ES2411655T3 - Derivados de aminoindazol activos como inhibidores de quinasas, procedimiento para su preparación y composiciones farmacéuticas que los comprenden - Google Patents
Derivados de aminoindazol activos como inhibidores de quinasas, procedimiento para su preparación y composiciones farmacéuticas que los comprenden Download PDFInfo
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- ES2411655T3 ES2411655T3 ES03725180T ES03725180T ES2411655T3 ES 2411655 T3 ES2411655 T3 ES 2411655T3 ES 03725180 T ES03725180 T ES 03725180T ES 03725180 T ES03725180 T ES 03725180T ES 2411655 T3 ES2411655 T3 ES 2411655T3
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- chloride
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- -1 kinase inhibitors Chemical class 0.000 title claims description 49
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 10
- YDTDKKULPWTHRV-UHFFFAOYSA-N 1H-indazol-3-amine Chemical class C1=CC=C2C(N)=NNC2=C1 YDTDKKULPWTHRV-UHFFFAOYSA-N 0.000 title description 9
- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 226
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- 125000003118 aryl group Chemical group 0.000 claims abstract description 34
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
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- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 19
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- 239000001257 hydrogen Substances 0.000 claims abstract description 17
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 8
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- BVIWKIBBSPTOPO-UHFFFAOYSA-N n-(6-phenyl-1h-indazol-3-yl)butanamide Chemical compound C=1C=C2C(NC(=O)CCC)=NNC2=CC=1C1=CC=CC=C1 BVIWKIBBSPTOPO-UHFFFAOYSA-N 0.000 claims abstract description 5
- CZTAWAQITKVBNQ-UHFFFAOYSA-N n-(6-pyridin-3-yl-1h-indazol-3-yl)butanamide Chemical compound C=1C=C2C(NC(=O)CCC)=NNC2=CC=1C1=CC=CN=C1 CZTAWAQITKVBNQ-UHFFFAOYSA-N 0.000 claims abstract description 5
- KEXXQGBZRBKVRC-UHFFFAOYSA-N n-(6-thiophen-3-yl-1h-indazol-3-yl)butanamide Chemical compound C=1C=C2C(NC(=O)CCC)=NNC2=CC=1C=1C=CSC=1 KEXXQGBZRBKVRC-UHFFFAOYSA-N 0.000 claims abstract description 5
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 2
- ZXFLCNBGECGYQK-UHFFFAOYSA-N n-[6-(3,5-difluorophenyl)-1h-indazol-3-yl]butanamide Chemical compound C=1C=C2C(NC(=O)CCC)=NNC2=CC=1C1=CC(F)=CC(F)=C1 ZXFLCNBGECGYQK-UHFFFAOYSA-N 0.000 claims abstract 2
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 26
- SJGGDZCTGBKBCK-UHFFFAOYSA-N 3-acetylphenylboronic acid Chemical compound CC(=O)C1=CC=CC(B(O)O)=C1 SJGGDZCTGBKBCK-UHFFFAOYSA-N 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 22
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 claims description 22
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- 108091000080 Phosphotransferase Proteins 0.000 claims description 13
- 102000020233 phosphotransferase Human genes 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- QQLRSCZSKQTFGY-UHFFFAOYSA-N (2,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C=C1F QQLRSCZSKQTFGY-UHFFFAOYSA-N 0.000 claims description 11
- SQTUYFKNCCBFRR-UHFFFAOYSA-N (2,4-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C(OC)=C1 SQTUYFKNCCBFRR-UHFFFAOYSA-N 0.000 claims description 11
- KTOJGSDLJNUAEP-UHFFFAOYSA-N (2,5-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC(F)=CC=C1F KTOJGSDLJNUAEP-UHFFFAOYSA-N 0.000 claims description 11
- QOZLFNQLIKOGDR-UHFFFAOYSA-N (2,5-dimethoxyphenyl)boronic acid Chemical compound COC1=CC=C(OC)C(B(O)O)=C1 QOZLFNQLIKOGDR-UHFFFAOYSA-N 0.000 claims description 11
- OOMZKLJLVGQZGV-UHFFFAOYSA-N (2,5-dimethylphenyl)boronic acid Chemical compound CC1=CC=C(C)C(B(O)O)=C1 OOMZKLJLVGQZGV-UHFFFAOYSA-N 0.000 claims description 11
- NPLZNDDFVCGRAG-UHFFFAOYSA-N (2-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C#N NPLZNDDFVCGRAG-UHFFFAOYSA-N 0.000 claims description 11
