methyl 1-(4-bromobenzyl)piperidine-4-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl 1-(4-bromobenzyl)piperidine-4-carboxylate
• 英文别名: Methyl 1-[(4-bromophenyl)methyl]piperidine-4-carboxylate
• 化学式: C₁₄H₁₈BrNO₂
• mdl: MFCD13227271
• 分子量: 312.206
• InChiKey: AEEHPLQMKPWLTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 1-(4-bromobenzyl)piperidine-4-carboxylate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 生成 1-[4-((2S,3'S)-2-methyl[1,3']bipyrrolidinyl-1'-yl)benzyl]piperidine-4-carboxylic acid methyl amide
  参考文献：
  名称：

  Design and synthesis of a novel series of histamine H3 receptor antagonists through a scaffold hopping strategy

  摘要：

  Lead compounds 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl-[1,3'] bipyrrolidinyl-1'-yl)-phenyl]-benzamide (1), tetrahydro-pyran-4-carboxylic acid [((2S, 3'S)-2-methyl-[1,3'] bipyrrolidinyl-1'-yl)-phenyl]-amide (2), and 3,5-dimethyl-isoxazole-4-carboxylic acid [((2S, 3'S)-2-methyl-[1,3'] bipyrrolidinyl-1'-yl)-phenyl]-amide (3) discovered in our laboratory, displayed high histamine H-3 receptor (H3R) affinity, good selectivity and weak human Ether-a-go-go-Related Gene (hERG) channel affinity with desirable overall physico-chemical and pharmacokinetic (PK) profiles. Herein, we describe the design and synthesis of a novel series of H3R antagonists utilizing a scaffold hopping strategy. Further structure-activity relationship (SAR) studies of the series culminated in the identification of ((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-naphthalene-2-carboxylic acid (tetrahydro-pyran-4-yl)-amide (4c) and -[4-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-phenyl]-N-(tetrahydro-pyran-4-yl)-acetamide (4d), which exhibited good H3R affinity in vitro, good selectivity, and desirable PK properties. Compounds 4c and 4d were also assessed in cardiac safety experiments. In particular, the effects of the compounds on action potentials recorded from ventricular myocytes isolated from guinea pigs were used to screen compounds that not only displayed a low affinity towards hERG channel, but also had lower interference with other cardiac ion channels. Compound 4c did not alter the major parameters in this model system at <= 10 mu M, and no significant induction of any major haemodynamic effect when intravenously administered at 3 mg/kg dose to anaesthetized mongrel dogs. Compound 4c is a new promising lead as orally potent and selective H3R antagonist belonging to a distinct structural class. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.036
• 作为产物：
  描述：

  4-哌啶甲酸甲酯 、 对溴苯甲醛 在 盐酸 、 三乙酰氧基硼氢化钠 、 水 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 生成 methyl 1-(4-bromobenzyl)piperidine-4-carboxylate
  参考文献：
  名称：

  [EN] SUBSTITUTED N-HETEROCYCLOALKYL BIPYRROLIDINYLPHENYL AMIDE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
  [FR] DÉRIVÉS DE N-HÉTÉROCYCLOALKYL-BIPYRROLIDINYLPHÉNYLAMIDE SUBSTITUÉS, PRÉPARATION ET UTILISATION THÉRAPEUTIQUE DE CEUX-CI

  摘要：

  本发明公开并声明了一系列式（I）的取代N-杂环烷基双吡咯啉基苯酰胺衍生物。其中R、R1、R2、R3、R4、X、m、n和p如本文所述。更具体地，本发明的化合物是H3受体调节剂，因此在治疗和/或预防包括与中枢神经系统相关的疾病在内的多种受H3受体调节的疾病方面作为药用剂特别有用。此外，本发明还公开了制备式（I）的取代N-杂环烷基双吡咯啉基苯酰胺衍生物及其中间体的方法。

