1. A novel compound for treatment of proliferative diseases comprising N4-(6,7,8trimethoxyquinazolin- 4-yl)biphenyl-4,4'-diamine of formula (1). NH2 HN (I)

2. The said compound N4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine of claim-l showing anticancer activity against broad range of cancer cell lines.

3. The said cancer cell lines of claim-2 are leukemia HL-60 (TB), K-562, MOLT-4, RPMI-8226, SR cell lines, non-small cell lung cancer A549/ATCC, EKVX, HOP62, HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, NCI-H522 cell lines, colon cancer COLO 205, HCC-2998, HCT-116, HCT-15, HT29, KM12, SW-620 cell lines, CNS cancer SF-268, SF-295, SF-539, SNB-19, SNB-75, U251 cell lines, melanoma LOX IMVI, MALME-3M, M-14, MDA-MB-435, SK-MEL-2, SKMEL- 28, SK-MEL-5, UACC-257, UACC-62 cell lines, ovarian cancer IGROVI, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, NCI/ADR-RES, SK-OV-3 cell lines, renal cancer 786-0, A-498, ACHN, CAKI-l, RXF 393, SNI2C, TK-IO, UO-31 cell lines, prostate cancer PC-3, DU-145 cell lines, breast cancer MCF7, MDA-MB2311ATCC, HS 578T, BT-549, T-47D cell lines.

4. The said compound N4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine of claim-l showing GI50 value in range 0.38-42.6 IlM against the said cancer cell lines of claim-3.

5. The said compound N4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine of claim-l showing best activity against melanoma LOX IMVI cell line.

6. The GIso value against melanoma LOX IMVI cell line of claim-5 is 0.38 IlM. 14 , L 1 7 The 0150 value against leukemia K-562, non-small cell lung cancer NCI H-522, colon cancer HCT-I5 and KM-I2, melanoma M-I4, MDA-MB-435 and UACC62, renal cancer ACHN and CAKI-I cell lines of claim-3 is 0.45, 0.98, 0.55, 0.64, 0.55,0.87,0.79,0.70 and 0.55 IlM respectively.

FIELD OF THE INVENTION:
The present invention relates the compound N4-(6,7,8-trimethoxyquinazolin-4yl)
biphenyl-4,4'-diamine as a new agent for treatment ofproliferative diseases.
BACKGROUND OF THE INVENTION:
Cancer is continuing to be a major health problem in developing as well as undeveloped
countries (EI-Azab et aI, 2010). At present, wide range of cytotoxic drugs with different
mechanisms of action are used to treat human cancer, either alone or in combination.
Also many compounds are in different phases of clinical trials.
Quinazoline derivatives, particularly aminoquinazolines, have been identified as a new
class ofcancer chemotherapeutic agents with significant therapeutic efficacy against solid
tumors (EI-Azab et aI, 2010).
Aminoquinazolines are potent and highly selective EGFR (epidermal growth factor
receptor) inhibitors. Aminoquinazolines are ATP competitive dual kinase inhibitor of
EGFR and HER2 (Human epithelial receptor)/neu (ErbB-2) which inhibits receptor
autophosphorylation and activation. Aminoquinazolines show their competitive
inhibitory action by binding to ligand binding site in extracellular domain ofEGFR (Pytel
et aI, 2009). Aminoquinazolines are also potent and highly selective inhibitors of protein
kinases (Cakici et aI, 2010, Tsou et aI, 2001). Inhibition of EGFR and protein kinases
results in inhibition of tumor growth and progression (Kamath et aI, 2006).
With growing interest in aminoquinazoline compounds, their synthesis and biological
studies have assumed enormous importance (Liu et aI, 2007). So, we have synthesized a
novel analogue of 4-anilinoquinazoline having 3,4,5 trimethoxyphenyl moiety.
SUMMARY OF THE INVENTION:
The present invention provides a new compound N4-(6,7,8-trimethoxyquinazolin-4yl)
biphenyl-4,4'-diamine for the treatment of proliferative diseases. The said compound
N4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine has the formula (I) of
drawing. NH2
HN
(I)
2
In one aspect, the present invention provides means for treating proliferative diseases in a
human or animal subject in need of such treatment comprising administering to said
subject an amount of the compound of formula (I) effective to reduce or prevent cellular
proliferation in the subject.
