OA11376A

OA11376A - Thienopyrimidine and thienopyridine derivatives useful as anticancer agents.

Info

Publication number: OA11376A
Application number: OA1200000133A
Authority: OA
Inventors: Michael John Munchhof; Susan Beth Sobolov-Jaynes
Original assignee: Pfizer Prod Inc
Priority date: 1997-11-11
Filing date: 2000-05-05
Publication date: 2004-01-28
Also published as: AP976A; US6492383B1; ZA9810253B; CA2309690A1; NO20002162L; EP1028964A1; SK6652000A3; PA8462401A1; NO20002162D0; PE129099A1; TW593321B; CN101328186A; GT199800180A; HN1998000168A; HUP0100287A3; UY25344A1; EA200000391A1; CO4990956A1; MY132073A; CZ20001709A3

Claims

-67- 011376 5 CLAIMS

or a pharmaceuticalty acceptable sait or hydrate thereof, wherein:wherein X1 is N or CH; 10 R1 is H, Ci-C6 alkyl or -C(O)(C,-C6 alkyl); R2 is Ce-Cw aryl or 5-13 membered heterocyclic, wherein said R2 groups are optionallysubstituted by 1 to 5 R5 substituents, each R3 is independently selected from H, -C(O)OR9, and Ci-C6 alkyl wherein said alkyl isoptionally substituted by 1 to 3 R5 groups; 15 R4 is R3, -OR9, or -NR9R10; each R5 is independently selected from halo, cyano, nitro, trifluoromethoxy,trifluoromethyl, azido, -C(O)R8. -C(O)OR8, -OC(O)R8, -OC(O)OR8, -NR6C(O)R7, -C(O)NR6R7,-NR®R7. -OR9, -SO2NR6R7, C,-C6 alkyl, -(CH2)iO(CH2)qNR6R7, -(CH2),O(CH2)„OR9. -(CH2),OR9,-S(O)j(Ci-C6 alkyl), -(CH2),(C6-C10 aryl), -(CH2),(5-10 membered heterocyclic), -C(O)(CH2),(C6- 20 C10 aryl), -(CH2),O(CH2)j(C6-C50 aryl), -(CH2),O(CH2)q(5-10 membered heterocyclic). -C(O)(CH2)t(5-10 membered heterocyclic), -(CH2)jNR7(CH2)qNR6R7, -<CH2)iNR7CH2C(O)NR6R7,-(CH2)jNR7(CH2)qNR9C(O)R8, -(CH2)iNR7(CH2),O(CH2)qOR9. -(CH2)jNR7(CH2)„S(O)1(C,-C6 alkyl).-(CH2)jNR7(CH2),R6. -S02(CH2)t(C6-C1o aryl), and -SO2(CH2),(5-10 membered heterocyclic), , wherein j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 6, q is an integer 25 ranging from 2 to 6, the -(CH2)q- and -(CH2)t- moieties of the foregoing Rs groups optionallyinclude a carbon-carbon double or triple bond where t is an integer between 2 and 6, and thealkyl, aryl and heterocyclic moieties of the foregoing R5 groups are optionally substituted by 1 to3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, -C(O)R8,-C(O)OR8, -OC(O)R8, -OC(O)OR8, -NReC(O)R7, -C(O)NR6R7, -<CH2),NR6R7, CrC6 alkyl, 30 -(CH2),(C6-C,o aryl), -(CH2),(5-10 membered heterocyclic), -(CH2),O(CH2)„OR9, and -(CH2),OR9. wherein t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6; each R6 and R7 is independently selected from H, C,-C6 alkyl, -(CH2),(C6-Ci0 aryl),-(CH2),(5-10 membered heterocyclic). -(CH2),O(CH2)qOR9. and -{CH2),OR9, wherein t is aninteger ranging from 0 to 6 and q is an integer ranging from 2 to 6, and the alkyl, aryl and 35 heterocyclic moieties of the foregoing R6 and R7 groups are optionally substituted by 1 to 3substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, -C(O)R8, -68- 011376 10 15 20 25 30 -C(O)0R8. -CO(O)R8, -0C(O)OR8, -NR9C(O)Rw, -C(O)NR9Rw, -NR9Rw, c,-c6 alkyl,-(CH2),(C6-C,o aryl), -(CH2),(5-10 membered heterocyclic), -(CH2),O(CH2)qOR9, and -(CH2),OR9.wherein t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6, with theproviso that where R6 and R7 are both attached to the same nitrogen, then R6 and R7 are notboth bonded to the nitrogen directly through an oxygen; each R8 is independently selected from H, C,-Cw alkyl, -(CH2),(C6-C,o aryl), and-(CH2),(5-10 membered heterocyclic), wherein t is an integer ranging from 0 to 6; each R9 and R10 is independently selected from H and CrC6 alkyl; R" is H, CrC6 alkyl, -C(O)NR®R9, -C(O)(C6-C,0 aryl), -{CHjMCe-Cw aryl), or -<CH2),(5-10membered heterocyclic), wherein t is an integer ranging from 0 to 6, wherein said R11 groups,otherthan H, are optionally substituted by 1 to 5 R5 groups; and, R12 is H, C,-C6 alkyl, -C(O)(Ci-Cs alkoxy), -8(0)/0,-06 alkyl), -SO2(CH2),(C6-CW aryl),-(CH2),(Ce-C,o aryl), -(CH2),(5-10 membered heterocyclic), -(CH2),O(CH2)qOR9, or -(CH2),OR9,wherein j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 6 and q is an integerranging from 2 to 6.
2- Diethylaminomethyl-4-(6-phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-phenol;5-Methyl-1-[4-(6-phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-phenyl]-1,2-dihydro-pyrazol-3- one; [4-(4,5-Dichloro-imidazol-1-yl)-phenyl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 10 (6-Phenyl-thieno[3,2-dlpyrimidin-4-yl)-[4-(3-trifluoromethyl-pyrazol-1 -yl)-phenyl]-amine; (4-(4-Methyl-pipera2in-1-yl)-phenyl]-(6-phenyl-thieno{3I2-dÎpyrimidin-4-yl)-amine;[4-<4-Methyl-piperidin-1-yl)-phenyl]-(6-phenyl-thienof3,2-d]pyrimidin-4-yl)-amine; l-{4-(6-Phenyl-thienol3,2-d]pyrimidin-4-ylamino)-phenyl]-1H-tetrazole-5-thiol; 3- (6-PhenyHhieno[3,2-d]pyrimidin-4-ylamino)-benzenesulfonamide; 15 (2-Methyl-benzothiazol-6-yl)-(6-Pheriyl-thieno(3,2-d]pyrimidin-4-yl>-amine; [4-(Morpholine-4-sulfonyl)-phenyl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; (3,5-Dimethyl-4-(thiophen-3-yimethoxy)-phenyl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)- amine; [4,5-Dimethoxy-2-(1H-tetrazol-5-yl)-phenyl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)- 20 amine; 5- [4-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-phenyl]-oxazolidine-2,4-dione;1-Ethyl-5-<6-phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-1,3-dihydro-indol-2-one; 6- (6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-3H-benzooxazol-2-one;Dibenzothiophen-4-yl-(6-phenyt-thieno[3,2-d]pyrimidin-4-yl)-amine; 25 N-(6-Pheny1-thieno[3,2-d]pyrimidin-4-yl)-N'-p-tolyt-benzene-1,2-diamine; (2-Furan-2-yl-1-methyl-1H-benzoimidazol-5-yl)-{6-phenyl-thieno[3,2-d]pyrimidin-4-yl)- amine; 5-(6-Phenyl-thieno(3,2-d]pyrimidin-4-ylamino)-benzo[b]thiophene-2-carbonitrile; (6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-{2-pyridin-4-yl-1H-benzoimidazol-5-yl)-amine; 30 [4-( 1 -Methyl-1 H-imidazol-2-ylsulfanyl)-phenyl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)- amine; (6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-[4-(pyridin-2-yloxy)-phenyl]-amine; [4-(5-Methyl-tetrazol-1-yl)-phenyl]-{6-phenyl-thieno[3,2-d]pyrimidin-4-yf)-amine; 1-[3-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamÎno)-phenyl]-1H-tetrazole-5-thiol; 35 4-[4-(6-Phenyl-thieno[3,2-dJpyrimidin-4-ylamino)-phenylamino]-phenol; [3-{3-Methyi-4,5-dihydro-pyrazol-1-yl)-phenyI]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)- amine; [6-{4-Fluoro-phenyl)-thieno[3,2-d]pyriniidin-4-yl]-(1H-indol-5-yl)-amine; Benzo[1,2,3]thiadiazol-6-yl-(6-phenyl-thieno[3,2-<i]pyrimidin~4-yl)-amine; 40 and the pharmaceutically acceptable salts and hydrates of the foregoing compounds.

