OA11376A - Thienopyrimidine and thienopyridine derivatives useful as anticancer agents. - Google Patents

Thienopyrimidine and thienopyridine derivatives useful as anticancer agents. Download PDF

Info

Publication number
OA11376A
OA11376A OA1200000133A OA1200000133A OA11376A OA 11376 A OA11376 A OA 11376A OA 1200000133 A OA1200000133 A OA 1200000133A OA 1200000133 A OA1200000133 A OA 1200000133A OA 11376 A OA11376 A OA 11376A
Authority
OA
OAPI
Prior art keywords
thieno
phenyl
indol
pyrimidin
amine
Prior art date
Application number
OA1200000133A
Other languages
English (en)
Inventor
Michael John Munchhof
Susan Beth Sobolov-Jaynes
Original Assignee
Pfizer Prod Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc
Publication of OA11376A publication Critical patent/OA11376A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (30)

  1. -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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 12. The pharmaceutical composition of daim 11 wherein said hyperproliferativedisorder is cancer.
  13. 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. 14. The pharmaceutical composition of daim 11 wherein said hyperproliferative. disorder is noncancerous.
  15. 15. The pharmaceutical composition of claim 14 wherein said disorder is a benign hyperplasia of the skin or prostate.
  16. 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. 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. 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. 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. 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. 21. The use of a compound of claim 1 for the manufacture of a médicamentfor treatment of a hyperproliferative disorder.
  22. 22. The use of claim 21, wherein said hyperproliferative disorder is cancer.
  23. 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. 24. The use of daim 21 wherein said hyperproliferative disorder isnoncancerous.
  25. 25. The use of claim 24 wherein said disorder is a benign hyperplasia of the skin or prostate.
  26. 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. 27. The use of a compound of claim 1 for the manufacture of a médicamentfor treating pancreatitis or kidney disease.
  28. 28. The use of a compound of claim 1 for the manufacture of a médicament40 for treatment of blastocyte implantation. -85- 011376 10
  29. 29. Xrhe use of a compound of clalm 1 for the manufacture or a médicamentfor treating a'aisease related ta vasculogenesis or angiogenesis.
  30. 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.
OA1200000133A 1997-11-11 2000-05-05 Thienopyrimidine and thienopyridine derivatives useful as anticancer agents. OA11376A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US6509797P 1997-11-11 1997-11-11

Publications (1)

Publication Number Publication Date
OA11376A true OA11376A (en) 2004-01-28

Family

ID=22060322

Family Applications (1)

Application Number Title Priority Date Filing Date
OA1200000133A OA11376A (en) 1997-11-11 2000-05-05 Thienopyrimidine and thienopyridine derivatives useful as anticancer agents.

Country Status (37)

Country Link
US (1) US6492383B1 (fr)
EP (1) EP1028964A1 (fr)
JP (1) JP2001522853A (fr)
KR (1) KR100446363B1 (fr)
CN (2) CN1280580A (fr)
AP (1) AP976A (fr)
AR (1) AR018517A1 (fr)
AU (1) AU9454198A (fr)
BG (1) BG65180B1 (fr)
BR (1) BR9814018A (fr)
CA (1) CA2309690A1 (fr)
CO (1) CO4990956A1 (fr)
CZ (1) CZ20001709A3 (fr)
DZ (1) DZ2646A1 (fr)
EA (1) EA005889B1 (fr)
GT (1) GT199800180A (fr)
HN (1) HN1998000168A (fr)
HR (1) HRP20000286A2 (fr)
HU (1) HUP0100287A3 (fr)
ID (1) ID23978A (fr)
IL (1) IL135636A0 (fr)
IS (1) IS5464A (fr)
MA (1) MA24694A1 (fr)
MY (1) MY132073A (fr)
NO (1) NO20002162L (fr)
NZ (1) NZ520093A (fr)
OA (1) OA11376A (fr)
PA (1) PA8462401A1 (fr)
PE (1) PE129099A1 (fr)
PL (1) PL340589A1 (fr)
SK (1) SK6652000A3 (fr)
TN (1) TNSN98203A1 (fr)
TW (1) TW593321B (fr)
UA (1) UA72881C2 (fr)
UY (2) UY25238A1 (fr)
WO (1) WO1999024440A1 (fr)
ZA (1) ZA9810253B (fr)

