1-benzoyl-piperidin-4-ylmethyl methanesulfonate | 184921-12-8

• 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: 1-benzoyl-piperidin-4-ylmethyl methanesulfonate
• 英文别名: 1-Benzoylpiperidin-4-ylmethyl methanesulfonate；(1-benzoylpiperidin-4-yl)methyl methanesulfonate
• CAS: 184921-12-8
• 化学式: C₁₄H₁₉NO₄S
• 分子量: 297.375
• InChiKey: PSTZVGSGBUFTNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 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：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzoyl-piperidin-4-ylmethyl methanesulfonate 在 sodium hydride 、 diborane(6) 作用下， 以 四氢呋喃 为溶剂， 反应 48.25h， 生成 3-(1-Benzyl-piperidin-4-ylmethoxy)-pyridine
  参考文献：
  名称：

  Novel piperidine .sigma. receptor ligands as potential antipsychotic drugs

  摘要：

  Sigma receptor ligands represent a new class of potential antipsychotic drugs. This paper presents the structure-activity relationships leading to novel disubstituted piperidine sigma ligands, which have little or no affinity for dopamine D2 receptors. Selectivity for sigma sites over dopamine D2 or serotonin 5-HT2 receptors appears to be governed by the chemical nature of the piperidine nitrogen substituent, its distance from the basic nitrogen, and its orientation relative to the other piperidine substituent. Several of these compounds have good oral potency in some animal models used to evaluate potential antipsychotic drugs. The N-cyclopropylmethyl ketones and ethers (e.g. 6i (DuP 734), 6q, 18a, and 18n) have the best in vivo potency. Compounds 6i (DuP 734) and 6q did not cause catalepsy in the rat, even at very high doses. On the basis of the pharmacology profiles of these sigma ligands, we propose these compounds may be effective antipsychotic drugs, which do not induce extrapyramidal side effects or tardive dyskinesia.

  DOI：

  10.1021/jm00101a012
• 作为产物：
  描述：

  1-苯甲酰基-4-哌啶羧酸乙酯 在 锂硼氢 、 硼酸三甲酯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 48.58h， 生成 1-benzoyl-piperidin-4-ylmethyl methanesulfonate
  参考文献：
  名称：

  Novel piperidine .sigma. receptor ligands as potential antipsychotic drugs

  摘要：

  Sigma receptor ligands represent a new class of potential antipsychotic drugs. This paper presents the structure-activity relationships leading to novel disubstituted piperidine sigma ligands, which have little or no affinity for dopamine D2 receptors. Selectivity for sigma sites over dopamine D2 or serotonin 5-HT2 receptors appears to be governed by the chemical nature of the piperidine nitrogen substituent, its distance from the basic nitrogen, and its orientation relative to the other piperidine substituent. Several of these compounds have good oral potency in some animal models used to evaluate potential antipsychotic drugs. The N-cyclopropylmethyl ketones and ethers (e.g. 6i (DuP 734), 6q, 18a, and 18n) have the best in vivo potency. Compounds 6i (DuP 734) and 6q did not cause catalepsy in the rat, even at very high doses. On the basis of the pharmacology profiles of these sigma ligands, we propose these compounds may be effective antipsychotic drugs, which do not induce extrapyramidal side effects or tardive dyskinesia.

  DOI：

  10.1021/jm00101a012

文献信息

• Benzyl-piperidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05753679A1

  公开（公告）日：1998-05-19

  Benzly-piperidine derivatives of formula I and their pharmaceutically acceptable salts are used in the control of psychotic disorders which are caused by damage to the dopamine system, especially schizophrenia. ##STR1## A is ##STR2## B is ##STR3## R.sup.1, R.sup.2 and R.sup.3 are independently hydrogen, amino, nitro, halogen, lower-alkly or lower-alkoxy. R.sup.4, R.sup.5 and R.sup.6 are independently hydrogen, nitro, halogen, lower-alkyl, lower-alkoxy, cyano, trifluoromethyl, amino, lower-alkylamino or di-lower-alkylamino. R.sup.7, R.sup.2 and R.sup.9 are independently hydrogen, amino or nitro.