In another aspect, the present invention provides means for treating proliferative diseases
in a human or animal subject in need of such treatment comprising administering to said
subject an amount of the compound of formula (I) effective to reduce or prevent cellular
proliferation in the subject with at least one additional agent for the treatment of cancer.
In other aspects, the present invention provides therapeutic compositions, comprising
compound of formula (I) optionally in combination with one or more additional agents
for the treatment of cancer, as are commonly employed in cancer therapy.
The compound of the invention is useful in the treatment of cancers, including, for
example, leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma,
ovarian cancer, prostate cancer, renal cancer and breast cancer.
In another aspect, the present invention provides pharmaceutical compositions
comprising compound (I) together with a pharmaceutically acceptable carrier suitable for
administration to a human or animal subject, either alone or together with other
anticancer agents.
In other aspects, the invention provides means for using the compound (I). For example
compound (I) can be used in the treatment of cancer. Compound (I) can also be used in
the manufacture of medicament for the treatment ofcancer.
BREIF DESCRIPTION OF DRAWINGS:
Figure 1 describes one dose mean graph (at concentration of 10-5 M) of compound (I) on
NCI (National Cancer Institute) 60 cancer cell lines.
Figure 2 shows dose response curve of compound (I) against NCI 60 cancer cell lines.
Figure 3 shows dose response curves of compound (I) against individual sub panels of
cancer cells.
Figure 4 describes in vitro testing results of compound (I) against NCI 60 cancer cell
lines.
Figure 5 shows mean graphs of compound (I) against NCI 60 cancer cell lines.
DETAILED DESCRIPTION OF INVENTION:
Synthesis of compound (I)
The process of synthesis of said compound (I) comprises of following 7 steps-
3
i) Preparation of methyl 3,4,5-trimethoxybenzoate (2)
To a 500 ml round bottom flask concentrated sulphuric acid (0.5 ml) was added and
stirred with a solution of 3,4,5- trimethoxybenzoic acid (0.5 mmol) in absolute methanol
(20 ml), and the mixture was heated under reflux for 6 hours. About 90% of excess
methanol was removed by evaporation, and the residue was poured into ice water (300
ml). The product was extracted with diethyl ether (2 x40 ml), and the combined extracts
were washed with 2% aqueous sodium hydroxide solution (2 x 50 mt) followed by water
(200 ml). Evaporation of ether gave the desired product.
ii) Preparation of methyl 2-nitro-3,4,5-trimethoxybenzoate (3)
To a three-necked 100 ml round bottom flask, equipped with a magnetic stirrer bar,
methyl 3,4,5- trimethoxybenzoate (2.0g, 8.8 mmol) in 35% acetic acid (10 ml) was added
at room temperature. The solution was stirred at 10-300e on an ice bath and 70%
concentrated nitric acid (2.5 ml) was added drop wise over a period of 30 minutes. After
addition of the acid, the solution was stirred for 1-2 hours. The mixture was diluted with
cold water (60 ml), and the resulting precipitate was filtered and washed well with water,
and dried to give product as pale yellow solid. Product was recrystallized from ethanol:
water (2: 1 v:v). Pale yellow needles were obtained.
iii) Preparation of 2-nitro-3,4,5-trimethoxybenzoic acid (4)
To a 250 ml three necked round bottom flask, equipped with a magnetic stirrer, were
added methyl 2-nitro-3,4,5- trimethoxybenzoate (14.0 g, 50 mmol) and 0.8 mol/L sodium
hydroxide solution (120 ml, 100 mmol) in 95% ethanol (60 ml). The mixture was stirred
at 45-50oe in a water bath for 1-2 hours and the course of the reaction was followed by
TLe (eluent: petroleum/ethyl acetate, 1: I, v:v). After the completion of the reaction, the
mixture was cooled by ice water, and concentrated hydrochloric acid was added dropwise
with stirring while maintaining the temperature at 200 e for the mixture pH 2-3. The
resulting precipitate was filtered and washed with water, dried to give desired compound.