Families Citing this family (195)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2289791T3 (es) 1997-08-22 2008-02-01 Astrazeneca Ab Derivados de oxindolilquinazolina como inhibidores de la angiogenesis.
EP1006113A1 (fr) 1998-12-02 2000-06-07 Pfizer Products Inc. Dérivés de 2-(2-oxo-éthylidène)-imidazolidin-4-one et leur utilisation pour inhiber la croissance anormale des cellules
UA71945C2 (en) 1999-01-27 2005-01-17 Pfizer Prod Inc Substituted bicyclic derivatives being used as anticancer agents
GB9918057D0 (en) * 1999-07-30 1999-10-06 Univ Bristol Therapeutic agents
UA74803C2 (uk) 1999-11-11 2006-02-15 Осі Фармасьютікалз, Інк. Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування
GB0010757D0 (en) * 2000-05-05 2000-06-28 Astrazeneca Ab Chemical compounds
BR0111377A (pt) * 2000-06-06 2003-06-03 Pfizer Prod Inc Derivados de tiofeno úteis como agentes anticancerìgenos
WO2002012227A2 (fr) * 2000-08-09 2002-02-14 Astrazeneca Ab Composes chimiques
JP2004509876A (ja) 2000-09-20 2004-04-02 メルク　パテント　ゲゼルシャフト　ミット　ベシュレンクテル　ハフトング ４−アミノ−キナゾリン
US6503914B1 (en) * 2000-10-23 2003-01-07 Board Of Regents, The University Of Texas System Thienopyrimidine-based inhibitors of the Src family
AUPR213700A0 (en) * 2000-12-18 2001-01-25 Biota Scientific Management Pty Ltd Antiviral agents
KR20020051675A (ko) * 2000-12-23 2002-06-29 이상남 4-페닐아미노티에노 [3,2-디] 피리미딘 유도체 및 이의제조방법
ME00502B (me) 2001-01-05 2011-10-10 Amgen Fremont Inc Antitjela za insulinu sličan receptor faktora i rasta
ES2263743T3 (es) * 2001-04-13 2006-12-16 Pfizer Products Inc. Derivados de 4-aminopiridopirimidina sustituidos con un grupo biciclico.
WO2003000194A2 (fr) 2001-06-21 2003-01-03 Pfizer Inc. Derives bicycliques de pyridine et de pyrimidine utiles en tant qu'agents anticancereux
US7829566B2 (en) 2001-09-17 2010-11-09 Werner Mederski 4-amino-quinazolines
AR039067A1 (es) 2001-11-09 2005-02-09 Pfizer Prod Inc Anticuerpos para cd40
AU2002357193A1 (en) * 2001-12-19 2003-07-09 Smithkline Beecham Corporation Thienopyrimidine compounds as protein tyrosine kinase inhibitors
WO2003055890A1 (fr) * 2001-12-21 2003-07-10 Bayer Pharmaceuticals Corporation Composes derives de thienopyrimidine utilises comme inhibiteurs de la prolylpeptidase, inducteurs d'apoptose et agents de traitement anticancereux
JP4505228B2 (ja) * 2002-01-10 2010-07-21 バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト Ｒｈｏ−キナーゼ阻害剤
EP1470121B1 (fr) 2002-01-23 2012-07-11 Bayer HealthCare LLC Derives pyrimidine en tant qu'inhibiteurs de kinase rho
MXPA04007196A (es) 2002-01-23 2005-06-08 Bayer Pharmaceuticals Corp Inhibidores de rho-quinasa.
WO2003064428A1 (fr) * 2002-01-29 2003-08-07 H. Lundbeck A/S Furano- et thienopyrimidines en tant qu'inhibiteurs de la neurokinase
WO2003070241A1 (fr) * 2002-02-15 2003-08-28 Rigel Pharmaceuticals, Inc. Inhibiteurs de la polymerisation de tubuline
US20030225273A1 (en) * 2002-03-21 2003-12-04 Michaelides Michael R. Thiopyrimidine and isothiazolopyrimidine kinase inhibitors
UA77303C2 (en) 2002-06-14 2006-11-15 Pfizer Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use
DE60304718T2 (de) 2002-08-06 2007-04-26 Astrazeneca Ab Kondensierte pyridine und pyrimidine mit tie2 (tek) aktivität
TWI335913B (en) * 2002-11-15 2011-01-11 Vertex Pharma Diaminotriazoles useful as inhibitors of protein kinases
CL2003002287A1 (es) 2002-11-25 2005-01-14 Wyeth Corp COMPUESTOS DERIVADOS DE TIENO[3,2-b]-PIRIDINA-6-CARBONITRILOS Y TIENEO[2,3-b]-PIRIDINA-5-CARBONITRILOS, COMPOSICION FARMACEUTICA, PROCEDIMIENTO DE PREPARACION Y COMPUESTOS INTERMEDIARIOS, Y SU USO EN EL TRATAMIENTO DEL CANCER, APOPLEJIA, OSTEOPOROSIS
US7276519B2 (en) 2002-11-25 2007-10-02 Wyeth Thieno[3,2-b]pyridine-6-carbonitriles and thieno[2,3-b]pyridine-5-carbonitriles as protein kinase inhibitors
WO2004056806A1 (fr) 2002-12-19 2004-07-08 Pfizer Inc. Composes de 2-(1h-indazol-6-ylamino)-benzamides en tant qu'inhibiteurs de proteines kinases utiles pour le traitement de maladies ophtalmiques
CA2529611C (fr) 2002-12-20 2009-12-15 Pfizer Products Inc. Derives de pyrimidine destines au traitement de la croissance cellulaire anormale
DK1603570T5 (da) 2003-02-26 2013-12-09 Sugen Inc Aminoheteroarylforbindelser som proteinkinaseinhibitorer
ES2280040T3 (es) * 2003-07-24 2007-09-01 Bayer Pharmaceuticals Corporation Compuestos de tetrahidrobenzotienopirimidinamina sustituidos utiles para tratar trastornos hiperproliferativos.
HN2004000285A (es) 2003-08-04 2006-04-27 Pfizer Prod Inc ANTICUERPOS DIRIGIDOS A c-MET
WO2005013982A1 (fr) * 2003-08-06 2005-02-17 Vertex Pharmaceuticals Incorporated Composes d'aminotriazole utiles en tant qu'inhibiteurs des proteines kinases
DK1660090T3 (da) 2003-08-14 2012-12-17 Array Biopharma Inc Quinazolin-analoger som receptor-tyrosinkinase-inhibitorer
US7501427B2 (en) 2003-08-14 2009-03-10 Array Biopharma, Inc. Quinazoline analogs as receptor tyrosine kinase inhibitors
ES2314444T3 (es) 2003-08-29 2009-03-16 Pfizer Inc. Tienopiridina-fenilacetaminasy sus derivados utiles como nuevos agentes antiangiogenicos.
AR045563A1 (es) 2003-09-10 2005-11-02 Warner Lambert Co Anticuerpos dirigidos a m-csf