2-Amino-3-(3-{4-(4-( 1 H-indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzyl}-3H- imidazol-4-yl)-propionic acid methyl ester, 3-{4-[4-(1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-€-yl]-benzylamino}-2,2-dimethyl- propan-1-ol; (9-Ethyl-9H-carbazol-3-yl)-(6-phenyl-thienoI3,2-d]pyrimidin-4-yl)-amine; 10 [1 -(2-Diethylamino-ethyl)-1 H-indol-5-yl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; [1-(3-Diethylamino-propyl)-1H-indol-5-yl]-(6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-amine;(2-Bromo-thieno(3,2-b]pyridin-7-yl)-(1 H-indol-5-yl)-amine; [6-(4-Aminomethyl-phenyl)-thieno(3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine;

2. A compound of claim 1 wherein said compound is a compound of formula 1wherein R11 is -(CH2),(C6-Cio aryl) or -(CH2),(5-10 membered heterocyclic), wherein t is aninteger ranging from 0 to 6, wherein said R11 groups are optionally substituted by 1 to 5 Rs groups.
3-Hydroxy-2-(4-[4-(1H-indol-5-yiamino)-thieno[3t2-dJpyrimidin-6-yl]-benzylamino}- 15 propionic acid methyl ester; Furan-2-yl-(4-{4-[4-( 1 H-indol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzyl}-piperazin-1 -yl)-methanone; [6-(4-Dimethylaminomethyl-phenyl)-thieno[3I2-d]pyrimidin-4-yl]-{1H-indol-5-yl)-amine; 2-({4-(4-(1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzyl}-methyl-amino)- 20 éthanol; (1 -{4-(4-( 1 H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzyl)-pynOlidin-2-yl)-methanol; 2-(2 -(4-(4-(4-( 1 H-lndol-5-yIamino)-thieno[3,2-d]pynmidin-6-y1]-benzyl}-piperazin-1 -yl)-ethoxyj-ethanol; 25 4-(4-(1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzoic acid; (3-Methyl-1H-indol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; ( 1 H-lndol-5-yl)-(2-methyl-6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-amine;N-(4-Methoxy-phenyl)-N'-(2-methyl-6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-benzene-1,4- diamine; 30 N-(2-Benzyloxy-ethyl)-N'-(6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine; 5-(6-Phenyl-thieno(3,2-d]pyrimidin-4-ylamino)-1 H-indole-3-carbaldehyde;(3-Bromo-1H-indol-5-y!)-(6-phenyl-thieno(3,2-d]pyhmidin-4-yi>-amine; N-( 1 H-lndol-3-ylmethyl)-N'-(6-phenyl-thteno{3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine;N-(6-Bromo-thieno(3,2-d]pyrimidin-4-yl)-N,-(4-methoxy-phenyl)-benzene-1,4-diamine; 35 N-(4-Methoxy-phenyl)-N*-[6-(2-nitro-phenyl)-thieno{3,2-dlpyrimidin-4-yll-benzene-1,4- diamine; N-(4-Methoxy-phenyl)-N‘-[6-(4-methoxy-phenyl)-thieno(3,2-d]pyrimidin-4-yl]-benzene-1,4-diamine; N-(4-Methoxy-phenyl)-N’-(6-thiophen-2-yl-thieno[3,2-d]pyrimidin-4-yl)-benzene-1,4- 40 diamine; -75- Π Ί ή 2 7 aυ ι ιό/Ο 5 N-(4-Methoxy-phenyl)-N'-Î6-{6-methoxy-pyridin-3-yl)-thieno[3,2-d]pyrimidin-4-yl]- benzene-1,4-diamine; (1H-lndol-5-yl)-[6-(4-thiomorpholin-4-ylmethyl-phenyl)-thieno[3,2-d]pyrimidin-4-yl]- amine; 6-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-benzothiazole-2-thioi; 10 N-(4-Methoxy-phenyl)-N’-thieno[3,2-d]pyrimidin-4-yl-benzene-1,4-diamine; N-(2-Methoxy-phenyl)-N’-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine,N-(6-Phenyl-thieno(3,2-d]pyrimidin-4-yl)-N'-o-tolyl-benzene-1,4-diamine;N-(6-Phenyl-thieno(3,2-d]pyrimidin-4-yl)-N'-p-tolyl-benzene-1,4-diamine;N-(3.4-Dimethoxy-phenyl)-N'-{6-phenyl-thienol3,2-d]pyrimidin-4-yl)-benzene-1,4- 15 diamine; N-(6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-N‘-(3,4,5-trimethoxy-phenyl)-benzene-1,4-diamine; N-{6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-N'-m-tolyl-benzene-1,4-diamine;N-(4-Chloro-phenyl)-N‘-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine; 20 (1H-lndol-5-yl)-[6-(6-methoxy-pyridin-3-yl)-thienoI3,2-d]pyrimidin-4-yl]-amine; N-(4-dimethylamino-phenyl)-N'-{6-phenyl-thienol3,2-d]pyrimidin-4-yl)-benzené-1,4- diamine; N-(3-Methoxy-phenyt)-N'-(6-phenyl-thieno{3,2-d]pyrimidin-4-yJ)-benzene-1,4-diamine; ( 1,3-Dibromo-1 H-indol-5-yl}-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 25 (6-Chloro-1H-indol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yi)-amine; |5-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-1H-indoi-3-yl]-methanol; (6-Phenyl-thieno{3,2-d]pyrimidin-4-yl)-{3-[(3-pyrazol-1-yl-propylamino)-methyl]-1H-indol- 5-yl}-amine; U5-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-1H-indol-3-ylmethyl]-amino}-acetic acid 30 methyl ester, 2-{[5-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-1H-indol-3-ylmethyI]-amino}-ethanol;5-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-1H-indole-3-carbaldehyde oxime;(3-Methyliminomethyl-1H-indol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine;[3-{2-Nitro-vinyl)-1H-indol-5-yl]-<6-phenyl-thieno[3,2-d]pyrimidin-4-yi)-amine; 35 4-{4-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-phenylamino]-phenol;

3. A compound of claim 2 wherein R11 is phenyl or pyridyl, wherein said phenyl andpyridyl are optionally substituted by 1 to 5 R5 groups.
