ZA200405025B - 3-Cyanoquinolines as inhibitors of EGF-R and Her2 kinases - Google Patents
3-Cyanoquinolines as inhibitors of EGF-R and Her2 kinases Download PDFInfo
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- ZA200405025B ZA200405025B ZA200405025A ZA200405025A ZA200405025B ZA 200405025 B ZA200405025 B ZA 200405025B ZA 200405025 A ZA200405025 A ZA 200405025A ZA 200405025 A ZA200405025 A ZA 200405025A ZA 200405025 B ZA200405025 B ZA 200405025B
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- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 title description 9
- 239000003112 inhibitor Substances 0.000 title description 8
- 108091000080 Phosphotransferase Proteins 0.000 title description 7
- 102000020233 phosphotransferase Human genes 0.000 title description 7
- 101150029707 ERBB2 gene Proteins 0.000 title description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 329
- 150000001875 compounds Chemical class 0.000 claims description 109
- -1 nitro, carboxy Chemical group 0.000 claims description 79
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 27
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical group 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
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- 239000000203 mixture Substances 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 13
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 13
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- 239000000126 substance Substances 0.000 claims description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 125000004970 halomethyl group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 150000001721 carbon Chemical class 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 230000012010 growth Effects 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 229930192474 thiophene Natural products 0.000 claims description 7
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 5
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
- 125000000539 amino acid group Chemical group 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 5
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- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 208000035984 Colonic Polyps Diseases 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
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- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 210000003238 esophagus Anatomy 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 210000000867 larynx Anatomy 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
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- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 2
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 claims description 2
- ICMFXKPVTNHUTG-UHFFFAOYSA-N 2,2-bis(dimethylamino)butanamide Chemical compound CCC(N(C)C)(N(C)C)C(N)=O ICMFXKPVTNHUTG-UHFFFAOYSA-N 0.000 claims description 2
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
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- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 claims description 2
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- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 2
- KHPIRECQOJCDSH-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-3-(dimethylamino)butanamide Chemical compound C=12C=C(NC(=O)CC(C)N(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 KHPIRECQOJCDSH-UHFFFAOYSA-N 0.000 claims description 2
- ZOQGOOXQXUTMMX-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-methoxyquinolin-6-yl]-3,4-bis(3-hydroxypyrrolidin-1-yl)butanamide Chemical compound C=12C=C(NC(=O)CC(CN3CC(O)CC3)N3CC(O)CC3)C(OC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 ZOQGOOXQXUTMMX-UHFFFAOYSA-N 0.000 claims description 2
- RPXQGRBJRFCZNX-UHFFFAOYSA-N n-[4-(3-chloro-4-phenylmethoxyanilino)-3-cyano-7-ethoxyquinolin-6-yl]-3,6-bis(dimethylamino)hexanamide Chemical compound C=12C=C(NC(=O)CC(CCCN(C)C)N(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=C1 RPXQGRBJRFCZNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