US7332521B2 (en) * 2003-09-25 2008-02-19 Wyeth Substituted indoles
US7419978B2 (en) 2003-10-22 2008-09-02 Bristol-Myers Squibb Company Phenyl-aniline substituted bicyclic compounds useful as kinase inhibitors
AU2004309166B2 (en) 2003-12-23 2008-02-21 Pfizer Inc. Novel quinoline derivatives
US7470712B2 (en) * 2004-01-21 2008-12-30 Bristol-Myers Squibb Company Amino-benzazoles as P2Y1 receptor inhibitors
WO2005070900A1 (fr) * 2004-01-22 2005-08-04 Altana Pharma Ag N-4-(6-(hetero)aryle-pyrimidine-4-ylaminophenyle)-bezenesulfonamides en tant qu'inhibiteurs de kinase
JP4842929B2 (ja) * 2004-05-27 2011-12-21 ファイザー・プロダクツ・インク 癌治療に有用なピロロピリミジン誘導体
GB0412467D0 (en) * 2004-06-04 2004-07-07 Astrazeneca Ab Chemical compounds
US7173031B2 (en) * 2004-06-28 2007-02-06 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
EP1763526B1 (fr) 2004-06-28 2009-06-24 Bayer Schering Pharma AG Pyrimidines 4,6-disubstituees et leur utilisation comme inhibiteurs des proteines kinases
KR20080019733A (ko) 2004-07-16 2008-03-04 화이자 프로덕츠 인코포레이티드 항-아이지에프-1알 항체를 사용하는 비-혈액학적악성종양에 대한 조합 치료
ES2438017T3 (es) 2004-07-30 2014-01-15 Methylgene Inc. Inhibidores de la señalización del receptor del VEGF y del receptor del HGF
DE602005020465D1 (de) 2004-08-26 2010-05-20 Pfizer Enantiomerenreine aminoheteroaryl-verbindungen als proteinkinasehemmer
GB0423653D0 (en) * 2004-10-25 2004-11-24 Piramed Ltd Pharmaceutical compounds
CA2583812A1 (fr) * 2004-10-28 2006-05-11 Irm Llc Composes et compositions servant de modulateurs de la voie de signalisation hedgehog
US7576080B2 (en) * 2004-12-23 2009-08-18 Memory Pharmaceuticals Corporation Certain thienopyrimidine derivatives as phosphodiesterase 10 inhibitors
MX2007008676A (es) * 2005-01-19 2007-07-25 Hoffmann La Roche Derivados de 5-aminoindol.
CA2601157A1 (fr) 2005-03-16 2006-09-28 Osi Pharmaceuticals, Inc. Biomarqueurs predictifs de reponse anticancereuse a des inhibiteurs de kinase de recepteur de facteur de croissance epidermique
RU2413735C2 (ru) 2005-03-31 2011-03-10 Эдженсис, Инк. Антитела и родственные молекулы, связывающиеся с белками 161p2f10b
CA2763671A1 (fr) 2005-04-26 2006-11-02 Pfizer Inc. Anticorps de la p-cadherine
AU2006313456B2 (en) 2005-05-20 2011-06-23 Methylgene Inc. Inhibitors of VEGF receptor and HGF receptor signaling
KR101378716B1 (ko) * 2005-05-20 2014-04-10 메틸진 인코포레이티드 Ｖｅｇｆ 수용체 및 ｈｇｆ 수용체 신호전달의 억제제
US20060281768A1 (en) * 2005-06-10 2006-12-14 Gaul Michael D Thienopyrimidine and thienopyridine kinase modulators
CA2655799A1 (fr) * 2005-06-22 2006-12-28 Develogen Aktiengesellschaft Thienopyrimidines pour compositions pharmaceutiques
US7608592B2 (en) 2005-06-30 2009-10-27 Virobay, Inc. HCV inhibitors
WO2007026221A2 (fr) * 2005-09-02 2007-03-08 Pfizer Inc. Procede ameliores d'elaboration de derives d'heteroaryl amide benzocondenses de thienopyridines
NZ566774A (en) 2005-09-07 2011-11-25 Pfizer Human monoclonal antibodies to activin receptor-like kinase-1
CA2623125A1 (fr) 2005-09-20 2007-03-29 Osi Pharmaceuticals, Inc. Marqueurs biologiques predictifs d'une reaction anticancereuse aux inhibiteurs kinase du recepteur du facteur de croissance 1 analogue a l'insuline
AR056200A1 (es) * 2005-09-27 2007-09-26 Wyeth Corp Tieno [2,3-b]piridin-5-carbonitrilos como inhibidores de proteina quinasa
WO2007056208A2 (fr) * 2005-11-02 2007-05-18 Cytovia, Inc. N-arylalkyl-thienopyrimidin-4-amines et analogues en tant qu'activateurs de caspases et inducteurs d'apoptose et utilisation de ceux-ci
US20070099877A1 (en) * 2005-11-02 2007-05-03 Cytovia, Inc. N-aryl-thienopyrimidin-4-amines and analogs as activators of caspases and inducers of apoptosis and the use thereof
WO2007056214A2 (fr) * 2005-11-02 2007-05-18 Cytovia, Inc N-alkyl-n-aryl-thienopyrimidin-4-amines et analogues en tant qu'activateurs de caspases et inducteurs d'apoptose et utilisation associee
ATE446294T1 (de) 2005-11-15 2009-11-15 Array Biopharma Inc N4-phenyl-chinazolin-4-aminderivate und verwandte verbindungen als inhibitoren der erbb-typ-i- rezeptortyrosinkinase zur behandlung hyperproliferativer krankheiten
JP2009526761A (ja) * 2006-01-30 2009-07-23 アレイ バイオファーマ、インコーポレイテッド ヘテロ二環式チオフェン化合物および使用の方法
AR060061A1 (es) * 2006-03-22 2008-05-21 Methylgene Inc Inhibidores de la actividad de la proteina tirosina quinasa
CA2644910C (fr) * 2006-03-31 2014-01-28 Abbott Laboratories Composes d'indazole
CA2651898A1 (fr) * 2006-04-07 2007-10-18 Develogen Aktiengesellschaft Thienopyrimidines ayant une activite inhibitrice mnk1/mnk2 utilisees dans des compositions pharmaceutiques
EP2258700A1 (fr) 2006-05-09 2010-12-08 Pfizer Products Inc. Dérivés d'acides aminés cycloalkyles et compositions pharmaceutiques les contenant
EP1889847A1 (fr) 2006-07-10 2008-02-20 DeveloGen Aktiengesellschaft Dérivés de pyrrolopyrimidine pour applications pharmaceutiques
WO2008058126A2 (fr) 2006-11-06 2008-05-15 Supergen, Inc. Dérivés d'imidazo[1,2-b]pyridazine et de pyrazolo[1,5-a]pyrimidine et utilisation de ceux-ci comme inhibiteurs de protéines kinases
MX2009005950A (es) 2006-12-07 2009-10-12 Genentech Inc Compuestos inhibidores de fosfoinositido 3-quinasas y metodos de uso.
