AR056187A1 - Derivados de imidazo[1,2-a)piridina: preparacion, composiciones farmaceuticas y uso para preparar medicamentos - Google Patents
Derivados de imidazo[1,2-a)piridina: preparacion, composiciones farmaceuticas y uso para preparar medicamentosInfo
- Publication number
- AR056187A1 AR056187A1 ARP060101088A ARP060101088A AR056187A1 AR 056187 A1 AR056187 A1 AR 056187A1 AR P060101088 A ARP060101088 A AR P060101088A AR P060101088 A ARP060101088 A AR P060101088A AR 056187 A1 AR056187 A1 AR 056187A1
- Authority
- AR
- Argentina
- Prior art keywords
- group
- alkyl
- alkenyl
- optionally substituted
- heterocycloalkyl
- Prior art date
Links
- 239000003814 drug Substances 0.000 title abstract 2
- 229940079593 drug Drugs 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 16
- 125000000217 alkyl group Chemical group 0.000 abstract 16
- 125000001072 heteroaryl group Chemical group 0.000 abstract 15
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 15
- 125000003118 aryl group Chemical group 0.000 abstract 14
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 14
- 125000004404 heteroalkyl group Chemical group 0.000 abstract 14
- 125000002252 acyl group Chemical group 0.000 abstract 12
- 125000000304 alkynyl group Chemical group 0.000 abstract 12
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 12
- 125000001188 haloalkyl group Chemical group 0.000 abstract 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 abstract 12
- -1 heterocycloalkyloxy Chemical group 0.000 abstract 11
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 abstract 10
- 125000003282 alkyl amino group Chemical group 0.000 abstract 9
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract 6
- 125000004103 aminoalkyl group Chemical group 0.000 abstract 6
- 125000004104 aryloxy group Chemical group 0.000 abstract 6
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 6
- 125000000262 haloalkenyl group Chemical group 0.000 abstract 6
- 229910052736 halogen Inorganic materials 0.000 abstract 6
- 150000002367 halogens Chemical class 0.000 abstract 6
- 125000004366 heterocycloalkenyl group Chemical group 0.000 abstract 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract 6
- 125000003302 alkenyloxy group Chemical group 0.000 abstract 5
- 125000004171 alkoxy aryl group Chemical group 0.000 abstract 5
- 125000003545 alkoxy group Chemical group 0.000 abstract 5
- 125000005133 alkynyloxy group Chemical group 0.000 abstract 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 abstract 5
- 125000001769 aryl amino group Chemical group 0.000 abstract 5
- 125000000000 cycloalkoxy group Chemical group 0.000 abstract 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 5
- 125000004442 acylamino group Chemical group 0.000 abstract 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 abstract 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 abstract 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 abstract 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 4
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 4
- 125000005553 heteroaryloxy group Chemical group 0.000 abstract 4
- 125000005018 aryl alkenyl group Chemical group 0.000 abstract 3
- 125000005135 aryl sulfinyl group Chemical group 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 3
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 abstract 2
- 102000003964 Histone deacetylase Human genes 0.000 abstract 2
- 108090000353 Histone deacetylase Proteins 0.000 abstract 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
