FIELD OF THE INVENTION:
The present invention relates to novel thiazolo and oxazolo pyrimidinone compounds
of formula (I), their pharmaceutically acceptable salts, and their isomers, steroisomers,
conformers, tautomers, polymorphs, hydrates and solvates. The present invention also
encompasses pharmaceutically acceptable compositions of said compounds and process for
preparing novel compounds. The invention further relates to the use of the above-mentioned
compounds for the preparation of medicament for use as pharmaceuticals.
BACKGROUND OF THE INVENTION:
The transcription factor HIF (Hypoxia Inducible Factor) has a central role in oxygen
homeostasis. An early response to tissue hypoxia is induction of Hypoxia Inducible Factor
(HIF), a basic helix-loop-helix (bHLH) PAS (Per/Arnt/Sim) transcriptional activator that
mediates changes in gene expression in response to changes in cellular oxygen concentration.
HIF is a heterodimer consisting of a constitutively expressed beta subunit and one of the two
alpha subunits, HIFα1 and HIFα2.1
In oxygenated (normoxic) cells, HIFα subunits are rapidly degraded by a mechanism
that involves ubiquitination by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase
complex. Under hypoxic conditions, HIFa is not degraded, and an active HIFα/β complex
accumulates in the nucleus and activates the expression of several genes including glycolytic
enzymes, glucose transporter (GLUT)-1, erythropoietin (EPO), vascular endothelial growth
factor (VEGF) and adrenomedullin.1
Thus, HIF activation is one of the prominent adaptive mechanisms associated with
hypoxia/ ischemia. As mentioned, HIF activation results in enhanced expression of genes
which perform multiple functions to cope up with and to recover from hypoxic/ischemic
conditions.2
In oxygenated cells (normoxic), two conserved proline residues of HIFa subunits
undergo hydroxylation. This reaction is catalysed by HIF prolyl-hydroxylases (PHD). Prolyl
hydroxylated HIFa interacts with pVHL and rapidly gets degraded by proteasome
machinery. In addition, in normoxic cells, one conserved asparagine of HIFa also undergoes
hydroxylation. This reaction is catalysed by HIF asparagyl hydroxylase (FIH). Asparagyl
hydroxylated HIFa can not interact with transcriptional co-activator CBP/p300.

Under hypoxic/ ischemic conditions, both HIF prolyl and HIF aspargyl hydroxylase
activities are drastically lowered due to limiting amount of molecular oxygen. As a result,
HIFα is not destined for proteasome degradation and hence stabilized. Further, HIFα can
interact with transcriptional co-activator CBP/p300. Such stabilized and transcriptionally
active HIFa then forms heterodimer with HIF-beta subunit and translocates to the nucleus
and bring about transactivation of HIF target genes1.
Inhibition of HIF prolyl hydroxylases and HIF asparagyl hydroxylase, thus can be a
powerful approach for oxygen- independent activation of HIF. Such HIF activation by
pharmacological means results in enhanced expression of genes which perform multiple
functions to cope up with and to recover from hypoxic/ischemic conditions. HIF targets
include genes responsible for vasomotor regulation (e.g. Adrenomedullin, eNOS, Haem
Oxygrenase), energy metabolism (e.g. Glut-1, carbonic anhydrase-9), angiogenic signaling
(e.g. VEGF, VEGF receptor-1) and erythropoiesis (e.g. Erythropoietin, Transferrin,
transferrin receptor)1. Therefore, HIF activation can offer significant therapeutic benefits in
various disease conditions such as anemia of various types and tissue injuries caused by
hypoxia/ischemia in conditions like acute kidney injury, myocardial infarction, stroke,
hepatic ischemia-reperfusion injury, peripheral vascular diseases and transplantation of liver
or kidney3,4,5,6,7,8
Anemia is characterised by decrease in normal number of red blood cells, which is
generally caused by loss of blood (hemorrhage), excessive red blood cell destruction
(hemolysis) or deficient red blood cell production (ineffective hematopoiesis). Since
hemoglobin normally carries oxygen from the lungs to the tissues, anemia leads to hypoxia in
organs. Since all human cells depend on oxygen for survival, anemia can have a wide range
of clinical consequences.
Anemia occurs often in elderly, in cancer patients, particularly those receiving
chemotherapy & undergoing radiation, patients with renal diseases and in a wide variety of
conditions associated with chronic diseases. Frequently, the cause of anemia is reduced
erythropoietin (EPO) production resulting in prevention of erythropoiesis.
Erythropoietin (EPO), a naturally occurring hormone that is produced in response to
HIFa, stimulates the production of erythrocytes. EPO is normally secreted by the kidneys,
and endogenous EPO is increased under conditions of reduced oxygen (hypoxia)9.

Exogeneous administration of EPO is one of the accepted modalities of treatment of
anemia particularly in chronic renal failure patients, cancer patients undergoing radiation
and/or chemotherapy; however its use is limited by high cost and increased risk for
thrombosis and hypertension1 .
Ischemia is defined as an absolute or relative shortage of oxygen to a tissue or organ
and can result from disorders such as atherosclerosis, diabetes, thromboembolisms,
hypotension, etc. The heart, brain and kidney are especially sensitive to ischemic stress
caused by low blood supply.
Ischemia can be an acute (sudden onset and short duration) or chronic (slow onset
with long duration or frequent recurrence). Acute ischemia is often associated with regional,
irreversible tissue necrosis (an infarct), whereas chronic ischemia is usually associated with
transient hypoxic tissue injury. If the decrease in perfusion is prolonged or severe, however,
chronic ischemia can also be associated with an infarct. Infarctions commonly occur in the
spleen, kidney, lungs, brain, and heart, producing disorders such as intestinal infarction,
pulmonary infarction, ischemic stroke, and myocardial infarction.
Ischemic and hypoxic disorders are a major cause of morbidity and mortality.
Currently, treatment of ischemic and hypoxic disorders is focused on relief of
symptoms and treatment of causative disorders but none of these therapies directly address
the tissue damage produced by the ischemia and hypoxia.
Exogenous administration of some of the HIF target genes such as erythropoietin,
VEGF, adrenomedullin has shown significant functional recovery in ischemia and ischemia-
reperfusion injury of heart, kidney, brain and liver.11,12,13,14
Due to deficiencies in current treatments of anemia & diseases due to hypoxia and
ischemia, there remains a need for compounds that are effective in treating anemias of
different types such as anemia in elderly or anemia associated with chronic diseases or renal
failure or cancer or infection or dialysis or surgery or chemotherapy and in ischemic/hypoxic
disorders such as acute kidney injury, myocardial infarction, stroke, hepatic ischemia-
reperfusion injury and peripheral vascular diseases.
The compounds of this invention provide a means for inhibiting HIF hydroxylases
and thereby activating the HIF, which results in enhanced expression of the wide spectrum of
target genes including erythropoietin (EPO), vascular endothelial growth factor (VEGF),

adrenomedullin etc. and thus useful in treating various disorders including anemia of
different types and conditions associated with ischemia/hypoxia.
EP 661269 discloses substituted heterocyclic carboxylic acid amides and their use as
inhibitors of prolyl-4-hydroxylase and as inhibitors of collagen biosynthesis.
Additionally, various patent publications such as WO2003049686, WO2003053997,
WO2004108121, WO2007146425, WO2007146438 disclose the compounds that stabilize
HIFα and their use for the prevention and treatment of conditions associated with ischemia &
hypoxia and EPO associated conditions like anemia and neurological disorders.
JP 5039293 discloses a various fused and substituted thiazolopyrimidine derivative or
it's salt, useful as an immunomodulating agent.
International publications WO2009039321 and WO2009039322 disclose bicyclic
heteroaromatic N-substituted glycine derivatives, which are antagonists of HIF prolyl
hydroxylases and are useful for treating diseases benefiting from the inhibition of these
enzymes like anemia.
SUMMARY OF THE INVENTION:
In one embodiment, the present invention provides novel compounds of formula (I),

their pharmaceutically acceptable salts and their isomers, stereoisomers, conformers,
tautomers, polymorphs, hydrates, and solvates;
Wherein,
when Y is NR4, O, S or SO2, m is 1 to 2 and when Y is C(R5)(R6) m is 1 to 4;
n is 1 to 6;
P is -OH, -OR7, -NH2, -NHR7, -NR7 R7-, -NHSO2R7, -NHCOR7, -NHOH or -NHOR7;
X is -OH, -OR7, -SR7, -SOR7, -SO2R7, -NHR7 or-NR7R7';
Z is S or O;
R is hydrogen, linear or branched (C1-C8)alkyl, -(C1-C8)alkylaryl or -(C1-C8)alkylheteroaryl;

R1 and R2 are independently selected from hydrogen, linear or branched -(C1-C8)alkyl, - (C3-
C7) cycloalkyl, aryl, heteroaryl, -CH2-aryl and -CH2-heteroaryl, or
R1 and R2 may join together to form a 3-6 membered monocyclic or 9-12 membered bicyclic
ring;
R together with either R1 or R2 of adjacent carbon atom may form a 3-6 membered
monocyclic or 8-11 membered bicyclic heteroaryl or heterocyclyl ring;
R3 and R3' at each occurance is independently selected from hydrogen, linear or branched
(C1-C8)alkyl, (C1-C5) alkoxy and halo;
R3 and R3' may also present in gem di-halo, gem di-alkyl or spirocycoalkyl arrangement;
R4 is selected from the group consisting of hydrogen, linear or branched (C1-C8) alkyl, (C3-
C7) cycloalkyl, aryl, heteroaryl, -(C1-C8) alkyl-aryl, -(C1-C8)alkyl-heteroaryl, -(C1-C2)alkyl-
heterocyclyl, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -C(S)NR8R9 and -SO2R8, wherein aryl and
heteroaryl radicals are optionally substituted with one or more substituent selected from the
group consisting of-(C1-C8) alkyl, -(C3-C7) cycloalkyl, heterocyclyl, aryl, heteroaryl, -OH, -
alkoxy, halo, CN, -CF3, -OCF3, -O-aryl, -SO2-(C1-C8)-alkyl, -SO2-aryl, -NH2, -NHR10, -
NR10R10', -NH-CO-(C1-C8) alkyl, -NH-SO2-(C1-C8)alkyl, -NH-SO2-aryl, -COOH, -
C(O)NH-alkyl, -CONH-aryl, -CONH-heteroaryl , -C(O)O-(C1-C8)alkyl, -C(O)O-aryl, -
SO2NH-(C1-C8)alkyl, -SO2NH-aryl and -SO2NH-heteroaryl;
R5 and R6 are independently selected from the group consisting of hydrogen, linear or
branched (C1-C8)alkyl, (C3-C7) cycloalkyl, aryl, heteroaryl, fluoro, -COOH, -CONH-(C1-
C8)alkyl, -NHCO-(C1-C8)alkyl, -NHCO-aryl , -NHCO-heteroaryl, -NH-SO2(C1-C8)alkyl, -
NH-SO2-aryl and - NH-SO2-heteroaryl;
R5 and R6 may join together to form a 3-6 membered carbocyclic, heteroaryl or heterocyclyl
ring;
R7, R7', R10 and R10' are independently selected from linear or branched (C1-C8)alkyl, (C3-C7)
cycloalkyl and -(C1-C8)alkylaryl;
R7 and R7' or R10 and R10' together with nitrogen atom to which they are attached, may form
5-6 membered monocyclic or 8-14 membered bicyclic saturated and partially saturated ring.
The ring may contain 1 to 3 heteroatom selected from N, S & O. Wherein saturated and
partially saturated ring may be optionally substituted with one or more substituent
independently selected from the group consisting of -(C1-C8)alkyl, -(C3-C7) cycloalkyl,
6