JP2010514810A (ja) * 2006-12-29 2010-05-06 ライジェル ファーマシューティカルズ， インコーポレイテッド Ａｘｌインヒビターとして有用な置換トリアゾール
WO2008082839A2 (fr) * 2006-12-29 2008-07-10 Abbott Laboratories Inhibiteurs de la pim kinase comme agents chimiothérapeutiques destinés à lutter contre le cancer
US20080161254A1 (en) * 2007-01-03 2008-07-03 Virobay, Inc. Hcv inhibitors
US7893060B2 (en) * 2007-06-12 2011-02-22 F. Hoffmann-La Roche Ag Thiazolopyrimidines and their use as inhibitors of phosphatidylinositol-3 kinase
EP2014662A1 (fr) * 2007-07-12 2009-01-14 Bayer Schering Pharma Aktiengesellschaft Indolylalkylthienopyrimidylamine en tant que modulateurs du récepteur EP2
EP2014663A1 (fr) * 2007-07-12 2009-01-14 Bayer Schering Pharma AG Thienopyrimidylamine en tant que modulateurs du récepteur EP2
CA2704711C (fr) 2007-09-24 2016-07-05 Genentech, Inc. Composes inhibiteurs de la pi3k a base de thiazolopyrimidine
CA2702500A1 (fr) * 2007-10-18 2009-04-23 Boehringer Ingelheim International Gmbh Preparation de dihydrothienopyrimidines et d'intermediaires utilises lors de celle-ci
JP5348725B2 (ja) * 2007-10-25 2013-11-20 ジェネンテック， インコーポレイテッド チエノピリミジン化合物の製造方法
ES2402322T3 (es) * 2007-11-15 2013-04-30 Gilead Sciences, Inc. Inhibidores de la replicación del virus de la inmunodeficiencia humana
EA019869B1 (ru) * 2007-11-28 2014-06-30 Дана Фарбер Кансер Инститьют, Инк. Низкомолекулярные миристатные ингибиторы тирозинкиназы bcr-abl и способы их применения
CA2724008A1 (fr) * 2008-01-11 2009-09-11 Glenmark Pharmaceuticals, S.A. Derives de pyrimidine condensee en tant que modulateurs de trpv3
WO2009100225A1 (fr) 2008-02-07 2009-08-13 Virobay, Inc. Inhibiteurs de la cathepsine b
NZ588355A (en) 2008-03-05 2012-03-30 Methylgene Inc Inhibitors of protein tyrosine kinase activity
US8119647B2 (en) 2008-04-23 2012-02-21 Glenmark Pharmaceuticals S.A. Fused pyrimidineone compounds as TRPV3 modulators
UY32072A (es) 2008-08-26 2010-03-26 Boehringer Ingelheim Int Tienopirimidinas para composiciones farmacéuticas
WO2010045495A2 (fr) 2008-10-16 2010-04-22 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Anticorps entièrement humains dirigés contre un antigène associé au mélanome de masse moléculaire élevée et leurs utilisations
KR101126736B1 (ko) * 2008-11-27 2012-04-12 주식회사 레고켐 바이오사이언스 티로신 키나아제 저해 화합물, 이의 이성질체 또는 이의 약학적으로 허용가능한 염 및 이를 포함하는 약학적 조성물
TW201041892A (en) 2009-02-09 2010-12-01 Supergen Inc Pyrrolopyrimidinyl Axl kinase inhibitors
WO2010099139A2 (fr) 2009-02-25 2010-09-02 Osi Pharmaceuticals, Inc. Thérapie anti-cancer combinée
JP2012519170A (ja) 2009-02-26 2012-08-23 オーエスアイ・ファーマシューティカルズ，エルエルシー 生体内の腫瘍細胞のｅｍｔステータスをモニターするためのｉｎｓｉｔｕ法
WO2010099363A1 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
WO2010098866A1 (fr) 2009-02-27 2010-09-02 Supergen, Inc. Inhibiteurs cyclopentathiophène/cyclohexathiophène de l'adn méthyltransférase
WO2010099138A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Procédés pour l'identification d'agents qui inhibent les cellules tumorales de type mésenchymateuses ou leur formation
WO2010099364A2 (fr) 2009-02-27 2010-09-02 Osi Pharmaceuticals, Inc. Méthodes d'identification d'agents qui inhibent les cellules cancéreuses mésenchymateuses ou leur formation
JP5709766B2 (ja) 2009-03-12 2015-04-30 ジェネンテック， インコーポレイテッド 造血器腫瘍の治療のためのホスホイノシチド３キナーゼ阻害剤化合物と化学療法剤の併用
BRPI1009022A2 (pt) * 2009-05-27 2016-03-08 Hoffmann La Roche "composto, composição farmacêutica, processo para produzir uma composição farmacêutica, uso de um composto, método para tratamento de uma doença ou transtorno e kit"
US8158625B2 (en) * 2009-05-27 2012-04-17 Genentech, Inc. Bicyclic indole-pyrimidine PI3K inhibitor compounds selective for P110 delta, and methods of use
AU2010273585B2 (en) 2009-07-13 2015-04-23 Genentech, Inc. Diagnostic methods and compositions for treatment of cancer
EP2459191A1 (fr) 2009-07-31 2012-06-06 OSI Pharmaceuticals, LLC Polythérapie par inhibiteur de mtor et inhibiteur de l angiogenèse
JP2013503846A (ja) 2009-09-01 2013-02-04 ファイザー・インク ベンズイミダゾール誘導体
RU2012114094A (ru) 2009-09-11 2013-10-20 Дженентек, Инк. Способ идентификации пациента с увеличенной вероятностью ответа на противораковый агент
AU2010297344A1 (en) 2009-09-17 2012-02-23 F. Hoffmann-La Roche Ag Methods and compositions for diagnostics use in cancer patients
WO2011073521A1 (fr) 2009-12-15 2011-06-23 Petri Salven Méthodes pour l'enrichissement de cellules progénitrices endothéliales adultes et leurs utilisations
EP4166558A1 (fr) 2010-02-12 2023-04-19 Pfizer Inc. Sels et polymorphes de 8-fluoro-2-{4-[(méthylamino} méthyl] phényl}-1 ,3,4,5-tetrahydro-6h-azepino[5,4,3- cd]indol-6-one
MX2012009851A (es) 2010-02-26 2012-09-12 Boehringer Ingelheim Int Tienopirimidinas que contienen un grupo alquilo sustituido para composiciones farmaceuticas.
JP5575274B2 (ja) 2010-02-26 2014-08-20 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 医薬組成物のためのｍｎｋｌ／ｍｎｋ２阻害活性を有する４−［シクロアルキルオキシ（ヘテロ）アリールアミノ］チエノ「２，３−ｄ］ピリミジン
UY33241A (es) 2010-02-26 2011-09-30 Boehringer Ingelheim Int ?Tienopirimidinas que contienen heterocicloalquilo para composiciones farmacéuticas?.
WO2011109572A2 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de kinase du récepteur du facteur de croissance insulinique 1