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| MXPA06002846A (es) * | 2003-09-15 | 2006-06-14 | Wyeth Corp | Quinolinas sustituidas como inhibidores de la enzima de la proteina tirosina cinasa. |
| US7365203B2 (en) * | 2003-09-15 | 2008-04-29 | Wyeth | Process for the synthesis of 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-ethoxy-quinoline-3-carbonitrile |
| DK2392564T3 (da) * | 2003-09-26 | 2014-01-13 | Exelixis Inc | c-Met-modulatorer og anvendelsesfremgangsmåder |
| US7781591B2 (en) | 2006-06-13 | 2010-08-24 | Wyeth Llc | Substituted 3-cyanopyridines as protein kinase inhibitors |
| CN101337930B (zh) | 2003-11-11 | 2010-09-08 | 卫材R&D管理有限公司 | 脲衍生物的制备方法 |
| AU2005272815A1 (en) | 2004-08-13 | 2006-02-23 | Genentech, Inc. | Thiazole based inhibitors of ATP-utilizing enzymes |
| EP1797881B1 (en) | 2004-09-17 | 2009-04-15 | Eisai R&D Management Co., Ltd. | Medicinal composition with improved stability and reduced gelation properties |
| TW200616612A (en) * | 2004-10-08 | 2006-06-01 | Wyeth Corp | Method for the teatment of polycystic kidney disease field of invention |
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| GB0509227D0 (en) * | 2005-05-05 | 2005-06-15 | Chroma Therapeutics Ltd | Intracellular enzyme inhibitors |
| US7624279B2 (en) * | 2005-06-29 | 2009-11-24 | Lenovo Singapore Pte. Ltd. | System and method for secure O.S. boot from password-protected HDD |
| EP2281901B1 (en) | 2005-08-02 | 2013-11-27 | Eisai R&D Management Co., Ltd. | Anti-tumour pharmaceutical composition with angiogenesis inhibitors |
| KR101354828B1 (ko) | 2005-11-04 | 2014-02-18 | 와이어쓰 엘엘씨 | ｍＴＯＲ 저해자, 헤르셉틴, 및/또는 ＨＫＩ-272의항신생물성 조합 |
| EP2036557B1 (en) | 2006-05-18 | 2015-10-21 | Eisai R&D Management Co., Ltd. | Antitumor agent for thyroid cancer |
| BRPI0712737A2 (pt) * | 2006-06-13 | 2012-05-08 | Wyeth Corp | composto; composição farmacêutica; método e tratamento ou inibição de uma condição ou transtorno patológico mediado por uma proteìna quinase em um mamìfero; e uso do composto |
| KR101472600B1 (ko) | 2006-08-28 | 2014-12-15 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암에 대한 항종양제 |
| JP5319306B2 (ja) | 2007-01-29 | 2013-10-16 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 未分化型胃癌治療用組成物 |
| US8022216B2 (en) | 2007-10-17 | 2011-09-20 | Wyeth Llc | Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof |
| US8952035B2 (en) | 2007-11-09 | 2015-02-10 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
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| EP3135285B1 (en) | 2008-06-17 | 2018-08-15 | Wyeth LLC | Antineoplastic combinations containing hki-272 and vinorelbine |
| EP2326329B1 (en) | 2008-08-04 | 2017-01-11 | Wyeth LLC | Antineoplastic combinations of 4-anilino-3-cyanoquinolines and capecitabine |
| ITMI20082336A1 (it) * | 2008-12-29 | 2010-06-30 | Univ Parma | Composti inibitori irreversibili di egfr con attivita' antiproliferativa |
| SG173014A1 (en) | 2009-01-16 | 2011-08-29 | Exelixis Inc | Malate salt of n- (4- { [ 6, 7-bis (methyloxy) quin0lin-4-yl] oxy}phenyl)-n' - (4 -fluorophenyl) cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer |
| DK3000467T3 (da) | 2009-04-06 | 2023-03-27 | Wyeth Llc | Behandling med neratinib mod brystkræft |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
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| EA025451B1 (ru) * | 2010-08-26 | 2016-12-30 | Симфони Эволюшн, Инк. | Модулятор киназы рецепторного типа и способы лечения поликистозной болезни почек |
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| CN110452232A (zh) * | 2019-09-17 | 2019-11-15 | 北京振东光明药物研究院有限公司 | 阿法替尼杂质化合物及其制备方法与应用 |
| CN111943933B (zh) * | 2020-09-02 | 2021-05-28 | 重庆医科大学 | 一种来那替尼杂质d的制备方法 |
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|---|---|---|---|---|
