be
either obtained commercially or synthesized following the method as mentioned in Organic
Synthesis., Collective Volume. III, p. 763.
Compounds of formula (III) where X = O, used in the above scheme can be synthesized
according to the procedure described in Ushenko, N.K. and Gorizdra, T.E., Ukrain.Khim.zhur.,
16, 545 (1950).

Aldehydes (II) and Amines (VI) used in scheme 1 were either commercially available or
synthesized from reduction of substituted ester followed by oxidation of corresponding alcohol.
The invention is explained in detail in the examples given below which are provided by way of
illustration only and therefore should not be construed to limit the scope of the invention.
PREPARATORY EXAMPLES
Example 1:
(4-{4-Oxo-5- [l-phenyl-methylidene]-4,5-dihydro-thiazoI-2-ylamino}-phenyl)-aeetic acid (1)
(Compound No. 1)
Step A: Preparation of 5-[l-Phenyl-methylidene]-2-thioxo-thiazolidin-4-one (IV):
A mixture of benzaldehyde (II) (I g, 9 m mol), rhodanine (1.2 g, 9 m mol) (III), and sodium
acetate (2.2 g, 27 m mol) in acetic acid (10 ml) was heated under reflux temperature for 5-6 h.
Subsequently the reaction mixture was cooled to room temperature, poured into water (20 ml)
and the solid obtained was filtered, washed with cold methanol (5 ml) and dried to obtain 1.47 g
of the title compound (IV) as a solid.
Step B: Preparation of 2-Methyl-5-[l-phenyl-methylidene]-thiazol-4-one (V):
1.4 g (6.3 m mol) of the product (IV) from step A, was dissolved in ethanol (10 ml)and stirred
at 5-10°C.To the solution Hunig's base (2.2 ml, 12 m mol) was added, followed by iodomethane
(0.5 ml, 7.5 m mol) and the reaction mixture stirred at room temperature for 4-5 hrs. The reaction
mixture was concentrated under vacuum, water (20 ml) was added to the residue and the solid
obtained was filtered and washed with ether (10 ml) to afford 1.26 g of the title compound (V) as
a solid.

Step C: Preparation of (4-{4-Oxo-5- [l-phenyl-methylidene]-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-acetic acid (1).
A mixture of 1.2 g (5.1 m mol) of the product (V) from step B, p-amino phenyl acetic acid ethyl
ester (0.9 g, 5.1 m mol) and potassium tertiary butoxide (1.2 g, 10 m mol) in tert butanol (10ml)
was heated under reflux for 6-7 hrs. The reaction mixture was concentrated under vacuo, residue
was suspended in water (20 ml), and obtained solid was taken in methanol (10 ml) to which IN
NaOH solution (4.8 ml, 4.8 m mol) was added at 0-5°C. The reaction mixture was stirred at room
temperature for 2 h and then concentrated under vacuo. To the residue, water (3 ml) was added
and washed with diethyl ether (5 ml). Finally, the aqueous layer was acidified with 2 N HC1 to
afford 0.41 g of the hydrolyzed product as a solid (1).
Alternatively, Step C could be performed under microwave condition according to the following
procedure.
A mixture of the product (V) from step B (1.2 g, 5.1 m mol), p-Amino phenyl acetic acid ethyl
ester (0.9 g, 5.1 m mol), potassium tertiary butoxide (1.2 g, 10 m mol) in tert butanol (10 ml) was
heated in a microwave synthesizer (CEM Discover®) at 100 watts for 30 min. The reaction
mixture was concentrated under vacuo, residue was suspended in water (10 ml) and solid
obtained was hydrolyzed as per the above-mentioned procedure to obtain 0.28 g of the title
compound (1) as a solid.
1H NMR (400 MHz, DMSO-d6) 5 3.58 (2H, s), 7.00-7.02 (1H, d), 7.28-7.33 (2H, t), 7.41-7.55
(4H, m), 7.62-7.64 (1H, d), 7.72 (1H, s), 7.95 (1H, s), 11.70 (1H, s), 12.17-12.50 (1H, bs).
MS,m/z:337(M-l)Example No 2: -
[4-(5-Benzyl-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid
Step D: - Preparation of 5-Benzyl-2-thioxo-thiazolidin-4-one (IVa)
To 1.77 g (5.9 mmol) of the product from example 124 (step A) was added a mixture of 6 ml of
THF and 25 ml of water followed by IN NaOH (3 ml) and cooled to 10°C. 1 ml of catalyst was

prepared by dissolving Dimethylglyoxime (232 mg), cobaltous chloride.6H2O (12 mg) in
dimethyl formamide (5 ml), and added to the reaction mixture. The reaction mixture was stirred
for 15 min, to which a solution of sodium borohydride (300 mg) and IN NaOH (1ml) diluted
with water (3.5 ml) was added. The reaction mixture was stirred for 4 h and then acetone (2.6
ml) was added to quench any remaining sodium borohydride. After stirring for half an hour,
water was added to reaction mixture and acidified with acetic acid. The solid so obtained was
filtered and dissolved in ethyl acetate (20 ml). The organic layer was successively washed with
water (10 ml) and brine (10ml), dried over sodium sulphate and concentrated to yield 1 g of the
title compound as a solid.
IVa was subsequently transformed into product ( Example 2) following the Step B and Step C
given in the example (1).
Compounds were prepared using the schemes noted above and the methods and procedures
described in Example 1 or Example 2. Following table (Table-1) shows the confirmation data for
some of the compounds of the present invention.





























METHOD OF INHIBITING PTP 1B ENZYME
In another embodiment of the present invention there is provided a method of inhibiting PTP1B
enzyme, by an effective amount of one or more of compound, represented by the formula (I), or
their pharmaceutically acceptable salts.
The compounds of the present invention possess the ability to inhibit an enzyme PTP 1B and
thereby useful in the treatment of diseases such as mediated by an enzyme PTP 1B
Inhibitory activity of compounds for this application is demonstrated using the following PTP 1B
enzyme inhibition assay.
Principle:
Protein tyrosine phosphatase 1B (PTP1B) is an intracellular enzyme which functions by
removing the phosphate groups from phosphorylated tyrosine residues of cellular proteins.
PTP 1B has been implicated as a negative regulator of insulin action and therefore is of
therapeutic interest. The ability of the test compounds to inhibit the activity of PTP 1B is
determined using an enzyme inhibition assay.
The assay is performed using two independent substrates of PTP 1B namely, p-nitrophenyl
phosphate (pNpp) and the phosphorylated Epidermal growth factor receptor peptide (EGFR).
In the assay performed with pNpp, the action of PTP 1B results in the release of p- nitrophenol,
which is yellow in colour and can be measured at 410nm. In the case of the assay using EGFR,
action of PTP 1B results in the release of free phosphate group. This is trapped using a reagent

containing ammonium molybdate and malachite green resulting in a colored complex whose
absorbance can be measured at 620nm.
Materials:
Dimethyl sulfoxide (DMSO)(Sigma)
Dithiothreitol (DTT)(Gibco)
Ethylenediamine tetra acetic acid (EDTA)(Gibco)
Igepal® CA-630 (Sigma)
1M N-(2-Hydroxyethyl)piperazine-N'-(2-ethanesulfonicacid);4-(2-Hydroxyethyl) piperazine-1 -
ethanesulfonic acid (HEPES) (Hyclone)
p-Nitrophenyl phosphate (pNpp) (SRL)
Recombinant human Protein-tyrosine phosphatase 1B (PTP1B) (amino acid 1-322 Biomol, USA)
Stock solutions:
1M HEPES (Store at 4°C)
10X EDTA 20 mM in 100 mM HEPES (Store aliquot at -20°C)
10X DTT 20 mM in 100 mM HEPES (Store aliquot at -20°C)
10% Igepal® CA-630 in 100 mM HEPES (Store at 4°C)
Prepare fresh daily:
100 mM HEPES
1% Igepal® CA-630
1X Assay buffer 50 mM HEPES (pH 7.4)
1 mM EDTA
1 mM DTT
0.05% Igepal® CA-630
Enzyme dilution:
Dilute recombinant Human PTP1B 1:150 in 1X Assay buffer for 10X stock.
Substrate preparation:
Prepare 10X stock of pNpp (50mM) in 1X Assay buffer
Compound preparation:
Prepare 100X stock in 100% DMSO, dilute 1:10 with 1X Assay buffer to get 10X stock in 10%
DMSO.

