6-cyclopropyloxy-3-pyridinylboronic acid | 1318780-09-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-cyclopropyloxy-3-pyridinylboronic acid
• 英文别名: 6-cyclopropoxypyridin-3-ylboronic acid；(6-Cyclopropoxypyridin-3-yl)boronic acid；(6-cyclopropyloxypyridin-3-yl)boronic acid
• CAS: 1318780-09-4
• 化学式: C₈H₁₀BNO₃
• 分子量: 178.983
• InChiKey: XQEIFCXTDWOGTB-UHFFFAOYSA-N

物化性质

• 沸点：
  358.3±52.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  62.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-cyclopropyloxy-3-pyridinylboronic acid 、 N2-(4-(1H-1,2,4-triazol-1-yl)benzyl)-6-chloro-N4-(2,2,2-trifluoroethyl)pyrido[3,2-d]pyrimidine-2,4-diamine 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.83h， 以0.202 g的产率得到N2-(4-(1H-1,2,4-triazol-1-yl)benzyl)-6-(6-cyclopropoxypyridin-3-yl)-N4-(2,2,2-trifluoroethyl)pyrido[3,2-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Optimization of Pharmacokinetics through Manipulation of Physicochemical Properties in a Series of HCV Inhibitors

  摘要：

  A novel series of HCV replication inhibitors based on a pyrido[3,2-d]primidine core were optimized for pharmacokinetics (PK) in rats. Several associations between physicochemical properties and PK were identified and exploited to guide the design of compounds. In addition, a simple new metric that may aid in the prediction of bioavailability for compounds with higher polar surface area is described (3*HBD-cLogP).

  DOI：

  10.1021/ml200163b
• 作为产物：
  描述：

  5-溴-2-环丙氧基吡啶 在 正丁基锂 、 硼酸三异丙酯 、 水 、 sodium hydroxide 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 1.08h， 生成 6-cyclopropyloxy-3-pyridinylboronic acid
  参考文献：
  名称：

  Optimization of Pharmacokinetics through Manipulation of Physicochemical Properties in a Series of HCV Inhibitors

  摘要：

  A novel series of HCV replication inhibitors based on a pyrido[3,2-d]primidine core were optimized for pharmacokinetics (PK) in rats. Several associations between physicochemical properties and PK were identified and exploited to guide the design of compounds. In addition, a simple new metric that may aid in the prediction of bioavailability for compounds with higher polar surface area is described (3*HBD-cLogP).

  DOI：

  10.1021/ml200163b

文献信息

• PYRROLOPYRIMIDINES AS CFTR POTENTIATORS
  申请人：CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.

  公开号：US20180141954A1

  公开（公告）日：2018-05-24

  The present invention relates to compounds of Formula I, wherein R 1a , R 1b , R 2 , R 3 , R 4 , W, Y, and Z are as described herein, and pharmaceutically acceptable salts thereof. The compounds are potentiators of Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The invention also discloses pharmaceutical compositions comprising the compound, optionally in combination with additional therapeutic agents, and methods of potentiating, in mammals, including humans, CFTR by administration of the compounds. These compounds are useful for the treatment of cystic fibrosis (CF), asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), constipation, Diabetes mellitus, dry eye disease, pancreatitis, rhinosinusitis, Sjögren's Syndrome, and other CFTR associated disorders.

  本发明涉及式I的化合物，其中R1a、R1b、R2、R3、R4、W、Y和Z如本文所述，并且其药学上可接受的盐。这些化合物是囊性纤维化跨膜传导调节器（CFTR）的增效剂。本发明还揭示了包括该化合物的药物组合物，可选地与额外治疗剂结合，并通过给予这些化合物来增强哺乳动物（包括人类）CFTR的方法。这些化合物可用于治疗囊性纤维化（CF）、哮喘、支气管扩张、慢性阻塞性肺病（COPD）、便秘、糖尿病、干眼症、胰腺炎、鼻窦炎、Sjögren综合征和其他与CFTR相关的疾病。