4-Methyl-N-[4-(6-phenyl-thieno(3,2-d]pyrimidin-4-ylamino)-phenyl]-benzenesulfonamide;N-Phenyl-N'-(6-phenyl-thieno{3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine; 35 (6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-(2H-pyrazol-3-yl)-amine; ( 1 H-Indazol-6-yl)-(6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-amine;N,N-Dimethyl-N'-(6-phenyl-thieno{3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine;(2,3-Dimethyl-1H-indol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine;N-Ethyl-N'-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine; 40 [4-(1H-lndol-5-ytamino)-thieno[3,2-d]pyrimidin-6-yl]-phenyl-methanone; ( 1 H-lndol-5-yl)-(6-p-tolyl-thieno[3,2-d]pynmidin-4-yt)-amine; -70- 011376 5 (5-Furan-2-yl-2H-pyrazol-3-yl)-thieno[3,2-d]pyrimidin-4-yl-amine; Thieno[3,2-d]pyrimidin-4-yl-(5-thiophen-2-yl-2H-pyrazol-3-yl)-amine; (5-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-thienoI3,2-d]pyrimidin-4-yl-amine; (2H-Pyrazol-3-yl)-thieno(312-d]pyrimidin-4-yl-amine; Thieno[3,2-d]pyrimidin-4-yl-(5-p-tolyl-2H-pyrazol-3-y1)-amine; 10 4-(4-(1 H-Indol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl}-benzaldehyde; (6-(4-Chloro-phenyl)-thieno(3t2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; [6-(4-Fluoro-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; (1H-lndol-5-yl)-(6-thiophen-3-yl-thieno(3,2-d]pyrimidin-4-yl)-amine; 2-(3-(4-Chloro-phenyl)-5-(thieno(3,2-d]pyrimidin-4-ylamino)-pyrazol-1-yl]-ethanol; 15 (1 H-lndol-5-yl)-[6-(4-trifluoromethyl-phenyl)-thieno[3,2-d]pynmidin-4-yl]-amine; (1H-lndol-5-yl)-(6-(4-methylsulfanyl-phenyl)-thieno[3,2-d]pyrimidin-4-yl}-arnine; (1H-lndol-5-yl)-(6-(3-nitro-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-amine; (6-(3-Chloro-4-fluoro-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; [5-(4-Methoxy-phenyl)-2H-pyrazol-3-yll-thieno[3,2-d]pyrimidin-4-yl-amine; 20 4-[5-(Thieno[3,2-d]pyrimidin-4-ylamino)-1 H-pyrazol-3-yl]-benzoic acid methyl ester, (5-Methyl-2H-pyrazol-3-yl)-thieno(3,2-d]pyrimidin-4-yl-amine; 5-(6-Phenyl-thieno(3,2-d]pyrimidin-4-ylamino)-1 H-indole-2-carboxylic acid ethyl ester;(6-Benzofuran-2-yl-thieno[3,2-d]pyrimidin-4-yl)-( 1 H-indol-5-yl)-amine;Thieno[3,2-d]pyrimidin-4-yl-(5-m-tolyl-2H-pyrazol-3-yl)-amine; 25 (5-(3-Chloro-phenyl)-2H-pyrazol-3-yl]-thieno[3,2-d]pyrimidin-4-yl-amine; [6-(4-Ethyl-phenyl)-thieno(3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; 4-(4-( 1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzoic acid methyl ester;4-[5-(Thieno[3,2-d]pyrimidin-4-ylamino)-1 H-pyrazol-3-ylJ-benzoic acid; ( 1 H-lndol-5-yl)-(6-thiophen-2-yl-thieno[3,2-d]pyrimidin-4-yl)-amine; 30 (5-(2-Chloro-phenyl)-2H-pyrazol-3-yl]-thieno[3,2-d]pyrimidin-4-yl-amine; (1H-lndol-5-yl)-(6-pyridin-3-yl-thieno[3,2-d]pyrimidin-4-yl)-amine;(1H-lndol-5-yl)-{6-(3-methoxy-phenyl)-thieno[3,2-d]pyrirnidin-4-yl]-amine; {4-(4-(1 H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl}-phenyl}-methanol; (6-(3,4-Dimethoxy-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; 35 [6-(4-Dimethylamino-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; (4-(1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-phenyi-methanol; 4-(1 H-lndol-5-ylamino)-thieno[3,2-d]pyrimidine-6-carboxylic acid (2-dimethylaminoethyl)-amide; ( 1 H-l ndol-5-yl)-[6-(4-trifluoromethoxy-phenyl)-thieno(3,2-dlpyrimidin-4-yl]-amine; 40 ( 1 H-lndol-5-yl)-(6-(2-methoxy-phenyi)-thieno(312-d]pyrimidin-4-yl}-amine; 4-(4-( 1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-y0-phenol; -71- 011376 5 [6-(5-Diethoxymethyl-thiophen-2-yl)-thieno(3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; 4-(1 H-lndol-5-ylamino)-thieno[3,2-d)pyrimidine-6-carboxylic acid (2-methoxy-ethyl)- amide; N-{4-[4-(1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzyl}-N',N'-dimethyl-ethane- 1,2-diamine; 10 (1H-lndol-5-yl)-(6-{4-[(2-methoxy-ethylamino)-methyl]-phenyl}-thieno(3,2-d]pyrimidin-4- yl)-amine; (1H-lndol-5-yl)-{6-[2-(4-methyl-piperazin-1-yl)-phenyl]-thieno[3,2-d]pyrimidin-4-yl}- amine; 4- (1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidine-6-carboxyiic acid propylamide; 15 2-(4-(4-( 1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzyiamino}-ethanol; [6-(2,4-Dimethoxy-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; [6-(4-Diethylamino-phenyl)-thieno(3,2-d]pyrimidin-4-yl]-(1H-indol-5-yl)-amine; [6-(4-Ethoxy-phenyl)-thieno(3,2-d]pyrimidin-4-yl]-(1H-indoI'5-yl)-amine; 3-(4-(4-( 1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzytamino}-propane-1,2-dioi; 20 (1H-lndol-5-yl)-(6-(4-propyiaminomethyl-phenyl)-thieno(3l2-d]pyrimidin-4-yl]-amine; (1H-lndol-5-yl)-(6-(4-((3-methoxy-propylamino)-methyl]-phenyl}-thieno{3,2-d]pyrimidin-4- yl)-amine; (6-(3-Fluoro-4-methoxy-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-(1H-indol-5-yi)-amine; (1H-lndol-5-yl)-(6-(3-methylsulfanyl-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-amine; 25 (1 H-lndol-5-yl)-[6-(5-methyl-thiophen-2-yl)-thieno[3,2-d]pyrimidin-4-yl]-amine; (1H-lndol-5-yl)-(6-{4-[(2-piperazin-1-yl-ethylamino)-methyl]-phenyl}-thieno[3,2- d]pyrimidin-4-yl)-amine; (6-Benzo(1,3Jdioxol-5-yl-thieno[3,2-d]pyrimidin-4-yl)-(1H-indol-5-yl)-amine; {6-(4-(1-Ethoxy-ethoxy)-phenyl]-thieno(3,2-d]pyrimidin-4-yl}-(1H-indol-5-yl)-amine; 30 (1 H-lndol-5-yl)-(6-(4-(2-pyrrolidin-1 -yl-ethoxy)-phenyl]-thieno(3,2-d]pyrimidin-4-yl}-amine; (1H-lndol-5-yl)-(6-{4-(2-methoxy-ethoxy)-phenyl]-thieno[3,2-d]pyrimidin-4-yl}-amine; (1H-lndol-5-yl)-{6-{4-((2-morpholin-4-yl-ethylamino)-methyt]-phenyl}-thieno(3,2- d]pyrimidin-4-yl)-amine; {6-[4-(2-Dimethylamino-ethoxy)-phenyl]-thieno[3,2-d]pyrimidin~4-yl}-(1H-indol-5-yl)- 35 amine; (1H-lndol-5-yl)-[6-(4-methylaminomethyl-phenyl)-ttiieno[3,2-d]pyrimidin-4-yl]-amine, 5- (6-Phenyl-thieno[3,2-d]pyrimidin~4-ylamino)-1,3-dihydro-indol-2-one;(1H-Benzotriazol-5-yl)-(6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-amine;(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylH4-(2H-tetrazol-5-yl}-phenyl]-amine; 40 N-{4-(4-{1 H-lndol-S-ytamino^thienofS^-dlpyrimidin-e-yll-benzylj-N'-methyl-ethane-l ,2- diamine; -72- 011376 5 (1 -Benzenesulfonyl-1 H-indol-5-yl)-(6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-amine; 3-{4-[4-(1H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzylamino}-propan-1-ol; ( 1 H-l ndol-5-yl)-{6-[4-(4-methyl-piperazin-1 -ylmethyl)-phenyl]-thieno(3,2-d]pyrimidin-4-yl}- amine; 2-{4-{4-{ 1 H-lndol-5-ylamino)-thieno[3,2-dJpyrimidin-6-yl]-benzylamino}-propane-1,3-diol; 10 2-((2-Hydroxy-ethyl)-{4-[4-(1 H-indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzyl}- amino)-ethanol; {5-(4-(1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-thiophen-2-yl}-methanol; 2-(2-{4-{4-(1H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzylamino}-ethoxy)- ethanol; 15 2-(2-{4-[4-(1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-ylJ-benzylamino}-ethylamino)- éthanol; [6-(4-{[2-( 1 H-lmidazol-4-yl)-ethylamino]-methyl}-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-( 1H-indol-5-yl)-amine; (1H-lndol-5-yl)-{6-{4-{2-morpholin-4-yl-ethoxy)-phenyl]-thieno[3,2-d]pyrimidin-4-yl}- 20 amine; 2- {4-(4-{1H-lndol-5-ylamino)-thieno[3l2-d]pyrimidin-6-yl]-phenoxy}-ethanol;[4-(2-Ethyl-oxazol-5-yl)-phenyl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine;N-(2-Methoxy-phenyl)-N'-(6-pheny1-thieno[3,2-d]pyrimidin-4-y1)-benzene-1,4-diamine;N-(4-Methoxy-phenyl)-N,-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine; 25 5-(4-(1 H-lndol-5-ylamino)-thieno{3,2-d]pyrimidin-6-yl]-thiophene-2-carbaldehyde; [5-(6-Phenyl-thieno{3,2-d]pyrimidin-4-ylamino)-1H-indol-2-yl]-methanol;(2-PhenyHH-indol-3-yl)-(6-phenyl-thieno(3,2-d]pyrimidin-4-yl)-amine;(9H-Carbazol-3-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine;(2-Methyl-1H-indol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 30 (1 -Phenyl-ethyl)-(6-phenyl-thieno{3,2-d]pyrimidin-4-yl)-amine; (1H-lndol-5-yl)-(6-(4-{[(thiophen-2-ylmethyl)-amino]-methyI}-phenyl)-thieno(3,2- d]pyrimidin-4-yl]-amine; 3- {4-(4-(1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-€-ylJ-benzylamino}-propionic acid methyl ester; 35 [6-(4-{[(Furan-2-ylmethyl)-amino]-methyl}-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-(1H-indol- 5-yl)-amine; 1-{3-{4-{4-(1H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzylamino}-propyl)- pyrrolidin-2-one; N-^-^IH-Indol-S-ylaminoJ-thienoIS^-dlpyrimidin-e-ylJ-benzylJ-N'.N'-dimethyl- 40 propane-1,3-diamine; ( 1 H-lndoi-5-yl)-{6-(4-morpholin-4-ylmethyl-phenyl)-thieno(3,2-d]pyrimidin-4-yl]-amine; -73- 011376 5 (2-(4-(4-(1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzylamino}-acetylamino)- acetic acid ethyl ester; 1 .(4-(4.(4-( 1 h-I ndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzyl}-piperazin-1 -yl)-ethanone; (6-(4-((2,2-Diphenyl-ethylamino)-methyl]-phenyl}-thieno(3,2-d]pyrimidin-4-yl)-(1H-indol-10 5-yl)-amine; (1H-lndol-5-yl)-{6-[4-(2-methoxymethyl-pyrrolidin-1-ylmethyl)-phenyl]-thieno[3,2- d]pyrimidin-4-yi)-amine; N-(2-(4-(4-(1H-lndol-5-yiamino)-thieno(3,2-d]pyrimidin-6-yl]-benzylamino}-ethyl)- acetamide; 15 [6-(4-Cyclopropylaminomethyl-phenyl)-thieno(3,2-dlpynmidin-4-yl]-(1 H-indol-5-yl)- amine; 2-{4-[4-(1H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzylamino}-butan-1-ol;2-((5-(4-(1 H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-th>ophen-2-ylmethyl}-amino)- éthanol; 20 (1H-lndol-5-yl)-(6-{4-((2-pyrrolidin-1-yl-ethylamino)-methyl]-ph?nyl}-thieno(3,2- d]pyrimidin-4-yl)-amine; (6-(4-(Benzylamino-methyl)-phenyl]-thieno(3,2-d]pyrimidin-4-yl}-(1H-indol-5-yl)-amine; 1-{4-(4-(1H-lndol-5-ylamino)-thieno(3,2-d]pyrimidin-6-yl]-benzyl}-piperidine-4-carboxylic acid amide; 25 (1H-lndol-5-yl)-{6-[4-(pyrrolidin-3-ylaminomethyl)-phenyl]-thieno(3,2-d]pyrimidin-4-yl}- amine; (6-(4-((3-lmidazoH -yl-propylamino)-methyl]-phenyl}-thienoI3,2-d]pyrimidin-4-yl)-( 1H-indol-5-yl)-amine; N-{4-{4-( 1 H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzyl}-N', N’-dimethyl-hexane-30 ,1,6-diamine; (1-Allyl-1H-indol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; ( 1 -Methyl-1 H-indol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine;(1H-lndol-5-ylH6-(4-{4-ptienyl-piperazin-1-ylmethyl)-phenyl]-thieno[3,2-d]pyrimidin-4-yl}- amine; 35 N-ÊS-^-OH-Indol-S-ylaminoJ-thienofS^-dlpyrimidin-e-yij-thiophen-Z-ylmethylj-N'.N'- dimethyl-ethane-1,2-diamine; N-{5-[4-(1H-lndol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-thiophen-2-ylmethyl}-N‘-methyl- ethane-1.2-diamine; (1H-lndol-5-yl)-(6-(5-I(2-methoxy-ethylamino)-methyl]-thiophen-2-yl}-thieno{3,2-40 d]pyrimidin-4-yl)-amine; -74- 011276