Product was recrystallized from ethanol.
iv) Preparation of 2-amino-3,4,5-trimethoxybenzoic acid (5)
To a 100 ml three necked round bottom flask, equipped with a magnetic stirrer, was
added tin powder (5.3 g, 45 mmol) in concentrated hydrochloric acid (18 ml) and stirred
at 200 e for 4-5 hours until a homogeneous solution was obtained. 2-nitro-3,4,5trimethoxybenzoic
acid (2.6 g, 10 mmol) was then added and the resulting mixture was
heated at 800e for 20 minutes. To the mixture concentrated hydrochloric acid (5 ml)
solution was added and again stirred for 10 minutes. The mixture was cooled to 0-10oe
and white solid was filtered and washed with concentrated hydrochloric acid. The solid
was then neutralized with 10% potassium carbonate solution until a pH of 9-10 was
obtained. The resulting mixture was stirred for 1-2 hours and filtered to give a gray solid.
The solid was again treated with 10% potassium carbonate solution, acidified with 30%
acetic acid solution to adjust the pH in the range 2-3. The resulting precipitate was
filtered and washed with water, dried to give desired compound. The compound was
recrystallized from ethanol: water (1: I v:v).
4
v) Preparation of 6,7,8-trimethoxyquinazoline-4-one (6)
To a 100 ml three necked round bottom flask, equipped with a magnetic stirrer, were
added 2-amino-3,4,5-trimethoxybenzoic acid (1.1 g, 5 mmol) and formamide (4 ml). The
resulting solution was refluxed at 12~140°C for 5-6 hours. After the reaction was over,
a suitable amount of water was added dropwise to the reaction mixture to dissolve the
excess of formamide at 100°C. Water (lO ml) was added dropwise, cooled to 600C, and
again another 10 ml of water was added in one shot. The reaction mixture was brought to
room temperature, filtered to give desired compound, which was recrystallized from
ethanol.
vi) Preparation of 4-chloro-6,7,8-trimethoxyquinazoline (7)
A mixture of 6,7,8-trimethoxyquinazoline-4-one (0.6 g, 2.5 mmol) and four drops of
N,N-dimethylaniline in phosphorus oxychloride (25 ml), and DMF (0.12 ml) was stirred
under reflux at 1O~105°C for 2-3 hours. The solvent was then removed under reduced
pressure. The residue was added into chloroform (20 ml) and the resulting mixture was
poured into ice water (30 g), neutralized with saturated potassium carbonate solution to a
pH of 4-5, and filtered. The mother liquor was extracted with chloroform (2 x20 ml), and
the combined organic layers were dried over anhydrous magnesium sulfate and filtered
again. After removal of the chloroform under reduced pressure, the desired compound
was recrystallized from petroleum ether.
vii) Preparation ofN4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine (I)
A solution of 4-chloroquinazoline (4.0 mmol) and desired amine (4.0 mmol) in 2propanol
(lOO ml) was stirred under reflux for 4-24 hours. The progress of reaction was
monitored by TLC using ethylacetate: n-hexane (2:3). After completion of reaction, the
stirring was stopped. The product obtained was filtered and dried. The crude product was
purified by recrystallisation from ethanol-water to give the title compound.
5
Scheme ofpreparation of the compound (I) is shown below-
Schemel
COOH
1
Methanol
Cone. H2S04
COOCH3
2
Cone. HN03 N02
COOCH3
3
NaOH
95% Ethanol
35% HCI
H3CO OCH3 H3CO OCH3 H3CO
II( II(
Formamide NH2 Sn/HCI N02 H3CO
COOH COOH
6
OCH3
5 4
POCI3 NH2
DMF
~
H3CO H'OO~ • 1# ) H3CO
2-Propanol
Benzidine H3CO N
OCH3 OCH3
7
All the chemicals used were laboratory grade. Purity of the compound (I) was assessed
by thin layer chromatography (TLC) using glass silica gel plates. TLC results were
readily detected visually by employing well known iodine vapour. Compound (I) was
characterized by infra red (lR) and nuclear magnetic resonance (NMR) spectroscopy.
NMR analysis was performed with a 300 MHz dpx300 spectrometer using TMS as
internal standard in DMSO. IR spectroscopy was performed with a ALPHA-E
(BRUKER) ATR spectrophotometer. Melting point was determined on a DECIBEL
digital melting point apparatus and is shown uncorrected. Nomenclature of compound (I)
6
was provided usmg ChemDraw Ultra verSIOn 10.0 software available from
CambridgeSoft.