- DGFCTCGCMKEILT-UHFFFAOYSA-N (2-ethoxyphenyl)boronic acid Chemical compound CCOC1=CC=CC=C1B(O)O DGFCTCGCMKEILT-UHFFFAOYSA-N 0.000 claims description 11
- UTKAEAGLVJFBMK-UHFFFAOYSA-N (2-methoxy-5-propan-2-ylphenyl)boronic acid Chemical compound COC1=CC=C(C(C)C)C=C1B(O)O UTKAEAGLVJFBMK-UHFFFAOYSA-N 0.000 claims description 11
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 claims description 11
- QXBWTYBCNFKURT-UHFFFAOYSA-N (2-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=CC=C1B(O)O QXBWTYBCNFKURT-UHFFFAOYSA-N 0.000 claims description 11
- JKIGHOARKAIPJI-UHFFFAOYSA-N (3,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C(Cl)=C1 JKIGHOARKAIPJI-UHFFFAOYSA-N 0.000 claims description 11
- KDVZJKOYSOFXRV-UHFFFAOYSA-N (3,4-dimethylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1C KDVZJKOYSOFXRV-UHFFFAOYSA-N 0.000 claims description 11
- DJGHSJBYKIQHIK-UHFFFAOYSA-N (3,5-dimethylphenyl)boronic acid Chemical compound CC1=CC(C)=CC(B(O)O)=C1 DJGHSJBYKIQHIK-UHFFFAOYSA-N 0.000 claims description 11
- IBTSWKLSEOGJGJ-UHFFFAOYSA-N (3-acetamidophenyl)boronic acid Chemical compound CC(=O)NC1=CC=CC(B(O)O)=C1 IBTSWKLSEOGJGJ-UHFFFAOYSA-N 0.000 claims description 11
- WJDZZXIDQYKVDG-UHFFFAOYSA-N (3-chloro-4-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(Cl)=C1 WJDZZXIDQYKVDG-UHFFFAOYSA-N 0.000 claims description 11
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 claims description 11
- KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 claims description 11
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 claims description 11
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 claims description 11
- OBQRODBYVNIZJU-UHFFFAOYSA-N (4-acetylphenyl)boronic acid Chemical compound CC(=O)C1=CC=C(B(O)O)C=C1 OBQRODBYVNIZJU-UHFFFAOYSA-N 0.000 claims description 11
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 claims description 11
- IAEUFBDMVKQCLU-UHFFFAOYSA-N (4-propan-2-ylphenyl)boronic acid Chemical compound CC(C)C1=CC=C(B(O)O)C=C1 IAEUFBDMVKQCLU-UHFFFAOYSA-N 0.000 claims description 11
- CCQKIRUMTHHPSX-UHFFFAOYSA-N (5-fluoro-2-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(F)C=C1B(O)O CCQKIRUMTHHPSX-UHFFFAOYSA-N 0.000 claims description 11
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 claims description 11
- UWDFWVLAHRQSKK-UHFFFAOYSA-N [3-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(OC(F)(F)F)=C1 UWDFWVLAHRQSKK-UHFFFAOYSA-N 0.000 claims description 11
- RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 claims description 11
- PZRPBPMLSSNFOM-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=C(B(O)O)C=C1 PZRPBPMLSSNFOM-UHFFFAOYSA-N 0.000 claims description 11
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 11
- ZAZKJZBWRNNLDS-UHFFFAOYSA-N methyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OC ZAZKJZBWRNNLDS-UHFFFAOYSA-N 0.000 claims description 11
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 11
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- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 10
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- 239000003795 chemical substances by application Substances 0.000 claims description 10
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical group [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- RYWGPCLTVXMMHO-UHFFFAOYSA-N (4-chlorophenyl) carbonochloridate Chemical compound ClC(=O)OC1=CC=C(Cl)C=C1 RYWGPCLTVXMMHO-UHFFFAOYSA-N 0.000 claims description 6
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Classifications
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- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
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- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
- C40B50/14—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Heart & Thoracic Surgery (AREA)
- Virology (AREA)
- Hospice & Palliative Care (AREA)
- Communicable Diseases (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Structural Engineering (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38109202P | 2002-05-17 | 2002-05-17 | |
