CN103214482B - 作为受体酪氨酸激酶抑制剂的咪唑并[1,2-a]吡啶化合物 - Google Patents
作为受体酪氨酸激酶抑制剂的咪唑并[1,2-a]吡啶化合物 Download PDFInfo
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- CN103214482B CN103214482B CN201310054054.1A CN201310054054A CN103214482B CN 103214482 B CN103214482 B CN 103214482B CN 201310054054 A CN201310054054 A CN 201310054054A CN 103214482 B CN103214482 B CN 103214482B
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- Prior art keywords
- pyridin
- quinoline
- imidazo
- compound
- base
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- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 title description 5
- 150000005234 imidazo[1,2-a]pyridines Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 205
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- 229910052760 oxygen Inorganic materials 0.000 claims description 111
- 238000002360 preparation method Methods 0.000 claims description 108
- 239000001301 oxygen Substances 0.000 claims description 105
- 229910052731 fluorine Inorganic materials 0.000 claims description 99
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 82
- -1 2-(7-(2-methoxy ethoxy) imidazo [1,2-a] pyridin-3-yl) quinoline-8-yl oxygen Chemical compound 0.000 claims description 76
- 239000011737 fluorine Substances 0.000 claims description 70
- 238000000034 method Methods 0.000 claims description 51
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 32
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- APCBTRDHCDOPNY-ZETCQYMHSA-N tert-butyl (3s)-3-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](O)C1 APCBTRDHCDOPNY-ZETCQYMHSA-N 0.000 description 1
- XRNLYXKYODGLMI-UHFFFAOYSA-N tert-butyl 3-fluoro-4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)C(F)C1 XRNLYXKYODGLMI-UHFFFAOYSA-N 0.000 description 1
- HRVGBPJUNNBCAC-UHFFFAOYSA-N tert-butyl 4-[[2-[7-(2-methoxyethoxy)imidazo[1,2-a]pyridin-3-yl]quinolin-8-yl]amino]-4-methylpiperidine-1-carboxylate Chemical compound C=1N=C2C=C(OCCOC)C=CN2C=1C(N=C12)=CC=C1C=CC=C2NC1(C)CCN(C(=O)OC(C)(C)C)CC1 HRVGBPJUNNBCAC-UHFFFAOYSA-N 0.000 description 1
- DMBKWEHXTOCLTC-UHFFFAOYSA-N tert-butyl 4-amino-4-methylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C)(N)CC1 DMBKWEHXTOCLTC-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- IZUZIVIUDTZPFE-UHFFFAOYSA-N tert-butyl decanoate Chemical compound CCCCCCCCCC(=O)OC(C)(C)C IZUZIVIUDTZPFE-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
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Classifications
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
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- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US90985707P | 2007-04-03 | 2007-04-03 | |
| US60/909,857 | 2007-04-03 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| CN200880018702A Division CN101679423A (zh) | 2007-04-03 | 2008-03-27 | 作为受体酪氨酸激酶抑制剂的咪唑并[1,2-a]吡啶化合物 |
Publications (2)
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| CN103214482A CN103214482A (zh) | 2013-07-24 |
| CN103214482B true CN103214482B (zh) | 2016-06-29 |
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| CN201310054054.1A Expired - Fee Related CN103214482B (zh) | 2007-04-03 | 2008-03-27 | 作为受体酪氨酸激酶抑制剂的咪唑并[1,2-a]吡啶化合物 |
| CN200880018702A Pending CN101679423A (zh) | 2007-04-03 | 2008-03-27 | 作为受体酪氨酸激酶抑制剂的咪唑并[1,2-a]吡啶化合物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200880018702A Pending CN101679423A (zh) | 2007-04-03 | 2008-03-27 | 作为受体酪氨酸激酶抑制剂的咪唑并[1,2-a]吡啶化合物 |
Country Status (25)
| Country | Link |
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| EP (1) | EP2137184B1 (OSRAM) |
| JP (1) | JP5374492B2 (OSRAM) |
| KR (1) | KR101538179B1 (OSRAM) |
| CN (2) | CN103214482B (OSRAM) |
| AU (1) | AU2008237507B2 (OSRAM) |
| BR (1) | BRPI0809998B8 (OSRAM) |
| CA (1) | CA2682981C (OSRAM) |
| CO (1) | CO6251377A2 (OSRAM) |
| CY (1) | CY1114277T1 (OSRAM) |
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| ES (1) | ES2420113T3 (OSRAM) |
| HR (1) | HRP20130660T1 (OSRAM) |
| IL (1) | IL201300A0 (OSRAM) |
| MX (1) | MX2009010728A (OSRAM) |
| MY (1) | MY157724A (OSRAM) |
| NZ (1) | NZ580327A (OSRAM) |
| PL (1) | PL2137184T3 (OSRAM) |
| PT (1) | PT2137184E (OSRAM) |
| RS (1) | RS52862B (OSRAM) |
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| TW (1) | TWI429434B (OSRAM) |