4. A compound of claim 1 wherein said compound is a compound of formula 1wherein X1 is CH.
5-Methyl-1 -[4-(6-phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-phenyl]-1,2-dihydro-pyrazol-3- one; (2-Methyl-benzothiazol-6-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine;(S-Methylaminomethyl-IH-indoi-S-ylHe-phenyl-thienofS^-dlpyrimidin^-yO-amine;(4-Methoxy-2-methyl-phenyl)-(5-phenyl-thieno[3,2-d}pyrimidin-4-yl)-amine;[4-(4-Chloro-phenoxy)-phenyl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 40 -76- 011376 5 6-(6-Phenyl-thieno[3.2-d]pyrimidin-4-ylamino)-1 H-benzo(d][1,3]oxazine-2,4-dione;

5. A compound of claim 1 wherein said compound is a compound of formula 1wherein R2 is phenyl optionally substituted by 1 to 5 R5 substituents.
6. A compound of claim 1 wherein said compound is a compound of formula 1wherein R2 is a group of the formula

or

-69- 011276 5 wherein X2 is -S- or -N(R6)-, X3 is N or CH, the dashed line in formula 3 represents an optional double bond, and the above R2 groups of formulas 3 and 5 are optionally substituted by 1to 5 R5 substituents and the R2 groups of formulas 4 and 6 are optionally substituted by 1 to 3 R5substituents.
7. A compound of claim 6 wherein R2 is a group of formula 3 above wherein said 10 group is optionally substituted by 1 to 5 R5 substituents.
8. A compound of claim 1 wherein said compound is selected from the groupconsisting of: (3-Ethynyl-phenyl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine;(3-Ethynyl-phenyl)-[6-(4-methoxy-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-amine ; 15 Benzo[b]thiophen-5-yl-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; (1H-lndol-5-yl)-[6-(4-methoxy-phenyl)-thieno[3,2-d]pyrimidin-4-yl]-amine; (1H-lndol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; (6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-(2-pyrrol-1-yl-phenyl)-amine; (5-Phenyl-1H-pyrazol-3-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 20 (5-Phenyl-1H-pyrazol-3-yl)-thieno[3,2-d]pyrimidin-4-yl-amine; ( 1 H-lndol-5-yl)-thieno[3,2-d]pyrimidin-4-yl-amine; N-(5-Phenyl)-1 -(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-1 H-[1,2,4]triazole-3,5-diamine; 3- [3-Phenyl-5-(6-phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-pyrazol-1-yl]-propionitrile·,(5-Furan-2-yl-2H-pyrazol-3-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 25 (6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-(5-thiophen-2-yl-2H-pyrazol-3-yl)-amine·, N-(6-Phenyl-thieno[3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine;N-[4-(6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-phenyl]-benzamide;N-Methyl-N'-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-benzene-1,4-diamine;(1H-lndazol-5-yl)-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 30 [5-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; Benzothiazol-6-yl-(6-phenyl-thieno[3,2-d]pyrimidin-4-yl)-amine; 4- (6-Phenyl-thieno[3,2-d]pyrimidin-4-ylamino)-benzamide;
9. A compound according to claim 1 selected from the group consisting of -77- 011376 5 (2-(4-Fluoro-phenyl)-thieno(3,2-b]pyridin-7-yl]-(1H-indol-5-yl)-amine; (1H-lndol-5-yl)-(2-thiophen-2-yl-thieno(3,2-b]pyridin-7-yl)-amine; 4-(7-( 1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzaldehyde; (1H-lndol-5-yl)-(2-(4-methylsulfanyl-phenyl)-thieno(3,2-b]pyridin-7-yl]-amine; (1H-lndol-5-yl)-thieno(3,2-b]pyridin-7-yl-amine; 10 2-(4-(7-( 1 H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-ylJ-phenoxy}-ethanol; (2-(4-Dimethylamino-phenyl)-thieno(3,2-b]pyridin-7-ylJ-(1H-indol-5-yl)-amine; 4-(7-( 1H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzoic acid methyl ester; (1 H-lndol-5-yl)-(2-thiophen-3-yl-thieno(3,2-b]pyridin-7-yl)-amine;(1H-lndol-5-yl)-(2-(4-((2-methoxy-ethyiamino)-methyl]-phenyl}-thieno(3,2-b]pyndin-7-yl)- 15 amine; Furan-2-yl-(4-(4-[7-(1H-indol-5-ylamino)-thieno(3l2-b]pyridin-2-yl]-benzyl}-piperazin-1- yl)-methanone; 4-(7-( 1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-phenol; 2-(2-(4-(7-(1 H-lndol-5-ylamino)-thieno(3,2-blpyridin-2-yl]-benzylamino}-ethoxy)-ethanol; 20 2-(4-[7-(1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-ethanol; N-{4-[7-(1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl(-benzyl}-N*,N'-dimethyV.hexane- 1,6-diamine; 2-({4-(7-(1H-lndol-5-ylamino)-thieno(3,2-b(pyridin-2-yl]-benzyl}-methyl-amino)-ethanol; (1H-lndol-5-yl)-(2-(4-[(2-piperazin-1-yl-ethylamino)-methyl]-phenyl}-thieno(3,2-b]pyridin- 7-yl)-amine; (2-(4-((3-lmidazol-1-yl-propylamino)-methyl]-phenyl}-thieno(3,2-b]pyridin-7-yl)-(1H-indol- 5-yl)-amine; 2-((2-Hydroxy-ethyl)-(4-{7-(1H-indol-5-ylamino)-thieno[3,2-b]pyrïdin-2-yl]-benzyl}-amino) éthanol; 30 (2-(4-Dimethylaminomethyl-phenyl)-thieno(3,2-b]pyridin-7-yl]-{ 1 H-indol-5-yl)-amine; N-(4-i7-(1H-lndol-5-ylaniino)-thieno[3,2-b]pyridin-2-yl]-benzyl}-N,,N'-dimethyl-ethane- 