N-(3-(6-bromo-1H-imidazo[4,5-b]pyridin-2-yl)-4-fluorophenyl)pyrrolidine-1-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(3-(6-bromo-1H-imidazo[4,5-b]pyridin-2-yl)-4-fluorophenyl)pyrrolidine-1-carboxamide
• 英文别名: N-[3-(6-bromo-1H-imidazo[4,5-b]pyridin-2-yl)-4-fluorophenyl]pyrrolidine-1-carboxamide
• 化学式: C₁₇H₁₅BrFN₅O
• 分子量: 404.241
• InChiKey: BVXKYFIDCVYFNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  73.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基苯硼酸 、 N-(3-(6-bromo-1H-imidazo[4,5-b]pyridin-2-yl)-4-fluorophenyl)pyrrolidine-1-carboxamide 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 0.08h， 以41%的产率得到N-(3-(6-(3-aminophenyl)-3H-imidazo[4,5-b]pyridin-2-yl)-4-fluorophenyl)pyrrolidine-1-carboxamide
  参考文献：
  名称：

  Substituted 2-Phenylimidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis

  摘要：

  A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosorna brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.

  DOI：

  10.1021/jm401178t
• 作为产物：
  描述：

  1-吡咯烷羰酰氯 、 3-[6-bromo-1H-imidazo[4,5-b]pyridin-2-yl]-4-fluoroaniline 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 以56%的产率得到N-(3-(6-bromo-1H-imidazo[4,5-b]pyridin-2-yl)-4-fluorophenyl)pyrrolidine-1-carboxamide
  参考文献：
  名称：

  Substituted 2-Phenylimidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis

  摘要：

  A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosorna brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.

  DOI：

  10.1021/jm401178t

文献信息

• US20140275013A1
  申请人：——

  公开号：US20140275013A1

  公开（公告）日：2014-09-18
• US9233961B2
  申请人：——

  公开号：US9233961B2

  公开（公告）日：2016-01-12
• [EN] COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES<br/>[FR] COMPOSÉS ET COMPOSITIONS POUR LE TRAITEMENT DE MALADIES PARASITAIRES
  申请人：IRM LLC

  公开号：WO2014151630A2

  公开（公告）日：2014-09-25

  The present invention is related to compounds of Formula A or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further relates to pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a parasite, such as Leishmaniasis, Human African Trypanosomiasis and Chagas disease.
• Substituted 2-Phenylimidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis
  作者：Hari Babu Tatipaka、J. Robert Gillespie、Arnab K. Chatterjee、Neil R. Norcross、Matthew A. Hulverson、Ranae M. Ranade、Pendem Nagendar、Sharon A. Creason、Joshua McQueen、Nicole A. Duster、Advait Nagle、Frantisek Supek、Valentina Molteni、Tanja Wenzler、Reto Brun、Richard Glynne、Frederick S. Buckner、Michael H. Gelb

  DOI：10.1021/jm401178t

  日期：2014.2.13

  A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosorna brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.