Procedure:
PTP1B inhibition assay was performed using recombinant human PTP1B. PTP1B (0.016
ug/well) was incubated in a buffer containing 50mM HEPES, ImM DTT, ImM EDTA and
0.05% Igepal® CA-630 with or without inhibitor (10X stock, final DMSO concentration is 1%)
for 30 mins at 25°C. This was followed by addition of p-Nitrophenyl phosphate (pNpp) substrate
(5 mM). The final volume of the reaction mixture is 50 µL and experiment was done in 96 well
half area plate. The incubation was continued for 30 mins at 25°C. The conversion of pNpp to p-
Nitrophenol (pNp) was measured at 410 nm in Spectramaxplus Spectrophotometer (Molecular
Devices, USA).



According to another embodiment, the invention is to provide a method of prevention or
treatment of disease conditions caused by overexpressed or altered by the PTP 1B enzyme
through administration to a patient in need an therapeutically effective amount of compound of
formula (I) or their pharmaceutically acceptable salts or pharmaceutical composition of
compound of general formula (I) or their pharmaceutically acceptable salts.
According to another embodiment, the present invention provides a method of treating or
delaying the onset and progression of diabetes, comprising administering a therapeutically
effective amount of a compound of formula (I) or their pharmaceutically acceptable salts.
According to another embodiment, the present invention provides a method of treating impaired
glucose tolerance and insulin resistance, comprising administering a therapeutically effective
amount of a compound of formula (I) or their pharmaceutically acceptable salts.

According to another embodiment, the present invention provides a method of treating obesity
comprising administering a therapeutically effective amount of a compound of formula (I) or
their pharmaceutically acceptable salts.
Yet another embodiment of the present invention is to provide a method of treatment of
autoimmune disorders, acute and chronic inflammatory disorders, osteoporosis, cancer,
malignant disorders comprising administering a therapeutically effective amount of a compound
of formula (I) or their pharmaceutically acceptable salts.
Yet another embodiment of the invention is to use compound of general formula (I) or their
pharmaceutically acceptable salts in the manufacture of medicaments useful for prevention or
treatment of disease conditions in a mammal mediated by overexpressed or altered PTP 1B
enzyme.
Yet another embodiment of the invention is to use compound of general formula (I) or their
pharmaceutically acceptable salts in the manufacture of medicaments useful for treatment or
delaying the onset or progression of diabetes.
Yet another embodiment of the invention is to use compound of general formula (I) or their
pharmaceutically acceptable salts in the manufacture of medicaments useful for treatment of
impaired glucose tolerance and insulin resistance.
Yet another embodiment of the invention is to use compound of general formula (I) or their
pharmaceutically acceptable salts in the manufacture of medicaments useful for treatment of
obesity.
Yet another embodiment of the invention is to use compound of general formula (I) or their
pharmaceutically acceptable salts in the manufacture of medicaments useful for treatment of
autoimmune disorders, acute and chronic inflammatory disorders, osteoporosis, cancer,
malignant disorders.

In a further embodiment of the invention, in addition to the treatment of disorders mediated by
PTP 1B, the compound of formula (I) or their pharmaceutically acceptable salts are also useful
for the development and standardization of in vitro and in vivo test systems for the evaluation of
the effects of inhibitors of PTP 1B for the search of a new therapeutic agents.
In further embodiment, the invention encompasses pharmaceutical compositions for treating
PTP-1B mediated diseases as defined above comprising a therapeutically effective amount of the
active compound of general formula (I) and one or more other pharmaceutically active
compounds, such as anti-diabetic compounds, anti-obesity compounds, and compounds that
improve the lipid profile of the patient.
Thus, the methods of treatment or prevention described herein may further be comprised of
administering to said patient a second anti-diabetic compound in an amount effective to treat,
control, or prevent diabetes with the PTP-1B inhibitors of this invention.
Similarly, the methods of treatment or prevention described herein may further be comprised of
administering to said patient a second anti-obesity compound in an amount effective to treat,
control, or prevent obesity with the PTP-1B inhibitors of this invention.
Similarly, the methods of treatment or prevention described herein may further be comprised of
administering to said patient a cholesterol lowering compounds, in an amount effective to
improve the lipid profile in combination with a PTP-1B inhibitor of this invention. This may be
beneficial in treating or preventing atherosclerosis and other metabolic conditions that often are
associated with Type 2 diabetes.
Examples of other pharmaceutically active compounds that may be combined with a compound
of Formula (I) and administered in combination with the PTP-1B inhibitors comprises of the
following therapeutic classes but not limited to antidiabetics including insulin sensitizers such as
PPAR.gamma. agonists; biguanides; insulin or insulin mimetics; sulfonylureas; alpha.-
glucosidase inhibitors; PPAR.alpha/gamma dual.agonists; glucokinase activators; glycogen

phosphorylase inhibitors; AGE breakers; AGE inhibitors; meglitinides; SGLT2 inhibitors and the
like, cholesterol lowering agents such as HMG-CoA reductase inhibitors; sequestrants; nicotinyl
alcohol, nicotinic acid or a salt thereof; fibrates; inhibitors of cholesterol absorption for example
beta-sitosterol; acyl CoAxholesterol acyltransferase inhibitors; and the like, antiobesity
including appetite suppressants; neuropeptide Y5 inhibitors; leptin, which is a peptidic hormone;
beta3 adrenergic receptor agonists; cannabinoid receptor antagonists; PPAR.gamma. antagonists
and partial agonists; bile acid transporter inhibitors; and the like.
Where a second active compound is used in addition to an active compound of formula (I) as
described herein, the two compounds may be administered together in a single composition,
concomitantly, or on separate dosing schedules.
Effect of treatment with Compound of formula (I) on Fasted Glucose, Non
Fasted Glucose and Insulin Tolerance test in Diet Induced Obese Mice
Objective
To assess the effect of Compound of formula (I) (200 mg/kg, i.p.) on fasted and non-fasted blood
glucose and insulin tolerance test in high fat fed C57BL/6 male mice.
Animals and Diet;
In house bred C57BL/6 male mice (about 8 weeks old) were put on high fat diet. Diets for these
animals were purchased from Research Diet, USA.
Materials:
Human actrapid®, Accu-Check Sensor® glucometer and glucometer strips.
Method:
Blood was collected by tail snip for the estimation of non-fasted and 4 hr fasted blood glucose
(day 0) using an Accu-Check Sensor glucometer. Animals were then randomized into two
groups, Compound of formula (I) (Compound No. 28) treated (200 mg/kg, i.p. for 4 days) and