- OFDNQWIFNXBECV-VFSYNPLYSA-N dolastatin 10 Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-VFSYNPLYSA-N 0.000 abstract 2
- 125000000232 haloalkynyl group Chemical group 0.000 abstract 2
- ZQUSYVORYNBGLG-FQEVSTJZSA-N (2s)-2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)pyrazole-3-carbonyl]amino]-4-methylpentanoic acid Chemical compound COC1=CC=CC(OC)=C1C1=CC(C(=O)N[C@@H](CC(C)C)C(O)=O)=NN1C1=CC=NC2=CC(Cl)=CC=C12 ZQUSYVORYNBGLG-FQEVSTJZSA-N 0.000 abstract 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 102000004190 Enzymes Human genes 0.000 abstract 1
- 108090000790 Enzymes Proteins 0.000 abstract 1
- 125000004465 cycloalkenyloxy group Chemical group 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 125000004447 heteroarylalkenyl group Chemical group 0.000 abstract 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 abstract 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 abstract 1
- 150000005234 imidazo[1,2-a]pyridines Chemical class 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- 230000002062 proliferating effect Effects 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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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Abstract
Los compuestos de hidroximato son inhibidores de histona deacetilasa. Se divulgan compuestos de imidazo[1,2-a]piridina y métodos para su preparacion. Estos compuestos pueden ser utiles como medicamentos para el tratamiento de trastornos proliferativos así como enfermedades relacionadas o asociadas con enzimas que tienen actividad de histona deacetilasa (HDAC). Reivindicacion 1: Un compuesto caracterizado porque tiene la formula (1), en donde R1 está seleccionado del grupo que consiste en H, halogeno, -CN, -NO2, -CF3, -OCF3, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, heteroalquilo, cicloalquilo, cicloalquenilo, heterocicloalquilo, heterocicloalquenilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo, arilalquenilo, cicloalquilheteroalquilo, arilheteroalquilo, heterocicloalquilheteroalquilo, heteroarilheteroalquilo, hidroxi, hidroxialquilo, alcoxi, alcoxialquilo, alcoxiarilo, alqueniloxi, alquiniloxi, cicloalquiloxi, heterocicloalquiloxi, ariloxi, heteroariloxi, arilalquiloxi, fenoxi, benciloxi, amino, alquilamino, aminoalquilo, acilamino, arilamino, sulfonilamino, sulfinilamino, -COOH, - COR5, -COOR5, -CONHR5, -NHCOR5, -NHCOOR5, - NHCONHR5, C(=NOH)R5, - alquilNCOR5, alcoxicarbonilo, alquilaminocarbonilo, sulfonilo, alquilsulfonilo, alquilsulfinilo, arilsulfonilo, arilsulfinilo, aminosulfonilo, SR6 y acilo, cada uno de los cuales puede estar opcionalmente substituido; o R1 = L; R2 está seleccionado del grupo que consiste en H, halogeno, -CN, -NO2, -CF3, -OCF3, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, heteroalquilo, cicloalquilo, cicloalquenilo, heterocicloalquilo, heterocicloalquenilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo, arilalquenilo, cicloalquilheteroalquilo, arilheteroalquilo, heterocicloalquilheteroalquilo, heteroarilheteroalquilo, hidroxi, hidroxialquilo, alcoxi, alcoxialquilo, alcoxiarilo, alqueniloxi, alquiniloxi, cicloalquiloxi, heterocicloalquiloxi, ariloxi, heteroariloxi, arilalquiloxi, fenoxi, benciloxi, amino, alquilamino, aminoalquilo, acilamino, arilamino, sulfonilamino, sulfinilamino, -COOH, - COR5, -COOR5, -CONHR5, -NHCOR5, -NHCOOR5, -NHCONHR5, C(=NOH)R5, - alquilNCOR5, alcoxicarbonilo, alquilaminocarbonilo, sulfonilo, alquilsulfonilo, alquilsulfinilo, arilsulfonilo, arilsulfinilo, aminosulfonilo, SR6 y acilo, cada uno de los cuales puede estar opcionalmente substituido; o R2 = L; R3 