N-(piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide | 185030-18-6

• 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: N-(piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide
• 英文别名: 2-cyclopentyl-2-hydroxy-2-phenyl-N-piperidin-4-ylacetamide
• CAS: 185030-18-6
• 化学式: C₁₈H₂₆N₂O₂
• 分子量: 302.417
• InChiKey: SQDQPTRJYPZAEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  61.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide 在 sodium chloride 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 生成 N-[1-(cycloheptylmethyl)piperidin-4-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide
  参考文献：
  名称：

  1,4-di-substituted piperidine derivatives

  摘要：

  该发明提供了一种新型的1,4-二取代哌啶衍生物，其通式为##STR1##及其药学上可接受的盐，其中：Ar代表苯基或含有一个或两个异原子（选自氧原子、硫原子和氮原子）的五元或六元杂环芳基，环上的一个或两个可选氢原子可被卤素原子和较低的烷基基团替代；R1代表3到6个碳原子的环烷基基团或3到6个碳原子的环烯烃基团；R2代表5到15个碳原子的饱和或不饱和脂肪烃基团；X代表O或NH。这些化合物对M.sub.3胆碱能受体具有选择性拮抗活性，因此可以安全地使用，并具有最少的副作用。

  公开号：

  US05750540A1
• 作为产物：
  描述：

  4-氨基-1-苄基哌啶 在 20percent Pd(OH)2 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 氯仿 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 22.0h， 生成 N-(piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide
  参考文献：
  名称：

  A Potent, Long-Acting, Orally Active (2R)-2-[(1R)-3,3-Difluorocyclopentyl]-2-hydroxy-2-phenylacetamide:  A Novel Muscarinic M₃ Receptor Antagonist with High Selectivity for M₃ over M₂ Receptors

  摘要：

  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.

  DOI：

  10.1021/jm0003135

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。
• Substituted piperidine derivatives as muscarinic M.sub.3 receptor
  申请人：Banyu Pharmaceutical Coaltd

  公开号：US06130232A1

  公开（公告）日：2000-10-10

  This invention provides substituted heteroaromatic ring derivatives which are represented by a general formula [I] below: ##STR1## [in the formula, R.sup.1 and R.sup.2 may be same or different and each signifies hydrogen, halogen or lower alkyl; R.sup.3 signifies C.sub.3 -C.sub.6 cycloalkyl or cycloalkenyl; R.sup.4 signifies a heteroaromatic ring group which may be condensed with a benzene ring and which has 1 or 2 hetero atoms selected from a group consisting of nitrogen, oxygen and sulfur atoms (said heteroaromatic ring group being optionally substituted with lower alkyl, halogen, lower alkoxy, amino or hydroxymethyl); and X stands for O or NH] or their pharmaceutically acceptable salts. The substituted heteroaromatic ring derivatives of the present invention have selective M.sub.3 muscarinic receptor antagonist activity, and hence they are useful as therapeutic or prophylactic agents which are safe and efficacious with little side effects, of respiratory diseases such as asthma, chronic airway obstruction and pulmonary fibrosis, etc.; urinary diseases which induce such urination disorders as pollakiurea, urgency and urinary incontinence, etc.; and gastrointestinal diseases such as irritable bowel syndrome, spasm of gastrointestinal tract and gastrointestinal hyperkinesis.

  本发明提供了一种由下式[I]表示的取代杂芳环衍生物：##STR1## [在公式中，R.sup.1和R.sup.2可以相同或不同，分别表示氢、卤素或低烷基；R.sup.3表示C.sub.3-C.sub.6环烷基或环烯基；R.sup.4表示一种杂芳环基团，可以与苯环融合，并且具有从氮、氧和硫原子中选择的1或2个杂原子（该杂芳环基团可以选用低烷基，卤素，低烷氧基，氨基或羟甲基进行取代）；X代表O或NH]或其药学上可接受的盐。本发明的取代杂芳环衍生物具有选择性的M.sub.3肌动蛋白受体拮抗作用，因此它们可用作治疗或预防剂，对于呼吸道疾病，如哮喘、慢性气道阻塞和肺纤维化等，具有安全、有效且副作用小的作用；对于引起排尿障碍，如尿频、尿急和尿失禁等的泌尿系统疾病；以及对于肠易激综合征、胃肠道痉挛和胃肠道过度运动等胃肠道疾病。
• 1,4-DISUBSTITUTED PIPERIDINE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0823423B1

  公开（公告）日：2004-06-16
• SUBSTITUTED HETEROAROMATIC DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0863141B1

  公开（公告）日：2001-09-12
• 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