vehicle control group (10 ml/kg, i.p. for 4 days) with their non-fasted and 4 hr fasted blood
glucose evenly matched.
On day 2 post dosing, 4 hr fasted blood glucose level was estimated.
Similarly on day 4, one hour post dosing, non fasted blood glucose value was estimated and then
the animals were subjected to insulin tolerance test. Blood samples were collected for glucose
estimation at 15, 30, 60 and 120 min. post insulin challenge.
Analysis
Percent change in fasted and non-fasted blood glucose was calculated from their corresponding
baseline blood glucose values (day 0). In the insulin tolerance test, the glucose values at various
time points during were plotted against time and the AUC blood glucose was calculated.
Results:
Fasted and non-fasted blood glucose
The percent change in fasted and non-fasted blood glucose values in the treatment group were
significantly decreased as compared to the vehicle control group (figure 1, A and B)
Intraperitoneal Insulin Tolerance Test (ITT)
During the ITT performed at the end of 4 days of treatment, Compound treated animals showed
significant decreases in blood glucose post insulin challenge as compared to vehicle treated
animals indicating improved insulin sensitivity as seen from AUC blood glucose (figure 2)
Discussion:
Various researchers have reported that Protein Tyrosine Phosphatases particularly PTP-1B
function as negative regulators of insulin signaling cascade, which leads to suppression of insulin
action. Reducing PTP1B abundance not only enhances insulin sensitivity and improves glucose
metabolism but also protects against obesity induced by high fat diet (Barry J. Goldstein, 2002).

High fat fed C57BL/6 mice are prone to develop obesity, hyperinsulinemia, insulin resistance
glucose intolerance, and diabetes (Bo Ahren et al 2004). Compounds of formula (I) inhibit PTP-
1B enzyme in the in vitro assay. During in vivo studies, compound of formula (I) (compound no
28) has shown significant improvement in fasted and non-fasted blood glucose and has improved
insulin sensitivity as seen from insulin tolerance test. Thus it can be concluded that compound of
formula (I) by virtue of its inhibitory action on enzyme Protein Tyrosine Phosphatase (PTP-1B)
are promising for the treatment and prevention of diseases mediated by PTP 1B, particularly
diabetes, insulin resistance.

REFERENCES:
Barry J. Goldstein (2002) The Journal of Endocrinology & Metabolism 87(6), 2474-2480
Bo Ahren. et al. (2004) Diabetes. 53 (3): S215-S219
Cheng et al. (2002) Developmental Cell 2, 497-503
Elchebly et al. (1999) Science 283, 1544-1548
Flint AJ et. Al. (1993) The EMBO J. 12, 1937-1946
Gum RJ. et al. (2003) Diabetes 52, 21-28
Hubbard SR. (1997) The EMBO J. 16 (18), 5573-81
Kishor M. Wasan & Norbert A. Looije (2005) J Pharm Pharmaceut Sci (www.cspscanada.org)
8(2), 259-271
Klaman et al. (2000) Molecular & Cellular Biology 20(15), 5479-5489
Mauro LJ et al. (1994) J Biol Chem 269, 30659-30667
Moller et al. (2000) Current Opinion in Drug Discovery & Development 3 (5), 527-540
Noguchi T.et al. (1994) Mol. Cell. Biol. 14, 6674-6682
Rocchini AP. (2002) NEJM 346, 854-55
Rondinone et al. (2002) Diabetes 51, 2405-2411
Sinha R. et al. (2002) NEJM 346, 802-10
Taylor SD. & Hill B. (2004) Expert Opin. Investig. Drugs 13(3), 199-214
Wiener JR. et al. (1994) J. Natl. Cancer Inst. 86 (5): 372-378
Zinker et al. (2002) PNAS 99 (17), 11357-11362
Biochemical Pharmacology 54: 703-711(1997).
From the foregoing description, one skilled in the art can easily ascertain the essential
characteristics of this invention, and without departing from the spirit and scope thereof, can
make various changes and modifications of the invention to adapt it to various usages and
conditions.

We claim:
1. A compound represented by formula (I),





'L' is selected from -NH-, -NH-CH2-, -NH-CH (CH3)-, -NH-CH-C(O)NH-, -NH-CH2-
CH2-, -NHNH-, -NH-CH(COOH)-CH2, -N(CH2COOH);
'C is a member selected from the group consisting of:
i) Phenyl ii) Naphthyl iii) Indolyl iv) Thiazolyl v) Benzimidazolyl
'Y' is selected from the group consisting of:


p is 1, 2 or 3;
R1 is selected from the group consisting of:
i) Hydrogen ii) -CH2COOR4 iii) -X(CH2)n -aryl, where n is selected from 0, 1 or 2, and
X is selected from S, NH or O, iv) -S-alkyl, v) -OR4 vi)OCH2cycloalkyl, wherein
cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl
or cyclooctyl vii) -CH2CONH2, viii)-CN, ix) Halo x) alkyl xi) -SO2aryl xii) -CF3 xiii) -
CO2R4 xiv) -COalkyl xv) -NH2 xvi) -NO2 xvii) -CH2CONH-PhCH2COOR4 xviii)
Tetrazolyl xix) Triazolyl xx) Pyrrolyl xxi) Benzimidazolyl xxii) Pyrazolyl xxiii)
Phthalamoyl xxiv) Phenyl optionally substituted with one or more group selected from
cyano, amino, carboxy, halo, nitro, alkyl, hydroxyl, -O-alkyl xxv) Biphenyl xxvi) -
OCH2CO2R4 xxvii) Pyridyl xxviii) Thienyl xxix) Dimethylamino xxx), -CH2OH xxxi) -
CF2H xxxii) -SO2NHR4 xxxiii) NHCOalkyl xxxiv) -OCF3


i) Hydrogen ii) -CH2COOR4 iii) -S-alkyl iv) -OR4 v) -CH2CONH2 vi)-CN, vii) Halo
viii) alkyl ix) -CF3 x) -COOR4 xi) aryl xii) -COalkyl xiii) -NH2 xiv) -NO2 xv) -CF2H
xvi) thienyl xvii) NHCOalkyl xviii) -OCF3;
R4 is selected from hydrogen or alkyl;
R5 is selected from the group consisting of
i) -COOR4 wherein R4 is as defined above,
ii) -C(O)C(O)OH,

R6 is selected from the group consisting of
i) hydrogen,
ii) -OR4,
iii) alkyl,
iv) halo,
v) heterocyclyl,
vi) -S alkyl,

vii) -S-aryl,
viii) -COOH,
ix) Benzyl,
x) heteroaryl;
R7 is selected from the group consisting of
i) alkyl,
ii) hydrogen,
iii) halo;
or R6 and R7 together may form cycloalkane ring selected from the group of
cyclopentane, cyclohexane, cyclobutane;
R8 and R9 are independently selected from the group consisting of
i) hydrogen,
ii) halo,
iii) -OR4,
iv) alkyl,
v) -CONHR4,
i) -COalkyl;
R10 is selected from the group consisting of
i) Alkyl, ii)Aryl;
R11 is selected from the group consisting of
i) hydrogen,
ii) alkyl,
iii) aryl;
and with the proviso that:
i) when R5 is -C(O)C(O)OH, then ' Y' is (i), and p is null
ii) when A is phenyl and is substituted by R1 at fourth position then R1 is not
-X(CH2)n-aryl;
or a pharmaceutically acceptable salt or prodrug thereof.