  Benzly-哌啶I类衍生物及其药学上可接受的盐用于控制由多巴胺系统损伤引起的精神障碍，尤其是精神分裂症。 ##STR1## A为 ##STR2## B为 ##STR3## R.sup.1、R.sup.2和R.sup.3各自独立地为氢、氨基、硝基、卤素、低级烷基或低级烷氧基。 R.sup.4、R.sup.5和R.sup.6各自独立地为氢、硝基、卤素、低级烷基、低级烷氧基、氰基、三氟甲基、氨基、低级烷基氨基或二低级烷基氨基。 R.sup.7、R.sup.2和R.sup.9各自独立地为氢、氨基或硝基。
• Discovery of novel 4‐methylpiperidinyl benzamide derivatives as <scp> 5‐HT ₄ </scp> receptor agonist for the treatment of gastrointestinal disorders
  作者：Sunho Choi、Min Jung Lee、Kwang‐Hyun Ahn

  DOI：10.1002/bkcs.12667

  日期：——

  Novel 4-methypiperidinyl benzamide derivatives were synthesized and evaluated for in vitro and in vivo prokinetic activities. In these derivatives, 3-methoxypiperidine moiety of norcisapride, a pharmacophore of cisapride and DA-6650, were replaced to 4-methylpiperidinyl moiety without chiral center. Among these derivatives, Compound 28b had a potent 5-HT4 receptor-binding affinity (IC50 = 0.067 μM)

  合成了新型 4-甲基哌啶基苯甲酰胺衍生物，并评估了体外和体内的促运动活性。在这些衍生物中，去甲西沙必利的 3-甲氧基哌啶部分、西沙必利的药效团和 DA-6650 被替换为没有手性中心的 4-甲基哌啶基部分。在这些衍生物中，化合物28b具有强效的 5-HT 4受体结合亲和力 (IC 50  = 0.067 μM)，并且在不抑制 CYP3A4 (IC 50  = 7.272 μM) 和阻断人类 ether-à-go-go-related 的情况下提高了安全性基因 (hERG) 通道 (IC 50  > 10 μM)。体内大鼠模型，化合物28b与对照组相比，胃排空率提高 (68.2%)，排便重量增加两倍以上。此外，它在刺激大鼠模型中显示出内脏超敏反应的缓解作用。因此，化合物28b被选为临床前候选药物，作为促动力剂，具有良好的安全性，可用于治疗胃肠道疾病。
• BENZYL PIPERIDINE DERIVATIVES AS PHARMACEUTICAL AGENTS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0871613A1

  公开（公告）日：1998-10-21
• US5753679A
  申请人：——

  公开号：US5753679A

  公开（公告）日：1998-05-19
• [EN] BENZYL PIPERIDINE DERIVATIVES AS PHARMACEUTICAL AGENTS<br/>[FR] DERIVES DE BENZYLPIPERIDINE EN TANT QU'AGENTS PHARMACEUTIQUES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：WO1996035666A1

  公开（公告）日：1996-11-14

  (EN) The invention is concerned with compounds of general formula (I) wherein: A signifies A1, A2, A3, A4, A5, A6, A7 or A8; n signifies 0-2; B signifies B1, B2 or B3; R1, R2 and R3 each independently signify hydrogen, amino, nitro, halogen, lower-alkyl or lower-alkoxy; R4, R5 and R6 each independently signify hydrogen, nitro, halogen, lower-alkyl, lower-alkoxy, cyano, trifluoromethyl, amino, lower-alkylamino or di-lower-alkylamino; R7, R8 and R9 each independently signify hydrogen, amino or nitro, as well as pharmaceutically acceptable salts of compounds of formula (I). These compounds can be used in the control of psychotic disorders which are caused by damage to the dopamine system.(FR) Composés de formule générale (I) dans laquelle A représente A1, A2, A3, A4, A5, A6, A7 ou A8; n représente 0 à 2, B représente B1, B2 ou B3; R1, R2 et R3 représentent chacun indépendamment hydrogène, amino, nitro, halogène, alkyle inférieur ou alcoxy inférieur; R4, R5 et R6 représentent chacun indépendamment hydrogène, nitro, halogène, alkyle inférieur, alcoxy inférieur, cyano, trifluorométhyle, amino, alkylamino inférieur ou di-alkylamino inférieur; R7, R8 et R9 représentent chacun indépendamment hydrogène, amino ou nitro, ainsi que sels pharmaceutiquement acceptables des composés de formule (I). Lesdits composés peuvent être utilisés pour lutter contre des troubles psychotiques qui sont causés par une altération du système de la dopamine.