heterocyclyl, aryl, heteroaryl, -OH, -alkoxy, halo, -CN, -CF3, -OCF3, -O-aryl, -SO2-(C1-C8)-
alkyl, -SO2-aryl, -NH2, -NHR10, -NR10R10', -NH-CO-(C1-C8)alkyl, -NH-SO2-(C1-C8)alkyl, -
NH-SO2-aryl, -COOH, -C(O)NH-alkyl, -CONH-aryl, -CONH-heteroaryl , -C(O)O-(C1-
C8)alkyl, -C(O)O-aryl, -SO2NH-(C1-C8)alkyl, -SO2NH-aryl and -SO2NH-heteroaryl;
Rg is selected from the group consisting of linear or branched (C1-C8) alkyl, (C3-C7)
cycloalkyl, -(C1-C8)alkyl-(C3-C7)cycloalkyl, heterocyclyl, aryl, -(C1-C8)alkyl-aryl, -(C1-
C2)alkyl- heterocyclyl, heteroaryl and -(C1-C8)alkyl-heteroaryl, wherein aryl and heteroaryl
radicals are optionally substituted with one or more substituent selected from linear or
branched (C1-C8)alkyl, (C3-C7)cycloalkyl, -(C1-C8)alkyl-(C3-C7)cycloalkyl, aryl, heteroaryl,
heterocyclyl, -OH, alkoxy, halo, -CN, -CF3, -OCF3, -O-aryl, -SO2-(C1-C8)alkyl, -SO2-aryl, -
NH2, -NHR10, -NR10R10', -NH-CO-(C1-C8)alkyl, -NH-SO2-(C1-C8)alkyl, -C(O)OH, -
C(O)NH-(C1-C8)alkyl, -CONH-aryl, -CONH-heteroaryl, -NHC0NH-(C1-
C8)alkyl, -NHCONH-aryl, -SO2NH-(C1-C8)alkyl, -SO2NH-aryl and -SO2NH-
heteroaryl;
R9 is hydrogen, linear or branched (C1-C8)alkyl or -(C1-C8)alkylaryl;
R8 and R9 together with nitrogen atom to which they are attached, may form 5-6 membered
saturated ring.
In another embodiment, the present invention pertains to a compound as above,
however only including pharmaceutically acceptable salts thereof.
In another embodiment, the present invention includes synthetic intermediates that
are useful in preparing the compounds of formula (I) and process for preparing such
intermediates.
Another embodiment of the present invention is a method for preparation of a
compound of formula (I) as herein described in Schemes A, B, C, D & E.
Another embodiment of the present invention is a pharmaceutical composition
comprising a compound of formula (I), optionally in admixture with a pharmaceutically
acceptable adjuvant, diluent or carrier.
Another embodiment of the present invention is a method for treating anemia by
administering a therapeutically effective amount of a compound of formula (I) to a mammal
in need thereof.

Another embodiment of the present invention is a method for treating anemia of
elderly or anemia associated with conditions like chronic diseases, renal failure, cancer,
infection, dialysis, surgery, and chemotherapy by administering a therapeutically effective
amount of a compound of formula (I) to a mammal in need thereof.
Another embodiment of the present invention is a method for prevention or treatment
of tissue damage caused by renal ischemia, cardiovascular ischemia, cerebrovascular
ischemia, hepatic ischemia or peripheral vascular ischemia by administering a therapeutically
effective amount of a compound of formula (I) to a mammal in need thereof.
Another embodiment of the present invention is a method for prevention or treatment
of tissue damage caused by ischemic disorders including acute kidney injury, myocardial
infarction, stroke, hepatic ischemia-reperfusion injury and peripheral vascular diseases by
administering a therapeutically effective amount of a compound of formula (I) to a mammal
in need thereof.
Another embodiment of the present invention is a method for prevention or treatment
of tissue damage caused by ischemia-reperfusion injury while transplantation procedures of
organs like liver or kidney by administering a therapeutically effective amount of a
compound of formula (I) to a mammal in need thereof.
Another embodiment of the present invention is the use of a compound of formula (I)
for the preparation of a medicament for treating anemia.
Another embodiment of the present invention is the use of a compound of formula (I)
for the preparation of a medicament for treating anemia of elderly or anemia associated with
conditions like chronic diseases, renal failure, cancer, infection, dialysis, surgery and
chemotherapy.
Another embodiment of the present invention is the use of a compound of formula (I)
for the preparation of a medicament for prevention or treatment of tissue damage caused by
renal ischemia, cardiovascular ischemia, cerebrovascular ischemia, hepatic ischemia or
peripheral vascular ischemia.
Another embodiment of the present invention is the use of a compound of formula (I)
for the preparation of a medicament for prevention or treatment of tissue damage caused by
ischemic disorders including acute kidney injury, myocardial infarction, stroke, hepatic
ischemia-reperfusion injury and peripheral vascular diseases.

Another embodiment of the present invention is the use of a compound of formula (I)
for the preparation of a medicament for prevention or treatment of tissue damage caused by
ischemia-reperfusion injury while transplantation procedures of organs like liver or kidney.
DETAILED DESCRIPTION OF THE INVENTION:
In one embodiment, the present invention provides novel compounds of formula (I),

their pharmaceutically acceptable salts and their isomers, stereoisomers, conformers,
tautomers, polymorphs, hydrates and solvates, wherein R, R1, R2, R3, R3', X, Y, Z, m, n and P
are as defined above.
A family of specific compounds of particular interest within the above formula (I)
consists of compound and pharmaceutically acceptable salts thereof as follows:
Compd. Chemical Name
No.
1 [(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino] -acetic acid
2 3-(Carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,8-dihydro-4H,6H-9-thia-
l,4a,7-triaza-fluorene-7-carboxylic acid ethyl ester
3 [(2-Hydroxy-7-methanesulfonyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fiuorene-3 -carbonyl)-amino] -acetic acid
4 {[2-Hydroxy-7-(3-methyl-butyryl)-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
5 {[2-Hydroxy-4-oxo-7-(propane-2-sulfonyl)-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
6 1 -[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino] -cyclopentanecarboxylic acid

Compd. Chemical Name
No.
7 {[2-Hydroxy-4-oxo-7-(toluene-4-sulfonyl)-5,6,7,8-tetrahydro-4H-9-thia-
l,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
8 [(2-Hydroxy-4-oxo-7-phenylcarbamoyl-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3-carbonyl)-amino]-acetic acid
9 [(7-Cyclopropanecarbonyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl)-amino]-acetic acid
10 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo [a] azulene-3 -carbonyl)-amino] -acetic acid
11 [(2-Hydroxy-4-oxo-7,8-dihydro-4H,6H-cyclopenta[4,5]thiazolo[3,2-
a]pyrimidine-3-carbonyl)-amino]-acetic acid
12 [(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3 -
carbonyl)-amino]-acetic acid, sodium salt
13 [(7-tert-Butyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3 -carbonyl)-amino] -acetic acid
14 3-[(2-Hydroxy-4-oxo-7,8-dihydro-4H,6H-cyclopenta[4,5]thiazolo[3,2-
a]pyrimidine-3 -carbonyl)-amino] -propionic acid
15 3-[(7-tert-Butyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l ,4a-diaza-
fluorene-3-carbonyl)-amino]-propionic acid
16 {[7-(4-Fluoro-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
17 {[7-(5-Chloro-thiophene-2-sulfonyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-
4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
18 {[2-Hydroxy-4-oxo-7-(5-trifluoromethyl-pyridin-2-yl)-5,6,7,8-tetrahydro-
4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino }-acetic acid
19 {[2-Hydroxy-4-oxo-7-(4-trifluoromethoxy-benzenesulfonyl)-5,6,7,8-
tetrahydro-4H-9-thia-l,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
20 {[7-(2,2-Dimethyl-propionyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-
thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
21 {[7-(4-Butyl-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-

Compd. Chemical Name
No.
triaza-fluorene-3 -carbonyl] -amino} -acetic acid
22 {[2-Hydroxy-4-oxo-7-(4-trifluoromethoxy-benzoyl)-5,6,7,8-tetrahydro-4H-
9-thia-l1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
23 {[7-(4-Chloro-benzyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3 -carbonyl] -amino} -acetic acid
24 {[7-(4-Fluoro-phenylthiocarbamoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-
4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
25 [(2-Hydroxy-7-isopropylthiocarbamoyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl)-amino]-acetic acid
26 3-(Carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,8-dihydro-4H,6H-9-thia-
1,4a,7-triaza-fluorene-7-carboxylic acid benzyl ester
27 {[7-(2-Cyclopropyl-acetyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3 -carbonyl] -amino} -acetic acid
28 ({7-[2-(4-Chloro-phenyl)-acetyl]-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-
thia-1,4a,7-triaza-fluorene-3 -carbonyl} -amino)-acetic acid
29 {[7-(2-Cyclopentyl-acetyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3 -carbonyl] -amino} -acetic acid
30 3-[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-propionic acid
31 {[2-Hydroxy-7-(4-methoxy-benzyl)-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
32 2-[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo [a] azulene-3 -carbonyl)-amino] -propionic acid
33 {[7-(6-Chloro-pyridine-3-carbonyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-
9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
34 [(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3 -carbonyl)-amino] -acetic acid
35 {[7-(6-Chloro-pyridazin-3-yl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-
thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid

Compd. Chemical Name
No.
36 {[7-(3-Cyano-pyridin-2-yl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
37 {[7-(3-Chloro-4-methoxy-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-
9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
38 [(2-Hydroxy-4-oxo-5,6,7,8,9,10-hexahydro-4H-ll-thia-l,4a-diaza-
cycloocta[a] indene-3 -carbonyl)-amino] -acetic acid
39 [(2-Hydroxy-7-indan-5-ylmethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a,7-
triaza-fluorene-3 -carbonyl)-amino] -acetic acid
40 2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino]-propionic acid
41 {[7-(3,5-Dimethoxy-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-
thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
42 {[2-Hydroxy-7-(4-methanesulfonyl-benzoyl)-4-oxo-5,6,7,8-tetrahydro-4H-
9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
43 2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-3-methyl-butyric acid (L-isomer)
44 2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino]-propionic acid (D-isomer)
45 {[7-(3,5-Dichloro-4-methoxy-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-
4H-9-thia-l,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
46 {[7-(3,5-Bis-trifluoromethyl-benzyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-
4H-9-thia-1,4a,7-triaza-fluorene-3 -carbonyl] -amino} -acetic acid
47 {[2-Hydroxy-4-oxo-7-(4-propyl-benzoyl)-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
48 {[7-(3,5-Bis-trifluoromethyl-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-
4H-9-thia-1,4a,7-triaza-fluorene-3 -carbonyl] -amino } -acetic acid
49 {[7-(3,4-Dichloro-benzyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
50 [(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-

Compd. Chemical Name
No.
carbonyl)-amino] -acetic acid, hydrochloride salt
51 {[2-Hydroxy-7-(7-methoxy-6-methyl-indan-4-ylmethyl)-4-oxo-5,6,7,8-
tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3 -carbonyl] -amino} -acetic acid
52 {[2-Hydroxy-4-oxo-7-(4-trifluoromethyl-benzyl)-5,6,7,8-tetrahydro-4H-9-
thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
53 [(7,7-Diethyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid
54 2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3 -carbonyl)-amino] -2-methyl-propionic acid
55 [(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-phenyl-acetic acid, L-isomer
56 [(7-Benzoylamino-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-
diaza-fluorene-3 -carbonyl)-amino] -acetic acid
57 [(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-oxa-l,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid
58 [(2-Hydroxy-7-methyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid
59 [(2-Hydroxy-4-oxo-7-propyl-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3 -carbonyl)-amino] -acetic acid
60 [(2-Hydroxy-6,6-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid
61 [(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3 -carbonyl)-methyl-amino] -acetic acid
62 1 -[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l ,4a-diaza-
fluorene-3 -carbonyl)-amino] -cyclohexanecarboxylic acid
63 1 -(7,7-Dimethyl-2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-
diaza-fluorene-3 -carbonyl)-piperidine-4-carboxylic acid
64 [(2-Hydroxy-4-oxo-7-phenyl-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid

Compd. Chemical Name
No.
65 [(2-Hydroxy-4-oxo-5,8-dihydro-4H,6H-7-oxa-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino] -acetic acid
66 [(2-Hydroxy-5,7,7-trimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3 -carbonyl)-amino] -acetic acid
67 [(2-Hydroxy-4,7,7-trioxo-5,6,7,8-tetrahydro-4H-71ambda*6*,9-dithia-l,4a-
diaza-fluorene-3-carbonyl)-amino]-acetic acid
68 [(2-Methylsulfanyl-4-oxo-5,8-dihydro-4H,6H-7,9-dithia-l,4a-diaza-
fluorene-3 -carbonyl)-amino] -acetic acid
69 [(5-Ethoxy-2-methylsulfanyl-4-0X0-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid ethyl ester
70 N-[(2'-hydroxy-4'-oxo-6',9'-dihydro-4'H,7'H-spiro[cyclopropane-1,8'-
pyrimido [2,1 -b] [ 1,3]benzothiazol] -3 '-yl)carbonyl] glycine
71 [(7-Isopropyl-2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3 -carbonyl)-amino] -acetic acid
72 3-(Carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-
thia-1,4a-diaza-fluorene-7-carboxylic acid
73 {[7-(3,5-Dimethyl-pyrazol-1-yl)-2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-
4H-9-thia-1,4a-diaza-fluorene-3 -carbonyl] -amino} -acetic acid
74 2-[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-fluorene-3-
carbonyl)-amino] -3 -methyl -pentanoic acid (L-isomer)
75 3-(lH-Indol-2-yl)-2-[(2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
l,4a-diaza-fluorene-3-carbonyl)-amino]-propionic acid (L-isomer)
76 3-(3H-Imidazol-4-yl)-2-[(2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-
thia-1,4a-diaza-fluorene-3-carbonyl)-amino]-propionic acid (L-isomer)
77 3-(4-Hydroxy-phenyl)-2-[(2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-
thia-1,4a-diaza-fluorene-3 -carbonyl)-amino] -propionic acid (L-isomer)
78 [(2-Hydroxy-4-oxo-7-pyridin-4-ylmethyl-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl)-amino]-acetic acid

Compd. Chemical Name
No.
79 2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carboxylic acid (2-oxo-2-pyrrolidin-1 -yl-ethyl)-amide
80 [(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid, Disodium salt
81 [(2-Ethoxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid
82 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-l 0-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, Disodium salt
83 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, arginine salt (2:1)
84 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, lysine salt
85 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, dipotassium salt
86 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo [a] azulene-3 -carbonyl)-amino] -acetic acid, calcium salt (2:1)
87 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, magnesium salt (2:1)
88 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, ammonium salt
89 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia- l,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, diethylamine salt
90 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, choline salt
91 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid, tromethamine salt
92 [(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo [a] azulene-3-carbonyl)-amino]-acetic acid, histidine salt

Compd. Chemical Name
No.
83 2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carboxylic acid carbamoylmethyl-amide
84 2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo[a]azulene-3-carboxylic acid hydroxycarbamoylmethyl-amide
85 [(4-Chloro-benzyl)-(2-methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-
thia-1,4a-diaza-benzo [a]azulene-3 -carbonyl)-amino] -acetic acid
86 4-[Cyclopentyl-(2-methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-
1,4a-diaza-benzo[a]azulene-3-carbonyl)-amino]-butyric acid

97 2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo[a]azulene-3-carboxylic acid (2-oxo-2-pyrrolidin-l -yl-ethyl)-amide
98 2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carboxylic acid cyclohexylcarbamoylmethyl-amide
99 2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo[a]azulene-3-carboxylic acid (benzylcarbamoyl-methyl)-amide
100 4-[Cyclopentyl-(2-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-
diaza-benzo [a] azulene-3 -carbonyl)-amino]-butyric acid
101 [Benzyl-(2-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo [a]azulene-3 -carbonyl)-amino] -acetic acid
DEFINITIONS:
The following definitions apply to the terms as used throughout this specification,
unless otherwise limited in specific instances:
The term "compound" employed herein refers to any compound encompassed by the
generic formula disclosed herein. The compounds described herein may contain one or more
double bonds and therefore, may exist as isomers, stereoisomers, such as geometric isomers,
E and Z isomers, and may possess asymmetric carbon atoms (optical centres) and therefore
may exist as enantiomers, diastereoisomers. Accordingly, the chemical structures described
herein encompasses all possible stereoisomers of the illustrated compounds including the
stereoisomerically pure form (e.g., geometrically pure) and stereoisomeric mixtures

(racemates). The compound described herein, may exist as a conformational isomers such as
chair or boat form. The compounds may also exist in several tautomeric forms including the
enol form, the keto form and mixtures thereof. Accordingly, the chemical structures
described herein encompass all possible tautomeric forms of the illustrated compounds. The
compounds described also include isotopically labeled compounds where one or more atoms
have an atomic mass different from the atomic mass conventionally found in nature.
Examples of isotopes that may be incorporated into the compounds of the invention include,
but are not limited to 2H, 3H, 13C, 14C, 15N, 180,170, etc. 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 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.
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 nomenclature of the compounds of the present invention as indicated herein is
according to ISIS® draw (version 2.2) from MDL & ACD/Labs Pro-version 12.0.
"Pharmaceutically acceptable salt" refers to a salt of a compound, which possesses
the desired pharmacological activity of the parent compound. Such salts include: (1) acid
addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid,
sulfuric acid, nitric acid, carbonic acid, phosphoric acid, and the like; or formed with organic
acids such as acetic acid, propionic acid, isobutyric acid, hexanoic acid,
cyclopentanepropionic acid, oxalic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid,
succinic acid, suberic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid,
benzoic acid, 3-(4-hydroxybenzoyl) benzoic acid, phthalic acid, cinnamic acid, mandelic
acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-
hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-

naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-
methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic
acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid,
glucuronic acid, galactunoric acid, glutamic acid, hydroxynaphthoic acid, salicylic acid,
stearic acid, muconic acid, and the like; or (2) salts formed when an acidic proton present in
the parent compound is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth
ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine,
diethanolamine, triethanolamine, N-methylglucamine and the like. Also included are salts of
amino acids such as arginate and the like (see, for example, Berge, S.M., et al.,
"Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977, 66,1-19).
As used herein, the term "polymorph" pertains to compounds having the same
chemical formula, the same salt type and having the same form of hydrate/solvate but having
different crystallographic properties.
As used herein, the term "hydrate" pertains to a compound having a number of water
molecules bonded to the compound.
As used herein, the term "solvate" pertains to a compound having a number of
solvent molecules bonded to the compound.
The present invention also encompasses compounds which are in a prodrug form.
Prodrugs of the compounds described herein are those compounds that readily undergo
chemical changes under physiological conditions (in vivo) to provide the compounds of the
present invention. Additionally, prodrugs can be converted to the compounds of the present
invention by chemical or biochemical methods in an ex vivo environment, for example,
transdermal patch reservoir with a suitable enzyme or chemical. Prodrugs are, in some
situation, easier to administer than the 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 pharmacological composition over the parent drug. Esters, peptidyl derivatives
and the like, of the compounds are the examples of prodrugs of the present invention. In vivo
hydrolysable (or cleavable) ester of a compound of the present invention that contains a
carboxy group is, for example, a pharmaceutically acceptable ester which is hydrolysed in
the human or animal body to produce the parent acid.

The term "substituted", as used herein, includes mono- and poly-substitution by a
named substituent to the extent such single and multiple substitution (including multiple
substitution at the same site) is chemically allowed and which means that any one or more
hydrogens on the designated atom is replaced with a selection from the indicated group,
provided that the designated atom's normal valence is not exceeded, and that the
substitution results in a stable compound, for example, when a substituent is keto, then the
two hydrogens on the atom are replaced. All substituents (R, R1, R2 ....) and their further
substituents described herein may be attached to the main structure at any heteroatom or
carbon atom which results in formation of stable compound.
As used herein, a "halo" or "halogen" substituent is a monovalent halogen radical
chosen from chloro, bromo, iodo and fluoro.
The term "alkyl" used either alone or in attachement with another group refers to a
saturated aliphatic hydrocarbon radical having the indicated number of carbon atoms and that
is unsubstituted or substituted. When a subscript is used with reference to an alkyl, the
subscript refers to the number of carbon atoms that group may contain. For example, a "C1-
C6" would refer to any alkyl group containing one to six carbons in the structure. Alkyl may
be straight chain, branched chain or cyclic. The said alkyl may be optionally substituted with
substituents at positions that do not significantly interfere with the preparation of compounds
falling within the scope of this invention. The said alkyl is optionally substituted with one to
two substituents independently selected from the group consisting of C1-3alkoxy, amino,
mono(C1-3alkyl)amino, di(C1-3alkyl)amino, C1-3alkyl, and hydroxy.
The term "alkoxy" referes to any alkyl group as defined herein above attached to the
parent molecular moiety through an oxygen breidge.
The term "aryl" refers to an aromatic group for example, which is a 6 to 10 membered
monocyclic or bicyclic carbon-containing ring system, which may be unsubstituted or
substituted.
The term "heteroaryl" refers to an aromatic group for example, which is a 5 to 14
membered monocyclic or bicyclic ring system, which has at least one heteroatom, which may
be unsubstituted or substituted. The term "heteroatom" as used herein includes oxygen, sulfur
and nitrogen.

The term "heterocyclyl" refers to a fully or partially saturated cyclic group, for
example, which is a 3 to 14 membered monocyclic or bicyclic ring system, which has at least
one heteroatom, which may be unsubstituted or substituted. The term "heteroatom" as used
herein includes oxygen, sulfur and nitrogen.
As used herein, "room temperature" refers to a temperature between 25 ° C and 35 ° C.
As used herein, the term "mammal" means a human or an animal such as monkeys,
primates, dogs, cats, horses, cows, etc.
The terms "treating" or "treatment" of any disease or disorder as used herein to mean
administering a compound to a mammal in need thereof. The compound may be administered
thereby providing a prophylactic effect in terms of completely or partially preventing or
delaying the onset of a disease or disorder or sign or symptom thereof; and/or the compound
may be administered thereby providing a partial or complete cure for a disease or disorder
and/or adverse effect attributable to the disorder.
The phrase "a therapeutically effective amount" means the amount of a compound
that, when administered to a patient for treating a disease, is sufficient to effect such
treatment for the disease. 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 patient to be treated.
Throughout this specification and the appended claims it is to be understood that the
words "comprise" and "include" and variations such as "comprises", "comprising",
"includes", "including" are to be interpreted inclusively, unless the context requires
otherwise. That is, the use of these words may imply the inclusion of an element or elements
not specifically recited.
It has been surprisingly found that partially saturated tricyclic compounds containing
one or more heteroatom exhibits better in-vitro activity profile.
In another embodiment, present invention provides the process for preparing the
compounds of formula (I).
The following reaction schemes are given to disclose the synthesis of the compounds
according to the present invention.
Accordingly, the compounds of formula (I) of the present invention may be prepared
as described in the schemes below.

Formula (I) includes, but is not limited to, compounds of formula (Ia), (Ib), (Ic), (Id),
(Ie) (If), (Ig), (Ih), (Ii), (Ij) and (Ik); compound of formula (Ia) includes, but is not limited to,
compounds of formula (Ia-1) and (Ia-2); compound of formula (Ic) includes, but is not
limited to, compounds of formula (Ic-1), (Ic-2) and (Ic-3); compound of formula (Id) include,
but is not limited to, compounds of formula (Id-1) and (Id-2).
The compound of formula (Ia-Ik), which belongs to general formula (I), can be
prepared by the following methods described in schemes A, B, C, D & E.

Compounds belong to general formula (I) such as compound of formula (Ia), (Ib), (Ic)
and (Id), can be synthesized from the compound of formula (III) and (IV) as shown in
scheme A, wherein R, Rl, R2, R3, R3', Z, m and n are as defined above while Y and R4 are
defined in scheme A.
In general, the compound of formula (Ia) can be prepared by reacting the compound
of formula (III) with various amino esters having the following general formula,

wherein, n, R, R1, R2 are as defined as above, using suitable coupling reagent such as
carbodiimides, CDI (1,1'-Carbonyldiimidazole) or PyBop (benzotriazol-1-yl-
oxytripyrrolidinophosphonium hexafiuorophosphate) in the presence of base like tertiary
amine such as triethylamine and in aprotic solvent such as tetrahydrofuran, dichloromethane
etc.