wherein z is selected from aryl or heteroaryl, optionally substituted by a group
independently selected from H, alkyl, Halo, nitro, -OR4, CF3 and CONHR4;
R6 and R7 are independently selected from hydrogen or halogen ;
R8 and R9 are independently selected from the group consisting of
i) hydrogen,
ii) halo,
iii) -OR4,
iv) alkyl,
v) -CONHR4
vi) COOR4,
vii) -COalkyl
4. The compound as claimed in claim 1, wherein said compound is selected from the
group consisting of:
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound
no. 1)
{4-[5-(l-Carboxymethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2ylamino]-phenyl}-acetic
acid. (Compound no. 2)
{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 3)
{4-[5-(4-Methylsulfanyl-benzylidene)-4-oxo-4, 5-dihydro-thiazol-2-yIamino]-phenyl}-acetic acid.
(Compound no. 4)
[4-(5-Benzylidene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no. 5)
{4-[5-(4-Methoxy-naphthalen-l-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 6)
{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 7)
{4-[5-(lH-Indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 8)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
9)
{4-[5-(3-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 10)
{4-[5-(l-tert-Butoxycarbonylmethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 11)
[4-(4-Oxo-5-quinolin-2-ylmethylene-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
12)
{4-[5-(l-Benzofuran-2-yl-ethylidene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 13)
{3-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 14)

{4-[5-(l-Carbamoylmethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 15)
[3-(5-Naphthalen-2-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound
no. 16)
{4-[5-(2'-Cyano-biphenyl-4-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 17)
{4-[4-Oxo-5- (4-pyrrol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 18)
(4-{4-Oxo-5- [4-(lH-tetrazol-5-yl)-benzylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no. 19)
(4-{5-[2-Butyl-5-chioro-3-(2'-cyano-biphenyi-4-ylmethyl)-3H-imidazoI-4-ylmethylene]-4-oxo-4,5-dihydro-
thiazol-2-ylamino}-phenyl)-acetic acid. (Compound no. 20)
{3-[5-(3-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 21)
(4-{2-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-lamino]-acetyl amino}-
phenyl)-acetic acid. (Compound no. 22)
{3-[5-(l-Carbamoylmethyl-lH-indol-3-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 23)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-benzyl]-phosphonic acid diethyl
ester. (Compound no. 24)
4-Methyl-N-{2-[4-(5-naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazoI-2-ylamino)-phenyl]-acetyl}-
benzene sulfonamide. (Compound no. 25)
N- (2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4, 5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyI-benzenesuIfonamide. (Compound no. 26)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-methyl-
benzenesulfonamide. (Compound no. 27)
N- {2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-methyl-
benzenesulfonamide sodium salt. (Compound no. 28)
(4-{4-Oxo-5-[l-(toluene-4-sulfonyl)-lH-indol-3-ylmethylene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 29)
(3-{4-Oxo-5-[l-(toluene-4-sulfonyl)-lH-indol-3-ylmethylene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 30)
{4-[5-(3,4-Dichloro-benzylidene)-4-oxo-4, 5-dihydro-thiazol-2-ylarnino]-phenyl}-acetic acid. (Compound
no.31)
{4-[5-(3-Hydroxy-naphthalen-2-ylmethyIene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 32)
5-(3-Benzyloxy-naphthalen-2-ylmethylene)-2-[4-(lH-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one.
(Compound no. 33)
[4-(N'-{4-Oxo-5-[4-(lH-tetrazol-5-yl)-benzylidene]-4,5-dihydro-thiazol-2-yl}-hydrazino)-phenyl]-acetic
acid. (Compound no. 34)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-N-hydroxy-acetamide.
(Compound no. 35)
(4-{5-[4-(Morpholine-4-carbonyl)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no. 36)
{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 37)
{4-[5-(2-Butyl-5-chloro-3H-imidazol-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 38)
(4-{5-[4-(2-Fluoro-4-nitro-phenoxy)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic
acid. (Compound no. 39)

(4-{4-Oxo-5-[4-(piperazine-l-carbonyl)-benzylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no, 40)
5-(6-Methoxy-naphthalen-2-ylmethylene)-2-[4-(lH-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one.
(Compound no. 41)
3-[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionic acid.
(Compound no. 42)
3-{4-[5-(l-Carboxymethyl-1H-indol-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-lamino]-phenyl}-
propionic acid. (Compound no. 43)
{3-[2-(4-Methylsulfamoylmethyl-phenlamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-indol-l-yl}-acetic acid.
(Compound no. 44)
{4-[4-Oxo-5-(4-tetrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 45)
3-{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-propionic
acid. (Compound no. 46)
{5-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-acetic
acid. (Compound no. 47)
2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-butyric
acid. (Compound no. 48)
3-{4-[5-(3-Benzyloxy-naphthalen-2~ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-propionic
acid. (Compound no. 49)
(4-{5-[3-(l,3-Dioxo-l,3-dihydro-isoindol-2-yl)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-acetic acid. (Compound no. 50)
{4-[4-Oxo-5-(3-pyrrol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 51)
N-Methyl-C-[4-(5-naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-
methanesulfonamide. (Compound no. 52)
2-[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionicacid.
(Compound no. 53)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionicacid.
(Compound no. 54)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-succinic acid. (Compound
no.55)
{4-[5-(4-Hydroxy-3,5-dimethoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 56)
(4-{5-[l-(6-Methoxy-naphthalen-2-yl)-ethylidene]-4-oxo-4,5-dihydro-thiazol-2-lamino}-phenyl)-acetic
acid. (Compound no. 57)
3-{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-lamino]-phenyl}-propionic
acid. (Compound no. 58)
{4-[4-Oxo-5-(3,4,5-trimethoxy-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 59)
(4-{5-[l-(4-Bromo-phenyl)-1H-pyrrol-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 60)
(4-{4-Oxo-5-[l-(3-pyrrol-l-yl-phenyl)-ethylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-acetic acid.
(Compound no. 61)
{4-[4-Oxo-5-(l-phenyl-1H-pyrrol-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 62)
C-{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-N-methyi-
methanesulfonamide. (Compound no. 63)
C-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-N-ethyl-
methanesulfonamide. (Compound no. 64)
C-{4-[5-(2'-Cyano-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-N-methyl-

methanesulfonamide. (Compound no. 65)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-bromo-acetic acid.
(Compound no. 66)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-benzyl]-malonic acid. (Compound
no. 67)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-morpholin-4-yl-acetic acid.
(Compound no. 68)
N-(2-{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-lamino]-phenyl}-acetyl)-
4-methyl-benzenesulfonamide sodium salt. (Compound no. 69)
5-Naphthalen-2-ylmethylene-2-[4-(lH-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one. (Compound no.
70)
{4-[4-Oxo-5-(4-oxo-4H-chromen-3-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 71)
{4-[4-Oxo-5-(4-trifluoromethyl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 72)
{4-[5-(6-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 73)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4, 5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
74)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-bromo-sodium acetate.
(Compound no. 75)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-orpholin-4-yl-sodiumacetate.
(Compound no. 76)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-propionic acid.
(Compound no. 77)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate. (Compound
no. 78)
{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 79)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate.
(Compound no. 80)
{4-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 81)
{5-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-sodium
acetate. (Compound no. 82)
{4-[4-Oxo-5-(3-pyrrol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 83)
2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
butyrate. (Compound no. 84)
(4-{5-[3-(4-Fluoro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 85)
{4-[5-(9,9a-Dihydro-4aH-fluoren-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 86)
{4-[4-Oxo-5-(3-[l,2,4]triazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 87)
{4-[5-(3-Benzoimidazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 88)
3-[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium propionate.
(Compound no. 89)
(4-{4-Oxo-5-[3-(4-pyridin-2-yl-piperazin-l-yl)-benzylidene]-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 90)