1,2-diamine; (1-{4-[7-(1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl}-benzyl}-pyiTolidin-2-yl)-methanol;2-(4-(4-(7-( 1 H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzyl}-piperazin-1 -yl)-ethanol; 35 ( 1 H-lndol-5-yl)-(2-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-thieno(3,2-b]pyridin-7-yl}-amine; 1 -(4-(7-( 1 H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzyl}-piperidine-4-carboxylic acid amide; (4-(7-(1 H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-phenyl}-methanol; 2-(4-(7-(1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-butan-1-ol; 40 N-(4-(7-( 1 H-Indol-S-ylaminoJ-thienolS^-bJpyridin^-yll-benzyiy-N'-methyl-ethane-l ,2- diamine; -78- 011376 5 (1H-lndol-5-yl)-(2-(4-morpholin-4-ylmethyl-phenyl)-thieno[3,2-bJpyridin-7-yl]-amine; 3-(4-(7-( 1H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzylamino}-propan-1-ol; 1- (3-(4-(7-( 1H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzylamino}-propyl)-pyrrolidin-2-one; (1H-lndol-5-yl)-{2-(4-(2-methoxy-ethoxy)-phenyl]-thieno(3,2-b]pyridin-7-yl}-amine; 10 2-(2-(4-(7-(1 H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzylamino}-ethylamino)- éthanol; 3-(4-(7-( 1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-2,2-dimethyl-propan-1-ol; 3-(4-(7-( 1 H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzylamino}-propane-1,2-diol; 15 [2-(4-{[2-(1 H-lmidazol-4-yl)-ethylamino]-methyl}-phenyl)-thieno[3,2-b]pyridin-7-yl]-(1 H- indol-5-yl)-amine; N-(2-{4-[7-(1H-lndol-5-ylamino)-thieno[3l2-b]pyridin-2-yl]-benzylamino}-ethyl)- acetamide; 2- {4-(7-(1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-acetamide; 20 2-(4-(7-( 1H-lndol-5-ylamino)-thieno[3,2-bJpyridin-2-yl]-benzylamino}-propane-1,3-diol; N-(4-Methoxy-phenyl)-N'-[2-(3-nitro-phenyl)-thieno[3,2-b]pyridin-7-yl]-benzene-1,4- diamine; (7-Methoxy-1 H-indol-5-yl)-(2-phenyl-thieno(3,2-b]pyridin-7-yl)-amine; (1H-lndol-5-yl)-[2-(4-methylaminonrcethyl-phenyl)-thieno(3,2-b}pyridin-7-yl]-amine; 25 N-(4-[7-(1 H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzyl}-ethane-1,2-diamine; {4-(7-(1 H-lndol-5-ylamino)-thieno{3,2-b]pyridin-2-yl]-benzylamino}-acetic acid methyl ester; N-^-P-OH-lndol-S-yiaminoi-thienoP^-blpyridin^-yll-benzyQ-N'.N'-dimethyl-propane- 1,3-diamine; 30 (1H-lndol-5-yl)-(2-pyridin-2-yl-thieno[3,2-b]pyridin-7-yl)-amine; (1H-lndol-5-yl)-(2-(4-[(2-morpholin-4-yl-ethylamino)-methyl]-phenyl}-thieno[3,2-b]pyridin- 7-yl)-amine; (1H-lndol-5-yl)-(2-[4-(pyrroltdin-3-ylaminomethyl)-phenyl]-thieno(3,2-b]pyridin-7-yl}- amine; 35 1 -(4-(4-(7-( 1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzyt}-piperazin-1-yl)- ethanone; 1-(4-(7-(1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzyl}-pyrrolidine-2-carboxylicacid amide; N-(4-Methoxy-phenyl)-N'-(2-(6-methoxy-pyridin-3-yl)-thieno{3,2-b]pyridin-7-yl]-benzene-40 1,4-diamine; (1H-lndol-5-yl)-(2-pyridin-3-yi-thieno(3,2-b]pyridin-7-yl)-amine; -79- 5 4-{7-(1H-!ndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl}-but-3-yn-1-ol; N-(4-Methoxy-phenyl)-N'-(2-thiophen-2-yl-thieno[3,2-b]pyridin-7-yl)-benzene-1,4- diamine; N-(2-Hydroxy-ethyl)-4-(7-(1H-indol-5-ylamino)-thteno[3,2-b]pyridin-2-yl]-benzamide; N-(3-lmidazol-1-yl-propyl)-4-[7-(1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]- 10 benzamide; 3-{4-(4-{4-[7-(1H-lndol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzylamino}-butyl)- piperazin-1-yl]-propan-1-ol; ( 1 K-lndol-5-yl)-[2-(4-{[4-(4-meîhyl-piperazin-1 -yl)-butylamino]-methyl}-phenyl)-thieno[3.2-b]pyridin-7-yl]-amine; 15 2-[4-(4-{4-[7-(1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl}-benzylamino}-butyl)- piperazin-1 -yf]-ethanol; 1- lmidazol-1-yt-3-{4-r7-(1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yi]-benzylamino}-propan-2-ol; 5-{4-[7-( 1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-pentan-1 -ol; 20 2-[2-{4-{4-[7-(1H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzyl}-piperazin-1-yl)- ethoxy]-ethanol·, (1H-lndo!-5-yl)-(2-{4-[(2-methylsijlfanyl-ethylamino)-methyl]-phenyl}-thieno[3,2-blpyridin 7-yl)-amine; 2- [(2-Hydroxy-ethyl)-(3-{4-{7-{1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-25 benzylamino}-propyl)-amino]-ethanol; N-(2-Amino-ethyl)-N'-{4-[7-(1H-indol-5-ylamino)-thieno[3,2-blpyridin-2-yl]-benzyl}- ethane-1.2-diamine; 2-(3-{4-[7-{1H-lndol-5-ylamino)-thieno(3.2-b]pyridin-2-yl]-benzylamino}-propylamino)- éthanol; 30 . N-{4-[7-(1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzyl}-hexane-1,6-diaminé; (2-Methyl-1H-indol-5-yl)-I2-{4-morpholin-4-ylmethyl-phenyl)-thieno[3,2-b]pyridin-7-yl]- amine; 2-{4-[7-(2-Methyl-1 H-indol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzylamino}-ethanol;(1H-lndol-5-yl)-[2-(6-methoxy-pyridin-3-yl)-thieno[3,2-b]pyridin-7-yl]-amine; 35 {5-[7-{ 1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-pyridin-2-yl}-methanor, N,N-Dimethyl-N’-{4-[7-(2-methyl-1H-indol-5-ylamino)-thieno[3.2-b]pyridin-2-yl]-benzyl}- propane-1,3-diamine; 