(3,5-bis(trifluoromethyl)benzyl)(methyl)amine hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3,5-bis(trifluoromethyl)benzyl)(methyl)amine hydrochloride
• 英文别名: N-[3,5-bis(trifluoromethyl)benzyl]methylamine hydrochloride；N-methyl-3,5-bis(trifluoromethyl)benzylamine hydrochloride；1-[3,5-bis(trifluoromethyl)phenyl]-N-methylmethanamine hydrochloride；1-[3,5-bis(trifluoromethyl)phenyl]-N-methylmethanamine monohydrochloride；N-[3,5-bis(trifluoromethyl)benzyl]methylamine monohydrochloride；(3,5-bis-trifluoromethyl-benzyl)-methylamine hydrochloride；1-(3,5-Bis(trifluoromethyl)phenyl)-N-methylmethanamine hydrochloride；1-[3,5-bis(trifluoromethyl)phenyl]-N-methylmethanamine;hydrochloride
• 化学式: C₁₀H₉F₆N*ClH
• 分子量: 293.64
• InChiKey: ZHJANDCTQSKVGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3,5-bis(trifluoromethyl)benzyl)(methyl)amine hydrochloride 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 乙酸乙酯 、 乙腈 为溶剂， 反应 20.0h， 生成 (3S,4S)-N-[3,5-bis(trifluoromethyl)benzyl]-N-methyl-3-(2-methylphenyl)piperidine-4-carboxamide monohydrochloride
  参考文献：
  名称：

  Piperidine derivative and use thereof

  摘要：

  本发明提供了一种新颖的哌啶衍生物和含有该衍生物的催吐肽受体拮抗剂，以及由下式表示的化合物： 其中R1为羰胺甲基、甲磺酰乙基羰基等；R2为甲基或环丙基；R3为氢原子或甲基；R4为氯原子或三氟甲基；R5为氯原子或三氟甲基；以及由下式表示的基团： 是由下式表示的基团： 其中R6为氢原子、甲基、乙基或异丙基；R7为氢原子、甲基或氯原子；R8为氢原子、氟原子、氯原子或甲基；或3-甲基噻吩-2-基，并且其盐。

  公开号：

  US20080275085A1
• 作为产物：
  描述：

  3,5-双三氟甲基苯甲醛 、 甲胺 在 钾硼氢 、 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 1.83h， 以89.8%的产率得到(3,5-bis(trifluoromethyl)benzyl)(methyl)amine hydrochloride
  参考文献：
  名称：

  Discovery and Biological Characterization of (2R,4S)-1′-Acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4′-bipiperidine-1-carboxamide as a New Potent and Selective Neurokinin 1 (NK₁) Receptor Antagonist Clinical Candidate

  摘要：

  A large body of compelling preclinical evidence supports the clinical use of neurokinin (NK) receptor antagonists in a plethora of CNS and non-CNS therapeutic areas. The significant investment made in this area over the past 2 decades culminated with the observation that NK1 receptor antagonists elicited clinical efficacy in major depression disorders. In addition, aprepitant (Merck) was launched as a new drug able to prevent chemotherapy-induced nausea and vomiting (CINV). After the discovery by GlaxoSmithKline of vestipitant, a wide drug discovery program was launched aimed at identifying additional clinical candidates. New compounds were designed to maximize affinity at the NK1 receptor binding site while retaining suitable physicochemical characteristics to ensure excellent pharmacokinetic and pharmacodynamic properties in vivo. Herein we describe the discovery process of a new NK1 receptor antagonist (casopitant) selected as clinical candidate and progressed into clinical studies to treat major depression disorders.

  DOI：

  10.1021/jm1013264

文献信息

• Piperidine derivative and use thereof
  申请人：Shirai Junya

  公开号：US20080275085A1

  公开（公告）日：2008-11-06

  The present invention provides a novel piperidine derivative and a tachykinin receptor antagonist containing same, as well as a compound represented by the formula: wherein R 1 is carbamoylmethyl, methylsulfonylethylcarbonyl and the like; R 2 is methyl or cyclopropyl; R 3 is a hydrogen atom or methyl; R 4 is a chlorine atom or trifluoromethyl; R 5 is a chlorine atom or trifluoromethyl; and a group represented by the formula: is a group represented by the formula: wherein R 6 is a hydrogen atom, methyl, ethyl or isopropyl; R 7 is a hydrogen atom, methyl or a chlorine atom; and R 8 is a hydrogen atom, a fluorine atom, a chlorine atom or methyl; or 3-methylthiophen-2-yl, and a salt thereof.

  本发明提供了一种新颖的哌啶衍生物和含有该衍生物的催吐肽受体拮抗剂，以及由下式表示的化合物： 其中R1为羰胺甲基、甲磺酰乙基羰基等；R2为甲基或环丙基；R3为氢原子或甲基；R4为氯原子或三氟甲基；R5为氯原子或三氟甲基；以及由下式表示的基团： 是由下式表示的基团： 其中R6为氢原子、甲基、乙基或异丙基；R7为氢原子、甲基或氯原子；R8为氢原子、氟原子、氯原子或甲基；或3-甲基噻吩-2-基，并且其盐。
• Chemical compounds
  申请人：——

  公开号：US20040014770A1

  公开（公告）日：2004-01-22

  Formula (1) wherein R represents a halogen atom or a C 1-4 alkyl group; R 1 represents a C 1-4 alkyl group; R 2 represents hydrogen or a C 1-4 alkyl group; R 3 represents hydrogen, or a C 1-4 alkyl group; R 4 represents a trifluorometyl group; R 5 represents hydrogen, a C 1-4 alkyl group or C(0)R 6 ; R 6? represents C 1-4 alkyl, C 3-7 cycloalkyl, NH(C 1-4 alkyl) or N(C1-4alkyl) 2 ; m is zero or an integer from 1 to 3; n is an integer from 1 to 3 and pharmaceutically acceptable salts and solvates thereof; to processes for their preparation and their use in the treatment of conditions mediated bytachykinins.