{4-[4-Oxo-5-(3-pyrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 91)
{4-[4-Oxo-5-(3-tetrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 92)
5-(3-Benzyloxy-naphthalen-2-ylmethylene)-2-[4-(5H-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one
sodium salt. (Compound no. 93)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
94)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate. (Compound
no. 95)
3-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethy!ene)-4-oxo-4, 5-dihydro-thiazol-2-lamino]-phenyl}-sodium
propionate. (Compound no. 96)
[5-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-indol-l-yl]-sodium acetate.
(Compound no. 97)
5-(6-Methoxy-naphthalen-2-ylmethylene)-2-[4-(5H-tetrazol-5-ylmethyl)-phenylamino]-thiazol-4-one
sodium salt. (Compound no. 98)
{5-[5-(6-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-sodium
acetate. (Compound no. 99)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-oxazol-2-ylamino)-phenyl]-acetic acid. (Compound no.
100)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-oxazol-2-ylamino)-phenyl]-sodium acetate. (Compound
no. 101)
N-(2-{4-[4-Oxo-5-(4-phenyl-cyclohexa-1,5-dienylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-benzenesulfonamide sodium salt. (Compound no. 102)
N-(2-{4-[4-Oxo-5-(4-pyrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide. (Compound no. 103)
N-(2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesuIfonamide sodium salt. (Compound no. 104)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-chloro-
benzenesulfonamide sodium salts. (Compound no. 105)
4-Chloro-N-(2-{4-[5-(6-methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-benzenesulfonamide sodium salt. (Compound no. 106)
4-Chloro-N-(2-{4-[4-oxo-5-(4-pyrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide sodium salt. (Compound no. 107)
N-(2-{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide. (Compound no. 108)
[4-(4-Oxo-5-l,l';4',l"]terphenyl-ylmethylene-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid.
(Compound no. 109)
{4-[5-(6-Bromo-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 110)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-oxo-acetic acid.
(Compound no. 111)
4-Methyl-N-{2-[4-(5-naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-
benzenesulfonamide sodium salt. (Compound no. 112)
(4-{5-[3-(4-Fluoro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 113)
C-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-N-
methyl-methanesulfonamide. (Compound no. 114)
{4-[5-(2-Benzyloxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 115)
{4-[5-(3-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium

acetate. (Compound no. 116)
{4-[5-(3-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 117)
N-(2-{4-[5-(2-Benzyloxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-methyl-
benzenesulfonamide sodium salt. (Compound no. 118)
{4-[5-(2-Benzyloxy-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 119)
(4-{5-[2-(2'-Cyano-biphenyl-4-ylmethoxy)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 120)
[4-(5-Benzo[l,3]dioxol-5-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid.
(Compound no. 121)
{4-[5-(2-Benzyloxy-4-tetrazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 122)
{4-[5-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 123)
{4-[4-Oxo-5-(l-phenyl-5-pyrrol-l-yl-1H-pyrazol-3-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 124)
N-(2-{4-[5-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide. (Compound no. 125)
N-(2-{4-[5-(2,3-Dihydro-benzo[l,4]dioxin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide. (Compound no. 126)
N-(2-{4-[5-(2-Benzyloxy-4-tetrazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide sodium salt. (Compound no. 127)
[2-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-thiazol-4-yl]-sodium acetate.
(Compound no. 128)
{4-[4-Oxo-5-(3-phenethyloxy-naphthalen-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 129)
[2-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-thiazol-4-yl]-acetic acid. (Compound
no. 130)
N-(2-{4-[5-(3-Benzyloxy-4-tetrazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methyl-benzenesulfonamide sodium salt. (Compound no. 131)
{4-[5-(5-Methyl-l-phenyl-1H-pyrazol-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 132)
{2-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-thiazol-4-yl}-acetic
acid. (Compound no. 133)
{2-[5-(5-Methyl-l-phenyl-1H-pyrazol-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-thiazol-4-yl}-
acetic acid. (Compound no. 134)
{4-[5-(3-Cyclopentylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 135)
2-{4-[5-(3-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-3-phenyl-
sodium propionate. (Compound no. 136)
{4-[5-(4-Fluoro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound no.
137)
{4-[4-Oxo-5-(3-propoxy-naphthalen-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 138)
{4-[5-(l-Isopropyl-l,2,3,4-tetrahydro-quinolin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 139)
{4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 140)
{4-[5-(l-Methyl-l,2,3,4-tetrahydro-quinolin-6-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 141)

(4-{4-Oxo-5-[3-(tetrahydro-furan-2-ylmethoxy)-naphthalen-2-ylmethylene]-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetic acid. (Compound no. 142)
4-[5-(6-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 143)
{4-[5-(3,5-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 144)
{4-[4-Oxo-5-(2-phenyl-thiazol-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate,
(compound no. 145)
{4-[5-(1 -Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 146)
{4-[4-Oxo-5-(4-tetrazol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 147)
{4-[4-Oxo-5-(4-pyrrol-l-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodiumacetate.
(Compound no. 148)
{4-[5-(4-Benzyloxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 149)
{4-[5-(l-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 150)
{4-[5-(l-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 151)
{4-[5-(4'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 152)
[4-(5-[2,2']Bithiophenyl-5-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate.
(Compound no. 153)
3-{4-[5-(1-Hydroxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
propionate. (Compound no. 154)
2-{4-[5-(l-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
butyroate. (Compound no. 155)
{5-[5-(l-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-indol-l-yl}-
sodiumacetate. (Compound no. 156)
(4-{5-[5-Bromo-2-(2'-cyano-biphenyl-4-ylmethoxy)-benzylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 157)
N-(2-{4-[5-(4'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylmethyl]-phenyl}-acetyl)-
4-methyl-benzenesulfonamide sodium salt. (Compound no. 158)
{5-[5-(4'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylmethyl]-indol-l-yl}-sodium
acetate. (Compound no. 159)
{4-[5-(2,3-Dihydro-benzofuran-5-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 160)
4-{4-[2-(4-Carboxymethyl-phenylamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-phenyl}-l-methyl-
pyridinium; chloride sodium salt. (Compound no. 161)
(4-{5-[3-(4-Nitro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 162)
{4-[5-(6-Carboxymethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 163)
{4-[5-(3,7-Dimethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 164)
{4-[5-(6-Fluoro-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 165)
{4-[5-(3,5-Dimethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 166)
(4- {5 -[3 -(4-Methy 1-benzy loxy)-naphthalen-2-y lmethylene]-4-oxo-4,5 -dihydro-thiazol-2-ylamino} -phenyl)-

