(R)-2-[3-(1-pyrrolidinyl)-1-propynyl]-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester | 130523-33-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (R)-2-[3-(1-pyrrolidinyl)-1-propynyl]-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester
• 英文别名: (R)-t-butyl 2-[3-(1-pyrrolidinyl)-1-propynyl]-1-pyrrolidinecarboxylate；tert-butyl (2R)-2-(3-pyrrolidin-1-ylprop-1-ynyl)pyrrolidine-1-carboxylate
• CAS: 130523-33-0
• 化学式: C₁₆H₂₆N₂O₂
• 分子量: 278.395
• InChiKey: LVDNNKJGKTWTDP-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-[3-(1-pyrrolidinyl)-1-propynyl]-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester 在 盐酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 (R)-1-acetyl-2-<3-(1-pyrrolidinyl)-1-propynyl>pyrrolidine
  参考文献：
  名称：

  Chemical and biochemical studies of 2-propynylpyrrolidine derivatives. Restricted-rotation analogs of N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5)

  摘要：

  A series of optically pure 2-[substituted-3-aminopropynyl]pyrrolidine derivatives, which are restricted-rotation analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5, compound 1), have been prepared from d- and l-proline. The compounds when tested in a series of in vitro muscarinic assays [[3H]CD (cortex), [3H]QNB (cortex), [3H]PZ (cortex), [3H]QNB (heart), [3H]QNB + GppNHp (heart)] were found to have weaker muscarinic properties than compound 1. The decrease in affinity was attributed to the increased size of the molecule resulting from the addition of a methylene group to form the pyrrolidine ring. The use of optically active compounds provided a more detailed examination of the complex pharmacological effects of the flexible muscarinic agent 1. The R enantiomers in the acetamide derivatives 12b, 12d, and 12f had a 5-10-fold greater affinity for the muscarinic receptor than the corresponding S enantiomers. A 5-fold difference or less found in the (R)- and (S)-carbamate derivatives 9, 15, and 16 suggested close overlap of the two enantiomers in the receptor binding domain. The affinity differences found in the enantiomeric acetamido derivatives when compared to those of the carbamate analogues may be the result of limited rotation of the acetamido group.

  DOI：

  10.1021/jm00174a015
• 作为产物：
  描述：

  N-(tert-butoxycarbonyl)-D-proline 在 dimethyl sulfide borane 、 4 A molecular sieve 、 仲丁基锂 、 溶剂黄146 、 三苯基膦 、 pyridinium chlorochromate 、 copper(l) chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 (R)-2-[3-(1-pyrrolidinyl)-1-propynyl]-1-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Chemical and biochemical studies of 2-propynylpyrrolidine derivatives. Restricted-rotation analogs of N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5)

  摘要：

  A series of optically pure 2-[substituted-3-aminopropynyl]pyrrolidine derivatives, which are restricted-rotation analogues of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5, compound 1), have been prepared from d- and l-proline. The compounds when tested in a series of in vitro muscarinic assays [[3H]CD (cortex), [3H]QNB (cortex), [3H]PZ (cortex), [3H]QNB (heart), [3H]QNB + GppNHp (heart)] were found to have weaker muscarinic properties than compound 1. The decrease in affinity was attributed to the increased size of the molecule resulting from the addition of a methylene group to form the pyrrolidine ring. The use of optically active compounds provided a more detailed examination of the complex pharmacological effects of the flexible muscarinic agent 1. The R enantiomers in the acetamide derivatives 12b, 12d, and 12f had a 5-10-fold greater affinity for the muscarinic receptor than the corresponding S enantiomers. A 5-fold difference or less found in the (R)- and (S)-carbamate derivatives 9, 15, and 16 suggested close overlap of the two enantiomers in the receptor binding domain. The affinity differences found in the enantiomeric acetamido derivatives when compared to those of the carbamate analogues may be the result of limited rotation of the acetamido group.

  DOI：

  10.1021/jm00174a015

文献信息

• 1-substituted-2-(3-amino-1-propynyl)pyrrolidine derivatives
  申请人：American Cyanamid Company

  公开号：US05001142A1

  公开（公告）日：1991-03-19

  Compounds of the formula: ##STR1## pharmaceutical compositions containing the compounds and methods of using the compounds in the treatment of central cholinergic disfunction in a mammal are disclosed.

  公开了化合物的公式：##STR1## 包含这些化合物的药物组合物以及在哺乳动物中治疗中枢胆碱能功能障碍的方法。
• Dibromovinyl and acetylene-1-pyrrolidinecarboxylic acid intermediates
  申请人：American Cyanamid Company

  公开号：US05128483A1

  公开（公告）日：1992-07-07

  Compounds of the formula: ##STR1## wherein A is t-butoxy carbonyl, which compounds are useful as intermediates for preparing 1-Substituted-2-(3-amino-1-propynyl)pyrrolidine derivatives having cholinergic agonist activity.

  公式为：## STR1 ## 其中A为叔丁氧羰基的化合物，可用作制备具有胆碱能激动剂活性的1-取代-2-(3-氨基-1-丙炔基)吡咯烷衍生物的中间体。
• Heterocyclic acetylenic amines having central nervous system activity
  申请人：The Upjohn Company

  公开号：US05137905A1

  公开（公告）日：1992-08-11

  Heterocyclic acetylenic amine compounds having the following structural formula ##STR1## having cholinergic agonist or antagonist activity useful in the treatment of mental disorders, extrapyramidal motor disorders, disorders of the parasympathetic nervous system and glaucoma or as analgesics for the treatment of pain. Typical central nervous system disorders for which the subject compounds can be used include cognitive disorders of all ages, including senile dementia, Alzheimer's disease and other related disorders. The compounds are particularly developed to improve mental performance when a mental deficiency is diagnosed.

  具有以下结构式##STR1##的杂环乙炔胺化合物具有胆碱能激动剂或拮抗剂活性，可用于治疗精神障碍、锥体外运动障碍、副交感神经系统障碍和青光眼，或作为镇痛剂用于治疗疼痛。这些化合物可用于各个年龄段的认知障碍，包括老年性痴呆症、阿尔茨海默病和其他相关疾病。这些化合物特别是为了在诊断出智力缺陷时改善智力表现而开发的。
• TRYBULSKI, EUGENE J.;KRAMSS, RICHARD H.;MANGANO, RICHARD M.;RUSINKO, ANDR+, J. MED. CHEM., 33,(1990) N2, C. 3190-3198
  作者：TRYBULSKI, EUGENE J.、KRAMSS, RICHARD H.、MANGANO, RICHARD M.、RUSINKO, ANDR+

  DOI：——

  日期：——
• HETEROCYCLIC ACETYLENIC AMINES HAVING CENTRAL NERVOUS SYSTEM ACTIVITY
  申请人：THE UPJOHN COMPANY

  公开号：EP0440670A1

  公开（公告）日：1991-08-14