  公开号：

  WO2011143161A1

文献信息

• [EN] SUBSTITUTED N-HETEROCYCLOALKYL BIPYRROLIDINYLPHENYL AMIDE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF<br/>[FR] DÉRIVÉS DE N-HÉTÉROCYCLOALKYL-BIPYRROLIDINYLPHÉNYLAMIDE SUBSTITUÉS, PRÉPARATION ET UTILISATION THÉRAPEUTIQUE DE CEUX-CI
  申请人：SANOFI SA

  公开号：WO2011143161A1

  公开（公告）日：2011-11-17

  The present invention discloses and claims a series of substituted N- heterocycloalkyl bipyrrolidinylphenyl amide derivatives of formula (I). (Formula (I)) Wherein R, R1, R2, R3, R4, X, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, this invention also discloses methods of preparation of substituted N-heterocycloalkyl bipyrrolidinylphenyl amide derivatives of formula (I) and intermediates therefor.

  本发明公开并声明了一系列式（I）的取代N-杂环烷基双吡咯啉基苯酰胺衍生物。其中R、R1、R2、R3、R4、X、m、n和p如本文所述。更具体地，本发明的化合物是H3受体调节剂，因此在治疗和/或预防包括与中枢神经系统相关的疾病在内的多种受H3受体调节的疾病方面作为药用剂特别有用。此外，本发明还公开了制备式（I）的取代N-杂环烷基双吡咯啉基苯酰胺衍生物及其中间体的方法。
• New (hetero)aryl compounds with MCH antagonistic activity and medicaments comprising these compounds
  申请人：Roth Juergen Gerald

  公开号：US20070111981A1

  公开（公告）日：2007-05-17

  The present invention relates to (hetero)aryl compounds of general formula I wherein the groups and radicals A, B, Q, W, X, Y, Z, R 1 , R 2 , R 4a , R 4b , R 5a , R 5b , have the meanings given in claim 1 . Moreover the invention relates to pharmaceutical compositions containing at least one compound according to the invention. By virtue of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.

  本发明涉及一般式I的（杂）芳基化合物，其中A、B、Q、W、X、Y、Z、R1、R2、R4a、R4b、R5a和R5b基团和基团具有权利要求1中给出的含义。此外，本发明涉及至少含有本发明中的一种化合物的制药组合物。由于其MCH受体拮抗活性，根据本发明的制药组合物适用于治疗代谢紊乱和/或进食障碍，尤其是肥胖症、贪食症、厌食症、暴食症和糖尿病。
• [EN] AZETIDINYL COMPOUNDS COMPRISING A CARBOXYLIC ACID GROUP FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS AZÉTIDINYLES COMPRENANT UN GROUPE ACIDE CARBOXYLIQUE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：CELGENE CORP

  公开号：WO2022266162A1

  公开（公告）日：2022-12-22

  Provided herein are compounds and compositions thereof for modulating S1P5. In some embodiments, the compounds and compositions are provided for treatment of neurological diseases.

  本文提供了用于调节S1P5的化合物及其组合物。在某些实施例中，这些化合物和组合物被用于治疗神经系统疾病。
• Exemplifying Prediction of Preferred Coupling Partners in Developing a Buchwald–Hartwig Coupling for the Synthesis of a c-Kit Inhibitor
  作者：Quanbing Wu、Xin Xiong、Yudong Cao、Lijuan He、Zhongbo Fei

  DOI：10.1021/acs.oprd.8b00043

  日期：2018.4.20

  Two convergent syntheses for compound 1 are described that apply Buchwald Hartwig coupling as the key step. This development work provides a direct comparison of the coupling results from different coupling partners and illustrates that more efficiency can be achieved by selecting the right coupling partners.
• (HETERO)ARYL COMPOUNDS WITH MCH ANTAGONISTIC ACTIVITY AND MEDICAMENTS COMPRISING THESE COMPOUNDS
  申请人：BOEHRINGER INGELHEIM INTERNATIONAL GMBH

  公开号：EP1943231A1

  公开（公告）日：2008-07-16