7-Chloro-3-(4-chlorophenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine | 897769-21-0

• 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-3-(4-chlorophenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine
• CAS: 897769-21-0
• 化学式: C₁₄H₁₁Cl₂N₃
• mdl: MFCD09983104
• 分子量: 292.167
• InChiKey: AWBIGBCHZDKWET-UHFFFAOYSA-N

物化性质

• 溶解度：
  1.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  双(2-甲氧基乙基)胺 、 7-Chloro-3-(4-chlorophenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine 生成
  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
• 作为产物：
  描述：

  对氯苯乙腈 在 盐酸肼 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 生成 7-Chloro-3-(4-chlorophenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Optimization of 3-phenylpyrazolo[1,5- a ]pyrimidines as potent corticotropin-releasing factor-1 antagonists with adequate lipophilicity and water solubility

  摘要：

  In our efforts to identify potent CRF1 antagonists with proper physicochemical properties, a series of 3-phenylpyrazolo[1,5-a]pyrimidines bearing polar groups, such as amino, hydroxyl, methoxy, sulfoxide, were designed and synthesized. Several positions of the core structure were identified, where a polar group was tolerated with slight reduction in receptor binding. NBI 30545 (18n) was found to have good binding affinity and potent antagonistic activity at the human CRF1 receptor. Moreover, this compound had proper lipophilicity (log D = 2.78) and good solubility in water (>10 mg/mL), and exhibited good plasma and brain exposure when given orally. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.019