N-(3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)-1-phenyl-1H-pyrazole-5-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)-1-phenyl-1H-pyrazole-5-carboxamide
• 英文别名: N-[3-[(2-oxo-1,3-dihydroimidazo[4,5-b]pyridin-7-yl)oxy]phenyl]-2-phenylpyrazole-3-carboxamide
• 化学式: C₂₂H₁₆N₆O₃
• 分子量: 412.407
• InChiKey: BEIFGXUDOCVFHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-苯基-1H-吡唑-5-羰酰氯 、 7-(3-aminophenoxy)-1H-imidazo[4,5-b]pyridin-2(3H)-one 以to afford the title compound (15 mg, 17%)的产率得到N-(3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl)-1-phenyl-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  Imidazo[4, 5-B]pyridin-2-one and oxazolo[4, 5-B] pyridin-2-one compounds and analogs thereof as cancer therapeutic compounds

  摘要：

  本发明涉及某些咪唑并[4,5-b]吡啶-2-酮和噁唑并[4,5-b]吡啶-2-酮化合物及其类似物，其中包括抑制RAF（例如B-RAF）活性，抑制细胞增殖，治疗癌症等。本发明还涉及包含这种化合物的制药组合物，以及在体外和体内使用这种化合物和组合物来抑制RAF（例如B-RAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖以及治疗疾病和状况，这些疾病和状况通过抑制RAF、RTK等而得到改善，包括增生性疾病如癌症（例如结直肠癌、黑色素瘤）等。

  公开号：

  US07951819B2

文献信息

• IMIDAZO[4, 5-B]PYRIDIN-2-ONE AND OXAZOLO[4, 5-B]PYRIDIN-2-ONE COMPOUNDS AND ANALOGS THEREOF AS CANCER THERAPEUTIC COMPOUNDS
  申请人：Niculescu-Duvaz Dan

  公开号：US20090325945A1

  公开（公告）日：2009-12-31

  The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: wherein: J is independently —O— or —NR N1− ; R N1 , if present, is independently —H or a substituent; R N2 is independently —H or a substituent; Y is independently —CH═ or —N═; Q is independently —(CH 2 ) j -M-(CH 2 ) k — wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently O—, —S—, —NH—, —NMe-, or —CH 2 —; each of R P1 , R P2 , R P5 , and R P4 is independently —H or a substituent; and additionally R P1 and R P2 taken together may be CH═CH—CH═CH—; and additionally R P1 and R P5 taken together may be CH═CH—CH═CH—; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently CH 2 —, —NR N —, —C(═X)—, or —S(═O) 2 —; either: exactly one linker moiety is —NR N —, or: exactly two linker moieties are —NR N —; either: exactly one linker moiety is —C(═X)—, and no linker moiety is —S(═O) 2 —, or: exactly one linker moiety is —S(═O) 2 —, and no linker moiety is —C(═X)—; no two adjacent linker moieties are —NR N —; X is independently ═O or ═S; each R N is independently —H or a substituent; A is independently: C 6-14 carboaryl, C 5-14 heteroaryl, C 3-12 carbocyclic, C 3-12 heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

  本发明涉及特定的咪唑并[4,5-b]吡啶-2-酮和噁唑并[4,5-b]吡啶-2-酮化合物及其类似物，其中，它们可以抑制RAF（例如B-RAF）活性，抑制细胞增殖，治疗癌症等。特别是本发明涉及以下式的化合物：其中：J独立地为—O—或—NRN1−；RN1（如果存在）独立地为—H或取代基；RN2独立地为—H或取代基；Y独立地为—CH═或—N═；Q独立地为—（CH2）j-M-（CH2）k—，其中：j独立地为0、1或2；k独立地为0、1或2；j+k为0、1或2；M独立地为O—、—S—、—NH—、—NMe-或—CH2—；RP1、RP2、RP5和RP4中的每一个独立地为—H或取代基；并且另外RP1和RP2一起可以是CH═CH—CH═CH—；并且另外RP1和RP5一起可以是CH═CH—CH═CH—；L独立地为：由2、3或4个连接基成的连接基团；每个连接基单元独立地为CH2—、—NRN—、—C（═X）—或—S（═O）2—；要么：恰好有一个连接基单元为—NRN—，或：恰好有两个连接基单元为—NRN—；要么：恰好有一个连接基单元为—C（═X）—，且没有连接基单元为—S（═O）2—，或：恰好有一个连接基单元为—S（═O）2—，且没有连接基单元为—C（═X）—；没有两个相邻的连接基单元为—NRN—；X独立地为═O或═S；每个RN独立地为—H或取代基；A独立地为：C6-14碳基芳基、C5-14杂环芳基、C3-12环烷基、C3-12杂环烷基；并且独立地未取代或取代；以及其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、N-氧化物、化学保护形式和前药。本发明还涉及包含这样的化合物的药物组合物，以及这样的化合物和组合物的使用，无论是在体外还是在体内，来抑制RAF（例如B-RAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并治疗通过抑制RAF、RTK等而改善的疾病和情况，如癌症（例如结肠癌、黑色素瘤）等。
• Imidazo[4, 5-B]pyridin-2-one and oxazolo[4, 5-B] pyridin-2-one compounds and analogs thereof as cancer therapeutic compounds
  申请人：Cancer Research Technology Limited

  公开号：US07951819B2

  公开（公告）日：2011-05-31

  The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

  本发明涉及某些咪唑并[4,5-b]吡啶-2-酮和噁唑并[4,5-b]吡啶-2-酮化合物及其类似物，其中包括抑制RAF（例如B-RAF）活性，抑制细胞增殖，治疗癌症等。本发明还涉及包含这种化合物的制药组合物，以及在体外和体内使用这种化合物和组合物来抑制RAF（例如B-RAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖以及治疗疾病和状况，这些疾病和状况通过抑制RAF、RTK等而得到改善，包括增生性疾病如癌症（例如结直肠癌、黑色素瘤）等。
• IMIDAZO[4,5-B]PYRIDIN-2-ONE COMPOUNDS AND ANALOGS THEREOF AS CANCER THERAPEUTIC COMPOUNDS
  申请人：Cancer Research Technology Limited

  公开号：EP2013207B1

  公开（公告）日：2012-04-25
• US7951819B2
  申请人：——

  公开号：US7951819B2

  公开（公告）日：2011-05-31
• [EN] IMIDAZO[4, 5-B]PYRIDIN-2-ONE AND OXAZOLO[4, 5-B]PYRIDIN-2-ONE COMPOUNDS AND ANALOGS THEREOF AS CANCER THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS D'IMIDAZO[4,5-B]PYRIDIN-2-ONE ET D'OXAZOLO[4,5- B]PYRIDIN-2-ONE ET LEURS ANALOGUES EN TANT QUE COMPOSÉS DE TRAITEMENT DU CANCER
  申请人：CANCER REC TECH LTD

  公开号：WO2007125330A1

  公开（公告）日：2007-11-08

  [EN] The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: wherein: J is independently -O- or -NR^{N1 -};
  [FR] La présente invention concerne certains composés d'imidazo[4,5-b]pyridin-2-one et d'oxazolo[4,5 b]pyridin-2-one et leurs analogues qui, entre autres actions, inhibent l'activité RAF (par exemple B RAF), inhibent la prolifération cellulaire, traitent le cancer, etc. L'invention concerne plus particulièrement des composés répondant à la formule (I) dans laquelle : J est indépendamment -O- ou -NR^{N1 -};