CA2783665A1 (fr) 2010-03-03 2011-09-09 OSI Pharmaceuticals, LLC Marqueurs biologiques predictifs d'une reponse anticancereuse aux inhibiteurs de kinase du recepteur du facteur de croissance insulinique 1
WO2011130654A1 (fr) 2010-04-16 2011-10-20 Genentech, Inc. Foxo3a utilisée comme biomarqueur prédictif pour l'efficacité d'un inhibiteur de la voie des kinases p13k/akt
CN102250112A (zh) * 2010-05-18 2011-11-23 上海再启生物技术有限公司 7-溴-4-氨基噻吩并嘧啶的制备方法
HUE035589T2 (en) * 2010-05-26 2018-05-28 Korea Inst Sci & Tech An anti-inflammatory compound having an anti-tyrosine kinase inhibitory activity and a pharmaceutical composition containing it
WO2011149126A1 (fr) * 2010-05-26 2011-12-01 한국과학기술연구원 Composition pharmaceutique comprenant un composé anti-inflammatoire présentant une fonction d'inhibition de la tyrosine kinase
WO2011153224A2 (fr) 2010-06-02 2011-12-08 Genentech, Inc. Procédés diagnostiques et compositions de traitement du cancer
EP2582727B8 (fr) 2010-06-16 2017-04-19 University of Pittsburgh- Of the Commonwealth System of Higher Education Anticorps dirigés contre l'endoplasmine et leur utilisation
US20130225581A1 (en) 2010-07-16 2013-08-29 Kyowa Hakko Kirin Co., Ltd Nitrogen-containing aromatic heterocyclic derivative
KR20130126576A (ko) 2010-07-19 2013-11-20 에프. 호프만-라 로슈 아게 항암요법에 반응할 가능성이 증가된 환자를 확인하는 방법
CA2805618A1 (fr) 2010-07-19 2012-01-26 F. Hoffmann-La Roche Ag Methode d'identification d'un patient presentant une probabilite accrue de repondre a un traitement anticancereux
EP2596026B1 (fr) 2010-07-23 2020-04-08 Trustees of Boston University Inhibiteurs anti-despr comme agents thérapeutiques pour l'inhibition de l'angiogenèse pathologique et de l'invasivité des cellules tumorales et pour l'imagerie moléculaire et l'administration ciblée
AU2011303597A1 (en) 2010-09-17 2013-04-11 Purdue Pharma L.P. Pyridine compounds and the uses thereof
WO2012042421A1 (fr) 2010-09-29 2012-04-05 Pfizer Inc. Procédé de traitement de la croissance cellulaire anormale
CA2813162C (fr) 2010-10-20 2015-06-16 Pfizer Inc. Derives de pyridine-2 en tant que modulateurs des recepteurs smoothened
US20140004209A1 (en) 2010-12-22 2014-01-02 Genentech, Inc. Autophagy inducer and inhibitor combination therapy for the treatment of neoplasms
WO2012106522A2 (fr) * 2011-02-04 2012-08-09 Duquesne University Of The Holy Spirit Inhibiteurs pyrimidines bicycliques et tricycliques de tyrosine kinase ayant une activité antitubuline, et méthodes de traitement d'un patient
WO2012116040A1 (fr) 2011-02-22 2012-08-30 OSI Pharmaceuticals, LLC Marqueurs biologiques prédictifs d'une réponse anticancéreuse aux inhibiteurs de la kinase du récepteur du facteur de croissance 1 analogue à l'insuline dans le carcinome hépatocellulaire
US9150644B2 (en) 2011-04-12 2015-10-06 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Human monoclonal antibodies that bind insulin-like growth factor (IGF) I and II
DK2699598T3 (en) 2011-04-19 2019-04-23 Pfizer COMBINATIONS OF ANTI-4-1BB ANTIBODIES AND ADCC-INducing ANTIBODIES FOR TREATMENT OF CANCER
WO2012149014A1 (fr) 2011-04-25 2012-11-01 OSI Pharmaceuticals, LLC Utilisation de signatures de gènes de tem dans la découverte de médicaments contre le cancer, diagnostics et traitement du cancer
AR088218A1 (es) 2011-07-19 2014-05-21 Infinity Pharmaceuticals Inc Compuestos heterociclicos utiles como inhibidores de pi3k
EP3812387A1 (fr) 2011-07-21 2021-04-28 Sumitomo Dainippon Pharma Oncology, Inc. Inhibiteurs de protéine kinase hétérocycliques
EP2758402B9 (fr) 2011-09-22 2016-09-14 Pfizer Inc Dérivés de pyrrolopyrimidine et de purine
EP2764025B1 (fr) 2011-10-04 2017-11-29 IGEM Therapeutics Limited Anticorps ige anti-hmw-maa
CN103087077B (zh) * 2011-11-03 2016-05-18 上海希迈医药科技有限公司 噻吩并嘧啶和呋喃并嘧啶类衍生物、其制备方法及其在医药上的应用
WO2013068902A1 (fr) 2011-11-08 2013-05-16 Pfizer Inc. Procédés de traitement de troubles inflammatoires utilisant des anticorps anti-m-csf
EP2802590B1 (fr) * 2012-01-10 2017-03-01 F. Hoffmann-La Roche AG Composés de thiénopyrimidine
FR2988722B1 (fr) 2012-04-03 2014-05-09 Sanofi Sa Nouveaux derives de thienopyrimidines, leurs procedes de preparation et leurs utilisations therapeutiques
WO2013152252A1 (fr) 2012-04-06 2013-10-10 OSI Pharmaceuticals, LLC Polythérapie antinéoplasique
CN103360407B (zh) * 2012-04-10 2016-06-22 上海希迈医药科技有限公司 一种噻吩并嘧啶类衍生物、其制备方法及其在医药上的应用
CN103664991B (zh) * 2012-09-19 2016-12-28 中国科学院福建物质结构研究所 噻吩[2,3‑d]嘧啶衍生物、其制备方法及其用途
EP2909181B1 (fr) 2012-10-16 2017-08-09 Tolero Pharmaceuticals, Inc. Modulateurs de pkm2 et procédés pour les utiliser
US9260426B2 (en) 2012-12-14 2016-02-16 Arrien Pharmaceuticals Llc Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors
EP2959014B1 (fr) 2013-02-25 2019-11-13 Genentech, Inc. Procédés et compositions pour détecter et traiter un mutant d'akt résistant aux médicaments
MX394360B (es) 2013-03-14 2025-03-24 Sumitomo Pharma Oncology Inc Inhibidores de jak2 y alk2 y metodos para su uso.
US9206188B2 (en) 2013-04-18 2015-12-08 Arrien Pharmaceuticals Llc Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors
TW201534597A (zh) 2013-06-20 2015-09-16 Ab Science 作為選擇性蛋白質激酶抑制劑之苯并咪唑衍生物
