4-(2-chloro-4-methoxyphenyl)-5-methyl-2H-pyrazol-3-ylamine | 817636-89-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(2-chloro-4-methoxyphenyl)-5-methyl-2H-pyrazol-3-ylamine
• 英文别名: 5-amino-3-methyl-4-(2-chloro-4-methoxyphenyl)pyrazole；4-(2-Chloro-4-methoxyphenyl)-5-methyl-1H-pyrazol-3-amine
• CAS: 817636-89-8
• 化学式: C₁₁H₁₂ClN₃O
• 分子量: 237.689
• InChiKey: UHMWJVNPZKRUJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  63.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-chloro-4-methoxyphenyl)-5-methyl-2H-pyrazol-3-ylamine 在 溶剂黄146 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 12.0h， 生成 (1-ethyl-propyl)-[3-(4-methoxy-2-chlorophenyl)-2-methyl-6,7-dihydro-5H-1,4,8a-triaza-s-indacen-8-yl]-amine
  参考文献：
  名称：

  6,7-Dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidines and their derivatives as novel corticotropin-releasing factor 1 receptor antagonists

  摘要：

  To identify an orally active corticotropin-releasing factor 1 receptor antagonist, a series of 6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidines and their derivatives were designed, synthesized and evaluated. An in vitro study followed by in vivo and pharmacokinetic studies of these heterotricyclic compounds led us to the discovery of an orally active CRF1 receptor antagonist. The results of a structure-activity relationship study are presented. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.055
• 作为产物：
  描述：

  4-溴-3-氯苯甲醚 在 palladium diacetate 、 三苯基膦 溶剂黄146 、 肼 作用下， 以 二乙二醇二甲醚 、 水 、 甲苯 为溶剂， 反应 14.5h， 生成 4-(2-chloro-4-methoxyphenyl)-5-methyl-2H-pyrazol-3-ylamine
  参考文献：
  名称：

  METHANESULFONIC ACID SALT OF PYRAZOLOPYRIMIDINE COMPOUND, CRYSTAL THEREOF, AND PROCESS FOR PRODUCING THE SAME

  摘要：

  公开号：

  EP1637531B1

文献信息

• [EN] CYCLOHEXYL AMIDE DERIVATIVES AS CRF RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE CYCLOHEXYLAMIDE À TITRE D'ANTAGONISTES DU RÉCEPTEUR CRF
  申请人：NOVARTIS AG

  公开号：WO2011095450A1

  公开（公告）日：2011-08-11

  There are described cyclohexyl amide derivatives useful as corticotropin releasing factor (CRF) receptor antagonists Formula (I).

  描述了作为促肾上腺皮质激素释放因子（CRF）受体拮抗剂有用的环己基酰胺衍生物的化学式（I）。
• Cyclohexyl Amide Derivatives as CRF Receptor Antagonists
  申请人：Beattie David

  公开号：US20120316185A1

  公开（公告）日：2012-12-13

  There are described cyclohexyl amide derivatives useful as corticotropin releasing factor (CRF) receptor antagonists Formula (I).

  以下是描述的环己基酰胺衍生物，可用作促肾上腺皮质激素释放因子（CRF）受体拮抗剂的公式（I）。
• 8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d] pyrazolo[1,5-a]pyrimidine methanesulfonate as a CRF antagonist
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US07947697B1

  公开（公告）日：2011-05-24

  8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazolo[1,5-a]pyrimidine methanesulfonate of the structural formula (I) has Corticotropin Releasing Factor (CRF) antagonist activity and is useful in treating neuropsychiatric and digestive system diseases.

  8-(3-戊基氨基)-2-甲基-3-(2-氯-4-甲氧基苯基)-6,7-二氢-5H-环戊[d]嘧啶-1,5-a-吡咯烷甲磺酸盐的结构式（I），具有促肾上腺皮质激素释放因子（CRF）拮抗剂活性，并可用于治疗神经精神和消化系统疾病。
• Cyclohexyl amide derivatives as CRF receptor antagonists
  申请人：Beattie David

  公开号：US08835444B2

  公开（公告）日：2014-09-16

  There are described cyclohexyl amide derivatives useful as corticotropin releasing factor (CRF) receptor antagonists Formula (I).

  以下是描述环己基酰胺衍生物的公式（I），其可用作促肾上腺皮质激素释放因子（CRF）受体拮抗剂。
• 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
  作者：Paul J. Gilligan、Caryn Baldauf、Anthony Cocuzza、Dennis Chidester、Robert Zaczek、Lawrence W. Fitzgerald、John McElroy、Mark A. Smith、H.-S.L. Shen、Jo Anne Saye、David Christ、George Trainor、David W. Robertson、Paul Hartig

  DOI：10.1016/s0968-0896(99)00271-0

  日期：2000.1

  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.