(2S,5RS)-N-(2-(6-(2-acetamidobenzo[d]thiazol-4-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-5-methylpyrrolidine-2-carboxamide | 905706-96-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,5RS)-N-(2-(6-(2-acetamidobenzo[d]thiazol-4-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-5-methylpyrrolidine-2-carboxamide
• 英文别名: (2S)-N-(2-(6-(2-acetamidobenzo[d]thiazol-4-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-5-methylpyrrolidine-2-carboxamide；(2S)-N-[2-[6-[(2-acetamido-1,3-benzothiazol-4-yl)oxy]pyrimidin-4-yl]-5-(trifluoromethyl)phenyl]-5-methylpyrrolidine-2-carboxamide
• CAS: 905706-96-9
• 化学式: C₂₆H₂₃F₃N₆O₃S
• 分子量: 556.568
• InChiKey: DZXGELYJLDXQGH-RUINGEJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2S,5RS)-N-(2-(6-(2-acetamidobenzo[d]thiazol-4-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-5-methylpyrrolidine-2-carboxamide 、 异丁醛 在 三乙酰氧基硼氢化钠 作用下， 以 乙腈 为溶剂， 生成 (2S)-N-(2-(6-(2-acetamidobenzo[d]thiazol-4-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-1-isobutyl-5-methylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists

  摘要：

  Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of 1. Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to 1. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.112
• 作为产物：
  描述：

  (2S,5RS)-tert-butyl 2-((2-(6-(2-acetamidobenzo[d]thiazol-4-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)carbamoyl)-5-methylpyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (2S,5RS)-N-(2-(6-(2-acetamidobenzo[d]thiazol-4-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-5-methylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists

  摘要：

  Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of 1. Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to 1. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.112

文献信息

• Vanilloid receptor ligands and their use in treatments
  申请人：Bo Y. Yunxin

  公开号：US20060183745A1

  公开（公告）日：2006-08-17

  Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  具有一般结构的化合物及其组合物，用于治疗急性、炎症性和神经性疼痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合征、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎性肠道疾病、炎性眼部疾病、炎性或不稳定膀胱疾病、牛皮癣、伴有炎症成分的皮肤疾病、慢性炎症症状、炎症性疼痛及相关的过敏性疼痛和触痛、神经性疼痛及相关的过敏性疼痛和触痛、糖尿病性神经病痛、烧伤性神经痛、交感神经维持性疼痛、去神经综合征、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、消化或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。
• US7301022B2
  申请人：——

  公开号：US7301022B2

  公开（公告）日：2007-11-27
• Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists
  作者：Markian M. Stec、Yunxin Bo、Partha P. Chakrabarti、Lillian Liao、Mqhele Ncube、Nuria Tamayo、Rami Tamir、Narender R. Gavva、James J.S. Treanor、Mark H. Norman

  DOI：10.1016/j.bmcl.2008.07.112

  日期：2008.9

  Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of 1. Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to 1. (C) 2008 Elsevier Ltd. All rights reserved.