  公式（1）中，R代表卤原子或C1-4烷基；R1代表C1-4烷基；R2代表氢或C1-4烷基；R3代表氢或C1-4烷基；R4代表三氟甲基基团；R5代表氢、C1-4烷基或C(0)R6；R6代表C1-4烷基、C3-7环烷基、NH(C1-4烷基)或N(C1-4烷基)2；m为零或1至3的整数；n为1至3的整数及其药学上可接受的盐和溶剂化合物；以及它们的制备过程和在通过tachykinins介导的疾病治疗中的用途。
• [EN] N-BENZYL-3-PHENYL-3-HETEROCYCLYL-PROPIONAMIDE COMPOUNDS AS TACHYKININ AND/ OR SEROTONIN REUPTAKE INHIBITORS<br/>[FR] COMPOSES DE N-BENZYL-3-PHENYL-3-HETEROCYCLYL-PROPIONAMIDE EN TANT QU'INHIBITEURS DE RECAPTAGE DE LA TACHYKININE ET/OU DE LA SEROTONINE
  申请人：GLAXO GROUP LTD

  公开号：WO2004005255A1

  公开（公告）日：2004-01-15

  The present invention relates to heterocyclic derivatives of formula (1) wherein R1 represents a 5 or 6 membered heteroaryl group, in which the 5-membered heteroaryl group contains at least one heteroatom selected from oxygen, sulphur or nitrogen and the 6-membered heteroaryl group contains from 1 to 3 nitrogen atoms, or R1 represents a 4,5 or 6 membered heterocyclic group, wherein saids 5 or 6 membered heteroaryl or the 4,5 or 6 membered heterocyclic group may optionally be substituted by one to three substituents, which may be the same or different, selected from (CH2)pR6, wherein p is zero or an integer from 1 to 4 and wherein R and R2- R6 are each as defined in the description and pharmaceutically acceptable salts and solvates thereof; process for their preparation and their use in the treatment of conditions mediated by tachykinins and/or by selective inhibition of serotonin reuptake transporter protein.

  本发明涉及式（1）的杂环衍生物，其中R1代表一个5或6成员杂芳基团，在其中5成员杂芳基团至少含有氧、硫或氮中选择的一个杂原子，而6成员杂芳基团含有1至3个氮原子，或者R1代表一个4、5或6成员杂环基团，其中所述的5或6成员杂芳基或4、5或6成员杂环基团可以选择地被1至3个取代基取代，所述取代基可以相同或不同，选择自(CH2)pR6，其中p为零或1至4的整数，其中R和R2-R6如描述中定义，并且其药学上可接受的盐和溶剂化合物；其制备方法及其在通过催产素介导的疾病和/或通过选择性抑制血清素再摄取转运蛋白的治疗中的用途。
• Discovery Process and Pharmacological Characterization of 2-(<i>S</i>)-(4-Fluoro-2-methylphenyl)piperazine-1-carboxylic Acid [1-(<i>R</i>)-(3,5-Bis-trifluoromethylphenyl)ethyl]methylamide (Vestipitant) as a Potent, Selective, and Orally Active NK₁ Receptor Antagonist
  作者：Romano Di Fabio、Cristiana Griffante、Giuseppe Alvaro、Giorgio Pentassuglia、Domenica A. Pizzi、Daniele Donati、Tino Rossi、Giuseppe Guercio、Mario Mattioli、Zadeo Cimarosti、Carla Marchioro、Stefano Provera、Laura Zonzini、Dino Montanari、Sergio Melotto、Philip A. Gerrard、David G. Trist、Emiliangelo Ratti、Mauro Corsi

  DOI：10.1021/jm900023b

  日期：2009.5.28

  NK1 receptor antagonists a new series of suitably substituted C-phenylpiperazine derivatives was identified by an appropriate chemical exploration of related N-phenylpiperazine analogues, with the specific aim to maximize their in vitro affinity and optimize in parallel their pharmacokinetic profile. Among the compounds synthesized, 2-(S)-(4-fluoro-2-methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3

  为了发现新的类似药物的NK 1受体拮抗剂，通过对相关的N-苯基哌嗪类似物进行适当的化学探索，鉴定了一系列新的适当取代的C-苯基哌嗪衍生物，其具体目的是最大程度地提高它们的体外亲和力并同时优化其药代动力学概况。在合成的化合物中，鉴定出2-（S）-（4-氟-2-甲基苯基）哌嗪-1-甲酸[1-（R）-（3,5-双三氟甲基苯基）乙基]甲酰胺（vestipitant）作为最强效和选择性的NK 1之一有史以来发现过的受体拮抗剂，表现出适当的药代动力学性质和体内活性。根据其临床前概况，选择该化合物作为候选药物。
• [EN] HETEROTRICYCLIC AMIDE DERIVATIVES AS NEUROKININ-l (NKl) RECEPTOR LIGANDS<br/>[FR] DERIVES D'AMIDE HETEROTRICYCLIQUES EN TANT QUE LIGANDS DU RECEPTEUR DE NEUROKININE-1 (NK1)
  申请人：UNIV SIENA

  公开号：WO2007074491A1

  公开（公告）日：2007-07-05

  (EN) The present invention relates to compounds of formula 1, method of preparation and uses thereof.(FR) La présente invention concerne des composés de formule 1, ainsi que leur procédé de fabrication et leurs utilisations.

  本发明涉及公式1的化合物，其制备方法和用途。