(2R)-[(1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetic acid | 203321-58-8

• 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: (2R)-[(1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetic acid
• 英文别名: (2R)-2-((1S)-3,3-difluorocyclopentyl)-2-hydroxy-2-phenylacetic acid；(2R)-2-[(1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetic acid
• CAS: 203321-58-8
• 化学式: C₁₃H₁₄F₂O₃
• 分子量: 256.249
• InChiKey: GPUGYUSBIRXKND-GWCFXTLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methyl-3-pentenyl)-4-aminopiperidine 、 (2R)-[(1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetic acid 在 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 氯仿 为溶剂， 反应 14.0h， 以73%的产率得到(2R)-N-[1-(4-methyl-3-pentenyl)piperidin-4-yl]-2-[(1S)-3,3-difluorocyclopentyl]-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
• 作为产物：
  描述：

  (2R,5R)-2-tert-butyl-5-[(1S)-3-oxocyclopentyl]-5-phenyl-1,3-dioxolan-4-one 生成 (2R)-[(1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetic acid
  参考文献：
  名称：

  Fluorine-containing 1,4-disubstituted piperidine derivatives

  摘要：

  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。

  公开号：

  US05948792A1

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。
• MUSCARINIC RECEPTOR ANTAGONISTS
  申请人：Kumar Naresh

  公开号：US20100056496A1

  公开（公告）日：2010-03-04

  The present invention generally relates to muscarinic receptor antagonists, which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The present invention also relates to processes for preparing compounds described herein, pharmaceutical compositions thereof, and methods for treating diseases mediated through muscarinic receptors. Formula (I) or a pharmaceutically accepted salt, pharmaceutically acceptable solvate, enantiomers, diastereomer, polymorph or N-oxide thereof, wherein X is.

  本发明通常涉及抗胆碱受体拮抗剂，这些拮抗剂可用于治疗经由胆碱受体介导的呼吸系统、泌尿系统和消化系统的各种疾病，此外，本发明还涉及制备所述化合物的过程、其制药组合物以及治疗经由胆碱受体介导的疾病的方法。其中，公式（I）或其药学上可接受的盐、药学上可接受的溶剂化物、对映体、非对映异构体、多晶形或N-氧化物，其中X为。
• N-ACYL CYCLIC AMINE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1061076A1

  公开（公告）日：2000-12-20

  The invention relates to compounds represented by the general formula [I] [wherein Ar means an aryl group or a heteroaryl group which may have a substitutive group selected from a group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group; R1 means a C3-C6 cycloalkyl group which is substitutable with a fluorine atom; R2 and R4 mean hydrogen atoms, groups represented by -(A1)m-NH-B or the like; R3 and R5 mean hydrogen atoms, C1-C6 aliphatic hydrocarbon groups or the like which are substitutable with a lower alkyl group(s) ; n means 0 or 1; and X means an oxygen atom or a sulfur atom]. Compounds according to the invention, since they not only have potent selective antagonistic activity against muscarinic M3 receptors but also exhibit excellent oral activity, durability of action and pharmacokinetics, are very useful as safe and effective remedies against respiratory, urinary and digestive diseases with little adverse side effects.

  本发明涉及通式[I]所代表的化合物。 [其中 Ar 指芳基或杂芳基，可带有选自卤原子、低级烷基和低级烷氧基的取代基团；R1 指可被氟原子取代的 C3-C6 环烷基；R2和R4指氢原子、由-(A1)m-NH-B代表的基团或类似基团；R3和R5指氢原子、可被低级烷基取代的C1-C6脂族烃基或类似基团；n指0或1；X指氧原子或硫原子]。 根据本发明的化合物不仅对毒蕈碱类 M3 受体具有强效的选择性拮抗活性，而且具有良好的口服活性、作用持久性和药代动力学，因此非常适合作为安全有效的治疗呼吸系统、泌尿系统和消化系统疾病的药物，且不良副作用小。
• 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
• COMPOSITIONS OF PHOSPHODIESTERASE TYPE IV INHIBITORS
  申请人：Ray Abhijit

  公开号：US20100004215A1

  公开（公告）日：2010-01-07

  Provided herein are pharmaceutical compositions comprising one or more phosphodiesterase inhibitors of type IV (“PDE-IV”), and at least one other active ingredient such as muscarinic receptor antagonists (MRA), β2-agonists, p38 MAP Kinase inhibitors, or corticosteroids and optionally one or more pharmaceutically acceptable excipients. In addition, methods of treating autoimmune, inflammatory or allergic diseases or disorders are provided.