WO2015051304A1 (fr) 2013-10-04 2015-04-09 Aptose Biosciences Inc. Compositions, biomarqueurs et leur utilisation dans le traitement du cancer
UA115388C2 (uk) 2013-11-21 2017-10-25 Пфайзер Інк. 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань
ES2727374T3 (es) 2014-04-04 2019-10-15 Crown Bioscience Inc Taicang Gen de fusión HNF4G-RSPO2
WO2015155624A1 (fr) 2014-04-10 2015-10-15 Pfizer Inc. Dérivés de dihydropyrrolopyrimidine
CR20160497A (es) 2014-04-30 2016-12-20 Pfizer Derivados de diheterociclo enlazado a cicloalquilo
WO2016001789A1 (fr) 2014-06-30 2016-01-07 Pfizer Inc. Dérivés de pyrimidine en tant qu'inhibiteurs de pi3k destinés à être utilisés dans le traitement du cancer
US20170152226A1 (en) * 2014-07-16 2017-06-01 Novogen Ltd. Functionalised and substituted indoles as anti-cancer agents
JP6811706B2 (ja) 2014-07-31 2021-01-13 ザ ホンコン ユニヴァーシティ オブ サイエンス アンド テクノロジー Ｅｐｈａ４に対するヒトモノクローナル抗体及びそれらの使用
JP6621477B2 (ja) 2014-12-18 2019-12-18 ファイザー・インク ピリミジンおよびトリアジン誘導体ならびにａｘｌ阻害薬としてのそれらの使用
HK1251655A1 (zh) 2015-04-20 2019-02-01 Tolero Pharmaceuticals, Inc. 通过线粒体分析预测对阿伏西地的应答
CA2984421C (fr) 2015-05-01 2024-04-09 Cocrystal Pharma, Inc. Analogues de nucleosides a utiliser pour le traitement d'infections par des virus de la famille des flaviviridae et du cancer
KR102608921B1 (ko) 2015-05-18 2023-12-01 스미토모 파마 온콜로지, 인크. 생체 이용률이 증가된 알보시딥 프로드러그
WO2017009751A1 (fr) 2015-07-15 2017-01-19 Pfizer Inc. Dérivés de pyrimidine
JP7083497B2 (ja) 2015-08-03 2022-06-13 スミトモ ファーマ オンコロジー， インコーポレイテッド がんの処置のための併用療法
WO2017096165A1 (fr) 2015-12-03 2017-06-08 Agios Pharmaceuticals, Inc. Inhibiteurs de mat2a pour le traitement du cancer n'exprimant pas mtap
SG11201804901WA (en) 2015-12-22 2018-07-30 SHY Therapeutics LLC Compounds for the treatment of cancer and inflammatory disease
BR112018068066B1 (pt) * 2016-03-11 2023-11-28 Ac Immune Sa Compostos bicíclicos e seu uso, composição diagnóstica e farmacêutica, misturas, métodos de coleção de dados para diagnóstico, para determinar uma predisposição a, para monitorar transtorno residual e para prever a capacidade de resposta de um paciente sofrendo de transtorno ou anormalidade associado com agregados de alfa-sinucleína, métodos para determinar a quantidade de agregados de alfa-sinucleína e para preparar um composto, kit teste e kit para preparar uma preparação radio farmacêutica
CN107652273B (zh) * 2016-07-26 2020-05-01 沈阳药科大学 嘧啶类衍生物及其制备方法和应用
WO2018094275A1 (fr) 2016-11-18 2018-05-24 Tolero Pharmaceuticals, Inc. Promédicaments de l'alvocidib et leur utilisation en tant qu'inhibiteurs de protéines kinases
AU2017379847B2 (en) 2016-12-19 2022-05-26 Sumitomo Pharma Oncology, Inc. Profiling peptides and methods for sensitivity profiling
EA201992780A1 (ru) 2017-06-21 2020-06-02 ШАЙ ТЕРАПЬЮТИКС ЭлЭлСи Соединения, которые взаимодействуют с суперсемейством ras, для лечения рака, воспалительных заболеваний, ras-опатий и фиброзного заболевания
JP7196160B2 (ja) 2017-09-12 2022-12-26 スミトモ ファーマ オンコロジー， インコーポレイテッド Ｍｃｌ－１阻害剤アルボシジブを用いた、ｂｃｌ－２阻害剤に対して非感受性である癌の治療レジメン
US20200237766A1 (en) 2017-10-13 2020-07-30 Tolero Pharmaceuticals, Inc. Pkm2 activators in combination with reactive oxygen species for treatment of cancer
AU2019310590A1 (en) 2018-07-26 2021-01-14 Sumitomo Pharma Oncology, Inc. Methods for treating diseases associated with abnormal acvr1 expression and acvr1 inhibitors for use in the same
CN120040470A (zh) * 2018-11-20 2025-05-27 乔治敦大学 用于治疗神经退行性、肌退行性和溶酶体贮积病症的组合物和方法
US11034710B2 (en) 2018-12-04 2021-06-15 Sumitomo Dainippon Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US12391705B2 (en) 2018-12-19 2025-08-19 Shy Therapeutics, Llc Compounds that interact with the Ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease
WO2020132384A1 (fr) 2018-12-21 2020-06-25 Celgene Corporation Inhibiteurs thiénopyridine de ripk2
KR20260008165A (ko) 2019-02-12 2026-01-15 스미토모 파마 아메리카, 인크. 헤테로시클릭 단백질 키나제 억제제를 포함하는 제제
SG11202108519TA (en) 2019-02-13 2021-09-29 Ptc Therapeutics Inc Thioeno[3,2-b] pyridin-7-amine compounds for treating familial dysautonomia
WO2020167624A1 (fr) 2019-02-13 2020-08-20 Ptc Therapeutics, Inc. Composés de pyrrolo[2,3-d] pyrimidine pour le traitement de la dysautonomie familiale
EP3929185A4 (fr) * 2019-02-19 2023-02-15 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. Composé cyclique condensé contenant de l'azote, son procédé de préparation et son utilisation
MX2021010319A (es) * 2019-03-01 2021-12-10 Revolution Medicines Inc Compuestos biciclicos de heteroarilo y usos de estos.
WO2020191326A1 (fr) 2019-03-20 2020-09-24 Sumitomo Dainippon Pharma Oncology, Inc. Traitement de la leucémie myéloïde aiguë (aml) après échec du vénétoclax
KR20210141621A (ko) 2019-03-22 2021-11-23 스미토모 다이니폰 파마 온콜로지, 인크. Pkm2 조정제를 포함하는 조성물 및 그를 사용한 치료 방법
CN114269753B (zh) * 2019-09-29 2024-03-05 四川科伦博泰生物医药股份有限公司 一种含氮并环类化合物，包含其的药物组合物，其制备方法及其用途
CN115209955A (zh) * 2019-12-12 2022-10-18 Ptc医疗公司 治疗家族性自主神经功能障碍的化合物
WO2021155006A1 (fr) 2020-01-31 2021-08-05 Les Laboratoires Servier Sas Inhibiteurs de kinases dépendantes des cyclines et leurs utilisations
CN115746017B (zh) * 2022-11-30 2024-06-07 英维沃化工科技(广州)有限公司 一种噻吩并嘧啶类化合物及其制备方法和应用