sodium acetate. (Compound no. 167)
4-Methyl-N-[2-(4-{5-[3-(4-methyl-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide sodium salt. (Compound no. 168)
(4-{4-Oxo-5-[3-(thiophen-2-ylmethoxy)-naphthalen-2-ylmethylene]-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 169)
(4-[5-(lH-Indol-5-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 170)
[4-(5-Naphthalen-2-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetic acid ethyl ester.
(Compound no. 171)
3-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium propionate.
(Compound no. 172)
4-Methyl-N-[2-(4-{4-oxo-5-[4-(4-pyridin-2-yl-piperazin-l-yl)-benzylidene]-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide sodium salt. (Compound no. 173)
{4-[5-(4'-Methyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 174)
{4-[5-(6-Isopropyl-4-oxo-4H-chromen-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 175)
N-(2-{4-[5-(3-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
4-methyl-benzenesulfonamide sodium salt. (Compound no. 176)
3-{4-[5-(3-Methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
propionate. (Compound no. 177)
{4-[5-(2-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 178)
{4-[5-(3-Carboxymethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 179)
(4-{5-[3-(2-Methoxy-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 180)
(4-{5-[3-(3-Methoxy-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium acetate. (Compound no. 181)
(4-{5-[3-(4-Chloro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 182)
3-(4-{5-[3-(4-Methyl-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium propionate. (Compound no. 183)
3-(4-{5-[3-(4-Chloro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-sodium propionate. (Compound no. 184)
{4-[5-(6-Hydroxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 185)
[4-(5-Biphenyl-3-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodium acetate. (Compound
no. 186)
N-(2-{4-[5-(2-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide sodium salt. (Compound no. 187)
{4-[5-(3,7-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 188)
{4-[5-(4'-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 189)
{4-[5-(4-Morpholin-4-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 190)
4'-[2-(4-Carboxymethyi-phenylamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-biphenyl-4-carboxylic acid.
(Compound no. 191)
{4-[4-Oxo-5-(5-phenyl-thiophen-2-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 192)

[4-(5-Benzo[b]thiophen-3 -ylmethylene-4-oxo-4,5-dihy dro-thiazol-2-y lamino)-pheny 1]-sodium acetate.
(Compound no. 193)
{4-[5-(3'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 194)
{4-[5-(4'-Ethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 195)
{4-[4-Oxo-5-(4'-pyrrol-l-yl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 196)
(4- {5 -[3 -(2-Fluoro-benzy loxy)-naphthalen-2-y lmethy lene]-4-oxo-4,5 -dihydro-thiazol-2-ylamino} -phenyl)-
sodium acetate. (Compound no. 197)
{4-[5-(4'-Hydroxymethyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 198)
{4-[5-(4'-Hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 199)
5-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-2-carboxymethyl-benzoic acid.
(Compound no. 200)
{4-[5-(4'-Carboxymethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 201)
[4-( 1 -Carboxymethyl-5-naphthalen-2-yl-1 H-[ 1,2,4]triazol-3-ylamino)-pheny 1]-acetic acid. (Compound no.
202)
{4-[5-(3,8-Dimethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic
acid. (Compound no. 203)
4-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-sodiumbutyroate.
(Compound no. 204)
3-{4-[5-(6-Fluoro-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
propionate. (Compound no. 205)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-2-fluoro-phenyl]-sodium acetate.
(Compound no. 206)
{4-[5-(2'-Methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 207)
{4-[5-(4'-Difluoromethyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 208)
{4-[5-(3',5'-Difluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 209)
{4-[4-Oxo-5-(4'-sulfamoyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 210)
{4-[5-(3-Methyl-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 211)
N-(2-{4-[5-(4'-Hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide di-sodium salt. (Compound no. 212)
[3-(4-Oxo-2-{4-[2-oxo-2-(toluene-4-sulfonylamino)-ethyl]-phenylamino}-4H-thiazol-5-ylidenemethyl)-
naphthalen-2-yloxy]-acetic acid. (Compound no. 213)
N-(2-{4-[5-(4'-Ethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide sodium salt. (Compound no. 214)
N-(2-{4-[5-(4'-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide sodium salt. (Compound no. 215)
{4-[5-(3-Fluoro-4'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 216)
{4-[5-(3-Benzyloxy-4-tetrazol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 217)
Fluoro-{2fluoro-4-[5-(4'- methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-

phenyl}-acetic acid. (Compound no. 218)
N-{2-[4-(5-Biphenyl-4-ylraethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-
trifluoromethyl-benzenesulfonamide, sodium salt. (Compound no. 219)
{4-[5-(4'-Methylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 220)
{4-[5-(2',4'-Difluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 221)
{2-Fluoro-4-[4-oxo-5-(4'-pyrrol-l-yl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 222)
Thiophene-2-sulfonic acid {2-[4-(5-biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-
phenyl]-acetyl}-amide, sodium salt. (Compound no. 223)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-fluoro-
benzenesulfonamide, sodium salt. (Compound no. 224)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-
methanesulfonamide, sodium salt. (Compound no. 225)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-acetyl}-4-methoxy-
benzenesulfonamide, sodium salt. (Compound no. 226)
{4-[4-Oxo-5-(4'-trifluoromethoxy-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 227)
{4-[5-(3-Fluoro-4'-hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 228)
{4-[5-(3'-Fluoro-4'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 229)
{4-[5-(4'-Acetylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 230)
{4-[4-Oxo-5-(4'-trifluoromethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 231)
{4-[5-(4'-Cyclohexylmethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 232)
{4-[5-(3'-Fluoro-4'-hydroxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl} -acetic
acid, disodium salt. (Compound no. 233)
{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 234)
4-Methyl-N-(2-{4-[5-(4'-methylsulfai\yl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-benzenesulfonamide sodium salt. (Compound no. 235)
{2-Fluoro-4-[5-(6-methoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
sodium acetate. (Compound no. 236)
{4-[4-Oxo-5-(4-pyridin-4-yl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 237)
{4-[5-(3-Fluoro-4'-methylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-sodium acetate. (Compound no. 238)
N-(2-{4-[5-(3-Fluoro-4'-methylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-trifluoromethyl-benzenesulfonamide sodium salt. (Compound no. 239)
{4-[5-(6-Benzyloxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 240)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-2-fluoro-phenyl]-3-methoxy-but-2-
enoic acid ethyl ester. (Compound no. 241)
{4-[5-(4-Methyl-3-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium acetate.
(Compound no. 242)
{4-[5-(4'-Cyano-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 243)

{4-[5-(l-Biphenyl-4-yl-ethylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid. (Compound
no. 244)
N-{2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-oxazol-2-ylamino)-phenyl]-acetyl}-4-methyl-
benzenesulfonamide. (Compound no. 245)
{4-[5-(6-Isopropoxy-5-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 246)
{4-[5-(5-Chloro-2-methoxy-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 247)
2-[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-3-(4-fluoro-phenyl)-acrylic
acid ethyl ester. (Compound no. 248)
N-(2-{4-[5-(l-Biphenyl-4-yl-ethylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-methyl-
benzenesulfonamide. (Compound no. 249)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-hydroxyimino-acetic acid
ethyl ester. (Compound no. 250)
N-(2-{4-[5-(6-Isopropoxy-5-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-methyl-benzenesulfonamide. (Compound no. 251)
(4-{5-[5-(4-Methoxy-phenyl)-isoxazol-3-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
sodium acetate. (Compound no. 252)
{4-[5-(2-Fluoro-biphenyl-4-ylmethyl)-4-oxo-4,5-dihydro-oxazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 253)
N-(2-{4-[5-(5-Chloro-2-methoxy-4-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-methyl-benzenesulfonamide. (Compound no. 254)
{4-[5-(3',5'-Difluoro-4-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 255)
[4-(5-Biphenyl-4-ylmethylene-4-oxo-4,5-dihydro-thiazol-2-ylamino)-phenyl]-oxo-acetic acid. (Compound
no. 256)
l-{4-[5-(2-Fluoro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
cyclopentanecarboxylic acid sodium salt. (Compound no. 257)
N-(2-{4-[5-(6-Hydroxy-5-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-methyl-benzenesulfonamide. (Compound no. 258)
4-Methyl-N-(2-{4-[5-(4-methyl-3-pyrrol-l-yl-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-benzenesulfonamide, sodium salt. (Compound no. 259)
{4-[5-(3',5'-Difluoro-4-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-acetic acid. (Compound no. 260)
{2-Fluoro-4-[4-oxo-5-(3,2',4',5'-tetrafluoro-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 261)
-{4-[4-Oxo-5-(4'-propoxy-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-sodium
acetate. (Compound no. 262)
{4-[5-(4'-Cyclopropylmethoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 263)
{4-[5-(2-Benzyloxy-3,5-diiodo-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 264)
{4-[5-(2,4'-Dimethoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
acetic acid. (Compound no. 265)
3-{4-[5-(6-Ethoxycarbonylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-propionic acid. (Compound no. 266)
Bromo-(2-fluoro-4-{5-[l-(4-nitro-phenyl)-ethylidene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-phenyl)-
acetic acid. (Compound no. 267)
{4-[5-(4'-Benzylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
bromo-acetic acid. (Compound no. 268)
{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-oxazol-2-ylamino]-2-fluoro-phenyl}-