está seleccionado del grupo que consiste en H, alquilo, alquenilo, alquinilo, haloalquilo, heteroalquilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo y acilo cada uno de los cuales puede estar opcionalmente substituido; R4 está seleccionado del grupo que consiste en H, alquilo, alquenilo, alquinilo, haloalquilo, heteroalquilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo y acilo cada uno de los cuales puede estar opcionalmente substituido; cada Y está seleccionado de modo independiente del grupo que consiste en H, halogeno, -CN, -NO2, -CF3, -OCF3, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, haloalquinilo, heteroalquilo, cicloalquilo, cicloalquenilo, heterocicloalquilo, heterocicloalquenilo, arilo, heteroarilo, hidroxi, hidroxialquilo, alcoxi, alcoxialquilo, alcoxiarilo, alcoxiheteroarilo, alqueniloxi, alquiniloxi, cicloalquiloxi, cicloalqueniloxi, heterocicloalquiloxi, heterocicloalqueniloxi, ariloxi, heteroariloxi, arilalquilo, heteroarilalquilo, arilalquiloxi, amino, alquilamino, acilamino, aminoalquilo, arilamino, sulfonilo, alquilsulfonilo, arilsulfonilo, aminosulfonilo, aminoalquilo, alcoxialquilo, -COOH -C(O)OR6, -COR6, -SH, - SR7, -OR7, acilo y -NR8R9 cada uno de los cuales puede estar opcionalmente substituido; cada R5 está seleccionado de modo independiente del grupo que consiste en H, alquilo, alquenilo, alquinilo, haloalquilo, heteroalquilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo y acilo cada uno de los cuales puede estar opcionalmente substituido; cada R6 está seleccionado de modo independiente del grupo que consiste en H, alquilo, alquenilo, alquinilo, haloalquilo, heteroalquilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo y acilo cada uno de los cuales puede estar opcionalmente substituido; cada R7 está seleccionado de modo independiente del grupo que consiste en H, alquilo, alquenilo, alquinilo, haloalquilo, heteroalquilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo y acilo cada uno de los cuales puede estar opcionalmente substituido; cada R8 y R9 está seleccionado de modo independiente del grupo que consiste en H, alquilo, alquenilo, alquinilo, haloalquilo, heteroalquilo, cicloalquilo, heterocicloalquilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo y acilo cada uno de los cuales puede estar opcionalmente substituido; p es un entero seleccionado del grupo que consiste en 0, 1, 2 y 3; L está seleccionado del grupo que consiste en a) Cy-L1-W-; b) Cy-L1-W-L2-; c) Cy-(CH2)k-W-; d) L1-W-L2-; e) Cy-L1-; f) R12-W1-L1-W-; y g) -(CR20R21)m-(CR22R23)n-(CR24R25)o-NR26R27; en donde Cy está seleccionado del grupo que consiste en alquilo C1-15, aminoalquilo, heteroalquilo, heterocicloalquilo, cicloalquilo, arilo, ariloxi y heteroarilo, cada uno de los cuales puede estar opcionalmente substituido; L1 está seleccionado del grupo que consiste en un enlace, alquilo C1-5 y alquenilo C2-5, cada uno de los cuales puede estar opcionalmente substituido; L2 está seleccionado del grupo que consiste en alquilo C1-5 y alquenilo C2-5, cada uno de los cuales puede estar opcionalmente substituido; k es 0, 1, 2, 3, 4 o 5; W está seleccionado del grupo que consiste en un enlace, - O-, -S-, -S(O)-, -S(O)2-, -N(R10)-, -C(O)N(R10)-, -SO2N(R10)-, -N(R10)C(O)-, -N(R10)SO2-, -N(R10)C(O)N(R11)-, -C(O)N(R10)C(O)N(R11)- y -N(R10)C(O)N(R11)C(O)-; W1 está seleccionado del grupo que consiste en un enlace, -O-, -S-, -S(O)-, -S(O)2-, - N(R10)-, -C(O)N(R10)-, -SO2N(R10)-, -N(R10)C(O)-, -N(R10)SO2-, -N(R10)C(O)N(R11)-, -C(O)N(R10)C(O)N(R11)- y -N(R10)C(O)N(R11)C(O)-; cada R20, R21, R22, R23, R24 