(2R,5R)-2-(t-butyl)-5-[(1S)-3-hydroxycyclopentyl]-5-phenyl-1,3-dioxolan-4-one | 203321-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (2R,5R)-2-(t-butyl)-5-[(1S)-3-hydroxycyclopentyl]-5-phenyl-1,3-dioxolan-4-one
• 英文别名: (2R,5R)-2-tert-butyl-5-[(1S)-3-hydroxycyclopentyl]-5-phenyl-1,3-dioxolan-4-one
• CAS: 203321-60-2
• 化学式: C₁₈H₂₄O₄
• 分子量: 304.386
• InChiKey: UZFGSAJQIUZDDX-INDKVVHLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2R,5R)-2-(t-butyl)-5-[(1S)-3-hydroxycyclopentyl]-5-phenyl-1,3-dioxolan-4-one 在 二乙胺基三氟化硫 作用下， 以 氯仿 为溶剂， 反应 1.5h， 生成 (2R,5R)-2-tert-butyl-5-[(1S)-3-fluorocyclopentyl]-5-phenyl-1,3-dioxolan-4-one
  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 在 sodium borohydrid 作用下， 以 甲醇 为溶剂， 生成 (2R,5R)-2-(t-butyl)-5-[(1S)-3-hydroxycyclopentyl]-5-phenyl-1,3-dioxolan-4-one
  参考文献：
  名称：

  N-acyl cyclic amine derivatives

  摘要：

  该发明涉及由通式[I]表示的化合物 ##STR1## [其中Ar表示芳基或杂环基，可能具有从卤原子、较低烷基基团和较低烷氧基团中选择的取代基; R.sup.1表示可用氟原子取代的C.sub.3-C.sub.6环烷基基团; R.sup.2和R.sup.4表示氢原子，表示为--(A.sup.1).sub.m--NH--B或类似基团; R.sup.3和R.sup.5表示氢原子，可用较低烷基基团取代的C.sub.1-C.sub.6脂肪烃基团或类似基团; n表示0或1; X表示氧原子或硫原子]。根据该发明的化合物，由于它们不仅具有对M.sub.3胆碱能受体具有强效选择性拮抗活性，而且表现出优异的口服活性、持久作用和药代动力学特性，因此在对抗呼吸、泌尿和消化系统疾病时非常有用，且副作用很小，是安全有效的药物。

  公开号：

  US06140333A1

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。
• 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
• US5948792A
  申请人：——

  公开号：US5948792A

  公开（公告）日：1999-09-07
• US6040449A
  申请人：——

  公开号：US6040449A

  公开（公告）日：2000-03-21