The compound of formula (Ib) can be prepared by the oxidation of compounds of
formula (Ia) with suitable oxidizing reagent such as peracid or hydrogen peroxide in solvent
like dioxan, tetrahydrofuran or dichloromethane at room temperature for 2-6 hrs. The
compound of formula (Ib), upon alkaline hydrolysis in the presence of base including alkali
hydroxide such as sodium hydroxide and in inert solvent like tetrahydrofuran, water or
mixture thereof, provides compound of formula (Ic).
The compound of formula (III) can be prepared by heating appropriate amines of
formula (II) with 5-(bis-ethylsulfanyl-methylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione in
suitable solvent such as alcoholic solvent or dimethylformamide at 80-85°C for 2-24 hrs.
The compound of formula (Id) can be prepared by reacting the compound of formula
(IV) with various amino esters having the following general formula,

wherein, n, R, R1, R2 are as defined as above, in suitable solvent and base such as pyridine at
100-110°C for 2 to 6 hrs.
The compound of formula (Ic) can also be prepared by alkaline hydrolysis of
compound of formula (Id) in the presence of base including alkali hydroxide such as sodium
hydroxide and in inert solvent like tetrahydrofuran, water or mixture thereof.
The compound of formula (IV) can be prepared by reacting the appropriate amines of
formula (II) with triethyl methantricarboxylate in suitable solvent such as xylene, toluene or
bromobenzene at elevated temperature.
The compound of formula (II) such as thiazole-2-amines (Z is S) or oxazole-2-amines
(Z is O) is either synthesized using method described in literature (US 2006/0252837,
US4423048 and J.Med.Chemistry, 2002, 45(23), 5090-5097) or commercially available.


Several N-unsubstituted and N-substituted derivatives belongs to formula (I), such as
compounds of formula (Ie), (Ia-2) and (Ic-1) can be prepared from the compound of formula
(Ia-1), as shown in scheme B, wherein R, R1, R2, R3, R3', R4, R8, R9, m and n are as defined
above.
The compound of formula (Ic-1) can be prepared by oxidation of compounds of
formula (Ia-2) with peracid or hydrogen peroxide in solvent like tetrahydrofuran or
dichloromethane at room temperature for 2-6 hrs, followed by basic hydrolysis in the
presence of base including alkali hydroxide such as sodium hydroxide and in inert solvent
like tetrahydrofuran, water or mixture thereof at room temperature for 2-6 hrs.
The compound of formula (Ia-2) can be prepared by introducing various R4 groups in
compound of formula (Ie), by reacting it with suitable reagents such as sulfonyl chlorides,
carbonyl chlorides, chloroformates, isocyanates, carbamoyl chlorides, isothiocyanates and
carbamothioic chloride in the presence of organic base such as triethylamine, pyridine or N-
methylmorpholine and in solvent like tetrahydrofuran, dichloromethane or mixture thereof at
room temperature for 2-8 hrs.
The compound of formula (Ie) can be prepared by the deprotection of Boc group in
compounds of formula (Ia-1) using acidic reagent like trifluoroacetic acid in inert solvent like
tetrahydrofuran or dichloromethane at room temperature for 2-6 hrs.
The compound of formula (Ia-1) can be prepared from compound of formula (III) as
described in Scheme-A.


In an alternate way, various N-unsubstituted and N-substituted derivatives belongs to
formula (I), such as compounds of formula (If), (Id-2) and (Ic-3) can be prepared from the
compound of formula (Id-1) or (Ic-2), as shown in scheme C. wherein R, R1, R2, R3, R3', R4,
m and n are as defined above.
The compound of formula (Ic-3) can be prepared by alkaline hydrolysis of
compounds of formula (Id-2) in the presence of base including alkali hydroxide such as
sodium hydroxide and in inert solvent like tetrahydrofuran, water or mixture thereof at room
temperature for 2-6 hrs.
The compound of formula (Id-2) can be prepared by introducing various R4 group at
nitrogen of compounds of formula (If) by reacting with R4-Halo, wherein R4 is -CH2-aryl, in
the presence of suitable base like triethylamine, pyridine or N-methylmorpholine and solvent
such as dichloromethane or tetrahydrofuran at room temperature for 5-12 hrs.
The compounds of formula (If) can be obtained by the esterification of compounds of
formula (Ic-2) with ethanol in the presence of carbodiimide followed by removal of Boc
group using acidic reagent like trifluoroacetic acid in an inert solvent like tetrahydrofuran or
dichloromethane.
In an alternate way, the compound of formula (If) can be prepared by the Boc
deprotection of compounds of formula (Id-1) using similar conditions as described in
scheme-B.


Various compounds of formula (I) such as compounds of formula (Ig), (Ih) (Ii) and (Ij) can
be prepared from the compound of formula (Ia) or (Ib), as shown in scheme D, wherein R,
R1, R2, R3, R3', R7, R7',Y, z, m and n are as defined above.
The compound of formula (Ih) can be prepared by reacting the compound of formula
(Ig) with appropriate amine using coupling reagent such as carbodiimides, CDI or PyBop.
The compound of formula (Ij) can be prepared by alkaline hydrolysis of compound of
formula (Ii) in the presence of base including alkali hydroxide such as sodium hydroxide and
in inert solvent like tetrahydrofuran, water or mixture thereof.
The compound of formula (Ii) can be obtained by reacting compounds of formula (Ib)
with sodium alkoxide such as sodium ethoxide in suitable solvent such as tetrahydrofuran at
room temperature.
The compound of formula (Ig) can be prepared by alkaline hydrolysis of the
compound of formula (Ia).


Various compounds of formula (I), such as compounds of formula (Ik) can be
prepared as shown in scheme E, wherein R, R1, R2, R3, R3', Y, z, m and n are as defined
above. The compounds belong to formula (Ik), where P is -NH2, -NHR7, -NR7R7' NHOH and
NHOR7 can be obtained by coupling of formula (Ic) with appropriate amine in suitable
condition such as using coupling reagent such as carbodiimides in suitable aprotic solvent.
Further, compounds belong to formula (I), where P is NHSO2R7 and NHCOR7 can be
obtained by coupling of formula (IV) or (III) or (Ic) with suitable reagenets and conditions.
A general synthetic method is provided for each of the disclosed groups of chemical
compounds. One of ordinary skill will recognize to substitute appropriately modified starting
material containing the various substituents. One of ordinary skill will readily synthesize the
disclosed compounds according to the present invention using conventional synthetic organic
techniques and microwave techniques from starting material which are either purchased or
may be readily prepared using prior art methods.
The compounds of the present invention may have chiral centers and occur as
racemates, racemic mixtures and as individual diastereomers or enantiomers with all isomeric
forms being included in the present invention. Therefore, where a compound is chiral, the
separate enantiomers, substantially free of the other, are included within the scope of the
invention; further included are all mixtures of the two enantiomers.
The novel compounds of the present invention are not, however, to be construed as
forming the only genus that is considered as the invention, and any combination of the
compounds or their moieties may itself form a genus.
The novel compounds of the present invention were prepared according to the
procedure of the schemes as described herein above, using appropriate materials and are
further exemplified by the following specific examples. The examples are not to be
considered nor construed as limiting the scope of the invention set forth.
EXAMPLES:
Example-1:- Preparation of [(2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid (Compound no. 1).


Step-1: Synthesis of 2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carboxylic acid.
The suspension of 4,5,6,7-tetrahydro-benzothiazol-2-yl-amine (8 gm, 0.0519 mol)
and 5-(bis-ethylsulfanyl-methylene)-2,2-dimethyl-[1,3]dioxane-4,6-dione (14.2gm, 0.0572
mol) in ethanol (60 ml) was heated at 85-90°C for 10 hours. Reaction mixture was cooled to
room temperature and filtered. The solid, thus obtained, was washed with ethanol (20 ml)
followed by with diethyl ether (50 ml) and suck dried to give 7.2 gm of title compound as a
solid.
1H-NMR (400 MHz, DMSO-d6): δ 13.55 (1H, s), 3.30-3.34 (2H, m), 2.68-2.72 (2H, m),
2.48(3H,s), 1.88-1.92 (4H,m)
ESMS: 296.9(M++1)
Step-2: Synthesis of [(2-methylsuIfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-acetic acid ethyl ester.
To the solution of acid compound as obtained in step-1 (7.0 gm, 0.0236 mol) in
dichloromethane (250 ml), triehtylamine (9.85 ml, 0.070 mol) and glycine ethyl ester
hydrochloride (4.93 gm, 0.0354 mol) were added at room temperature. To the reaction
mixture, l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.81 gm, 0.0354
mol) was added portion wise at 10-15 °C and was allowed to stir at room temperature for 14
hours. Dichloromethane was distilled off under vacuum. To the residue, water (200 ml) was
added and stirred for 15 minutes. Solid, thus appeared, was filtered and washed with water. It
was further slurred in mixture of ethyl acetate (20 ml) and diethyl ether (30 ml) and filtered.
Solid, thus obtained, was suck dried to give 6.2 gm title compound.
1H-NMR (400 MHz, CDCl3): δ 9.78 (1H,bs), 4.18-4.25 (4H, m), 3.31-3.36 (2H, m), 2.64-
2.69(2H,m), 2.43(3H,s), 1.85-1.90 (4H,m),1.28(3H,t)
ESMS: 382(M++1)
Step-3; Synthesis of [(2-methanesulfonyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fiuorene-3-carbonyl)-amino]-acetic acid ethyl ester.
To the cooled solution of ester compound as obtained in step-2 (6.0 gm, 0.0157 mol)
in dichloromethane (60 ml), a solution of m-chloro perbenzoic acid (50-60%, 8.13 gm) in
dichloromethane (80 ml) was added at 5-10°C and stirred at same temperature for 1 hour.
The reaction mixture was partitioned between dichloromethane and water. Collected organic

layer was washed with sodium bicarbonate, dried over sodium sulphate and distilled off
under vacuum to give crude residue which was purified by column chromatography using
1% methanol-dichloromethane. The collected fractions were evaporated to give 2.5 gm of
title compound.
1H-NMR (400 MHz, CDCl3): δ 7.42 (1H, bs), 4.18-4.27 (4H, m), 3.36-3.37 (2H, m),
3.33 (3H,s), 2.72-2.76 (2H,m), 1.87-1.91 (4H,m),1.30 (3H,t)
ESMS: 413.9 (M++1)
Step-4: Synthesis of [(2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino] -acetic acid.
To the solution of sulfone derivative as obtained in step-3 (2.5 gm, 0.006 mol) in
tetrahydrofuran, a solution of sodium hydroxide (0.75 gm, 0.0187 mol) in water (15 ml) was
added and stirred at room temperature for 4 hours. Tetrahydrofuran was distilled under
vacuum and the remaining solution was acidified by 1N hydrochloric acid and stirred for 30
minutes. Solid, thus appeared, was filtered and washed with ethyl acetate (25 ml) and dried
under vacuum at 60°C for 8 hours to give 1.45 gm title compound as a solid.
1H-NMR (400 MHz, DMSO-d6 ): δ 9.70(1 H,t), 4.06 (2H,d), 3.15-3.21 (2H,m), 2.60-
2.70(2H,m), 1.76-1.80(4H,m)
ESMS: 322 (M+-1)
IR (KBr, CM-1): 3267.9,1734.5,1679.9
Example-2; Preparation of [(2-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-
diaza-benzo [a] azulene-3-carbonyl)-amino]-acetic acid (Compound no. 10)

Step-1: Synthesis of 2-methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-
diaza-benzo [a] azulene-3-carboxylic acid.
The title compound was prepared from 5,6,7,8-tetrahydro-4H-cycloheptathiazol-2-yl-
amine using similar method as described for step-1 of example-1.
1H-NMR (400 MHz, DMSO-d6): δ 3.56-3.59 (2H, m), 2.82-2.85 (2H, m), 2.42 (3H,s), 1.70-
1.83 (6H,m)
ESMS: 310.9 (M++1)