y R25 está seleccionado de modo independiente del grupo que consiste en H, halogeno, - CN, -NO2, -CF3, -OCF3, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, haloalquinilo, heteroalquilo, cicloalquilo, cicloalquenilo, heterocicloalquilo, heterocicloalquenilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo, arilalquenilo, cicloalquilheteroalquilo, heterocicloalquilheteroalquilo, heteroarilheteroalquilo, arilheteroalquilo, hidroxi, hidroxialquilo, alcoxi, alcoxialquilo, alcoxiarilo, alcoxiheteroarilo, alqueniloxi, alquiniloxi, cicloalquiloxi, heterocicloalquiloxi, ariloxi, arilalquiloxi, fenoxi, benciloxi heteroariloxi, amino, alquilamino, acilamino, aminoalquilo, arilamino, alcoxicarbonilo, alquilaminocarbonilo, sulfonilo, alquilsulfonilo, aminosulfonilo, arilsulfonilo, arilsulfinilo -COOH, -C(O)OR5, - COR5, -SH, -SR6, -OR6 y acilo, cada uno de los cuales puede estar opcionalmente substituido; o R20 y R21 cuando se toman juntos pueden formar un grupo de la formula =O o =S, y/o R22 y R23 cuando se toman juntos pueden formar un grupo de la formula =O o =S, y/o R24 y R25 cuando se toman juntos pueden formar un grupo de la formula =O o =S; cada R26 y R27 está seleccionado de modo independiente del grupo que consiste en H, halogeno, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, heteroalquilo, cicloalquilo, cicloalquenilo, heterocicloalquilo, heterocicloalquenilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo, arilalquenilo, cicloalquilheteroalquilo, heterocicloalquilheteroalquilo, heteroarilheteroalquilo, arilheteroalquilo, hidroxi, hidroxialquilo, alcoxi, alcoxialquilo, alcoxiarilo, alqueniloxi, alquiniloxi, cicloalquiloxi, heterocicloalquiloxi, ariloxi, arilalquiloxi, heteroariloxi, amino, alquilamino, aminoalquilo, acilamino, arilamino, fenoxi, benciloxi, COOH, alcoxicarbonilo, alquilaminocarbonilo, sulfonilo, alquilsulfonilo, alquilsulfinilo, arilsulfonilo, arilsulfinilo, aminosulfonilo, SR5, acilo y G, cada uno de los cuales puede estar opcionalmente substituido o R26 y R27 cuando se toman junto con el átomo de nitrogeno al que están unidos, forman un grupo heterocicloalquilo o heteroarilo, cada uno de los cuales puede estar opcionalmente substituido; m, n y o son cada uno enteros que están seleccionados de modo independiente del grupo que consiste en 0, 1, 2, 3 y 4; G es un grupo de formula -L3W3, en donde L3 está seleccionado del grupo que consiste en alquilo C1-5 y alquenilo C2-5, cada uno de los cuales puede estar opcionalmente substituido; W3 está seleccionado del grupo que consiste en un enlace, -OR12, -SR12, -S(O)R12, -S(O)2R12, -N(R12)2, -C(O)N(R12)2, -SO2N(R12)2, -NR12C(O)-, -NR12SO2R12, - NR12C(O)N(R12)2, -C(O)NR12C(O)N(R12) y -N(R12)C(O)N(R12)C(O)R12; R10 y R11 son iguales o diferentes y están está seleccionados de modo independiente de H, alquilo C1-6, alquenilo C1-6, heteroalquilo C1-10, cicloalquilo C4-9, heterocicloalquilo C4-9, arilo, heteroarilo, arilalquilo, y heteroarilalquilo y acilo cada uno de los cuales puede estar opcionalmente substituido; R12 está seleccionado del grupo que consiste en H, halogeno, -CN, -NO2, -CF3, -OCF3, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, heteroalquilo, cicloalquilo, cicloalquenilo, heterocicloalquilo, heterocicloalquenilo, arilo, heteroarilo, cicloalquilalquilo, heterocicloalquilalquilo, arilalquilo, heteroarilalquilo, arilalque
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| WO2008068392A1 (fr) * | 2006-12-07 | 2008-06-12 | Commissariat A L'energie Atomique | Nouveaux derives fluorophores imidazo [1,2-a] pyridin-3-yl-amine et leur procede de preparation |
