4-cyano-4-(2-methylphenyl)piperidine hydrochloride | 186347-30-8

• 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: 4-cyano-4-(2-methylphenyl)piperidine hydrochloride
• 英文别名: 4-(2-methylphenyl)piperidine-4-carbonitrile;hydrochloride
• CAS: 186347-30-8
• 化学式: C₁₃H₁₆N₂*ClH
• 分子量: 236.744
• InChiKey: FIYNQLXUUBJDIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  35.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-cyano-4-(2-methylphenyl)piperidine hydrochloride 、 1-甲酰基-4-氧代-4H-羟基喹啉-3-羧酸乙酯 在 水 、 溶剂黄146 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 16.5h， 生成 1-[[4-Cyano-4-(2-methylphenyl)piperidin-1-yl]methyl]-4-oxoquinolizine-3-carboxylic acid
  参考文献：
  名称：

  Discovery of a Selective Allosteric M₁ Receptor Modulator with Suitable Development Properties Based on a Quinolizidinone Carboxylic Acid Scaffold

  摘要：

  One approach to ameliorate the cognitive decline in Alzheimer's disease (AD) has been to restore neuronal signaling from the basal forebrain cholinergic system via the activation of the M-1 muscarinic receptor. A number of nonselective M-1 muscarinic agonists have previously shown positive effects on cognitive behaviors in AD patients, but were limited due to cholinergic adverse events thought to be mediated by the activation of the M-2 to M-5 subtypes. One strategy to confer selectivity for M-1 is the identification of positive allosteric modulators, which would target an allosteric site on the M-1 receptor rather than the highly conserved orthosteric acetylcholine binding site. Quinoline carboxylic acids have I been previously identified as highly selective M-1 positive allosteric modulators with good pharmacokinetic and in vivo properties. Herein is described the optimization of a novel quinolizidinone carboxylic acid scaffold with 4-cyanopiperidines being a key discovery in terms of enhanced activity. In particular, modulator 4i gave high plasma free fractions, enhanced central nervous system (CNS) exposure, was efficacious in a rodent in vivo model of cognition, and afforded good physicochemical properties suitable for further preclinical evaluation.

  DOI：

  10.1021/jm200400m
• 作为产物：
  描述：

  4-氰基-4-邻甲苯哌啶-1-羧酸叔丁酯 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 4-cyano-4-(2-methylphenyl)piperidine hydrochloride
  参考文献：
  名称：

  Alpha 1a adrenergic receptor antagonists

  摘要：

  这项发明涉及某些新颖化合物及其衍生物，它们的合成以及它们作为选择性α 1a 肾上腺素能受体拮抗剂的用途。这些化合物的一个应用是用于治疗良性前列腺增生。这些化合物在其能够放松富含α 1a 受体亚型的平滑肌组织方面具有选择性，同时不会引起低血压。这样的组织之一就是围绕尿道内膜的组织。因此，这些化合物的一个用途是为患有良性前列腺增生的男性提供急性缓解，使尿液流动更加顺畅。这些化合物的另一个用途是与人类5-α还原酶抑制剂化合物结合，从而实现对良性前列腺增生影响的急性和慢性缓解。

  公开号：

  US05922722A1

文献信息

• Alpha 1a adrenergic receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05922722A1

  公开（公告）日：1999-07-13

  This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These componds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

  这项发明涉及某些新颖化合物及其衍生物，它们的合成以及它们作为选择性α 1a 肾上腺素能受体拮抗剂的用途。这些化合物的一个应用是用于治疗良性前列腺增生。这些化合物在其能够放松富含α 1a 受体亚型的平滑肌组织方面具有选择性，同时不会引起低血压。这样的组织之一就是围绕尿道内膜的组织。因此，这些化合物的一个用途是为患有良性前列腺增生的男性提供急性缓解，使尿液流动更加顺畅。这些化合物的另一个用途是与人类5-α还原酶抑制剂化合物结合，从而实现对良性前列腺增生影响的急性和慢性缓解。
• Alpha-1a adrenergic receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05661163A1

  公开（公告）日：1997-08-26

  This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha-1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing orthostatic hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

  本发明涉及某些新型化合物及其衍生物，它们的合成以及它们作为选择性α-1a肾上腺素受体拮抗剂的用途。这些化合物的应用之一是用于治疗良性前列腺增生症。这些化合物在其选择性松弛富含α 1a受体亚型的平滑肌组织的能力方面是具有选择性的，而不会同时引起直立性低血压。这样的组织可以在尿道内膜周围找到。因此，这些化合物的一个用途是为患有良性前列腺增生症的男性提供急性缓解，使尿液流动更加顺畅。这些化合物的另一个用途是与人类5α-还原酶抑制剂化合物结合使用，从而实现良性前列腺增生症的急性和慢性缓解效果。
• ALPHA 1a ADRENERGIC RECEPTOR ANTAGONIST
  申请人：MERCK & CO., INC.

  公开号：EP0833637A1

  公开（公告）日：1998-04-08
• EP0833637A4
  申请人：——

  公开号：EP0833637A4

  公开（公告）日：1998-07-08
• ALPHA 1a ADRENERGIC RECEPTOR ANTAGONISTS
  申请人：MERCK & CO., INC.

  公开号：EP0865280A1

  公开（公告）日：1998-09-23