2-{(2-Hydroxy-ethyl)-(3-{4-(7-(2-methyl-1H-indol-5-ylamino>-thieno[3>2-b]pyridin-2-yl]- benzylamino}-propyl)-amino}-ethanol; 40 2-{4-[7-(2-Methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-propane- 1.3-diol; -80- 5 3-{4-{7-(2-Methyl-1H-indol-5-ylamino)-thienol3,2-b]pyridin-2-yl]-benzyIamino}-propane- 1,2-diol; 1- (3-{4-[7-(2-Methyl-1H-indol-5-ylamino)-thieno(3l2-blpyridin-2-yl]-benzylamino}-propyl)-pyrrolidin-2-one; N-(2-Amino-ethyl)-N,-{4-p-(2-methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-10 benzyl}-ethane-1,2-diamine; 2- (2-{4-[7-(2-Methyl-1H-indol-5-ylamino}-thieno[3,2-b]pyridin-2-yf]-benzyfamino}-ethylamino)-ethanol; 3- {4-[7-(2-MethyH H-indol-5-ylamino)-thieno(3,2-blpyridin-2-yl]-benzylamino}-propan-1 -ol; 15 1-{4-[7-(2-MethyH H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzyl}-piperidine-4- carboxylic acid amide; 2-(244-[7-{2-Methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}- ethoxy)-ethanol; 2- (Methyl-{4-[7-(2-methyl-1H-indol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzyl}-amino)- 20 éthanol; N-Methyl-N’-{4-[7-(2-methyl-1 H-indol-5-ylamino)-thieno{3,2-b]pyridin-2-yl]-benzyl}-ethane-1,2-diamine; (1H-lndol-5-yl)-[2-(3-nitro-phenyl)-thieno[3,2-b]pyridin-7-yl]-amine; N-{4-[7-{2-MethyH H-indol-5-ylamino)-thieno(3,2-b]pyridin-2-yl]-benzyl}-ethane-1,2- 25 diamine; (2-Methyl-1H-indol-5-yl)-(2-{4-{(2-piperazin-1-yl-ethylamino)-methyl]-phenyl}-thieno(3l2- b]pyridin-7-yl)-amine; N,N-Dimethyl-N'-{4-[7-(2-methyl-1H-indol-5-ylamino}-thieno{3,2-b]pyridin-2-yl]-benzyl}-ethane-1,2-diamine; 30 2-{4-{7-{2-Methyl-1 H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl}-benzylamino}-butan-1-ol·, (2-Methyl-1H-indol-5-yl)-(2-{4-l(2-morpholin-4-yl-ethylamino)-methy0-phenyl}-thieno[3,2- b]pyridin-7-yl)-amine; (2-MethyHH-indol-5-ylH2-[4-(pyTOlidin-3-ylaminomethyl)-phenyl]-thieno(3.2-b]pyridin- 7-yl}-amine; 35 {6-(7-( 1 H-lndol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-pyridin-3-yl}-methanol; {6-P-(2-Methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-pyridin-3-yl}-methanol; 3- [4-(4-{4-(7-(2-Methyl-1H-indol-5-ylamino)-thieno(3,2-b]pyridin-2-yl}-benzylamino}-butyl)-piperazin-1 -yl]-propan-1 -ol; 2-[4-(4-{4-{7-(2-Methyl-1H-indol-5-ylamino}-thiena[3,2-b]pyridin-2-yf}-benzylamino}-40 butyl)-piperazin-1 -yi]-ethanol; -81- οι un 5 (2-{4-[(3-lmidazol-1-yl-propylamino)-methyl]-phenyl}-thieno[3.2-b]pyridin-7-yl)-(2-methyl 1 H-indol-5-yl)-amine; 1- lmidazol-1-yl-3-{4-(7-(2-methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-ylJ-benzylamino}-propan-2-ol; 2- [(2-Hydroxy-ethyl)-(4-{4-[7-(2-methyl-1H-indol-5-ylamino)-thieno[3,2-b}pyridin-2-yl]- 1Q benzylamino}-butyl)-amino}-ethanot; N,N-Diethyl-N‘-{4-[7-(2-methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzyl}-propane-1,3-diamine; (2-(3-Amino-phenyl)-thieno[3>2-blpyridin-7-yl]-(1H-indol-5-yl)-amine; (2-Methyl-1H-indol-5-yl)-(2-{4-[(3-morphorm-4-yi-propylamino)-methyl]-phenyl}- 15 thieno[3,2-b]pyridin-7-yl)-amine; [2-(4-Dimethylaminomethyl-phenyl)-thieno[3,2-b]pyridin-7-yl]-(2-methyHH-indol-5-yl)- amine; 1- {5-(2-Pyridin-2-yl-thieno[3,2-b]pyridin-7-ylamino}-2,3-dihydro-indol-1-yl]-ethanone;(2,3-Dihydro*1H-indol-5-yl)-(2-pyridin-2-yl-thieno[3,2-b]pyridin-7-yl)-amine; 20 (1 H-Benzotriazol-5-yl)-(2-pyridin-2-yl-thieno[3,2-b]pyridin-7-yl)-amine; 5-(2-Phenyl-thieno[3.2-b]pyridin-7-ylamino)-1K-indole-3-carbaldehyde; (1K-lndazol-5-yl)-(2-pyridin-2-yl-thieno[3,2-b]pyridin-7-yl)-amine; (2-Methyl-1H-indol-5-yl)-(2-pyridin-2-yl-thieno(3,2-b]pyridin-7-yl)-amine; (1H-Benzoimidazol-5-yl)-(2-phenyl-thieno[3,2-b]pyridin-7-yl)-amine; 25 5-(2-Pyridin-2-yl-thieno[3,2-b]pyridin-7-ylamino)-1 H-indole-2-carboxylic acid dimethylamide; {5-[7-(2-Methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-pyridin-2-yl}-methanol; N-(3«lmidazol-1-yl-propyl)-6-[7-(1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]- nicotinamide; 30 N-(3-Hydroxy-propyl)-6-[7-(2-methyl-1H-indol-5-ytamino)-thieno[3,2-b]pyridin-2-yl]- nicotinamide; (2-(5-Amino-pyridin-2-yl)-thieno[3,2-b]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine; N-[2-{2-Hydroxy-ethoxy)-ethyl]-6-[7-(2-methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin- 2-yl]-nicotinamide; 35 [2-(3-Methyl·3H-imidazol-4-yl)-thieno[3,2-b]pyridin-7-yl]-{2-methyl-1H-indol-5-yl)-amine; 2- {1 -Methyl-5-f7-(2-methyH H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-1 H-imidazol-2-yl}-propan-2-ol; [2-( 1 -Methyl-1 H-imidazol-2-yl)-thieno(3,2-blpyridin-7-yl]-(2-methyl-1 H-indol-5-yl)-amine;(2-Methyl-1H-indol-5-yl)-(2-thiazol-2-yl-thieno(3,2-b]pyridin-7-yl)-amine; 40 2-{2-[7-{2-Methyl-1H-indol-5-ylamino)-thier)0[3,2-b]pyridin-2-yl]-thiazol-5-yl}-propan-2-ol; 4-{7-(2-Methyl-1H-indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzaldehyde; -82- 011376 5 and the pharmaceutically acceptable salts and hydrates thereof.
