7-chloro-2,5-dimethyl-3-(2-chloro-4-methylphenyl)pyrazolo-[1,5-a]pyrimidine | 202579-56-4

• 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-chloro-4-methylphenyl)pyrazolo-[1,5-a]pyrimidine
• CAS: 202579-56-4
• 化学式: C₁₅H₁₃Cl₂N₃
• 分子量: 306.194
• InChiKey: XKDWVZRXFZTJCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.63
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  30.19
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  双(2-甲氧基乙基)胺 、 7-chloro-2,5-dimethyl-3-(2-chloro-4-methylphenyl)pyrazolo-[1,5-a]pyrimidine 生成 [3-(2-chloro-4-methyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-bis-(2-methoxy-ethyl)-amine
  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：

  5-amino-4-(2-chloro-4-methylphenyl)-3-methylpyrazole 在 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 溶剂黄146 、 甲苯 为溶剂， 生成 7-chloro-2,5-dimethyl-3-(2-chloro-4-methylphenyl)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

• Azolo triazines and pyrimidines
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：US06358950B1

  公开（公告）日：2002-03-19

  Corticotropin releasing factor (CRF) antagonists of formula I or II: and their use in treating anxiety, depression, and other psychiatric, neurological disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

  公告释放因子（CRF）拮抗剂I或II的公式：及其在治疗焦虑，抑郁和其他精神，神经系统疾病以及免疫，心血管或心脏相关疾病的治疗中的使用，以及与心理病理障碍和压力相关的结肠过敏性治疗。