Step-2: Synthesis of [(2-methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-
diaza-benzo[a]azulene-3-carbonyl)-amino]-acetic acid ethyl ester.
The title compound was prepared using similar method as described for step-2 of
example-1.
1H-NMR (400 MHz, CDCl3): δ 9.78 (1H,bs), 4.19-4.25 (4H,m), 3.66-3.69 (2H,m), 2.72-
2.75 (2H,m), 2.42 (3H, s), 1.73-1.89 (6H,m), 1.27 (3H,t)
ESMS: 396 (M++1)
Step-3; Synthesis of [(2-methanesulfonyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-
diaza-benzo[a]azulene-3-carbonyl)-amino]-acetic acid ethyl ester.
To the cooled solution of compound as obtained in step-2 (3.0 gm, 0.0076mol) in
dichloromethane (60 ml), a solution of m-chloro perbenzoic acid (50-60%, 4.50 gm) in
dichloromethane (60 ml) was added at 5-10°C and stirred at same temperature for 3 hours.
Dichloromethane (100 ml) was added to reaction mixture and partitioned between
dichloromethane and water. Organic layer was washed with sodium bicarbonate, dried over
sodium sulphate and distilled off under vacuum to give crude residue which was stirred in
diethyl ether (100 ml). The solid, thus obtained, was collected by filtration and suck dried to
give 2.5 gm of title compound.
1H-NMR (400 MHz, CDCl3): δ 7.36 (1H,bs), 4.19-4.27 (4H,m), 3.68-3.71 (2H,m), 3.33 (3H,
s), 2.80-2.83 (2H,m), 1.78-1.91 (6H,m), 1.30 (3H,t)
ESMS: 428(M++1)
Step-4: Synthesis of [(2-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-diaza-
benzo [a] azulene-3-carbonyl)-amino] -acetic acid.
The title compound was prepared using similar method as described for step-4 of
example-1.
1H-NMR (400 MHz, DMSO-d6): 616.2 (1H, bs), 9.74 (1H, t), 4.06 (2H, d), 3.55-3.60 (2H,
m), 2.75-2.80 (2H, m), 1.70-1.84 (6H, m)
ESMS: 335.9(M+-1)
IR(KBr, CM4): 3268.2, 1739.6, 1674.6
Example-3: Preparation of 3-(carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,8-dihydro-
4H,6H-9-thia-1,4a,7-triaza-fluorene-7-carboxylicacid ethylester (Compound no. 2)

Step-1: Synthesis of 2-methylsulfanyl-4-oxo-5,8-dihydro-4H,6H-9-thia-1,4a,7-triaza-
fluorene-3,7-dicarboxylic acid 7-ethyl ester.
The title compound was prepared from 2-amino-6,7-dihydro-4H-thiazolo[5,4-
c]pyridine-5-carboxylic acid ethyl ester using similar method as described for step-1 of
example-1
1H-NMR (400 MHz, DMSO-d6): δ 13.52(1H, s), 4.60 (2H, bs), 4.09(2H, q), 3.69(2H, bs),
3.27(2H, bs), 2.43(3H, s), 1.22((3H, t)
ESMS: 370.1 (M++1)
Step-2: Synthesis of 3-(ethoxycarbonylmethyl-carbamoyl)-2-methylsulfanyl-4-oxo-5,8-
dihydro-4H,6H-9-thia-1,4a,7-triaza-fluorene-7-carboxylic acid ethyl ester.
The title compound was prepared using similar method as described for step-2 of
example-1.
1H-NMR (400 MHz, DMSO-d6): δ 9.50(1H,t), 4.58 (2H,bs), 4.03-4.15(6H, m), 3.67(2H,t),
3.24-3.34(2H, partailly overlapped by water signal), 2.34(3H,s), 1.18-1.23 (6H,m)
ESMS: 455.2 (M++1)
Step-3: Synthesis of 3-(ethoxycarbonylmethyl-carbamoyl)-2-methanesulfonyl-4-oxo-
5,8-dihydro-4H,6H-9-thia-1,4a,7-triaza-fluorene-7-carboxylic acid ethyl ester.
The title compound was prepared using similar method as described for step-3 of
example-2.
1H-NMR (400 MHz, DMSO-d6): δ 8.59 (1H,t), 4.62-4.68(2H,m), 4.02-4.15(4H, m), 3.97
(2H,d), 3.65-3.70(2H,m), 3.34(2H,hidden under water signal), 3.23 (3H,s), 1.18-1.28
(6H,m)
ESMS: 487.2 (M++1)
Step-4: Synthesis of 3-(carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,8-dihydro-
4H,6H-9-thia-1,4a,7-triaza-fluorene-7-carboxylic acid ethyl ester.
The title compound was prepared using similar method as described for step-4 of
example-1.

1H-NMR (400 MHz, DMSO-d6): δ 16.24 (1H,s), 12.9 (1H,bs), 9.66(1H,t), 4.55(2H,bs),
4.07-4.11(4H,m), 3.67(2H,t) 3.23-3.35 (2H, partially overlapped by water signal), 1.21(3H,t)
ESMS: 395 (M+-l)
IR (KBr, CM"1): 3260.2 ,1741,1672.8
Example-4: Preparation of {[2-hydroxy-4-oxo-7-(5-trifluoromethyI-pyridin-2-yl)-
5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyI]-amino}-acetic acid
(Compound no. 18)

Step-1: Synthesis of (5-(5-trifluoromethyl-pyridin-2-yl)-4,5,6,7-tetrahydro-thiazolo[5,4-
c] pyridin-2-ylamine).
The mixture of l-(5-trifluoromethyl-pyridin-2-yl)-piperidine-4-one (9.9 gm,0.0405
mol), pyrrolidine (3.53 ml, 0.0445 mol) and p-toluenesulfonic acid (100 mg) in cyclohexane
(50 ml) were refluxed for 3 hours and water was removed with Dean-Stark apparatus. The
resultant mixture was concentrated under reduced pressure, and the residue was dissolved in
methanol (100 ml). Sulfur powder (1.05 gm, 0.0405 mol) and cynamide (1.37 gm, 0.0405
mol) were added to the solution and stirred at room temperature for overnight. The resultant
solid was collected by filtration and washed with methanol (10 ml) to give 6.0 gm of title
compound.
1H-NMR (400 MHz, DMSO-d6): δ 8.43 (1H,s), 7.82 (1H,dd), 7.04 (1H,d), 6.82(2H,s), 4.62
(2H,s), 3.96 (2H, t), 2.55 (2H,t)
ESMS: 301(M++1)
Step-2; Synthesis of 2-hydroxy-4-oxo-7-(5-trifluoromethyl-pyridin-2-yl)-5,6,7,8-
tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carboxylic acid ethyl ester.
The mixture of 5-(5-trifluoromethyl-pyridin-2-yl)-4,5,6,7-tetrahydro-thiazolo[5,4-
c]pyridin-2-ylamine (5.7 gm, 0.019 mol) and triethyl methantricarboxylate (16.1 ml, 0.076
mol) in xylene (100 ml) was heated at 140-150 °C for 6 hours. Xylene was evaporated and
diethyl ether was then added and the suspension was stirred for 15 minutes. It was filtered
and washed with ether. The crude solid was digested with dichloromethane (200 ml) and

filtered to remove insoluble residue. Dichloromethane layer was distilled off under vacuum
to give 1.3 gm of title compound.
1H-NMR (400 MHz, CDCl3): δ 13.96 (1H,s), 8.44 (1H,s), 7.72 (1H,dd), 6.79 (1H,d), 4.80
(2H,s), 4.47 (2H, q), 3.94 (2H,t), 3.53-3.56 (2H,m), 1.44 (3H,t)
ESMS: 440.9 (M++1)
Step-3: Synthesis of {[2-hydroxy-4-oxo-7-(5-trifluoromethyI-pyridin-2-yl)-5,6,7,8-
tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid ethyl ester.
The mixture of compound as obtained in step-2 (1.2 gm, 0.0272 mol) with glycine
ethyl ester hydrochloride (0.42 gm, 0.0030 mol) was heated in dry pyridine (10 ml) at 100°C
for 5 hours. Pyridine was evaporated to dryness and residue was stirred in diethyl ether (50
ml). The solid, thus obtained, was collected by filtration and washed by ethanol (10 ml) and
diethyl ether (10 ml). It was suck dried to give 260 mg of title compound.
1H-NMR (400 MHz, CDCl3): δ 15.99(1H,s), 9.74 (1H,t), 8.45 (1H,s), 7.72 (1H,dd), 6.79
(1H,d), 4.80 (2H,s), 4.18-4.26 (4H, m), 3.97(2H,t), 3.53 (2H,t), 1.30 (3H,t)
ESMS: 498 (M++1)
Step-4: Synthesis of {[2-hydroxy-4-oxo-7-(5-trifluoromethyl-pyridin-2-yl)-5,6,7,8-
tetrahydro-4H-9-thia-1,4a,7-triaza-fiuorene-3-carbonyl]-amino}-acetic acid.
The title compound was prepared using similar method as described for step-4 of
example-1.
1H-NMR (400 MHz, DMSO-d6): δ 9.67 (1H,t), 8.48 (1H,s), 7.91 (1H,dd), 7.14 (1H,d), 4.85
(2H,s), 4.07 (2H,d), 4.01(2H,t), 3.34 (2H, hidden under signal of water)
ESMS: 467.9 (M+-1)
IR (KBr, CM-1): 3292.7,1725.7,1677.7
Example-5:- Preparation of {[7-(5-chloro-thiophene-2-sulfonyl)-2-hydroxy-4-oxo-
5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid
(Compound no. 17)


Step-1: Synthesis of 2-methyIsulfanyl-4-oxo-5,8-dihydro-4H,6H-9-thia-1,4a,7-triaza-
fluorene-3,7-dicarboxylic acid 7-tert-butyl ester.
The title compound was prepared from 2-amino-6,7-dihydro-4H-thiazolo[5,4-
c]pyridine-5-carboxylic acid tert-butyl ester using similar method as described for step-1 of
example-1.
1H-NMR (400 MHz, CDCl3): δ 13.38 (1H,bs), 4.56 (2H,bs), 3.76(2H,t) 3.42(2H, bs), 2.49
(3H,s), 1.50 (9H,s)
ESMS: 398.2 (M++1)
Step-2: Synthesis of 3-(ethoxycarbonylmethyl-carbamoyl)-2-methylsulfanyl-4-oxo-5,8-
dihydro-4H,6H-9-thia-1,4a,7-triaza-fluorene-7-carboxylic acid tert-butyl ester.
The title compound was prepared using similar method as described for step-2 of
example-1.
1H-NMR (400 MHz, CDCl3): δ 9.71 (1H,t), 4.52 (2H,bs), 4.18-4.25 (4H,m), 3.72(2H,t) 3.37-
3.44(2H, m), 2.43 (3H, s), 1.50 (9H,s), 1.27(3H,t)
ESMS: 483.2 (M++1)
Step-3: Synthesis of [(2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3-carbonyl)-amino]-acetic acid ethyl ester.
To the solution of N-Boc derivative as obtained in step-2 (19.0 gm, 0.0394 mol) in
dichloromethane (60 ml), trifluoroacetic acid (60 ml) was added over 0.5 hour at 0-5°C and
stirred at room temperature for 4 hours. Solvent were distilled under vacuum and water (100
ml) was added. It was basified with sodium bicarbonate solution and resulted solid was
collected by filtration. Solid was further washed by diethyl ether (50 ml) and dried under
vacuum at 60°C for 6 hours to give 11.0 gm of title compound.
1H-NMR (400 MHz, CDCl3): δ 9.74 (1H, bs), 4.18-4.25 (4H, m), 3.94 (2H,s), 3.34-3.37
(2H,m), 3.17 (2H,t), 2.43(3H,s), 1.28(3H,t)
ESMS: 382.9 (M++1)
Step-4: Synthesis of {[7-(5-chloro-thiophene-2-sulfonyl)-2-methylsulfanyl-4-oxo-5,6,7,8-
tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid ethyl ester.
To the mixture of amine derivative as obtained in step-3 (1.0 gm, 0.0026 mol) and
pyridine (0.31 ml, .0039 mol) in dichloromethane, a solution of 5-chloro-thiophene-2-
sulfonyl chloride (0.62 gm, 0.00287 mol) in dichloromethane (5 ml) was added at 0-5°C and