| IL125686A (en) * | 1996-02-13 | 2002-11-10 | Zeneca Ltd | Quinazoline derivatives, processes for their preparation, pharmaceutical preparations containing them and their use in the manufacture of a drug with an anti-angiogenic effect and / or an effect of reducing vascular permeability |
| US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| US6235740B1 (en) * | 1997-08-25 | 2001-05-22 | Bristol-Myers Squibb Co. | Imidazoquinoxaline protein tyrosine kinase inhibitors |
| AU763669B2 (en) * | 1998-09-29 | 2003-07-31 | Wyeth Holdings Corporation | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
| BR9914164A (pt) * | 1998-09-29 | 2001-06-26 | American Cyanamid Co | Composto, método para o tratamento, inibição do crescimento de, ou erradiacação de um neoplasma, e de doença de rim policìstico, em um mamìfero em necessidade do mesmo, composição farmacêutica, e, processo para preparar um composto |
| GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| AU2464601A (en) * | 1999-12-29 | 2001-07-09 | Wyeth | Tricyclic protein kinase inhibitors |
| WO2002044166A1 (en) * | 2000-11-02 | 2002-06-06 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
-
2002
- 2002-11-26 US US10/305,438 patent/US6821988B2/en not_active Expired - Fee Related
- 2002-11-26 IL IL16192102A patent/IL161921A0/xx unknown
- 2002-11-26 AT AT02794031T patent/ATE370123T1/de not_active IP Right Cessation
- 2002-11-26 TW TW091134370A patent/TW200300348A/zh unknown
- 2002-11-26 CN CN028275381A patent/CN1659145A/zh active Pending
- 2002-11-26 NZ NZ533118A patent/NZ533118A/en unknown
- 2002-11-26 RU RU2004119414/04A patent/RU2309150C2/ru not_active IP Right Cessation
- 2002-11-26 JP JP2003551115A patent/JP2005514384A/ja not_active Ceased
- 2002-11-26 EP EP02794031A patent/EP1448531B1/en not_active Expired - Lifetime
- 2002-11-26 AR ARP020104543A patent/AR037438A1/es not_active Application Discontinuation
- 2002-11-26 WO PCT/US2002/037918 patent/WO2003050090A1/en active IP Right Grant
- 2002-11-26 KR KR1020047007951A patent/KR20050044599A/ko not_active Application Discontinuation
- 2002-11-26 PL PL02370137A patent/PL370137A1/xx not_active Application Discontinuation
- 2002-11-26 MX MXPA04004969A patent/MXPA04004969A/es active IP Right Grant
- 2002-11-26 BR BR0214485-9A patent/BR0214485A/pt not_active IP Right Cessation
- 2002-11-26 CA CA002467573A patent/CA2467573A1/en not_active Abandoned
- 2002-11-26 DE DE60221886T patent/DE60221886D1/de not_active Expired - Lifetime
- 2002-11-26 UA UA20040605019A patent/UA77469C2/uk unknown
- 2002-11-26 AU AU2002359489A patent/AU2002359489B2/en not_active Ceased
- 2002-11-26 HU HU0402228A patent/HUP0402228A2/hu unknown
-
2004
- 2004-05-25 CO CO04048181A patent/CO5580828A2/es not_active Application Discontinuation
- 2004-05-26 EC EC2004005122A patent/ECSP045122A/es unknown
- 2004-06-23 NO NO20042634A patent/NO20042634L/no not_active Application Discontinuation
- 2004-06-24 ZA ZA200405025A patent/ZA200405025B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20030149056A1 (en) | 2003-08-07 |
| MXPA04004969A (es) | 2004-08-11 |
| RU2004119414A (ru) | 2006-02-27 |
| EP1448531B1 (en) | 2007-08-15 |
| ATE370123T1 (de) | 2007-09-15 |
| UA77469C2 (en) | 2006-12-15 |
| US6821988B2 (en) | 2004-11-23 |
| NO20042634L (no) | 2004-06-23 |
| AU2002359489A1 (en) | 2003-06-23 |
| BR0214485A (pt) | 2004-09-14 |
| WO2003050090A1 (en) | 2003-06-19 |
| ECSP045122A (es) | 2004-07-23 |
| CO5580828A2 (es) | 2005-11-30 |
| KR20050044599A (ko) | 2005-05-12 |
| AR037438A1 (es) | 2004-11-10 |
| TW200300348A (en) | 2003-06-01 |
| AU2002359489B2 (en) | 2008-10-30 |
| CN1659145A (zh) | 2005-08-24 |
| PL370137A1 (en) | 2005-05-16 |
| EP1448531A1 (en) | 2004-08-25 |
| RU2309150C2 (ru) | 2007-10-27 |
| IL161921A0 (en) | 2005-11-20 |
| DE60221886D1 (de) | 2007-09-27 |
| HUP0402228A2 (hu) | 2005-02-28 |
| JP2005514384A (ja) | 2005-05-19 |
| CA2467573A1 (en) | 2003-06-19 |
| NZ533118A (en) | 2006-07-28 |
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