Physical and spectral data of compound (I)
Physical characteristics and spectral data (ATR Infra Red and lH NMR) of compound (1)
is as follows-
Recrystallization solvent: Ethylacetate: n-henaxe (3:2)
Melting Point: 142-144 °c
Rf value (dichloromethane:carbontetrachloride:methanol in ratio 10: 10: 1): 0.703
ATR Infra Red em-I 3542,3513,3450 and 1584 (NH2, N-H), 3016, 928 and 856 (Ar-H),
2958, 1463 and 1413 (CH3), 1680 (C=N), 1504 (C=C of Ar), 1322 (C-N), 1222 and 1014
(C-O).
lH NMR (DMSO) 8 8.33 (lH, s, Ar-H), 7.28-7.19 (4H, m, Ar-H), 6.76 (lH, s, Ar-H),
6.59-6.51 (4H, m, Ar-H), 3.96 (lH, bs, NH), 3.82 (6H, s, OCH3), 3.72 (3H, s, OCH3),
3.04 (2H, bs, NH2).
Procedure of the in vitro cancer screening of compound (I)
Antiproliferative activity of compound (1) was done at National Cancer Institute (NCI),
Maryland, USA. NCI use following procedure for antiproliferative activity-
The human tumor cell lines of the cancer screening panel were grown in RPMI-1640
medium containing 5% fetal bovine serum and 2 mM L-glutamine. For a typical
screening experiment, cells were inoculated into 96 well microtiter plates in 100 ~L at
plating densities ranging from 5,000 to 40,000 cells/well depending on the doubling time
of individual cell lines. After cell inoculation, the microtiter plates were incubated at
37°C, 5% carbondioxide, 95% air and 100% relative humidity for 24 hours prior to
addition of experimental drugs. After 24 hours, two plates of each cell line were fixed in
situ with trichloro acetic acid (TCA), to represent a measurement of the cell population
for each cell line at the time of drug addition (Tz). Experimental drugs were solubilized
in dimethyl sulfoxide (DMSO) at 400-fold the desired final maximum test concentration
and stored frozen prior to use. At the time of drug addition, an aliquot of frozen
concentrate was thawed and diluted to twice the desired final maximum test
concentration with complete medium containing 50 ~g/ml gentamicin. Additional four,
10-fold or ~ log serial dilutions were made to provide a total of five drug concentrations
plus control. Aliquots of 100 ~l of these different drug dilutions were added to the
appropriate microtiter wells already containing 100 ~l of medium, resulting in the
required final drug concentrations.
Following drug addition, the plates were incubated for an additional 48 hours at 37°C,
5% carbondioxide, 95% air, and 100% relative humidity. For adherent cells, the assay
7
was terminated by the addition of cold TCA. Cells were fixed in situ by the gentle
addition of 50 III of cold 50% (w/v) TCA (final concentration, 10% TCA) and incubated
for 60 minutes at 4°C. The supernatant was discarded, and the plates were washed five
times with tap water and air dried. Sulforhodamine B (SRB) solution (lOO Ill) at 0.4%
(w/v) in 1% acetic acid was added to each well, and plates were incubated for 10 minutes
at room temperature. After staining, unbound dye was removed by washing five times
with I% acetic acid and the plates were air dried. Bound stain was subsequently
solubilized with 10 mM trizma base, and the absorbance was read on an automated plate
reader at a wavelength of 515 nm. For suspension cells, the methodology was the same
except that the assay was terminated by fixing settled cells at the bottom of the wells by
gently adding 50 III of 80% TCA (final concentration, 16% TCA). Using the seven
absorbance measurements {time zero, (Tz), control growth, (C), and test growth in the