| US381092P | 2002-05-17 | ||
| PCT/EP2003/004862 WO2003097610A1 (en) | 2002-05-17 | 2003-05-08 | Aminoindazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2411655T3 true ES2411655T3 (es) | 2013-07-08 |
Family
ID=29550068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03725180T Expired - Lifetime ES2411655T3 (es) | 2002-05-17 | 2003-05-08 | Derivados de aminoindazol activos como inhibidores de quinasas, procedimiento para su preparación y composiciones farmacéuticas que los comprenden |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1506176B1 (enExample) |
| JP (1) | JP4751063B2 (enExample) |
| AU (1) | AU2003227741A1 (enExample) |
| BR (1) | BR0311291A (enExample) |
| CA (1) | CA2486101C (enExample) |
| ES (1) | ES2411655T3 (enExample) |
| MX (1) | MXPA04011417A (enExample) |
| WO (1) | WO2003097610A1 (enExample) |
Families Citing this family (95)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0217757D0 (en) * | 2002-07-31 | 2002-09-11 | Glaxo Group Ltd | Novel compounds |
| US7297709B2 (en) | 2003-05-22 | 2007-11-20 | Abbott Laboratories | Indazole, benzisoxazole, and benzisothiazole kinase inhibitors |
| JP4810427B2 (ja) * | 2003-05-22 | 2011-11-09 | アボット・ラボラトリーズ | インダゾール、ベンズイソオキサゾールおよびベンズイソチアゾールキナーゼ阻害剤 |
| JP2007514759A (ja) | 2003-12-19 | 2007-06-07 | タケダ サン ディエゴ インコーポレイテッド | キナーゼ阻害剤 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE626284A (enExample) | 1962-04-28 | |||
| DE2458965C3 (de) | 1974-12-13 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | 3-Amino-indazol-N-carbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie sie enthaltende Arzneimittel |
| US4864032A (en) | 1987-07-02 | 1989-09-05 | Ortho Pharmaceutical Corporation | Process for the preparation of indazoles |
| JP3245765B2 (ja) | 1994-07-05 | 2002-01-15 | コニカ株式会社 | 写真用シアンカプラー |
| AU739642B2 (en) * | 1997-12-22 | 2001-10-18 | Bayer Healthcare Llc | Inhibition of p38 kinase activity using substituted heterocyclic ureas |
| US6387900B1 (en) * | 1999-08-12 | 2002-05-14 | Pharmacia & Upjohn S.P.A. | 3(5)-ureido-pyrazole derivatives process for their preparation and their use as antitumor agents |
| EE05405B1 (et) * | 2000-08-10 | 2011-04-15 | Pharmacia Italia S.P.A. | Kinaasi inhibiitoritena toimivad bitskloprasoolid, nende valmistamismeetod, kasutamine ja neid sisaldavad farmatseutilised kompositsioonid |
| JP2005516927A (ja) * | 2001-12-13 | 2005-06-09 | アボット・ラボラトリーズ | 癌治療用のキナーゼ阻害剤としての3−(フェニル−アルコキシ)−5−(フェニル)−ピリジン誘導体および関連化合物 |
| WO2003051847A1 (en) * | 2001-12-19 | 2003-06-26 | Smithkline Beecham P.L.C. | (1-h-indazol-3-yl) -amide derivatives as gsk-3 inhibitors |
| FR2836915B1 (fr) * | 2002-03-11 | 2008-01-11 | Aventis Pharma Sa | Derives d'aminoindazoles, procede de preparation et intermediaires de ce procede a titre de medicaments et compositions pharmaceutiques les renfermant |
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2003
- 2003-05-08 ES ES03725180T patent/ES2411655T3/es not_active Expired - Lifetime
- 2003-05-08 WO PCT/EP2003/004862 patent/WO2003097610A1/en not_active Ceased
- 2003-05-08 MX MXPA04011417A patent/MXPA04011417A/es unknown
- 2003-05-08 AU AU2003227741A patent/AU2003227741A1/en not_active Abandoned
- 2003-05-08 CA CA002486101A patent/CA2486101C/en not_active Expired - Lifetime
- 2003-05-08 JP JP2004505343A patent/JP4751063B2/ja not_active Expired - Lifetime
- 2003-05-08 BR BR0311291-8A patent/BR0311291A/pt not_active IP Right Cessation
- 2003-05-08 EP EP03725180.8A patent/EP1506176B1/en not_active Expired - Lifetime
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| WO2003097610A1 (en) | 2003-11-27 |
| EP1506176B1 (en) | 2013-04-24 |
| JP2005534635A (ja) | 2005-11-17 |
| CA2486101A1 (en) | 2003-11-27 |
| EP1506176A1 (en) | 2005-02-16 |
| BR0311291A (pt) | 2005-03-29 |
| AU2003227741A1 (en) | 2003-12-02 |
| CA2486101C (en) | 2009-07-07 |
| JP4751063B2 (ja) | 2011-08-17 |
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