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3277623D1 (en) * 1981-07-31 1987-12-17 Sloan Kettering Inst Cancer Anti-leukemic beta-glycosyl c-nucleosides
WO1989008113A1 (fr) * 1988-03-02 1989-09-08 Yoshitomi Pharmaceutical Industries, Ltd. COMPOSES DE 3,4-DIHYDROTHIENO[2,3-d]PYRIMIDINE ET LEURS APPLICATIONS PHARMACOLOGIQUES
AU651337B2 (en) 1990-03-30 1994-07-21 Dowelanco Thienopyrimidine derivatives
US5187168A (en) 1991-10-24 1993-02-16 American Home Products Corporation Substituted quinazolines as angiotensin II antagonists
JPH08828B2 (ja) * 1992-02-19 1996-01-10 ファイザー・インコーポレーテッド 抗腫瘍活性を高めるための複素環化合物
IL112249A (en) 1994-01-25 2001-11-25 Warner Lambert Co Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds
US5654307A (en) 1994-01-25 1997-08-05 Warner-Lambert Company Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
JP3290666B2 (ja) * 1995-06-07 2002-06-10 ファイザー・インコーポレーテッド 複素環式の縮合環ピリミジン誘導体
AR004010A1 (es) * 1995-10-11 1998-09-30 Glaxo Group Ltd Compuestos heterociclicos
PT778277E (pt) 1995-12-08 2003-11-28 Pfizer Derivados heterociclicos substituidos como antagonistas do crf
US6255310B1 (en) 1996-02-07 2001-07-03 Neurocrine Biosciences Inc. Thiophenopyrimidines
HRP970371A2 (en) 1996-07-13 1998-08-31 Kathryn Jane Smith Heterocyclic compounds
EA199900021A1 (ru) 1996-07-13 1999-08-26 Глаксо, Груп Лимитед Бициклические гетероароматические соединения в качестве ингибиторов протеинтирозинкиназы
US6187777B1 (en) 1998-02-06 2001-02-13 Amgen Inc. Compounds and methods which modulate feeding behavior and related diseases

