1-(4-methyl-3-pentenyl)-4-aminopiperidine | 185030-43-7

• 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: 1-(4-methyl-3-pentenyl)-4-aminopiperidine
• 英文别名: 4-amino-1-(4-methyl-3-pentenyl)piperidine；1-(4-methylpent-3-enyl)piperidin-4-amine；4-amino-1-(4-methyl-3-pentenyl)piperidin；1-(4-Methyl-3-penten-1-yl)-4-piperidinamine
• CAS: 185030-43-7
• 化学式: C₁₁H₂₂N₂
• 分子量: 182.309
• InChiKey: HMFBMHCGFUQALA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-methyl-3-pentenyl)-4-aminopiperidine 在 sodium hydroxide 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 38.0h， 生成 (2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-[(1S,3S)-3-aminocyclopentyl]-2-hydroxy-2-phenylacetamide
  参考文献：
  名称：

  Discovery of a muscarinic M 3 receptor antagonist with high selectivity for M 3 over M 2 receptors among 2-[(1 S ,3 S )-3-sulfonylaminocyclopentyl]phenylacetamide derivatives

  摘要：

  In the course of developing a metabolically stable M-3 receptor antagonist from the prototype antagonist, J-104129 (1), introduction of certain substituents into the cyclopentane ring of 1 was found to be effective not only in improving metabolic stability but also in greatly enhancing the subtype selectivity. Among the cyclopentane analogues, sulfonamide derivatives (10f) and (10g) displayed 160- and 310-fold selectivity for M-3 over M-2 receptors, and both were significantly more selective than the prototype antagonist (120-fold). Subsequent derivatization of the sulfonamide series led to the highly selective M-3 receptor antagonists (10h, 10i and 10j) with >490-fold selectivity for M-3 over M-2 receptors. Among them, p-nitrophenylsulfonamide (J-107320, 10h) exhibited 1 100-fold selectivity for M-3 receptors (K-i = 2.5 nM) over M-2 receptors (K-i = 2800 nM) in the human muscarinic receptor binding assay using [H-3]-NMS as a radio ligand. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00008-0
• 作为产物：
  描述：

  5-溴-2-甲基-2-戊烯 在 ammonium acetate 、 sodium cyanoborohydride 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 17.0h， 生成 1-(4-methyl-3-pentenyl)-4-aminopiperidine
  参考文献：
  名称：

  J-104129, a novel muscarinic M3 receptor antagonist with high selectivity for M3 over M2 receptors

  摘要：

  A new class of 4-acetamidopiperidine derivatives has been synthesized and investigated for human muscarinic receptor subtype selectivity. Introduction of a hydrocarbon chain of appropriate length into the piperidine nitrogen of the racemic N-(piperidin-4-yl)-2-cyclobutyl-2-hydroxy-2-phenylacetamide platform conferred up to 70-fold selectivity for human muscarinic M-3 receptors over M-2 receptors. Subsequent synthetic derivatizations resulted in highly potent M-3 receptor antagonists with selectivity greater than two orders of magnitude for M-3 over M-2 receptors, from which the analogue 4r was selected. Preparation of both enantiomers of 4r led to the identification of (2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide (J-104129, (R)-4r), which exhibited 120-fold selectivity for Mg receptors (K-i = 4.2 nM) over M-2 receptors (K-i = 490 nM). In isolated rat trachea, (R)-4r potently and specifically antagonized acetylcholine (ACh)-induced responses with a K-B value of 3.3 nM. The highly subtype-selective profile was also seen in isolated rat tissue assays (50-fold) and in anesthetized rats (> 250-fold). Oral administration of J-104129 ((R)-4r) antagonized ACh-induced bronchoconstriction with an ED50 value of 0.58 mg/kg in rats. Thus, J-104129 ((R)-4r) may effectively facilitate bronchodilation in the treatment of obstructive airway disease. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00177-7

文献信息

• Fluorine-containing 1,4-disubstituted piperidine derivatives
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US05948792A1

