N-(2-bromo-4-isopropylphenyl)-N-ethyl-2-chloro-6-methyl-1,3,5-triazin-4-amine | 169882-09-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(2-bromo-4-isopropylphenyl)-N-ethyl-2-chloro-6-methyl-1,3,5-triazin-4-amine
• 英文别名: N-(2-bromo-4-isopropylphenyl)-N-ethyl-4-chloro-6-methyl-1,3,5-triazine-2-amine；N-(2-bromo-4-propan-2-ylphenyl)-4-chloro-N-ethyl-6-methyl-1,3,5-triazin-2-amine
• CAS: 169882-09-1
• 化学式: C₁₅H₁₈BrClN₄
• 分子量: 369.692
• InChiKey: ORBWNSSLDHDVGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-乙基正丁胺 、 N-(2-bromo-4-isopropylphenyl)-N-ethyl-2-chloro-6-methyl-1,3,5-triazin-4-amine 在 N,N-二异丙基乙胺 作用下， 生成 N-(2-Bromo-4-isopropyl-phenyl)-N'-butyl-N,N'-diethyl-6-methyl-[1,3,5]triazine-2,4-diamine
  参考文献：
  名称：

  Non-Peptide Corticotropin-Releasing Hormone Antagonists:  Syntheses and Structure−Activity Relationships of 2-Anilinopyrimidines and -triazines

  摘要：

  Screening of our chemical library using a rat corticotropin-releasing hormone (CRH) receptor assay led to the discovery that 2-anilinopyrimidine 15-1 weakly displaced [I-125]-0-Tyr-oCRH from rat frontal cortex homogenates when compared to the known peptide antagonist alpha-helical CRH(9-41) (K-i = 5700 nM vs 1 nM). Furthermore, 15-1 weakly inhibited CRH-stimulated adenylate cyclase activity in the same tissue, but it was less potent than a-helical CRH(9-41) (IC50 = 20 000 nM vs 250 nM). Systematic structure-activity relationship studies, using the cloned human CRH1 receptor assay, defined the pharmacophore for optimal binding to hCRH(1) receptors. Several high-affinity 2-anilinopyrimidines and -triazines were discovered, some of which had superior pharmacokinetic profiles in the rat. This paper describes the structure-activity studies which improved hCRH(1) receptor binding affinity and pharmacokinetic parameters in the rat. Compound 28-17 (mean hCRH(1) K-i = 32 nM) had a significantly improved pharmacokinetic profile in the rat (19% oral bioavailability at 30 mg/kg) as well as in the dog (20% oral bioavailability at 5 mg/kg) relative to the early lead structures.

  DOI：

  10.1021/jm980222w
• 作为产物：
  描述：

  2,4-二氯-6-甲基-1,3,5-三嗪 、 N-ethyl-2-bromo-4-isopropylaniline 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 以68%的产率得到N-(2-bromo-4-isopropylphenyl)-N-ethyl-2-chloro-6-methyl-1,3,5-triazin-4-amine
  参考文献：
  名称：

  Aryl- and arylamino- substituted heterocycles as corticotropin releasing

  摘要：

  促肾上腺皮质激素释放因子（CRF）拮抗剂的化学式I：##STR1##及其在治疗精神障碍和神经疾病、焦虑相关障碍、创伤后应激障碍、上核性麻痹和进食障碍以及治疗与精神病理障碍和压力相关的结肠过敏性疾病以及哺乳动物免疫、心血管或心脏相关疾病的用途。

  公开号：

  US06103737A1

文献信息

• 1N-alkyl-n-arylpyrimidinamines and derivatives thereof
  申请人：DuPont Pharmaceuticals Company

  公开号：US06342503B1

  公开（公告）日：2002-01-29

  The present invention provides novel compounds, compounds and pharmaceutical compositions thereof, and methods of using same in the treatment of affective disorders, anxiety, depression, post-traumatic stress disorders, eating disorders, supranuclear palsy, irritable bowel syndrome, immune suppression, Alzheimer'disease, gastrointestinal diseases, anorexia nervosa, drug and alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems. The novel compounds provided by this invention are those of formula: wherein R1, R3, R4, R5, Z, Y, V, X, X′, J, K, L, and M are as defined herein.

  本发明提供了新颖的化合物、该化合物及其药物组合物，以及在治疗情感障碍、焦虑、抑郁、创伤后应激障碍、进食障碍、上核性麻痹、肠易激综合征、免疫抑制、阿尔茨海默病、胃肠疾病、厌食症、药物和酒精戒断症状、药物成瘾、炎症性疾病或生育问题中使用这些方法。本发明提供的新型化合物为以下公式的化合物： 其中R1、R3、R4、R5、Z、Y、V、X、X'、J、K、L和M如本文所定义。
• Use of the suzuki reaction for the synthesis of aryl-substituted heterocycles as corticotropin-releasing hormone (CRH) antagonists
  作者：Anthony J. Cocuzza、Dennis R. Chidester、Steven Culp、Lawrence Fitzgerald、Paul Gilligan

  DOI：10.1016/s0960-894x(99)00133-x

  日期：1999.4

  The Suzuki reaction has been used to synthesize a variety of aryl-substituted heterocyclic antagonists of the CRH1 receptor. Examples with several different heterocyclic cores are potent CRH receptor ligands. (C) 1999 (C) 1999 DuPont Pharmaceuticals. Published by Elsevier Science Ltd. All rights reserved.
• ARYL-AND ARYLAMINO-SUBSTITUTED HETEROCYCLES AS CORTICOTROPIN RELEASING HORMONE ANTAGONISTS
  申请人：Du Pont Pharmaceuticals Company

  公开号：EP0994860A1

  公开（公告）日：2000-04-26
• US6103737A
  申请人：——

  公开号：US6103737A

  公开（公告）日：2000-08-15
• [EN] ARYL-AND ARYLAMINO-SUBSTITUTED HETEROCYCLES AS CORTICOTROPIN RELEASING HORMONE ANTAGONISTS<br/>[FR] HETEROCYCLES ARYL- ET ARYLAMINO-SUBSTITUES UTILISES COMME ANTAGONISTES DE L'HORMONE CORTICOTROPE
  申请人：DU PONT PHARMACEUTICALS COMPANY

  公开号：WO1999001439A1

  公开（公告）日：1999-01-14

  (EN) Corticotropin releasing factor (CRF) antagonists of formula (I), and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.(FR) L'invention concerne des antagonistes du facteur libérateur de corticotropine représentés par la formule (I), et leur utilisation pour traiter les troubles psychiatriques, les affections neurologiques, les troubles liés à l'anxiété, les états de stress post-traumatiques, la paralysie supranucléaire et les troubles de l'alimentation, ainsi que le traitement des maladies immunitaires, cardio-vasculaires ou des maladies liées au coeur, et de l'hypersensibilité du côlon associée à des perturbations psychopathologiques et au stress chez les mammifères.