acetic acid. (Compound no. 269)
N-(2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-methoxy-benzenesulfonamide. (Compound no. 270)
2-{2-Fluoro-4-[4-oxo-5-(4-pyrrol-l-yl-benzyl)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-butyric acid.
(Compound no. 271)
{4-[5-(4'-Amino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid ethyl
ester. (Compound no. 272)
Methoxy-{4-[5-(4'-nitro-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thia
zol-2-ylamino]-phenyl}-acetic acid. (Compound no. 273)
4-Methyl-N-[2-(4-{5-[4'-(4-nitro-phenylsulfanyl)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide. (Compound no. 274)
N-[2-(4-{5-[4'-(2-Fluoro-4-nitro-phenylamino)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-4-methyl-benzenesulfonamide. (Compound no. 275)
[4'-(4-Oxo-2-{4-[2-oxo-2-(toluene-4-sulfonylamino)-ethyl]-phenylamino}-4H-thiazol-5-ylidenemethyl)-
biphenyl-4-yl]-acetic acid butyl ester. (Compound no. 276)
4-Methyl-N-[2-(4-{5-[4'-(4-nitro-phenoxy)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-benzenesulfonamide. (Compound no. 277)
4-Methyl-N-(2-{4-[4-oxo-5-(4-tetrazol-l-yl-benzylidene)-4,5-dihydro-oxazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide. (Compound no. 278)
N-(2-{4-[5-(4'-Acetyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide. (Compound no. 279)
Thiophene-2-sulfonic acid(2-{4-[5-(3-ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-acetyl)-amide. (Compound no. 280)
Bromo-{4-[5-(3,5-dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetic acid. (Compound no. 281)
2-{4-[5-(4'-Amino-3-fluoro-3'-methoxycarbonyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-octanedioic acid. (Compound no. 282)
{2-{4-[5-(3-Isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-5-
methyl-hexanoic acid. (Compound no. 283)
2-(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-octanedioic acid. (Compound no. 284)
2-{2-Fluoro-4-[5-(5'-fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-butyric acid. (Compound no. 285)
2-(2-Fluoro-4-{5-[l-(4-nitro-phenyl)-ethylidene]-4-oxo-4,5-dihydro-oxazol-2-ylamino}-phenyl)-propionic
acid. (Compound no. 286)
6-(4'-{2-[4-(Bromo-carboxy-methyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-biphenyl-
4-ylsulfanyl)-hexanoic acid. (Compound no. 287)
2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
octanedioic acid. (Compound no. 288)
2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-5-methyl-hexanoic acid. (Compound no. 289)
2-{2-Fluoro-4-[4-oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-butyric acid, (compound no. 290)
3-Methoxy-2-{4-[5-(4'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acrylic acid. (Compound no. 291)
Bromo-{4-[5-(5-bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl} -acetic acid. (Compound no. 292)
2-{2-Fluoro-4-[5-(4'-hydroxy-3'-hydroxymethyl-5'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-
thiazol-2-ylamino]-phenyl}-pentanoic acid. (Compound no. 293)
2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
octanedioic acid. (Compound no. 294)

4-Amino-4'-{2-[4-(l-carboxy-ethyl)-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-fluoro-biphenyl-
3-carboxylic acid methyl ester. (Compound no. 295)
4-Amino-4'-{2-[4-(bromo-carboxy-methyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-
fluoro-biphenyl-3-carboxylic acid methyl ester. (Compound no. 296)
4-Amino-4'-{2-[4-(l-carboxy-butyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-fluoro-
biphenyl-3-carboxylic acid methyl ester. (Compound no. 297)
4-Amino-4'-{2-[4-(carboxy-pyrrol-l-yl-methyl)-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-
fluoro-biphenyl-3-carboxylic acid methyl ester. (Compound no. 298)
N-(2-{4-[5-(3-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
nitro-benzenesulfonamide. (Compound no. 299)
{4-[5-(3-Benzyloxy-naphthalen-2-ylmethyl)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetic
acid. (Compound no. 300)
N-(2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-trifluoromethyl-benzenesulfonamide. (compound no. 301)
{4-[5-(4'-Acetyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 302)
[4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-(l-hydroxy-
ethyl)-phenyl]-acetic acid. (Compound no. 303)
2-{4-[5-(l,4-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
pentanoic acid. (Compound no. 304)
N-(2-{4-[5-(l,4-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-3-fluoro-4-methyl-benzenesulfonamide. (Compound no. 305)
6-(4'-{2-[4-(l-Carboxy-propyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-3'-fluoro-
biphenyl-4-ylsulfanyl)-hexanoic acid. (Compound no. 306)
2-{4-[4-Oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethyl)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-propionic
acid. (Compound no. 307)
{2-Fluoro-4-[5-(5'-fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-hydroxy-acetic acid. (Compound no. 308)
2-(4-{5-[4'-(5-Carboxy-pentylsulfanyl)-3-fluoro-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-octanedioic acid. (Compound no. 309)
(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-2-
fluoro-phenyl)-bromo-acetic acid. (Compound no. 310)
4-(3-{2-[4-(l-Carboxy-butyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-naphthalen-2-
yloxymethyl)-benzoic acid ethyl ester. (Compound no. 311)
N-(2-{4-[5-(5-Bromo-2-hydroxy-3-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-nitro-benzenesulfonamide. (compound no. 312)
2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-6-methyl-heptanoic acid. (Compound no. 313)
Ethylsulfanyl-{4-[5-(3-isopropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 314)
2-{4-[5-(l,4-Diethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
propionic acid. (Compound no. 315)
2-{4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-butyric acid. (Compound no. 316)
6-(4'-{2-[4-(Carboxy-phenylsulfanyl-methyl)-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-biphenyl-
4-ylsulfanyl)-hexanoic acid . (Compound no. 317)
N-(2-{2-Fluoro-4-[4-oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetyl)-4-propyl-benzenesulfonamide. (Compound no. 318)
N-(2-{4-[5-(2,4-Dimethoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetyl)-
4-methyl-benzenesulfonamide. (Compound no. 319)
N-(2-{4-[5-(4-Chloro-3-nitro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-ethyl-