stirred at room temperature for 4 hours. Reaction mixture was poured into water (50 ml) and
extracted with dichloromethane (50 ml x 2). The combined organic layer was dried over
sodium sulphate and distilled off under vacuum to yield a solid, which was slurred in
ethylactate (10 ml). It was filtered and suck dried to give 980 mg of title compound.
1H-NMR (400 MHz, DMSO-d6): δ 9.42-9.48 (1H,m), 7.68(1H,d), 7.39(1H,d), 4.32-4.36
(2H, m), 4.02-4.13(4H,m), 3.38-3.51(4H,hidden under signal of water), 2.34-2.36 (3H,m),
1.15-1.22(3 H,m)
ESMS: 564.8 (M++1)
Step-5: {[7-(5-Chloro-thiophene-2-sulfonyl)-2-methanesulfonyl-4-oxo-5,6,7,8-tetrahydro -
4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid ethyl ester.
To the cooled solution of compound as obtained in step-4 (950 mg, 0.0017 mol) in
dichloromethane (20 ml), a solution of m-chloro perbenzoic acid (50-60%, 0.72 gm) in
dichloromethane (30 ml) was added at 5-10°C and stirred at room temperature for 2 hours.
Reaction mixture was poured into water (100 ml) and extracted with dichloromethane (50 ml
x 2). Organic layer was washed with sodium bicarbonate, dried over sodium sulphate and
distilled off under vacuum to give 800 mg as a crude solid, which was used for next step
without purification.
Step-6: Synthesis of {[7-(5-chloro-thiophene-2-sulfonyl)-2-hydroxy-4-oxo-5,6,7,8-
tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid.
A mixture of compound as obtained in step 5 (0.8 g, 0.0013 mol) in tetrahydrofuran
(20 ml), a solution of sodium hydroxide (160 mg, 0.004 mol) in water (20 ml) was added.
The reaction mixture was stirred at room temperature for 2 hours. Solvent was distilled off
under vacuum and remaining mass was acidified with dilute hydrochloric acid and precipitate
was appeared, which was collected by filtration and washed with diethyl ether (40 ml). Solid
was dried under vacuum to give 220mg of title compound.
1H-NMR (400 MHz, DMSO-d6): δ 16.28 (1H,s), 12.9(1H,bs), 9.64 (1H,t), 7.65 (1H,d), 7.39
(1H,d), 4.30-4.40 (2H,m), 4.08 (2H,d), 3.40-3.50(2H,m), 3.34 (2H, hidden under signal of
water)
ESMS: 502.9(M+-1)
IR(KBr, CM-1): 3304.8, 1714.3, 1682.3

Example-6: Preparation of 2-MethyIsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-
1,4a-diaza-benzo [a] azulene-3-carboxylic acid (2-oxo-2-pyrrolidin-1-yl-ethyl)-amide
(Compound no. 79)

Step-1: Synthesis of [(2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-l,4a-
diaza-benzo [a] azulene-3-carbonyl)-amino] -acetic acid.
The title compound was prepared using similar hydrolysis conditions as described for
step-4 of example-1 starting from [(2-methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-
thia-l,4a-diaza-benzo[a]azulene-3-carbonyl)-amino]-acetic acid ethyl ester (step-2 of
example-2).
1H-NMR (400 MHz, DMSO-d6): δ 9.50(1H,t), 3.97(2H,d), 3.58-3.61(2H,m), 2.79-2.81
(2H,m), 2.32 (3H,s), 1.81-1.82 (2H,m), 1.70-1.71 (4H,m)
ESMS: 368.1(M++1)
Step-2: Synthesis of 2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-
diaza-benzo[a]azulene-3-carboxylic acid (2-oxo-2-pyrrolidin-1-yl-ethyl)-amide
To the stirred solution of compound obtained in step-1 (1.0 gm, 0.0027 mole) in
dichloromethane (20 ml), triethylamine (1.13ml, 0.0082 mole) and pyrrolidine (0.29gm,
0.0040 mole) were added. To the reaction mixture, l-(3-dimethylaminopropyl)-3-
ethylcarbodiimide hydrochloride (0.78 gm, 0.0040 mole) was added and stirred at room
temperature for 12 hrs. Organic layer was washed with 1N hydrochloric acid (50 ml) and
sodium bicarbonate solution. Organic solvent was distilled off to yield a solid, which was
stirred in methanol (20 ml), filtered and suck dried to give 0.35 gm of title compound.
1H-NMR (400 MHz, CDCl3): δ 10.07 (1H,bs), 4.18(2H,d), 3.69-3.71(2H,m), 3.53 (2H,t),
3.42 (2H,t), 2.70-2.73 (2H,m), 2.41 (3H,s), 1.96-2.04 (2H,m), 1.75-1.90 (8H,m)
ESMS: 421.1 (M++1)
IR(KBr, CM-1): 3297.3,1650.9,1601.8
Example-7: Preparation of [(2-Ethoxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-
diaza-benzo[a]azulene-3-carbonyl)-amino]-acetic acid ( Compound no. 81)


Step-1; Synthesis of [(2-Ethoxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo [a] azulene-3-carbonyl)-amino] -acetic acid ethyl ester.
The mixture of compound obtained in step-3 of example-2 (1.00 gm, 0.0023 mole)
and sodium ethoxide (0.318 gm, 0.0046 mole) in ethanol (20 ml) was stirred at 80 °C for 15
min and then 10 hr at room temperature. The reaction mixture was poured into 1N HCl and
extracted with ethyl acetate (50 ml x2). Ethyl acetate was distilled off and crude residue was
purified using 20% ethyl acetate in hexane. The fractions were distilled off to give 150 mg of
title compound.
1H-NMR (400 MHz, CDCl3): δ 9.20(1H,t), 4.49(2H,q), 4.18-4.24 (4H,m), 3.65-3.68 (2H,m),
2.70-2.73 (2H,m), 1.78-1.88 (6H,m), 1.43 (3H,t), 1.26(3H,t)
ESMS: 394.1 (M++1)
Step-2: Synthesis of [(2-Ethoxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo [a] azulene-3-carbonyl)-amino] -acetic acid.
The title compound was prepared using similar hydrolytic condition as described for
step-4 of example-1.
1H-NMR (400 MHz, DMSO-d6): δ 12.50 (1H,bs), 8.61 (1H,t), 4.34(2H,q), 3.88 (2H,d),
3.59-3.61(2H,m), 2.76-2.79 (2H,m), 1.68-1.81 (6H,m), 1.27 (3H,t)
ESMS: 364.3(M+-1)
IR(KBr, CM-1): 3316.2,1711.9,1655.8
Example-8: Preparation of 2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-
diaza-benzo [a] azulene-3-carboxylic acid cyclohexy lcarbamoylmethyl-amide
(Compound No. 98)


To the stirred suspension of [(2-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-
l,4a-diaza-benzo[a]azulene-3-carbonyl)-amino]-acetic acid (0.70 gm, 0.0020 mole) in
dichloromethane (20 ml), triethylamine (0.85 ml, 0.0062 mole) and cyclohexylamine (0.29
ml, 0.0025 mole) were added. To the reaction mixture, hydroxybenzotriazole (0.28 gm,
0.0020 mole) and l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.60 gm,
0.0031 mole) were added and stirred at room temperature for 12 hrs. Dichloromethane was
distilled off and 1N hydrochloric acid (50 ml) was added to the residue, the separated solid
was collected by filtration. The solid thus obtained was stirred in methanol (20 ml) at 60°C
for 0.5 hr, filtered and suck dried to give 0.60 gm title compound.
1H-NMR (400 MHz, CDCl3): δ 15.74 (1H,s), 9.94(1H,t), 5.86(1H, d), 4.05 (2H,d), 3.75-3.82
(1H,m), 3.63-3.65 (2H,m), 2.69-2.72 (2H,m), 1.78-1.93 (8H,m), 1.66-1.71 (2H,m), 1.58-
1.61(2H,m), 1.34-1.37 (2H,m), 1.14-1.16 (2H,m).
ESMS: 417.2 (M+-1)
IR(KBr, CM-1): 2929.3,1671.4,1653.4
The following representative compounds of the present invention were prepared in
analogus manner by using the synthetic schemes as described above:

Combination Therapy
Compounds of the present invention may be administered in combination with other
drugs that are used in the treatment/prevention/suppression or amelioration of the diseases or
conditions for which compounds of Formula (I) are useful. Such other drugs may be
administered contemporaneously or sequentially with a compound of Formula (I). When a
compound of Formula (I) is used contemporaneously with one or more other drugs, a

pharmaceutical composition containing such other drugs in addition to the compound of
Formula (I) is preferred. Accordingly, the pharmaceutical compositions of the present
invention include those that also contain one or more other active ingredients, in addition to a
compound of Formula (I).
Pharmaceutical compositions
In another embodiment of the invention, there is provided a pharmaceutical
composition comprising a therapeutically effective amount of one or more of a compound of
formula (I). While it is possible to administer therapeutically effective quantity of
compounds of 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) and at
least one active ingredient. These dosage forms may be administered by a variety of routes
including oral, topical, transdermal, subcutaneous, intramuscular, intravenous,
intreperitoneal, intranasal, pulmonary etc.
Oral compositions may be in the form of solid or liquid dosage form. Solid dosage
form may comprise pellets, pouches, sachets or discrete units such as tablets, multi-
particulate units, capsules (soft & hard gelatin) etc. Liquid dosage forms may be in the form
of elixirs, suspensions, emulsions, solutions, syrups etc. Composition intended for oral use
may be prepared according to any method known in the art for the manufacture of the
composition and such pharmaceutical compositions may contain in addition to active
ingredients, excipients such as diluents, disintegrating agents, binders, solubilizers,
lubricants, glidants, surfactants, suspending agents, emulsifiers, chelating agents, stabilizers,
flavours, sweeteners, colours etc. Some example of suitable excipients include lactose,
cellulose and its derivatives such as microcrystalline cellulose, methylcellulose, hydroxy
propyl methyl cellulose & ethylcellylose, dicalcium phosphate, mannitol, starch, gelatin,
polyvinyl pyrolidone, various gums like acacia, tragacanth, xanthan, alginates & its
derivatives, sorbitol, dextrose, xylitol, magnesium Stearate, talc, colloidal silicon dioxide,
mineral oil, glyceryl mono stearate, glyceryl behenate, sodium starch glycolate, cross
povidone, crosslinked carboxymethylcellulose, various emulsifiers such as polyethylene
glycol, sorbitol, fatty acid esters, polyethylene glycol alkylethers, sugar esters,

polyoxyethylene polyoxypropyl block copolymers, polyethoxylated fatty acid monoesters,
diesters and mixtures thereof.
Sterile compositions for injection can be formulated according to conventional
pharmaceutical practice by dissolving or suspending the active substance in a vehicle such as
water for injection, N -Methyl-2-Pyrrolidone, propylene glycol and other glycols, alcohols, a
naturally occurring vegetable oil like sesame oil, coconut oil, peanut oil, cotton sead oil or a
synthetic fatty vehicle like ethyl oleate or the like. Buffers, anti-oxidants, preservatives,
complexing agents like cellulose derivatives, peptides, polypeptides and cyclodextrins and
the like can be incorporated as required.
The dosage form can have a slow, delayed or controlled release of active ingredients
in addition to immediate release dosage forms.
The amount of active ingredient which is required to achieve a therapeutic effect will,
of course, vary with the particular compound, the route of administration, the subject under
treatment, and the particular disorder or disease being treated. The compounds of the
invention may be administered orally or parenteraly at a dose of from 0.001 to 1500 mg/kg
per day, preferably from 0.01 to 1500 mg/kg per day, more preferably from 0.1 to 1500
mg/kg per day, most preferably from 0.1 to 500 mg/kg per day. The dose range for adult
humans is generally from 5 mg to 35 g per day and preferably 5 mg to 2 g per day.
Dosage forms of presentation provided in discrete units may conveniently contain an
amount of compound of the invention which is effective at such dosage or as a multiple of
the same, for example units containing 5 mg to 500 mg.
Examples of pharmaceutical composition:

Accurately weighed quantity of compound no. 10 was dissolved in phosphate buffer
saline (pH 7.4) under aseptic environment. The solution was filtered through 0.22 micron

filter and filled into presterilized glass vials.The solution was purged with nitrogen during
process. These vials were further terminally sterilized by autoclave.
Biological testing:
In Vitro Erythropoietin induction:
Hep3B cell line (ATCC HB8064) was employed. Induction of erythropoietin was carried out
for the indicated dose of compounds for 16 hours duration. At the end of 16 hours, cell
culture medium was collected and centrifuged to remove any debris. Supernatant obtained
was analyzed for erythropoietin by ELISA (R&D systems, USA). The results were expressed
as fold induction as compared to vehicle control.