10. A compound of the formula 25 or 26

or a pharmaceutically acceptable sait or hydrate thereof, wherein:wherein X1 is N or CH; 10 Z’ is halo and Z2 is -NR1R2; or Z1 is R11 and Z2 is halo; orZ1 and Z2 are each independently halo; R1 is H, Ο,-Οβ alkyl or -C(O)(C,-C6 alkyl); R2 is C6-C10 aryl or 5-13 membered heterocyclic, wherein said R2 groups are optionally15 substituted by 1 to 5 R5 substituents, each R3 is independently selected from H, -C(O)OR9, and C^Ce alkyl wherein said alkyl isoptionally substituted by 1 to 3 Rs groups; R4is R3.-OR9. or-NR’R10; each R5 is independently selected from halo, cyano, nitro, trifluoromethoxy,20 trifluoromethyl, azido, -C(O)R8, -C(O)OR8, -OC(O)R8, -OC(O)OR8, -NR6C(O)R7, -C(O)NR6R7,-NR6R7, -OR9, -SO2NR8R7, CrC6 alkyl, -(CK2)jO(CH2)qNR8R7, -(CH2),O(CH2)qOR9, -(CH2),OR9,-SfO^CrCe alkyl). -(CH2),(C6-Cio aryl), -(CH2),(5-10 membered heterocyclic), -C(O)(CH2),(C6-C10 aryl), -(CH2),0(CH2))(C6-Cio aryl), -(CH2)tO(CH2)q(5-10 membered heterocyclic).-C(O)(CH2),(5-10 membered heterocyclic), -{CH2)jNR7(CH2)qNReR7, -(CH2)jNR7CH2C(O)NR6R7,25 -(CH2)jNR7(CH2)qNR9C(O)R8, -(CH2)jNR7(CH2),O(CH2)qOR9, -(CH2)jNR7(CH2)qS(O)j(C1-C6 alkyl),-(CH2)jNR7(CH2)tR6, -SO^CH^Ce-Cw aryl), and -SO2(CH2),(5-10 membered heterocyclic),wherein j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 6, q is an integerranging from 2 to 6, the -(CH2)q- and -(CH2)r moieties of the foregoing R5 groups optionallyinclude a carbon-carbon double or triple bond where t is an integer between 2 and 6, and the30 alkyl, aryl and heterocyclic moieties of the foregoing R5 groups are optionally substituted by 1 to3 substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, -C(O)R8,-C(O)OR8, -OC(O)R8, -OC(O)OR8, -NR6C(O)R7, -C(O)NR6R7, -(CH2),NR6R7, Ο,-Ce alkyl,-(CH2)t(Ce-C,o aryl), -(CH2),(5-10 membered heterocyclic), -(CH^OiCH^OR9, and -{CH2),OR9,wherein t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6; 011 376 -83- 5 each R6 and R7 is independently selected from H, Ci-C6 alkyl, -(CH2),(C6-C,o aryl), -(CH2),(5-1O membered heterocyclic), -(CH2),O(CH2)qOR9, and -<CH2),OR9, wherein t is aninteger ranging from 0 to 6 and q is an integer ranging from 2 to 6, and the alkyl, aryl andheterocyclic moieties of the foregoing R6 and R7 groups are optionally substituted by 1 to 3substituents independently selected from halo, cyano, nitro, trifluoromethyl, azido, -C{O)Ra, 10 -C(O)OR8, -CO(O)R8, -OC(O)OR8, -NR9C(O)R10, -C(O)NR9RW, -NR9R10, C,-C6 alkyl. -(CH2),(C6-C10 aryl), -(CH2),(5-10 membered heterocyclic), -(CH2)1O(CH2)qOR9, and -(CH2),OR9,wherein t is an integer ranging from 0 to 6 and q is an integer ranging from 2 to 6, with theproviso that where R6 and R7 are both attached to the same nitrogen, then R6 and R7 are notboth bonded to the nitrogen directly through an oxygen; 15 each R8 is independently selected from H, C,-Cw alkyl, -(CH2),(C6-C10 aryl), and -(CH2),(5-10 membered heterocyclic), wherein t is an integer ranging from 0 to 6; each R9 and R10 is independently selected from H and Ci-C6 alkyl; R” is H, Ci-C6 alkyl, -C(O)NR6R9, -C(O)(C6-C10 aryl). -(CHzMCg-Cw aryl), or -(CH2),(5-10 membered heterocyclic), wherein t is an integer ranging from 0 to 6, wherein said R11 groups, 20 other than H, are optionally substituted by tert-butyl-dimethyksilanyl and 1 to 3 R5 groups; and, R’2 is H. C,-C6 alkyl, -C(O)(C,-C6 alkoxy), -S(O)j(Ci-C6 alkyl), -SO2(CH2),(C6-C10 aryl), -(CH2),(C6-C10 aryl), -{CH2),(5-10 membered heterocyclic). -{CH2),O(CH2)qOR9, or -(CH2),OR9,wherein j is an integer ranging from 0 to 2, t is an integer ranging from 0 to 6 and q is an integerranging from 2 to 6. 25
11. A pharmaceutical composition for the treatment of a hyperproliferative disorder in a mammal which comprises a therapeutically effective amount of a compound of daim 1 and apharmaceutically acceptable carrier.
12. The pharmaceutical composition of daim 11 wherein said hyperproliferativedisorder is cancer.
13. The pharmaceutical composition of claim 12 wherein said cancer is brain, lung, kidney, rénal, ovarian, squamous cell, bladder, gastric, pancreatic, breast, head, neck,oesophageal, gynecological, prostate, colorectal or thyroid cancer.
14. The pharmaceutical composition of daim 11 wherein said hyperproliferative. disorder is noncancerous.
15. The pharmaceutical composition of claim 14 wherein said disorder is a benign hyperplasia of the skin or prostate.
16. A pharmaceutical composition for the treatment of a hyperproliferative disorder ina mammal which comprises a therapeutically effective amount of a compound of daim 1 incombination with an anti-tumor agent selected from the group consisting of mitotic inhibitors, 40 alkylating agents, anti-metabolites, intercalating antibiotics, enzymes, topoisomerase inhibitors. -84- 011376 ' 5 blologlcal response modifiera, anti-hormones, and antl-androgens, and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition for the treatment of pancreatitis or kidneydisease irt a mammal which comprises a therapeutically effective amount of a compound ofdaim 1 and a pharmaceutically acceptable carrier. 10
18. A pharmaceutical composition for the blastocyte implantation in a mammal which comprises a therapeutically effective amount of a compound of claim 1 and apharmaceutically acceptable carrier.
19. A pharmaceutical composition for treating a disease related tovasculogenesis or angiogenesis in a mammal which comprises a therapeutically effective 15 amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
20. The pharmaceutical composition of claim 19 wherein said disease isselected from the group consisting of tumor angiogenesis, chronlc Inflammatory diseasesuch as rheumatoid arthritis, afherosclerosis, skin diseases such as psoriasis, excema, andscleroderma, diabètes, diabetic retinopathy, retinopathy of prematurity, age-related macular 20 degeneration, hemangioma, glioma, melanoma, Kaposî's sarcoma and ovarian, breast,lung, pancreatic, prostate, colon and epidermoid cancer.
21. The use of a compound of claim 1 for the manufacture of a médicamentfor treatment of a hyperproliferative disorder.
22. The use of claim 21, wherein said hyperproliferative disorder is cancer.
23. The use of claim 22 wherein said cancer is brain, lung, squamous cell, rénal, kidney. ovarian, bladder, gastric. pancreatic, breast. head, neck, oesophageal.prostate, colorectal, gynecological or thyroid cancer.
24. The use of daim 21 wherein said hyperproliferative disorder isnoncancerous.
25. The use of claim 24 wherein said disorder is a benign hyperplasia of the skin or prostate.
26. The use of a compound of claim 1 in combination with an anti-tumor agentselected from the group consisting of mitotic inhibitors, alkylating agents, antl-metabolites,intercalating antibiotics, growth factor inhibitors, cell cycle inhibitors. enzymes. 35 topoisomerase inhibitors, biological response modifiers, anti-hormones, and anti-androgensfor the manufacture of a médicament for treating a hyperproliferative disorder.
27. The use of a compound of claim 1 for the manufacture of a médicamentfor treating pancreatitis or kidney disease.
28. The use of a compound of claim 1 for the manufacture of a médicament40 for treatment of blastocyte implantation. -85- 011376 10
29. Xrhe use of a compound of clalm 1 for the manufacture or a médicamentfor treating a'aisease related ta vasculogenesis or angiogenesis.
30. The use of daim 29 wherein said disease is selected from the groupconsisting of tumor angiogenesis, chronic inflammatory disease such as rheumatoidarthritis, atherosclerosis, skin diseases such as psoriasis, excema, and scleroderma,diabètes, diabetic retinopathy,' retinopathy of prematurity, age-relatad maculardegeneration, hemangioma, glioma, melanoma, Kaposi’s sarcoma and ovarian, breast,lung, pancreatic, prostate, "colon âpd epidermoid cancer.