  公开（公告）日：1999-09-07

  Novel fluorine-containing 1,4-disubstituted piperidine derivatives, represented by general formula \x9bI! ##STR1## such as, for example, (2R)-N-\x9b1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl!-2-\x9b(1R)-3,3-difluoroc yclopentyl!-2-hydroxy-2-phenylacetamide or pharmaceutically acceptable salt thereof, are potent and selective antagonists for muscarinic M.sub.3 receptors with little side effects. The compounds of formula \x9bI! exhibit excellent oral activity, duration of activity and pharmacolkinetics. They are useful for treatment and prophylaxis of respiratory diseases, such as chronic obstructive pulmonary diseases; urinary diseases, such as urinary incontinence; and digestive diseases, such as irritable bowel syndrome, and motion sickness.

  含氟的新型1,4-二取代哌啶衍生物，通式\x9bI! ##STR1##例如，(2R)-N-\x9b1-(6-氨基吡啶-2-基甲基)哌啶-4-基!-2-\x9b(1R)-3,3-二氟环戊基!-2-羟基-2-苯乙酰胺或其药用盐，是对M.sub.3受体具有强效和选择性拮抗作用的化合物，副作用很小。通式\x9bI!的化合物表现出优异的口服活性、活性持续时间和药代动力学。它们可用于治疗和预防呼吸系统疾病，如慢性阻塞性肺疾病；泌尿系统疾病，如尿失禁；以及消化系统疾病，如肠易激综合征和晕动病。
• PYRROLE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0906279B1

  公开（公告）日：2002-10-02
• A Potent, Long-Acting, Orally Active (2<i>R</i>)-2-[(1<i>R</i>)-3,3-Difluorocyclopentyl]-2-hydroxy-2-phenylacetamide:  A Novel Muscarinic M₃ Receptor Antagonist with High Selectivity for M₃ over M₂ Receptors
  作者：Morihiro Mitsuya、Kensuke Kobayashi、Kumiko Kawakami、Atsushi Satoh、Yoshio Ogino、Taro Kakikawa、Norikazu Ohtake、Toshifumi Kimura、Hiroyasu Hirose、Akio Sato、Tomosige Numazawa、Takuro Hasegawa、Kazuhito Noguchi、Toshiaki Mase

  DOI：10.1021/jm0003135

  日期：2000.12.1

  A novel series of (2R)-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamides was designed and synthesized based on the structure and biological profiles of an active metabolite 2 of our prototype muscarinic M-3 receptor selective antagonist 1, to develop a potent, long-acting, orally active M-3 antagonist for the treatment of urinary tract disorders, irritable bowel syndrome, and respiratory disorders. Investigation of (2R)-2-[(IR)-3,3-difluorocyclopentyl] -2-hydroxy-2-phenylacetamides containing a phenyl or heterocyclic ring as the piperidinyl side chain in place of the 4-methyl-3-pentenyl moiety of 15a revealed that this acid moiety was a versatile template for improving the selectivity for M-3 over M-2 receptors in comparison With the corresponding cyclopentylphenylacetic acid group: However, since the in vitro metabolic stability of these analogues was insufficient compared with that of 2, further derivatization was performed by introducing an appropriate hydrophilic group into the phenyl or 2-pyridyl ring. Thus, the 1;(6-aminopyridin-2-ylmethyl)piperidine analogue 15y exhibiting 190-fold selectivity for M-3 receptors (K-i = 2.8 nM) over M-2 receptors (K-i = 530 nM) in a human binding assay and-good in vitro metabolic stability in dog and human hepatic microsomes:was identified; This compound has excellent oral activity at 4 h after oral dosing (1 mg/kg), inhibiting methacholine-induced : bronchoconstriction in dogs, and may be useful in clinical situations in which M-3 over M-2 selectivity is desirable.
• WO2006/63010
  申请人：——

  公开号：——

  公开（公告）日：——
• FLUORINATED 1,4-DISUBSTITUTED PIPERIDINE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0930298B1

  公开（公告）日：2002-12-18