Above data indicates that the compounds of the present invention significantly
elevate the expression of erythropoietin in cells.
In vitro induction of Adrenomedullin:
Hep3B cell line (ATCC HB8064) was employed. Induction of adrenomedullin was
carried out for the indicated dose of compounds for 6 hours duration. At the end of 6 hours,
cells were lysed and total RNA was isolated. Expression of adrenomedullin mRNA along-
with expression of 18S rRNA was monitored by real-time PCR. Adrenomedullin mRNA

expression was normalized relative to the expression of 18S rRNA. The results were
expressed as fold induction of adrenomedullin mRNA relative to vehicle treated control.

Above data indicates that the compounds of the present invention significantly
elevate the expression of adrenomedullin in cells.
In Vitro induction of vascular endothelial growth factor (VEGF):
Hep3B cell line (ATCC HB8064) was employed. Induction of VEGF was carried out
for the indicated dose of compounds for 16 hours duration. At the end of 16 hours, cell
culture medium was collected and centrifuged to remove any debris. Supernatant obtained
was analyzed for VEGF by ELISA (R&D systems, USA). The results were expressed as fold
induction as compared to vehicle control.


Above data indicates that the compounds of the present invention significantly
elevate the expression of VEGF in cells.
Effect of compounds of present invention on anemia associated with Chronic Kidney
Disease (CKD):
The efficacy of the test compound to correct anemia associated with CKD was
studied in an animal model of anemia - 5/6 nephrectomized (5/6 NX) rats15'16'17. Animals
were randomized based upon anemia and kidney dysfunction parameters and divided into
two groups. One group received compound-10 (20mg/kg; b.i.d. i.p) for seven days while the
control received respective vehicle. Blood sampling was done on day 3 and 7 post initiation
of drug administration to check early markers of anemia correction.
Results:
Treatment with the test compound resulted in significant increase in circulating EPO
levels ranging from 115-3900 pg/ml as compared with undetectable levels (<45 pg/ml) of
circulating EPO in vehicle control. There was 3 and 5.6 fold increase in reticulocyte
production index on day 3 and day 7 respectively compared to control group with test
compound treatment. Similarly, there was 30%, 25% and 24% increase in hemoglobin
content, hematocrit percent and erythrocyte count respectively on day 7 of treatment
compared to control.
Effect of compound of present invention on ischemia-reperfusion injury to Kidney:

The efficacy of test compound to improve renal function was evaluated in a renal
ischemia and reperfusion induced acute kidney injury model in rats. The beneficial effect of
the compound was evaluated using two different treatment protocols. In one protocol
treatment with test compound was given before onset of ischemia (pre-treatment) and the
other protocol involed treatment with test compound initiated after the onset of ischemia
(post-treatment).
Pre-ischemia intervention protocol: Rats were randomised into two groups,
compound treated and vehicle control. Before initiation of bilateral renal ischemia, the
animals in compound treatment group received multiple doses of compound no. 10 (i.e. pre
treated) and control group received vehicle by i.p route.
Post-ischemia intervention protocol: Rats were randomised into two groups,
compound treated and vehicle control. After intiation of bilateral renal ischemia, the animals
in compound treatment group received multiple doses of compound no. 10 (i.e. post treated)
and control group received vehicle in similar fashion by i.p route.
Induction of Renal ischemia and reperfusion in rats: All animals were anesthetized
with pentobarbital sodium (50 mg/kg body wt). Homeothermic blanket was used to maintain
a constant body temperature of 37°C during surgery and ischemia. A midline incision was
made at the ventral side to access the kidneys and both renal pedicle were isolated and
occluded for 35 mins using microclips, which was verified by the change of the renal color.
After an ischemic period of 35 min, the microclips were removed and reperfusion initiated.
The abdomen was closed and skin & muscles sutured and animal allowed to recover. Blood
sample of 300 µl was taken via sublingual vein puncture at various predetermined time
points.
RESULTS:
In both protocols tested i.e pre-ischemia intervention and post-ischemia intervention,
renal function improvement was assessed by measuring serum creatinine and BUN (blood
urea nitrogen) at various time points post ischemia. Results are expressed below as %
reduction from their control group at 24hrs post initiation of ischemia.
Pre-ischemia intervention:

References:
1. Schofield CJ & Ratcliffe PJ (2004) Nature Review Molecular Cell Biology; 5; 343-354
2. Scmenza GL (2000) J Appl Physiol; 88; 1474-1480
3. Weidemann A et al. (2008) J Am Soc Nephrol; 19; 486-494
4. Bernhardt WM et al. (2006) J Am Soc Nephrol; 17; 1970-1978
5. Hill P et al (2008) J Am Soc Nephrol; 19; 39-46
6. Siddiq A et al. (2005) J Biol Chem; 280; 50; 41732-43
7. Nangaku M (2007) J Am Soc Nephrol; 18; 13-15
8. Amador A et al. (2007) Am J Transplantation; 7; 2180-2189
9. Fisher JW (2003) Exp Biol Med; 228; 1-14

10. Binley K et al. (2002) Blood; 100; 2406-2413
11. Luo YH et al. (2009) Hepatobiliary Pancreat Dis Int; 8; 294-299
12. Siren AL et al. (2000) PNAS; 98; 7; 4044-49
13. Sharpies EJ et al. (2004) J Am Soc Nephrol; 15; 2115-2124

14. Looi YH et al. (2006) Br J Pharmacol; 148; 599-609
15. Hahn S, et al (1999); Pediatr Nephrol; 13; 195-198
16. Priyadarshi A, et al (2002) Kidney Int; 61; 542-546
17. Shapiro JI, et al (1990) Am J Physiol; 258; 183-188

WE CLAIM:
1. A Compound of formula (I)

their pharmaceutically acceptable salts and their isomers, stereoisomers, conformers,
tautomers, polymorphs, hydrates, and solvates;
Wherein,
When Y is NR4, O, S or SO2, m is 1 to 2 and when Y is C(R5)(R6), m is 1 to 4;
n is 1 to 6;
P is -OH, -OR7, -NH2, -NHR7, -NR7 R7', -NHSO2R7, -NHCOR7, -NHOH or -NHOR7;
X is -OH, -OR7, -SR7, -SOR7, -SO2R7, -NHR7 or-NR7R7';
Z is S or O;
R is hydrogen, linear or branched (C1-C8)alkyl, -(C1-C8)alkylaryl or -(C1-C8)alkylheteroaryl;
R1 and R2 are independently selected from hydrogen, linear or branched -(C1-C8)alkyl, - (C3-
C7) cycloalkyl, aryl, heteroaryl, -CH2-aryl and -CH2-heteroaryl, or
R1 and R2 may join together to form a 3-6 membered monocyclic or 9-12 membered bicyclic
ring;
R together with either R1 or R2 of adjacent carbon atom may form a 3-6 membered
monocyclic or 8-11 membered bicyclic heteroaryl or heterocyclyl ring;
R3 and R3' at each occurance is independently selected from hydrogen, linear or branched
(C1-C8)alkyl, (C1-C5) alkoxy and halo;
R3 and R3' may also present in gem di-halo, gem di-alkyl or spirocycoalkyl arrangement;
R4 is selected from the group consisting of hydrogen, linear or branched (C1-C8) alkyl, (C3-
C7) cycloalkyl, aryl, heteroaryl, -(C1-C8) alkyl-aryl, -(C1-C8)alkyl-heteroaryl, -(C1-C2)alkyl-
heterocyclyl, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -C(S)NR8R9 and -SO2R8, wherein aryl and
heteroaryl radicals are optionally substituted with one or more substituent selected from the

group consisting of -(C1-C8) alkyl, -(C3-C7) cycloalkyl, heterocyclyl, aryl, heteroaryl, -OH, -
alkoxy, halo, CN, -CF3, -OCF3, -O-aryl, -SO2-(C1-C8)-alkyl, -SO2-aryl, -NH2, -NHR10, -
NR10R10' -NH-CO-(C1-C8) alkyl, -NH-SO2-(C1-C8)alkyl, -NH-SO2-aryl, -COOH, -
C(O)NH-alkyl, -CONH-aryl, -CONH-heteroaryl , -C(O)O-(C1-C8)alkyl, -C(O)O-aryl, -
SO2NH-(C1-C8)alkyl, -SO2NH-aryl and -SO2NH-heteroaryl;
R5 and R6 are independently selected from the group consisting of hydrogen, linear or
branched (C1-C8)alkyl, (C3-C7) cycloalkyl, aryl, heteroaryl, fluoro, -COOH, -CONH-(C1-
C8)alkyl, -NHCO-(C1-C8)alkyl, -NHCO-aryl , -NHCO-heteroaryl, -NH-SO2(C1-C8)alkyl, -
NH-SO2-aryl and - NH-SO2-heteroaryl;
R5 and R6 may join together to form a 3-6 membered carbocyclic, heteroaryl or heterocyclyl
ring;
R7, R7', R10 and R10' are independently selected from linear or branched (C1-C8)alkyl, (C3-C7)
cycloalkyl and -(C1-C8)alkylaryl;
R7 and R7' or R10 and R10' together with nitrogen atom to which they are attached, may form
5-6 membered monocyclic or 8-14 membered bicyclic saturated and partially saturated ring.
The ring may contain 1 to 3 heteroatom selected from N, S & O. Wherein saturated and
partially saturated ring may be optionally substituted with one or more substituent
independently selected from the group consisting of -(C1-C8)alkyl, -(C3-C7) cycloalkyl,
heterocyclyl, aryl, heteroaryl, -OH, -alkoxy, halo, -CN, -CF3, -OCF3, -O-aryl, -SO2-(C1-C8)-
alkyl, -SO2-aryl, -NH2, -NHR10, -NR10R10', -NH-CO-(C1-C8)alkyl, -NH-SO2-(C1-C8)alkyl, -
NH-SO2-aryl, -COOH, -C(O)NH-alkyl, -CONH-aryl, -CONH-heteroaryl , -C(O)O-(C1-
C8)alkyl, -C(O)O-aryl, -SO2NH-(C1-C8)alkyl, -SO2NH-aryl and -SO2NH-heteroaryl;
R8 is selected from the group consisting of linear or branched (C1-C8) alkyl, (C3-C7)
cycloalkyl, -(C1-C8)alkyl-(C3-C7)cycloalkyl, heterocyclyl, aryl, -(C1-C8)alkyl-aryl, -(C1-
C2)alkyl- heterocyclyl, heteroaryl and -(C1-C8)alkyl-heteroaryl, wherein aryl and heteroaryl
radicals are optionally substituted with one or more substituent selected from linear or
branched (C1-C8)alkyl, (C3-C7)cycloalkyl, -(C1-C8)alkyl-(C3-C7)cycloalkyl, aryl, heteroaryl,
heterocyclyl, -OH, alkoxy, halo, -CN, -CF3, -OCF3, -O-aryl, -SO2-(C1-C8)alkyl, -SO2-aryl, -
NH2, -NHR10, -NR10R10', -NH-CO-(C1-C8)alkyl, -NH-SO2-(C1-C8)alkyl, -C(O)OH, -
C(O)NH-(C1 -C8)alkyl, -CONH-aryl, -CONH-heteroaryl, -NHCONH-(C1 -