presence of drug at the five concentration levels (Ti)} , the percentage growth was
calculated at each of the drug concentrations levels. Percentage growth inhibition was
calculated as:
[(Ti-Tz)/(C-Tz)] x 100 for concentrations for which Ti>/=Tz
[(Ti-Tz)/Tz] x 100 for concentrations for which Ti100
K-562 0.45 >100 >100
MOLT-4 4.04 >100 >100
RPMI-8226 3.36 27.0 >100
SR 5.50 84.9 >100
Non-Small Cell A549/ATCC 4.52 13.91 >100 >100
Lung Cancer EKVX 5.40 >100 >100
HOP-62 22.4 >100 >100
HOP-92 22.9 >100 >100
NCI-H226 24.4 >100 >100
NCI-H23 17.6 >100 >100
NCI-H322M 24.0 >100 >100
NCI-H460 3.01 44.1 >100
NCI-H522 0.98 65.4 >100
Colon Cancer COLO 205 1.96 3.75 3.80 7.39
HCC-2998 1.05 >100
HCT-116 2.43 63.3 >100
HCT-15 0.55 >100 >100
HT29 18.6 66.8 >100
KM12 0.64 25.2 >100
SW-620 1.07 >100 >100
CNS Cancer SF-268 11.9 9.19 >100 >100
SF-295 1.72 7.79 >100
SF-539 2.43 >100 >100
SNB-19 8.24 >100 >100
SNB-75 15.2 55.8 >100
U251 15.7 >100 >100
Melanoma LOXIMVI 0.38 6.78 >100 >100
MALME-3M 19.1 85.8 >100
M-14 0.55 45.1 >100
MDA-MB-435 0.87 28.5 >100
SK-MEL-2 23.4 61.0 >100
SK-MEL-28 7.50 >100 >100
SK-MEL-5 2.01 5.58 76.1
UACC-257 6.42 >100 >100
UACC-62 0.79 >100 >100
10
Ovarian Cancer IGROV1 17.9 22.12 >100 >100
OVCAR-3 5.22 35.2. >100
OVCAR-4 32.8 >100 >100
OVCAR-5 42.6 >100 >100
OVCAR-8 13.5 57.0 >100
NCI/ADR-RES 1.92 >100 >100
SK-OV-3 40.9 >100 >100
Renal Cancer 786-0 3.26 12.73 >100 >100
A-498 14.7 50.9 >100
ACHN 0.70 >100 >100
CAKI-1 0.55 31.9 >100
RXF393 24.7 92.0 >100
SN12C 15.8 >100 >100
TK-lO 40.1 >100 >100
UO-31 2.03 58.5 >100
Prostate Cancer PC-3 10.7 15.6 79.4 >100
DU-145 20.5 >100 >100
Breast Cancer MCF7 4.02 6.71 >100 >100
MDA-MB-231/ATCC 9.85 >100 >100
HS 578T 9.94 46.2 >100
BT-549 6.14 67.7 >100
T-47D 3.61 87.7 >100
MID" 10.43
MIDa = Average sensitivity of all cell lines in 11M.
MIDb = Average sensitivity of all cell lines of a particular sub panel in 11M.
OlsoC = Concentration of the compound causing 50% decrease in net cell growth.
TOld = Concentration of the compound resulting in total growth inhibition.
LCsoe = Concentration of the compound causing net 50% loss of initial cells at the end of
the incubation period of 48 h.
11
References
1. Adel, S. EI-Azab; Mohamed, A. AI-Omar; Alaa A.M; Naglaa, 1. Abdel-Aziz;
Magda, A.-A. EI-Sayed; Abdulaziz , M. Aleisa; Mohamed, M. Sayed-Ahmed;
Sami, G. Abdel-Hamide. 2010 'Design, synthesis and biological evaluation of
novel quinazoline derivatives as potential antitumor agents: Molecular docking
study', E. J. Med. Chern., 45, 4188-4198.
2. Cakici, M.; Catir, M.; Karabuga, S.; Kilic, H.; Ulukanli, S.; Gulluce, M.; Orhan,
F. 2010 'Synthesis and biological evaluation of (S)-4-aminoquinazoline alcohols',
Tetrahedron: Asyrn., 21, 2027-2031.
3. Liu, L.T.; Yuan, T.T.; Liu, H.H.; Chena, S.F.; Wu, YT. 2007 'Synthesis and
biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as
potent EGFR inhibitors', Bioorg. Med. Chern. Lett., 17, 6373-6377.
4. Liu, Y; Poon, R.T.; Shao, W.; Sun, X.; Chen, H.; Kok, T.W.; Fan, S.T. 2007
'Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase
inhibitors suppresses growth of human hepatocellular carcinoma', Cancer Lett. ,
248,32-40.
5. Rostom SAF. 2006 'Synthesis and in vitro antitumor evaluation of some
indeno[1,2-c]pyrazol(in)es substituted with sulfonamide, sulfonylurea(-thiourea)
pharmacophores, and some derived thiazole ring systems', Bioorg. Med. Chern.,
14,6475-6485.
