7-chloro-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine | 262298-05-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-chloro-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine
• 英文别名: 7-chloro-3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine；Pyrazolo[1,5-a]pyrimidine, 7-chloro-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-
• CAS: 262298-05-5
• 化学式: C₁₆H₁₆ClN₃O
• 分子量: 301.776
• InChiKey: OBTBEIDAFQQNNW-UHFFFAOYSA-N

物化性质

• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  DL-氨基丙醇 、 7-chloro-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 2-[[3-(4-methoxy-2-methylphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl]amino]propan-1-ol
  参考文献：
  名称：

  Discovery of NBI-77860/GSK561679, a potent corticotropin-releasing factor (CRF1) receptor antagonist with improved pharmacokinetic properties

  摘要：

  Antagonists of the corticotropin-releasing factor (CRF) neuropeptide may prove effective in treating stress and anxiety related disorders. In an effort to identify antagonists with improved physico-chemical properties a new series of CRF1 antagonists were designed to substitute the propyl groups at the C7 position of the pyrazolo[1,5-a]pyrimidine core of 1 with heterocycles. Compound (S)-8d was identified as a high affinity ligand with a pK(i) value of 8.2 and a functional CRF1 antagonist with pIC(50) value of 7.0 in the in vitro CRF ACTH production assay. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.095
• 作为产物：
  描述：

  1-cyano-1-(2-methyl-4-methoxyphenyl)propan-2-one 在 一水合肼 、 溶剂黄146 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 反应 24.0h， 生成 7-chloro-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5- a ]-pyrimidine: A corticotropin-releasing factor (hCRF 1 ) antagonist

  摘要：

  Structure-activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF(1) antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF(1) K-i= 1.0 +/- 0.2 nM (n = 8)) was a potent antagonist of hCRF(1)-coupled adenylate cyclase activity in HEK293 cells (IC50 = 10.0 +/- 0.01 nM versus 10 nM r/hCRF, I? = 8); alpha-helical CRF(9-41) had weaker potency (IC50 = 286 +/- 63 nM, n = 3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency lime in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1. 30 mg/kg (po)) was inactive in this lest. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t(1/2), CL and V-d.ss values equal to 46.4 +/- 7.6 h, 0.49 +/- 0.08 L/kg/h and 23.0 +/- 4.2 L/kg, respectively. After oral dosing. the mean C-max, T-max, t(1/2) and bioavailability values were equal to 1260 +/- 290 nM, 0.75 +/- 0.25 h, 45.1 +/- 10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect Liability. (C) 2000 DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00271-0

文献信息

• Pyrazolo[1,5-alpha]pyrimidinyl derivatives useful as corticotropin-releasing factor (CRF) receptor antagonists
  申请人：SmithKline Beecham (Cork) Limited

  公开号：US07879862B2

  公开（公告）日：2011-02-01

  CRF receptor antagonists are disclosed which may have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in mammals. The CRF receptor antagonists of this invention have the following structure: (I); and pharmaceutically acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein R1, R2a, R2b, Y, Het, n, o, R6, Ar and R7 are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明公开了CRF受体拮抗剂，可用于治疗多种疾病，包括治疗哺乳动物CRF分泌过多所表现出的疾病。本发明的CRF受体拮抗剂具有以下结构：（I）；以及其药学上可接受的盐、酯、溶剂合物、立体异构体和前药，其中R1、R2a、R2b、Y、Het、n、o、R6、Ar和R7如本文所定义。本发明还公开了含有CRF受体拮抗剂和药学上可接受的载体组合的组合物，以及使用它们的方法。
• Pyrazolo[1,5-Alpha]Pyrimidinyl Derivatives Useful as Corticotropin-Releasing Factor (Crf) Receptor Antagonists
  申请人：Lanier Marion

  公开号：US20080194589A1

  公开（公告）日：2008-08-14

  CRF receptor antagonists are disclosed which may have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in mammals. The CRF receptor antagonists of this invention have the following structure: (I); and pharmaceutically acceptable salts, esters, solvates, stereoisomers and prodrugs thereof, wherein R 1 , R 2a , R 2b , Y, Het, n, o, R 6 , Ar and R 7 are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明揭示了CRF受体拮抗剂，可能在治疗多种疾病方面有用，包括治疗哺乳动物CRF过度分泌引起的疾病。本发明的CRF受体拮抗剂具有以下结构：（I）；以及其药物学上可接受的盐，酯，溶剂合物，立体异构体和前药，其中R1，R2a，R2b，Y，Het，n，o，R6，Ar和R7如本文所定义。还揭示了含有CRF受体拮抗剂与药学可接受载体组合的组合物，以及使用它们的方法。
• WO2006/44958
  申请人：——

  公开号：——

  公开（公告）日：——
• Bioorg. Med. Chem. Lett. 2010, 20, 7259-7264
  作者：

  DOI：——

  日期：——
• PYRAZOLO (1,5-ALPHA) PYRIMIDINYL DERIVATIVES USEFUL AS CORTICOTROPIN-RELEASING FACTOR (CRF) RECEPTOR ANTAGONISTS
  申请人：SB Pharmco Puerto Rico Inc.

  公开号：EP1802627A1

  公开（公告）日：2007-07-04