Also Published As

Publication number Publication date
EA200000391A1 (ru) 2000-12-25
PL340589A1 (en) 2001-02-12
ID23978A (id) 2000-06-14
IL135636A0 (en) 2001-05-20
CZ20001709A3 (cs) 2001-12-12
EP1028964A1 (fr) 2000-08-23
EA005889B1 (ru) 2005-06-30
ZA9810253B (en) 2000-05-10
AP976A (en) 2001-06-12
PE129099A1 (es) 1999-12-16
HUP0100287A3 (en) 2003-04-28
HUP0100287A2 (hu) 2001-09-28
IS5464A (is) 2000-04-19
HN1998000168A (es) 1999-01-08
NO20002162D0 (no) 2000-04-27
US6492383B1 (en) 2002-12-10
UY25344A1 (es) 1999-09-27
MY132073A (en) 2007-09-28
AR018517A1 (es) 2001-11-28
HRP20000286A2 (en) 2000-12-31
JP2001522853A (ja) 2001-11-20
GT199800180A (es) 2000-05-02
NO20002162L (no) 2000-07-10
BR9814018A (pt) 2000-09-26
CN101328186A (zh) 2008-12-24
MA24694A1 (fr) 1999-07-01
UY25238A1 (es) 2000-12-29
CO4990956A1 (es) 2000-12-26
CA2309690A1 (fr) 1999-05-20
DZ2646A1 (fr) 2003-03-15
TNSN98203A1 (fr) 2005-03-15
AP9801389A0 (en) 1998-12-31
UA72881C2 (uk) 2005-05-16
TW593321B (en) 2004-06-21
SK6652000A3 (en) 2002-05-09
CN1280580A (zh) 2001-01-17
KR100446363B1 (ko) 2004-09-01
KR20010031908A (ko) 2001-04-16
NZ520093A (en) 2004-03-26
WO1999024440A1 (fr) 1999-05-20
BG104412A (en) 2001-02-28
BG65180B1 (bg) 2007-05-31
PA8462401A1 (es) 2000-05-24
AU9454198A (en) 1999-05-31

Similar Documents

Publication Publication Date Title
OA11376A (en) Thienopyrimidine and thienopyridine derivatives useful as anticancer agents.
KR101483215B1 (ko) 단백질 키나아제 저해활성을 갖는 비시클릭 헤테로아릴 유도체
US6413971B1 (en) Fused bicyclic pyrimidine derivatives
EP2491043B1 (fr) COMPOSÉS THIÉNO[3,2-D]PYRIMIDINES SUBSTITUÉS DANS LES POSITIONS 2 ET 7 EN TANT QU&#39;INHIBITEURS DE PROTÉINE KINASE&amp; xA;
US6995171B2 (en) Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents
JP2003535867A (ja) 抗癌剤として有用なチオフェン誘導体
JP2013523711A (ja) アデノシンａ２ａ受容体拮抗薬としての４−アミノピリミジン誘導体
CN103703009A (zh) 作为二酰基甘油酰基转移酶抑制剂的新化合物
US20020004511A1 (en) Thiophene derivatives useful as anticancer agents
US20030162795A1 (en) Thienopyrimidine and thienopyridine derivatives useful as anticancer agents
JP5070058B2 (ja) 過増殖性疾患の処置のための上皮増殖因子受容体（ｅｇｆｒｓ）のチロシンキナーゼ活性のインヒビターとしてのベンゾチエノ’２，３−ｄ！ピリミジン化合物
AU2002301080B2 (en) Thienopyrimidine and Thienopyridine Derivatives Useful as Anticancer Agents
MXPA00004491A (en) Thienopyrimidine and thienopyridine derivatives useful as anticancer agents