| UA (1) | UA101611C2 (OSRAM) |
| WO (1) | WO2008124323A1 (OSRAM) |
| ZA (1) | ZA200907674B (OSRAM) |
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| EP2343298B9 (en) | 2005-12-13 | 2020-05-06 | Incyte Holdings Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
| CA2672213C (en) | 2006-12-22 | 2016-02-16 | Astex Therapeutics Limited | Bicyclic amine derivatives as protein tyrosine kinase inhibitors |
| MX2009006706A (es) | 2006-12-22 | 2009-07-02 | Astex Therapeutics Ltd | Compuestos heterociclicos biciclicos como inhibidores del receptor del factor de crecimiento de fibroblastos. |
| RS53245B2 (sr) | 2007-06-13 | 2022-10-31 | Incyte Holdings Corp | Soli inhibitora janus kinaze (r)-3-(4-(7h-pirolo(2,3-d) pirimidin-4-il)-1h-pirazol-1-il)-3-ciklopentilpropan-nitrila |
| GB0720041D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New Compounds |
| GB0720038D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New compounds |
| EP2296653B1 (en) | 2008-06-03 | 2016-01-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| GB0810902D0 (en) | 2008-06-13 | 2008-07-23 | Astex Therapeutics Ltd | New compounds |
| CA2952692C (en) | 2008-09-22 | 2020-04-28 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds |
| US20110184013A1 (en) * | 2008-10-01 | 2011-07-28 | Shelley Allen | Imidazo[1,2-a]Pyridine Compounds As Receptor Tyrosine Kinase Inhibitors |
| PT3372605T (pt) | 2008-10-22 | 2021-12-09 | Array Biopharma Inc | Compostos de pirazolo[1,5-a]pirimidina substituídos como inibidores de quinase trk |
| GB0906470D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
| GB0906472D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
| HRP20192203T1 (hr) | 2009-05-22 | 2020-03-06 | Incyte Holdings Corporation | 3-[4-(7h-pirolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il]oktan- ili heptan-nitril kao jak inhibitori |
| WO2010135650A1 (en) | 2009-05-22 | 2010-11-25 | Incyte Corporation | N-(HETERO)ARYL-PYRROLIDINE DERIVATIVES OF PYRAZOL-4-YL-PYRROLO[2,3-d]PYRIMIDINES AND PYRROL-3-YL-PYRROLO[2,3-d]PYRIMIDINES AS JANUS KINASE INHIBITORS |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| TW201113285A (en) | 2009-09-01 | 2011-04-16 | Incyte Corp | Heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors |
| BR112012010041A2 (pt) | 2009-10-30 | 2016-05-24 | Janssen Pharmaceutica Nv | derivados de imidazo [1,2-b] piridazina e seu uso como inibidores de pde10 |
| FR2953838B1 (fr) * | 2009-12-10 | 2012-02-24 | Sanofi Aventis | Derives de 9h-beta-carboline (ou 9h-pyridino[3,4-b]indole) trisubstitues, leur preparation et leur utilisation therapeutique |
| FR2953837B1 (fr) * | 2009-12-10 | 2012-03-09 | Sanofi Aventis | Derives 9h-pyridino[3,4-b]indole disubstitues, leur preparation et leur utilisation therapeutique |
| MY163791A (en) * | 2009-12-21 | 2017-10-31 | Array Biopharma Inc | SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS cFMS INHIBITORS |
| AR080754A1 (es) | 2010-03-09 | 2012-05-09 | Janssen Pharmaceutica Nv | Derivados de imidazo (1,2-a) pirazina y su uso como inhibidores de pde10 |
| SI3354652T1 (sl) | 2010-03-10 | 2020-08-31 | Incyte Holdings Corporation | Derivati piperidin-4-il azetidina kot inhibitorji JAK1 |
| BR112012026948A2 (pt) * | 2010-04-28 | 2019-09-24 | Daiichi Sankyo Co Ltd | composto, composição farmacêutica, e, métodos para melhorar o metabolismo ósseo, para previnir ou tratar uma doença associada com metabolismo ósseo e para previnir ou tratar osteoporose. |
| SMT201900203T1 (it) | 2010-05-20 | 2019-05-10 | Array Biopharma Inc | Composti macrociclici come inibitori di trk chinasi |
| MY161078A (en) | 2010-05-21 | 2017-04-14 | Incyte Holdings Corp | Topical formulation for a jak inhibitor |
| JP5917545B2 (ja) | 2010-11-19 | 2016-05-18 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｊａｋ阻害剤としてのシクロブチル置換ピロロピリジンおよびピロロピリミジン誘導体 |
| WO2012068440A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors |
| TWI527813B (zh) * | 2010-12-13 | 2016-04-01 | 亞雷生物製藥股份有限公司 | 作為III型受體酪胺酸激酶抑制劑之經取代Ｎ－（１Ｈ－吲唑－４－基）咪唑并 ［１，２－ａ］吡啶－３－甲醯胺化合物 |
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| SG11201503299YA (en) * | 2012-09-28 | 2015-06-29 | Univ Vanderbilt | Fused heterocyclic compounds as selective bmp inhibitors |
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