2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine | 171242-11-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine
• 英文别名: L-760735；2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)-ethoxy)-4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine；1-[5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl]-2H-triazol-4-yl]-N,N-dimethylmethanamine
• CAS: 171242-11-8
• 化学式: C₂₆H₂₈F₇N₅O₂
• 分子量: 575.529
• InChiKey: USRYEHHMJIRICK-ZNZBMKLDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine 在 盐酸 作用下， 以 异丙醇 、 甲苯 为溶剂， 反应 2.0h， 以95%的产率得到2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine hydrochloride
  参考文献：
  名称：

  P物质拮抗剂的合成：5-取代的4- N，N-二甲基氨基-1,2,3-三唑的高效合成

  摘要：

  据报道，从光学纯的吗啉缩醛衍生物2开始，可以高效合成P物质拮抗剂1。通过在活化的炔属中间体和叠氮化钠之间的1，3-偶极环加成，对5-二甲基氨基甲基-1，2，3-三唑部分进行了修饰。已经设计了两种构建1的三唑部分的方法。第一种方法是线性提供四个步骤的侧链，总产率为85-92％。反应性炔醛5允许温和的叠氮化物环化。三唑醛的简单还原胺化反应完成了1的合成。一种替代的，更有效的，收敛的合成方法，其使用从线性合成开发的类似方法进行设计，以提高工艺的整体效率，并消除与叠氮化物处理有关的问题。三唑加合物是通过两步，一锅操作离线制备的，作为构建单元4- N，N-二甲基氨基甲基-1,2,3-三唑-醛3。N，N-二甲基氨基丙炔的甲酰化和叠氮化物环化作为贯穿过程进行，以90％的测定产率得到三唑醛3。分离产物的总收率取决于方法，范围为67％至81％。3的醛基通过用NaBH（OAc）3的还原胺化反应，以接近定量的收

  DOI：

  10.1021/op050019s
• 作为产物：
  描述：

  (2R,3S)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-chlorobut-2-ynyl)-3-(4-fluorophenyl)morpholine 在 sodium azide 作用下， 以 1,4-二氧六环 、 二甲基亚砜 为溶剂， 反应 40.0h， 生成 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(5-(dimethylamino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine
  参考文献：
  名称：

  An Orally Active, Water-Soluble Neurokinin-1 Receptor Antagonist Suitable for Both Intravenous and Oral Clinical Administration

  摘要：

  1-(5-{[(2R,3S)-2-({(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholin-4-yl]methyl}-2H-1,2,3-triazol-4-yl)-N,N-dimethylmethanamine hydrochloride 3 is a high affinity, orally active, h-NK1 receptor antagonist with a long central duration of action and a solubility in water of > 100 mg/mL. The construction of the 5-dimethylaminomethyl 1,2,3-triazol-4-yl unit, which incorporates the solubilizing group of 3, was accomplished by thermal rearrangement of a propargylic azide in the presence of dimethylamine. Compound 3 is highly effective in pre-clinical tests that are relevant to clinical efficacy in emesis and depression.

  DOI：

  10.1021/jm0109558

文献信息

• Melanin Concentrating Hormone Receptor-1 Antagonist Pyridinones
  申请人：Armour R. Duncan

  公开号：US20080085884A1

  公开（公告）日：2008-04-10

  The present invention provides for MCHR1 antagonist compounds of formula (I) and the pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein the substituents are as defined herein, and the pharmaceutically acceptable salts, solvates and prodrugs thereof, which are useful in treating diseases or conditions wherein antagonism of the MCHR1 receptor is beneficial.

  本发明提供了式（I）的MCHR1拮抗剂化合物及其药用盐、溶剂合物和前药，其中取代基如本文所定义，并且其药用盐、溶剂合物和前药，可用于治疗对MCHR1受体拮抗有益的疾病或症状。
• [EN] DIAZEPINE AND DIAZOCANE COMPOUNDS AS MC4 AGONISTS<br/>[FR] COMPOSÉS DIAZÉPINES ET DIAZOCANES EN TANT QU'AGONISTES DE MC4
  申请人：PFIZER LTD

  公开号：WO2010015972A1

  公开（公告）日：2010-02-11

  The present invention relates to compounds of formula (I) wherein R1, R2, R3, R4, L and n are as defined in the specification. These compounds are useful as MC4 agonists.

  本发明涉及式(I)的化合物，其中R1、R2、R3、R4、L和n如规范中所定义。这些化合物可用作MC4激动剂。
• [EN] SUBSTITUTED ARYL AMIDES<br/>[FR] ARYLAMIDES SUBSTITUEE
  申请人：MERCK & CO INC

  公开号：WO2003087037A1

  公开（公告）日：2003-10-23

  Novel compounds of structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as psychotropic drugs in the treatment of psychosis, memory deficits, cognitive disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson s disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as, the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, and cirrhosis of the liver.

  结构式（I）的新化合物是大麻素-1（CB1）受体的拮抗剂和/或逆向激动剂，并且在治疗、预防和抑制由CB1受体介导的疾病方面具有用途。本发明的化合物可作为精神药物用于治疗精神病、记忆障碍、认知障碍、偏头痛、神经病、神经炎性疾病（包括多发性硬化和吉兰-巴雷综合征）以及病毒性脑炎、脑血管意外和头部创伤的炎症后遗症、焦虑症、压力、癫痫、帕金森病、运动障碍和精神分裂症。这些化合物还可用于治疗物质滥用障碍、肥胖症或进食障碍的治疗，以及哮喘、便秘、慢性肠假性梗阻和肝硬化的治疗。
• Use of a COX-2 inhibitor and a NK-1 receptor antagonist for treating inflammation
  申请人：——

  公开号：US20040097573A1

  公开（公告）日：2004-05-20

  The present invention provides the use of a COX-2 inhibitior and an NK-1 receptor antagonist for the treatment or prevention of inflammatory disorders.

  本发明提供了利用COX-2抑制剂和NK-1受体拮抗剂用于治疗或预防炎症性疾病的方法。
• Method of treating cancer
  申请人：——

  公开号：US20030215456A1

  公开（公告）日：2003-11-20

  The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a tachykinin receptor antagonist, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a tachykinin receptor antagonist. The invention also relates to methods of preparing such compositions.

  本发明涉及使用一种PSA结合物和一种催吐肽受体拮抗剂的组合来治疗癌症的方法，该方法包括向所述哺乳动物施用来自PSA结合物和催吐肽受体拮抗剂组成的一组中至少两种治疗剂的剂量，可以按任意顺序依次施用或同时施用。该发明还涉及制备这种组合物的方法。