| CN101772498A (zh) | 2007-04-10 | 2010-07-07 | H.隆德贝克有限公司 | 作为p2x7拮抗剂的杂芳基酰胺类似物 |
| WO2008134553A1 (en) * | 2007-04-26 | 2008-11-06 | Xenon Pharmaceuticals Inc. | Methods of using bicyclic compounds in treating sodium channel-mediated diseases |
| CN101855222A (zh) * | 2007-05-10 | 2010-10-06 | 通用电气健康护理有限公司 | 对大麻素cb2受体具有活性的咪唑并(1,2-a)吡啶和相关化合物 |
| US8481572B2 (en) | 2007-08-09 | 2013-07-09 | Urifer Ltd. | Pharmaceutical compositions and methods for the treatment of cancer |
| DE102007040336A1 (de) | 2007-08-27 | 2009-03-05 | Johann Wolfgang Goethe-Universität Frankfurt am Main | Neue Inhibitoren der 5-Lipoxygenase und deren Verwendungen |
| WO2009055917A1 (en) * | 2007-11-02 | 2009-05-07 | Methylgene Inc. | Inhibitors of histone deacetylase |
| EP2300470A2 (en) * | 2008-05-19 | 2011-03-30 | Sepracor Inc. | Imidazo[1,2-a]pyridine compounds as gaba-a receptor modulators |
| CN102216298B (zh) * | 2008-09-16 | 2014-04-16 | Csir公司 | 作为hiv-1逆转录酶抑制剂的咪唑并吡啶和咪唑并嘧啶 |
| US20110212943A1 (en) * | 2008-10-15 | 2011-09-01 | Orchid Research Laboratories Limited | Novel bridged cyclic compounds as histone deacetylase inhibitors |
| CN103140488A (zh) * | 2010-08-03 | 2013-06-05 | 加利福尼亚大学董事会 | 缓和组织损伤和坏死的化合物和组合物 |
| JP5931752B2 (ja) | 2011-02-01 | 2016-06-08 | 協和発酵キリン株式会社 | 縮環複素環誘導体 |
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| UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
| EP2881394B1 (en) | 2012-07-31 | 2018-03-21 | Kyowa Hakko Kirin Co., Ltd. | Condensed ring heterocyclic compound |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| JP2016520047A (ja) * | 2013-04-30 | 2016-07-11 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | ピラゾールアミドのPd触媒カップリング |
| JP2016527184A (ja) * | 2013-05-24 | 2016-09-08 | イオメット ファーマ リミテッド | Slc2a輸送体阻害剤 |
| KR102314290B1 (ko) * | 2013-06-25 | 2021-10-21 | 에프. 호프만-라 로슈 아게 | 척수성 근위축증을 치료하기 위한 화합물 |
| EP3062783B1 (en) | 2013-10-18 | 2020-08-12 | The General Hospital Corporation | Imaging histone deacetylases with a radiotracer using positron emission tomography |
| US10723705B2 (en) | 2015-08-14 | 2020-07-28 | Incyte Corporation | Heterocyclic compounds and uses thereof |
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| JPH11505524A (ja) * | 1995-05-01 | 1999-05-21 | 藤沢薬品工業株式会社 | イミダゾ1,2−aピリジンおよびイミダゾ1,2−aピリデジン誘導体、および骨吸収阻害剤としてのその用途 |
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| TW200501897A (en) | 2003-07-10 | 2005-01-16 | Kung-Sheng Pan | Shoes electrostatically embedded with objects |
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| US7538120B2 (en) * | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
| WO2005085214A1 (ja) * | 2004-03-05 | 2005-09-15 | Banyu Pharmaceutical Co., Ltd | ジアリール置換複素5員環誘導体 |
| BRPI0508696A (pt) * | 2004-03-17 | 2007-09-11 | Altana Pharma Ag | imidazopiridinas tricìclicas |
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| JP2008533198A (ja) | 2008-08-21 |
| CA2602328C (en) | 2014-07-29 |
| EP1863811B1 (en) | 2014-03-12 |
| TW200714600A (en) | 2007-04-16 |
| KR20080005207A (ko) | 2008-01-10 |
| WO2006101455A1 (en) | 2006-09-28 |
| MX2007011710A (es) | 2007-11-20 |
| CA2602328A1 (en) | 2006-09-28 |
| MY147647A (en) | 2012-12-31 |
| EP1863811A1 (en) | 2007-12-12 |
| ES2470766T3 (es) | 2014-06-24 |
| AU2006225355A1 (en) | 2006-09-28 |
| KR101300831B1 (ko) | 2013-08-30 |
| EP1863811A4 (en) | 2008-11-12 |
| CN101218238B (zh) | 2011-10-26 |
| JP5206405B2 (ja) | 2013-06-12 |
| CN101218238A (zh) | 2008-07-09 |
| AU2006225355B2 (en) | 2010-12-09 |
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