6. Alley, M.C.; Scudiero, D.A.; Monks, P.A.; Hursey, M. L.; Czerwinski, M.1.; Fine,
D.L.; Abbott, B.1.; Mayo, J.G.; Shoemaker, R.H.; Boyd, M.R. 1988 'Feasibility of
Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture
Tetrazolium Assay', Cancer Research, 48,589-601.
7. Grever, M.R.; Schepartz, S.A.; Chabner, RA. 1992 'The National Cancer
Institute: Cancer Drug Discovery and Development Program', Serninars in
Oncology, 19(6), 622~638.
8. Boyd, M.R.; Paull, K.D. 1995 'Some Practical Considerations and Applications of
the National Cancer Institute In Vitro Anticancer Drug Discovery Screen', Drug
Development Research, 34, 91-109.
9. Pytel, D.; Sliwinski, T.; Poplawski, T.; Ferriola, D.; Majsterek, 1. 2009 'Tyrosine
Kinase Blockers: New Hope for Successful Cancer Therapy', Anti-Cancer Agents
in Med. Chern., 9, 66-76.
10. Tsou, H.R.; Mamuya, N.; Johnson, RD.; Reich, M.F.; Gruber, RC.; Ye, F.;
Nilakantan, R.; Shen, R.; Discafani, c.; DeBlanc, R.; Davis, R.; Koehn, F.E.;
Greenberger, L.M.; Wang, Y.F.; Wissner, A. 2001 '6-Substituted-4-(3-
12
bromophenylamino)quinazolines as Putative Irreversible Inhibitors of the
Epidcnnal Growth Factor Receptor (EGFR) and HumanEpidermal Growth Factor
Receptor (HER-2) Tyrosine Kinases with Enhanced Antitumor Activity', J Med.
chern., 44, 2719-2734.
I! Kamath, S.; Buolamwini, J.K. 2006 'Targeting EGFR and HER-2 Receptor
Tyrosine Kinases for Cancer Drug Discovery and Development', Med. Research
Reviews, 26, 569-594.

We claim:
1. A novel compound for treatment of proliferative diseases comprising N4-(6,7,8trimethoxyquinazolin-
4-yl)biphenyl-4,4'-diamine of formula (1).
NH2
HN
(I)
2. The said compound N4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine of
claim-l showing anticancer activity against broad range of cancer cell lines.
3. The said cancer cell lines of claim-2 are leukemia HL-60 (TB), K-562, MOLT-4,
RPMI-8226, SR cell lines, non-small cell lung cancer A549/ATCC, EKVX, HOP62,
HOP-92, NCI-H226, NCI-H23, NCI-H322M, NCI-H460, NCI-H522 cell lines,
colon cancer COLO 205, HCC-2998, HCT-116, HCT-15, HT29, KM12, SW-620
cell lines, CNS cancer SF-268, SF-295, SF-539, SNB-19, SNB-75, U251 cell lines,
melanoma LOX IMVI, MALME-3M, M-14, MDA-MB-435, SK-MEL-2, SKMEL-
28, SK-MEL-5, UACC-257, UACC-62 cell lines, ovarian cancer IGROVI,
OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, NCI/ADR-RES, SK-OV-3 cell lines,
renal cancer 786-0, A-498, ACHN, CAKI-l, RXF 393, SNI2C, TK-IO, UO-31 cell
lines, prostate cancer PC-3, DU-145 cell lines, breast cancer MCF7, MDA-MB2311ATCC,
HS 578T, BT-549, T-47D cell lines.
4. The said compound N4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine of
claim-l showing GI50 value in range 0.38-42.6 IlM against the said cancer cell
lines of claim-3.
5. The said compound N4-(6,7,8-trimethoxyquinazolin-4-yl)biphenyl-4,4'-diamine of
claim-l showing best activity against melanoma LOX IMVI cell line.
6. The GIso value against melanoma LOX IMVI cell line of claim-5 is 0.38 IlM.
14
,
L 1
7 The 0150 value against leukemia K-562, non-small cell lung cancer NCI H-522,
colon cancer HCT-I5 and KM-I2, melanoma M-I4, MDA-MB-435 and UACC62,
renal cancer ACHN and CAKI-I cell lines of claim-3 is 0.45, 0.98, 0.55, 0.64,
0.55,0.87,0.79,0.70 and 0.55 IlM respectively.