benzenesulfonamide. (Compound no. 320)
N-(2-{4-[5-(3,5-Di-tert-butyl-4-hydroxy-benzyIidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-4-trifluoromethyl-benzenesulfonamide. (Compounds no. 321)
N-(2-{4-[5-(5-Bromo-2-methoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-4-
methyl-benzenesulfonamide. (Compound no. 322)
2-{4-[5-(3-Ethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-octanedioic
acid. (Compound no. 323)
2-(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-2-
fluoro-phenyl)-butyric acid. (Compound no. 324)
N-[2-(4-{5-[3-(Biphenyl-4-ylmethoxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-ylamino}-
phenyl)-acetyl]-4-methoxy-benzenesulfonamide. (Compound no. 325)
4-(3-{2-[4-(Carboxy-hydroxy-methyl)-3-fluoro-phenylamino]-4-oxo-4H-thiazol-5-ylidenemethyl}-
naphthaIen-2-yloxymethyl)-benzoic acid ethyl ester. (Compound no. 326)
4-[3-(2-{4-[2-(4-Fluoro-benzenesulfonylamino)-2-oxo-ethyl]-phenylamino}-4-oxo-4H-thiazol-5-
ylidenemethyl)-naphthalen-2-yloxymethyl]-benzoic acid ethyl ester. (Compound no. 327)
3-Fluoro-N-[2-(4-{5-[3-(4-fluoro-benzyloxy)-naphthalen-2-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-acetyl]-4-methyl-benzenesulfonamide. (Compound no. 328)
[6-(4-Oxo-2-{4-[2-oxo-2-(thiophene-2-sulfonylamino)-ethyl]-phenylamino}-4H-thiazol-5-ylidenemethyl)-
naphthalen-2-yloxy]-acetic acid tert-butyl ester. (Compound no. 329)
N-(2-{4-[5-(4'-Dimethylamino-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-methanesulfonamide. (Compound no. 330)
Bromo-{4-[5-(3,5-dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl}-acetic acid. (Compound no. 331)
2-{4-[5-(6-tert-Butoxycarbonylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
2-fluoro-phenyl}-butyric acid. (Compound no. 332)
N-(2-{4-[5-(4'-Hydroxy-3'-hydroxymethyl-5'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-
2-ylamino]-phenyl}-acetyl)-methanesulfonamide. (Compound no. 333)
2-{4-[5-(4'-Hydroxy-3'-hydroxymethyl-5'-methoxy-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-
ylamino]-phenyl}-6-methyl-heptanoic acid. (Compound no. 334)
{2-Fluoro-4-[4-oxo-5-(3,4,5-trimethoxy-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetic acid.
(Compound no. 335)
4-Methyl-N-(2-{4-[4-oxo-5-(3,4,5-trimethoxy-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
acetyl)-benzenesulfonamide. (Compound no. 336)
2-{4-[5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-
octanedioic acid. (Compound no. 337)
2-{4-[5-(2,4-Dimethoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-propionic
acid. (Compound no. 338)
Bromo-{4-[5-(4-chloro-3-nitro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetic
acid, (compound no. 339)
2-{4-[5-(5'-Fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-octanedioic acid. (Compound no. 340)
Bromo-{4-[5-(3,4-dipropoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-acetic
acid. (Compound no. 341)
2-{4-[5-(3,5-Dibromo-4-hydroxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-phenyl}-
propionic acid. (Compound no. 342)
Bromo-{2-fluoro-4-[4-oxo-5-(2',4',6'-trimethyl-biphenyl-4-ylmethylene)-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-acetic acid. (Compound no. 343)
4-Ethyl-N-(2-{4-[5-(2-fluoro-5-nitro-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-phenyl}-acetyl)-
benzenesulfonamide. (Compound no. 344)
{4-[5-(6-tert-Butoxycarbonylmethoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-
fluoro-phenyl}-acetic acid. (Compound no. 345)

2-{2-Fluoro-4-[4-oxo-5-(4-trifluoromethyl-benzylidene)-4,5-dihydro-thiazol-2-ylamino]-phenyl}-pentanoic
acid. (Compound no. 346)
Thiophene-2-sulfonic acid(2-{4-[5-(3,4-dipropoxy-benzylidene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-
fluoro-phenyl}-acetyl)-amide. (Compound no. 347)
2-{4-[5-(4'-Benzylsulfanyl-biphenyl-4-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-2-fluoro-
phenyl }-pentanoic acid. (Compound no. 348)
2-(2-Fluoro-4-{5-[4'-(2-fluoro-4-nitro-phenylamino)-biphenyl-4-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-
ylamino}-phenyl)-butyric acid, (compound no. 349)
{4-f5-(5'-Fluoro-4-hydroxy-2'-methoxy-biphenyl-3-ylmethylene)-4-oxo-4,5-dihydro-thiazol-2-ylamino]-
phenyl}-(4-methyl-piperazin-l-yl)-acetic acid. (Compound no. 350)
4'-[2-(4-Carboxymethyl-3-fluoro-phenylamino)-4-oxo-4H-thiazol-5-ylidenemethyl]-biphenyl-4-carboxylic
acid butyl ester. (Compound no. 351)
{4-[5-(3,5-Dipropoxy-naphthalen-2-ylmethylene)-4-oxo-4,5-dihydro-oxazol-2-ylamino]-2-fluoro-phenyl}-
acetic acid. (Compound no. 352)
and its pharmaceutically acceptable salts and prodrugs thereof.
5. A pharmaceutical composition comprising a therapeutically effective amount of a
compound of claim 1 and a pharmaceutically acceptable carrier, diluent or
excipient.
6. The pharmaceutical composition as recited in claim 5, wherein said
pharmaceutical composition is in the form of an oral formulation or a parenteral
formulation.
7. The pharmaceutical composition as recited in claim 5, further comprising a
second compound, which is an anti-diabetic or anti-obesity effective compound.
8. The pharmaceutical composition as claimed in claim 5, wherein said composition
is useful for inhibiting protein tyrosine phosphatase in a mammal in need thereof.
9. The pharmaceutical composition as claimed in claim 5, wherein said composition
is useful for treating disorders caused by overexpressed or altered protein tyrosine
phosphatase 1B, in a mammal in need thereof.
10. The pharmaceutical composition as claimed in claim 5, wherein said composition
is useful for treating glucose intolerance and insulin resistance, in a mammal in
need thereof.
11. The pharmaceutical composition as claimed in claim 5, wherein said composition
is useful for treating metabolic disorders mediated by insulin resistance or
hyperglycemia in a mammal in need thereof.
12. The pharmaceutical composition as claimed in claim 5, wherein said composition
is useful for treating or delaying the progression and onset of diabetes in a
mammal in need thereof.

13. The pharmaceutical composition as claimed in claim 5, wherein said composition
is useful for treating obesity in a mammal in need thereof.
14. The pharmaceutical composition as claimed in claim 5, wherein said composition
is useful for treating autoimmune disorders, acute and chronic inflammatory
disorders, osteoporosis or cancer in a mammal in need thereof.
15. Compounds, processes for their preparation, pharmaceutical compositions
containing them or methods for treatment or uses involving them as herein
described with reference to the examples.

The present invention encompasses the novel substituted heterocyclic compounds
represented by formula (I) or their pharmaceutically acceptable salts, wherein the
substituents in formula (I) have the meanings as defined in the specification.
The invention also encompasses process for preparing such compound, pharmaceutical
compositions and methods of treating or preventing PTP-1B mediated diseases.