4-(4-甲氧基-2-甲基苯基)-5-甲基-1H-吡唑-3-胺 | 262298-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(4-甲氧基-2-甲基苯基)-5-甲基-1H-吡唑-3-胺
• 英文名称: 4-(2-methyl-4-methoxyphenyl)-3-methyl-1H-pyrazol-5-amine
• 英文别名: 5-amino-4-(2-methyl-4-methoxyphenyl)-3-methylpyrazole；5-amino-3-methyl-4-(2-methyl-4-methoxyphenyl)pyrazole；4-(4-Methoxy-2-methylphenyl)-5-methyl-1H-pyrazol-3-amine
• CAS: 262298-03-3
• 化学式: C₁₂H₁₅N₃O
• 分子量: 217.271
• InChiKey: UHJQSFZJRDUCOT-UHFFFAOYSA-N

物化性质

• 沸点：
  395.1±42.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 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-(4-甲氧基-2-甲基苯基)-5-甲基-1H-吡唑-3-胺 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， 反应 19.0h， 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
• 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 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以83%的产率得到4-(4-甲氧基-2-甲基苯基)-5-甲基-1H-吡唑-3-胺
  参考文献：
  名称：

  8-(4-Methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazines: Selective and Centrally Active Corticotropin-Releasing Factor Receptor-1 (CRF₁) Antagonists

  摘要：

  This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discovery of analogue 12-3. which is a potent, selective CRF1 antagonist (hCRF(1) IC50 = 4.7 +/- 2.0 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 12-3 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 12-3 has been advanced to clinical trials.

  DOI：

  10.1021/jm9000242

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。
• Tricyclic and heterocyclic derivative compounds and drugs containing these compounds as the active ingredient
  申请人：——

  公开号：US20040072833A1

  公开（公告）日：2004-04-15

  Tri-heterocyclic compound of formula (I) 1 wherein each of W, X and Y is carbon or nitrogen; each of U and Z is CR 2 , NR 13 , nitrogen, oxygen, sulfur etc.; A ring is carbocyclic ring, heterocyclic ring; R 1 is alkyl, alkenyl, alkynyl, NR 4 R 5 , OR 6 etc.; R 3 is carbocyclic ring, heterocyclic ring; and a pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical comprising them as an active ingredient. A compound of formula (I) is useful, in order to possess corticotropin releasing factor receptor antagonistic activity, for the prevention and/or treatment of depression, anxiety, eating disorder, posttraumatic stress disorder, peptic ulcer, irritable bowl syndrome, Alzheimer's disease, drug addiction or alcohol dependence syndrome etc.

  式(I)的三异杂环化合物，其中W、X和Y中的每一个为碳或氮；U和Z中的每一个为CR2、NR13、氮、氧、硫等；环A为碳环或杂环；R1为烷基、烯基、炔基、NR4R5、OR6等；R3为碳环或杂环；以及其药学上可接受的盐，制备过程和将其作为活性成分的制药组合物。式(I)的化合物具有垂体促肾上腺皮质激素释放因子受体拮抗活性，对于预防和/或治疗抑郁症、焦虑症、进食障碍、创伤后应激障碍、消化性溃疡、肠易激综合症、阿尔茨海默病、药物成瘾或酒精依赖综合症等具有用途。
• Tri-heterocyclic compounds and a pharmaceutical comprising them as an active ingredient
  申请人：Nakai Hisao

  公开号：US20060122392A1

  公开（公告）日：2006-06-08

  Tri-heterocyclic compound of formula (I) wherein each of W, X and Y is carbon or nitrogen; each of U and Z is CR 2 , NR 13 , nitrogen, oxygen, sulfur etc.; A ring is carbocyclic ring, heterocyclic ring; R 1 is alkyl, alkenyl, alkynyl, NR 4 R 5 , OR 6 etc.; R 3 is carbocyclic ring, heterocyclic ring; and a pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical comprising them as an active ingredient. A compound of formula (I) is useful, in order to possess corticotropin releasing factor receptor antagonistic activity, for the prevention and/or treatment of depression, anxiety, eating disorder, posttraumatic stress disorder, peptic ulcer, irritable bowl syndrome, Alzheimer's disease, drug addiction or alcohol dependence syndrome etc.

  式(I)的三杂环化合物，其中W、X和Y中的每一个是碳或氮；U和Z中的每一个是CR2、NR13、氮、氧、硫等；一个环是碳环或杂环；R1是烷基、烯基、炔基、NR4R5、OR6等；R3是碳环或杂环；以及其药学上可接受的盐，制备过程和包含它们作为活性成分的药物。式(I)的化合物具有垂体促肾上腺皮质激素释放因子受体拮抗活性，可用于预防和/或治疗抑郁症、焦虑症、进食障碍、创伤后应激障碍、消化性溃疡、肠易激综合征、阿尔茨海默病、药物成瘾或酒精依赖综合征等。
• 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。
• TRI-HETEROCYCLIC COMPOUNDS AND A PHARMACEUTICAL COMPRISING THEM AS AN ACTIVE INGREDIENT
  申请人：NAKAI Hisao

  公开号：US20090137604A1

  公开（公告）日：2009-05-28

  Tri-heterocyclic compound of formula (I) wherein each of W, X and Y is carbon or nitrogen; each of U and Z is CR 2 , NR 13 , nitrogen, oxygen, sulfur etc.; A ring is carbocyclic ring, heterocyclic ring; R 1 is alkyl, alkenyl, alkynyl, NR 4 R 5 , OR 6 etc.; R 3 is carbocyclic ring, heterocyclic ring; and a pharmaceutically acceptable salt thereof, a process for the preparation thereof, a pharmaceutical comprising them as an active ingredient. A compound of formula (I) is useful, in order to possess corticotropin releasing factor receptor antagonistic activity, for the prevention and/or treatment of depression, anxiety, eating disorder, posttraumatic stress disorder, peptic ulcer, irritable bowl syndrome, Alzheimer's disease, drug addiction or alcohol dependence syndrome etc.

  公式（I）的三元杂环化合物，其中W、X和Y中的每一个是碳或氮；U和Z中的每一个是CR2、NR13、氮、氧、硫等；一个环是碳环或杂环；R1是烷基、烯基、炔基、NR4R5、OR6等；R3是碳环或杂环；以及其药学上可接受的盐，制备它们的方法，以其为活性成分的制药。公式（I）的化合物在具有促肾上腺皮质激素释放因子受体拮抗活性方面是有用的，用于预防和/或治疗抑郁症、焦虑症、饮食失调、创伤后应激障碍、消化性溃疡、肠易激综合症、阿尔茨海默病、药物成瘾或酒精依赖综合症等。