4-cyclopropyl-1H-pyrrolo[2,3-b]pyridine | 1309430-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4-cyclopropyl-1H-pyrrolo[2,3-b]pyridine
• CAS: 1309430-82-7
• 化学式: C₁₀H₁₀N₂
• 分子量: 158.203
• InChiKey: ZVVPBIPURXFPLM-UHFFFAOYSA-N

物化性质

• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-cyclopropyl-1H-pyrrolo[2,3-b]pyridine 在 aluminum (III) chloride 、 三乙胺 、 二异丙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.75h， 生成 3-(4-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-oxopropyl (pyridin-3-ylmethyl) carbamodithioate
  参考文献：
  名称：

  Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors

  摘要：

  Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.003
• 作为产物：
  描述：

  4-溴-1-对甲苯磺酰-7-氮杂吲哚 在 palladium diacetate 、 caesium carbonate 、 sodium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 24.0h， 生成 4-cyclopropyl-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors

  摘要：

  Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.03.003

文献信息

• Compounds and Methods for Kinase Modulation, and Indications Therefor
  申请人：Ibrahim Prabha N.

  公开号：US20110152258A1

  公开（公告）日：2011-06-23

  Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

  本文描述了化合物及其盐、制剂、共轭物、衍生物、形式和用途。在某些方面和实施例中，所述的化合物或其盐、制剂、共轭物、衍生物、形式对至少一种Raf蛋白激酶具有活性。在某些方面和实施例中，所述的化合物对抑制Ras突变细胞系的增殖具有活性。还描述了使用这些化合物的方法来治疗与B-Raf V600E突变蛋白激酶活性相关的疾病和病症，包括黑色素瘤、胶质瘤、多形性胶质母细胞瘤、毛细胞星形胶质瘤、结肠直肠癌、甲状腺癌、肺癌、卵巢癌、前列腺癌、肝癌、胆囊癌、胃肠间质瘤、胆道癌和胆管癌。还描述了使用这些化合物的方法来治疗与c-Raf-1蛋白激酶活性相关的疾病和病症，包括急性疼痛、慢性疼痛或多囊肾病。
• COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
  申请人：Plexxikon Inc.

  公开号：US20140288070A1

  公开（公告）日：2014-09-25

  Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

  本文描述了化合物及其盐、制剂、共轭物、衍生物、形式和用途。在某些方面和实施例中，所述的化合物或其盐、制剂、共轭物、衍生物、形式至少对一种Raf蛋白激酶具有活性。在某些方面和实施例中，所述的化合物具有抑制Ras突变细胞系增殖的活性。还描述了使用它们治疗疾病和病症的方法，包括与B-Raf V600E突变蛋白激酶活性相关的疾病和病症，包括黑色素瘤、胶质瘤、多形性胶质母细胞瘤、毛细胞星形细胞瘤、结直肠癌、甲状腺癌、肺癌、卵巢癌、前列腺癌、肝癌、胆囊癌、胃肠道间质瘤、胆道癌和胆管癌。还描述了使用它们治疗与c-Raf-1蛋白激酶活性相关的疾病和病症的方法，包括急性疼痛、慢性疼痛或多囊肾病。
• N-[2-fluoro-3-(4-amino-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-phenyl]-4-benzenesulfonamide derivatives as Raf protein kinase modulators for the treatment of cancer
  申请人：Plexxikon Inc.

  公开号：EP2501236B1

  公开（公告）日：2017-03-29
• US8673928B2
  申请人：——

  公开号：US8673928B2

  公开（公告）日：2014-03-18
• US9617267B2
  申请人：——

  公开号：US9617267B2

  公开（公告）日：2017-04-11