C8)alkyl, -NHCONH-aryl, -SO2NH-(C1-C8)alkyl, -SO2NH-aryl and -SO2NH-
heteroaryl;
R9 is hydrogen, linear or branched (C1-C8)alkyl or -(C1-C8)alkylaryl;
R8 and R9 together with nitrogen atom to which they are attached, may form 5-6 membered
saturated ring.
2. The compound as claimed in claim 1, which is selected from the group consisting of:
[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-carbonyl)-amino]-
acetic acid;
3-(Carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,8-dihydro-4H,6H-9-thia-1,4a,7-triaza-
fluorene-7-carboxylic acid ethyl ester;
[(2-Hydroxy-7-methanesulfonyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-
carbonyl)-amino]-acetic acid;
{[2-Hydroxy-7-(3-methyl-butyryl)-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino} -acetic acid;
{[2-Hydroxy-4-oxo-7-(propane-2-sulfonyl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino} -acetic acid;
1-[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-carbonyl)-amino]-
cyclopentanecarboxylic acid;
{[2-Hydroxy-4-oxo-7-(toluene-4-sulfonyl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3-carbonyl]-amino}-acetic acid;
[(2-Hydroxy-4-oxo-7-phenylcarbamoyl-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-
3-carbonyl)-amino]-acetic acid;
[(7-Cyclopropanecarbonyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl)-amino] -acetic acid;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid;
[(2-Hydroxy-4-oxo-7,8-dihydro-4H,6H-cyclopenta[4,5]thiazolo[3,2-a]pyrimidine-3-
carbonyl)-amino]-acetic acid;
[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-carbonyl)-amino]-
acetic acid, sodium salt;

[(7-tert-Butyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid;
3-[(2-Hydroxy-4-oxo-7,8-dihydro-4H,6H-cyclopenta[4,5]thiazolo[3,2-a]pyrimidine-3-
carbonyl)-amino]-propionic acid;
3-[(7-tert-Butyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-fluorene-3-
carbonyl)-amino]-propionic acid;
{[7-(4-Fluoro-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3-carbonyl]-amino}-acetic acid;
{[7-(5-Chloro-thiophene-2-sulfonyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3 -carbonyl] -amino} -acetic acid;
{[2-Hydroxy-4-oxo-7-(5-trifluoromethyl-pyridin-2-yl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3 -carbonyl] -amino} -acetic acid;
{[2-Hydroxy-4-oxo-7-(4-trifluoromethoxy-benzenesulfonyl)-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid;
{[7-(2,2-Dimethyl-propionyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino} -acetic acid;
{[7-(4-Butyl-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-
3 -carbonyl] -amino} -acetic acid;
{[2-Hydroxy-4-oxo-7-(4-trifluoromethoxy-benzoyl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3-carbonyl]-amino}-acetic acid;
{[7-(4-Chloro-benzyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-
3-carbonyl]-amino}-acetic acid;
{[7-(4-Fluoro-phenylthiocarbamoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3 -carbonyl] -amino} -acetic acid;
[(2-Hydroxy-7-isopropylthiocarbamoyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3-carbonyl)-amino]-acetic acid;
3-(Carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,8-dihydro-4H,6H-9-thia-1,4a,7-triaza-
fluorene-7-carboxylic acid benzyl ester;
{[7-(2-Cyclopropyl-acetyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3-carbonyl]-amino}-acetic acid;

({7-[2-(4-Chloro-phenyl)-acetyl]-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3 -carbonyl} -amino)-acetic acid;
{[7-(2-Cyclopentyl-acetyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino } -acetic acid;
3-[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-propionic acid;
{[2-Hydroxy-7-(4-methoxy-benzyl)-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3-carbonyl]-amino}-acetic acid;
2-[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-propionic acid;
{[7-(6-Chloro-pyridine-3-carbonyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3-carbonyl]-amino}-acetic acid;
[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid;
{[7-(6-Chloro-pyridazin-3-yl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino} -acetic acid;
{[7-(3-Cyano-pyridin-2-yl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3-carbonyl]-amino}-acetic acid;
{[7-(3-Chloro-4-methoxy-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3 -carbonyl] -amino} -acetic acid;
[(2-Hydroxy-4-oxo-5,6,7,8,9,10-hexahydro-4H-11 -thia-1,4a-diaza-cycloocta[a]indene-3-
carbonyl)-amino]-acetic acid;
[(2-Hydroxy-7-indan-5-ylmethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-
3-carbonyl)-amino]-acetic acid;
2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-fluorene-3-
carbonyl)-amino]-propionic acid;
{[7-(3,5-Dimethoxy-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino } -acetic acid;
{[2-Hydroxy-7-(4-methanesulfonyl-benzoyl)-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3-carbonyl]-amino}-acetic acid;

2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino] -3 -methyl-butyric acid (L-isomer);
2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-propionic acid (D-isomer);
{[7-(3,5-Dichloro-4-methoxy-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid;
{[7-(3,5-Bis-trifluoromethyl-benzyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3 -carbonyl] -amino} -acetic acid;
{[2-Hydroxy-4-oxo-7-(4-propyl-benzoyl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino} -acetic acid;
{[7-(3,5-Bis-trifluoromethyl-benzoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-
triaza-fluorene-3-carbonyl]-amino}-acetic acid;
{[7-(3,4-Dichloro-benzyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino} -acetic acid;
[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-carbonyl)-amino]-
acetic acid, hydrochloride salt;
{[2-Hydroxy-7-(7-methoxy-6-methyl-indan-4-ylmethyl)-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-
1,4a,7-triaza-fluorene-3-carbonyl]-amino}-acetic acid;
{[2-Hydroxy-4-oxo-7-(4-trifluoromethyl-benzyl)-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3 -carbonyl] -amino} -acetic acid;
[(7,7-Diethyl-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid;
2-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-2-methyl-propionic acid;
[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-phenyl-acetic acid, L-isomer;
[(7-Benzoylamino-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid;
[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-oxa-1,4a-diaza-fluorene-3-carbonyl)-amino]-
acetic acid;

[(2-Hydroxy-7-methyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-carbonyl)-
amino]-acetic acid;
[(2-Hydroxy-4-oxo-7-propyl-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-carbonyl)-
amino] -acetic acid;
[(2-Hydroxy-6,6-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid;
[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-methyl-amino] -acetic acid;
l-[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-cyclohexanecarboxylic acid;
1 -(7,7-Dimethyl-2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-piperidine-4-carboxylic acid;
[(2-Hydroxy-4-oxo-7-phenyl-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-carbonyl)-
amino]-acetic acid;
[(2-Hydroxy-4-oxo-5,8-dihydro-4H,6H-7-oxa-9-thia-1,4a-diaza-fluorene-3-carbonyl)-
amino]-acetic acid;
[(2-Hydroxy-5,7,7-trimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid;
[(2-Hydroxy-4,7,7-trioxo-5,6,7,8-tetrahydro-4H-71ambda*6*,9-dithia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid;
[(2-Methylsulfanyl-4-oxo-5,8-dihydro-4H,6H-7,9-dithia-1,4a-diaza-fluorene-3-carbonyl)-
amino]-acetic acid;
[(5-Ethoxy-2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid ethyl ester;
N-[(2'-hydroxy-4'-oxo-6',9'-dihydro-4'H,7'H-spiro[cyclopropane-1,8'-pyrimido[2,1 -
b] [ 1,3 ] benzothiazol] -3 '-y l)carbonyl] glycine;
[(7-Isopropyl-2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-fluorene-3-
carbonyl)-amino]-acetic acid;
3-(Carboxymethyl-carbamoyl)-2-hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-7-carboxylic acid;

{[7-(3,5-Drmethyl-pyrazol-1 -yl)-2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-
diaza-fluorene-3 -carbonyl] -amino} -acetic acid;
2-[(2-Hydroxy-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-carbonyl)-amino]-
3-methyl-pentanoic acid (L-isomer);
3-(lH-Indol-2-yl)-2-[(2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-l,4a-diaza-
fluorene-3-carbonyl)-amino]-propionic acid (L-isomer);
3-(3H-Imidazol-4-yl)-2-[(2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-propionic acid (L-isomer);
3-(4-Hydroxy-phenyl)-2-[(2-methylsulfanyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-
fluorene-3-carbonyl)-amino]-propionic acid (L-isomer);
[(2-Hydroxy-4-oxo-7-pyridin-4-ylmethyl-5,6,7,8-tetrahydro-4H-9-thia-1,4a,7-triaza-
fluorene-3-carbonyl)-amino]-acetic acid;
2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carboxylic acid (2-oxo-2-pyrrolidin-1-yl-ethyl)-amide;
[(2-Hydroxy-7,7-dimethyl-4-oxo-5,6,7,8-tetrahydro-4H-9-thia-1,4a-diaza-fluorene-3-
carbonyl)-amino]-acetic acid, Disodium salt;
[(2-Ethoxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-carbonyl)-
amino]-acetic acid;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, Disodium salt;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, arginine salt (2:1);
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino] -acetic acid, lysine salt;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, dipotassium salt;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, calcium salt (2:1);
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, magnesium salt (2:1);

[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, ammonium salt;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino] -acetic acid, diethylamine salt;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, choline salt;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, tromethamine salt;
[(2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid, histidine salt;
2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carboxylic acid carbamoylmethyl-amide;
2-Methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carboxylic acid hydroxycarbamoylmethyl-amide;
[(4-Chloro-benzyl)-(2-methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-acetic acid;
4-[Cyclopentyl-(2-methylsulfanyl-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo[a]azulene-3-carbonyl)-amino]-butyric acid;
2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-carboxylic
acid (2-oxo-2-pyrrolidin-1 -yl-ethyl)-amide;
2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-carboxylic
acid cyclohexylcarbamoylmethyl-amide;
2-Hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-carboxylic
acid(benzylcarbamoyl-methyl)-amide;
4-[Cyclopentyl-(2-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-
benzo [a] azulene-3 -carbonyl)-amino] -butyric acid;
[Benzyl-(2-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H,5H-10-thia-1,4a-diaza-benzo[a]azulene-3-
carbonyl)-amino]-acetic acid and pharmaceutically acceptable salts thereof.

3. A pharmaceutical composition comprising a therapeutically effective amount of one or
more compound of claim 1, in association with a pharmaceutically acceptable adjuvant,
diluent or carrier.
4. A method of treating anemia in a mammal, including human being, the method comprising
administering a therapeutically effective amount of a compound of claim 1.
5. A method of treating anemia of elderly or anemia associated with conditions like chronic
diseases, renal failure, cancer, infection, dialysis, surgery, and chemotherapy in a mammal,
the method comprising administering a therapeutically effective amount of a compound of
claim 1.

6. A method for prevention or treatment of tissue damage caused by renal ischemia,
cardiovascular ischemia, cerebrovascular ischemia, hepatic ischemia or peripheral vascular
ischemia in a mammal, including human being, the method comprises administering a
therapeutically effective amount of a compound of claim 1.
7. A method of prevention or treatment of tissue damage caused by ischemic disorders
including acute kidney injury, myocardial infarction, stroke, hepatic ischemia-reperfusion
injury and peripheral vascular diseases in a mammal, including human being, the method
comprises administering a therapeutically effective amount of a compound of claim 1.
8. Use of a compound as claimed in claim 1 for the preparation of a medicament for treating
anemia.
9. Use of a compound as claimed in claim 1 for the preparation of a medicament for treating
anemia of elderly or anemia associated with conditions like chronic diseases, renal failure,
cancer, infection, dialysis, surgery and chemotherapy.

10. Use of a compound as claimed in claim 1 for the preparation of a medicament for
prevention or treatment of tissue damage caused by renal ischemia, cardiovascular ischemia,
cerebrovascular ischemia, hepatic ischemia or peripheral vascular ischemia.
11. Use of a compound as claimed in claim 1 for the preparation of a medicament for
prevention or treatment of tissue damage caused by ischemic disorders including acute
kidney injury, myocardial infarction, stroke, hepatic ischemia-reperfusion injury and
peripheral vascular diseases.
12. A compound of formula (I), its process for the preparation and pharmaceutical
composition, as herein described with reference to the examples accompanying the
specification.

The present invention relates to novel compounds, their pharmaceutically acceptable salts,
and their isomers, steroisomers, conformers, tautomers, polymorphs, hydrates and solvates.
The present invention also encompasses pharmaceutically acceptable compositions of said
compounds and process for preparing novel compounds. The invention further relates to the
use of the above-mentioned compounds for the preparation of medicament for use as
pharmaceuticals.