SSR504734 | 742693-38-5

• 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: SSR504734
• 英文别名: 2-chloro-N-[(S)-phenyl-[(2S)-piperidin-2-yl]methyl]-3-(trifluoromethyl)benzamide；SSR-504734 free base
• CAS: 742693-38-5
• 化学式: C₂₀H₂₀ClF₃N₂O
• 分子量: 396.84
• InChiKey: MEZRZVWPLXVLSO-WMZOPIPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  41.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  SSR504734 在 盐酸 作用下， 以 异丙醇 为溶剂， 以99%的产率得到
  参考文献：
  名称：

  Derivative of n-[phenyl(piperidin-2-yl)methyl]benzamide, the preparation method thereof and application of same in therapeutics

  摘要：

  通式（I）的化合物，其中A代表以下两种情况之一：具有N—R1的化学式的基团，其中R1代表氢原子、烷基基团、环烷基基团、苯基烷基基团、烯基基团或炔基基团，或具有N+(O−)R1的化学式的基团，其中R1如上定义，或者具有N+(R′)R1的化学式的基团，其中R′代表烷基基团，R1如上定义；X代表氢原子或来自卤素原子、三氟甲基、烷基和烷氧基的一个或多个取代基；R2代表氢原子、来自卤素原子、三氟甲基、烷基和烷氧基的一个或多个取代基，具有以下基团的氨基：NR3R4，其中R3和R4各自代表氢原子或烷基基团，或者与携带它们的氮原子形成吡咯烷、哌啶或吗啉环，或者是一个可选择取代的苯基基团。在治疗中的应用。

  公开号：

  US20050159450A1
• 作为产物：
  描述：

  2-氯-3-(三氟甲基)苯甲酸 在 ammonium hydroxide 、 氯化亚砜 、 sodium tert-pentoxide 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 25.0h， 生成 SSR504734
  参考文献：
  名称：

  Concise Preparation of a Stable Cyclic Sulfamidate Intermediate in the Synthesis of a Enantiopure Chiral Active Diamine Derivative

  摘要：

  A classical resolution was studied and developed from 2-benzoyl-pyridine in order to prepare SSR504734, a novel antipsychotic derivative. The key step of this route is the substitution of a sulfamidate derivative by a benzamide anion with complete inversion of configuration. The sulfamidate is prepared in a two-step procedure by reacting erythro phenyl-piperidine-2-yl-methanol derivative with thionyl chloride followed by oxidation with ruthenium oxide. This sulfamidate is an easily scalable intermediate that produce a diamine intermediate with the expected configuration.

  DOI：

  10.1021/op500264v

文献信息

• Use of N-[Phenyl(piperidin-2-yl)methyl]benzamide derivatives in therapy
  申请人：DARGAZANLI Gihad

  公开号：US20070197601A1

  公开（公告）日：2007-08-23

  The present invention discloses and claims therapeutic use of a series of compounds of general formula (I) in which A, X and R 2 are as described herein. Specifically, the compounds of formula (I) exhibit a particular activity as specific inhibitors of the glycine transporters glyt1 and/or glty2.

  本发明揭示和声明了一系列通式(I)的化合物的治疗用途，其中A、X和R2如本文所述。具体而言，通式(I)的化合物表现出一种特定的活性，作为甘氨酸转运体glyt1和/或glyt2的特异性抑制剂。
• Synthesis and characterization of [125I]2-iodo N-[(S)-{(S)-1-methylpiperidin-2-yl}(phenyl)methyl]3-trifluoromethyl-benzamide as novel imaging probe for glycine transporter 1
  作者：Takeshi Fuchigami、Mamoru Haratake、Yasuhiro Magata、Terushi Haradahira、Morio Nakayama

  DOI：10.1016/j.bmc.2011.09.010

  日期：2011.11

  In this study, 2-iodo substituted 1-methylpiperidin-2-yl benzamide derivatives were synthesized and evaluated as candidate SPECT imaging agents for glycine transporter 1 (GlyT1). In JAR cells, which predominantly express GlyT1, 2-iodo N-[(S)-(S)-1-methylpiperidin-2-yl}(phenyl) methyl]3-trifluoromethyl-benzamide (5) showed excellent inhibitory activity of [H-3] glycine uptake (IC50 = 2.4 nM). Saturation assay in rat cortical membranes revealed that [I-125] 5 had a single high affinity binding site with a K-d of 1.54 nM and a B-max of 3.40 pmol/mg protein. In vitro autoradiography demonstrated that [I-125]5 showed consistent accumulation with GlyT1 expression. The in vitro binding was greatly inhibited by GlyT1 inhibitors but not by other site ligands, which suggested the high specific binding of [I-125]5 with GlyT1. In the biodistribution and ex vivo autoradiography studies using mice, [I-125]5 showed high blood-brain barrier permeability (1.68-2.17% dose/g at 15-60 min) and similar regional brain distribution pattern with in vitro results. In addition, pre-treatment of GlyT1 ligands resulted in significant decrease of [I-125]5 binding in the GlyT1-rich regions. This preliminary study demonstrated that radio-iodinated 5 is a promising SPECT imaging probe for GlyT1. (C) 2011 Elsevier Ltd. All rights reserved.
• DERIVES DE N-¬PHENYL(PIPERIDIN-2-YL)METHYL|BENZAMIDE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
  申请人：Sanofi-Aventis

  公开号：EP1499589B1

  公开（公告）日：2007-05-02
• POLYSIALIC ACID AND DERIVATIVES THEREOF, PHARMACEUTICAL COMPOSITION AND METHOD OF PRODUCING POLYSIALIC ACID
  申请人：Medizinische Hochschule Hannover (MHH)

  公开号：EP3829717A2

  公开（公告）日：2021-06-09
• PHARMACEUTICAL COMPOSITIONS AND METHODS FOR TREATING DRUG ADDICTION AND PREVENTING A DRUG RELAPSE
  申请人：Arizona Board of Regents, for and on behalf of, Arizona State University

  公开号：US20150141462A1

  公开（公告）日：2015-05-21

  The present invention relates to pharmaceutical compositions comprising (a) a pharmaceutically effective amount of an mGluR5 positive allosteric modulator, derivative, prodrug or a pharmaceutically acceptable salt thereof; (b) a pharmaceutically effective amount of an agent selected from an NMDA partial agonist or a GlyT1 inhibitor, derivative, prodrug or a pharmaceutically acceptable salt thereof; and (c) a pharmaceutically acceptable carrier. The present invention also relates to methods for treating drug addiction and preventing a drug relapse in a patient. The methods comprise (a) administering to the patient a pharmaceutically effective amount of an mGluR5 positive allosteric modulator, derivative, prodrug or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof; (b) administering to the patient a pharmaceutically effective amount of an agent selected from an NMDA partial agonist or a GlyT1 inhibitor, derivative, prodrug or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.