(3S)-3-azido-1-(phenylmethyl)pyrrolidine | 114636-29-2

• 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: (3S)-3-azido-1-(phenylmethyl)pyrrolidine
• 英文别名: (3S)-3-azido-1-benzylpyrrolidine；(3S)-1-benzyl-3-azidopyrrolidine
• CAS: 114636-29-2
• 化学式: C₁₁H₁₄N₄
• 分子量: 202.259
• InChiKey: KPXBMEKTAFSEQX-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  17.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S)-3-azido-1-(phenylmethyl)pyrrolidine 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 (S)-(-)-1-苄基-3-(叔丁氧羰基氨基)吡咯烷
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Naphthamides as Dopamine D₃ Receptor Ligands

  摘要：

  A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D-2 and D-3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1-alkylpiperidin-4-yl)-4-bromo-1-methoxy-2-naphthamides (1-6), (S)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (7-12), (R)-N-(1-alkylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamides (13-18), (S)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (19 -25), (R)-N-(1-alkyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamides (26-31), and N-(9-alkyl-9-azabicyclo-[3.3.1]nonan-3 beta -yl)-4- bromo-1-methoxy-2-naphthamides (32, 33). The results of in vitro radioligand binding studies indicated that the majority of the naphthamide analogues bound with high affinity at both the D-2 and D-3 dopamine receptor subtypes and most of the compounds demonstrated some selectivity for the dopamine D-3 dopamine receptor subtype. These results demonstrated that both the structure of the central amine moiety (piperidine, pyrrolidine, and 9-azabicyclo[3.3.1]nonane) ring and the N-(alkyl) substitution on the amine significantly effects the binding affinity at D-2 and D-3 dopamine receptors. The bulkiness of the N-(1-alkyl) substituent was found to (a) have no effect on pharmacologic selectivity, (b) increase the affinity at Ds receptors, or (c) decrease the affinity at D-2 receptors. The most potent analogue in this series was (S)-N-(1-cycloheptylpyrrolidin-3-yl)-4-bromo-1-methoxy-2-naphthamide (10), which had equilibrium dissociation (K-i) values of 1.8 and 0.2 nM for D-2 and D-3 receptors, respectively. The most selective analogue was (R)-N-(1-cycloheptyl-2-pyrrolidinylmethyl)-4-bromo-1-methoxy-2-naphthamide (30), which had K-i values of 62.8 and 2.4 nM for D-2 and D-3 receptors, respectively. Radioligand binding results for sigma receptors indicated that the structure of the amine moiety and the N-(l-alkyl) substitutions also significantly influence the affinity and selectivity of these compounds at the sigma (1) and sigma (2) sigma receptor subtypes. The two naphthamides containing a 9-azabicyclo[3.3.1]nonan-3 beta -yl central ring were found to be selective for sigma (2) receptors.

  DOI：

  10.1021/jm0100077
• 作为产物：
  描述：

  (S)-3-羟基-1-苄基吡咯烷 在 sodium azide 、 四丁基溴化铵 、 水 、 三乙胺 、 三苯基膦 、 lithium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 (3S)-3-azido-1-(phenylmethyl)pyrrolidine
  参考文献：
  名称：

  在新型抗肿瘤组蛋白脱乙酰基酶抑制剂的设计和生物力学评估中探索喹唑啉生物碱-Vasicine作为帽基的衍生物。

  摘要：

  1- Vasicine是一种喹唑啉生物碱，具有电子致密环，并且在其结构中具有其他功能。利用基于计算机模拟研究的靶向定向合成（TOS），合成了具有显着对接分数的分子，其中包含1- vasicine的不同衍生物作为帽。有趣的是，发现一个分子，即4a，它含有3-羟基吡咯烷作为帽基和一个六碳长的脂肪族链作为连接基，可以抑制HDAC。图4a显示了对I类HDAC同工型的更多特异性。与癌细胞系相比，还发现4a对正常细胞系的细胞毒性较小。4a通过多种机制抑制癌细胞的生长并诱导细胞死亡。但是，发现4a可以诱导细胞死亡而与ROS的产生无关，并且与许多基于天然产物的HDAC抑制剂不同，发现4a在体内条件下是无毒的。重要的是，我们首次报道了使用3-羟基吡咯烷帽合成具有良好效力的HDAC抑制剂的可能性。

  DOI：

  10.1021/acs.jmedchem.7b00322

文献信息

• [EN] 1-SUBSTITUTED-3-PYRROLIDINE DERIVATIVES AS MUSCARINIC RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE 1-SUBSTITUES-3-PYRROLIDINES COMME ANTAGONISTES DE RECEPTEURS MUSCARINIQUES
  申请人：RANBAXY LAB LTD

  公开号：WO2004056767A1

  公开（公告）日：2004-07-08

  This invention generally relates to the derivatives of 1 -substituted-3 -pyrroli dines having the structure of Formula (I): The compounds of this invention can function as..muscarinic receptor antagonists, and can be used for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to a process for the preparation of the compounds of the present invention. pharmaceutical compositions containing the compounds of the present invention and the methods for treating the diseases mediated through muscarinic receptors.

  这项发明通常涉及具有式（I）结构的1-取代-3-吡咯啉二烯衍生物：本发明的化合物可以作为..毒蕈碱受体拮抗剂，可用于治疗通过毒蕈碱受体介导的呼吸系统、泌尿系统和消化系统的各种疾病。该发明还涉及制备本发明化合物的方法、含有本发明化合物的药物组合物以及治疗通过毒蕈碱受体介导的疾病的方法。
• Stereocontrolled dopamine receptor binding and subtype selectivity of clebopride analogues synthesized from aspartic acid
  作者：Jürgen Einsiedel、Klaus Weber、Christoph Thomas、Thomas Lehmann、Harald Hübner、Peter Gmeiner

  DOI：10.1016/s0960-894x(03)00678-4

  日期：2003.10

  Employing the achiral 4-aminopiperidine derivative clebopride as a lead compound, chiral analogues were developed displaying dopamine receptor binding profiles that proved to be strongly dependent on the stereochemistry. Compared to the D1 receptor, the test compounds showed high selectivity for the D2-like subtypes including D2(long), D2(short), D3 and D4. The highest D4 and D3 affinities were observed

  利用非手性4-氨基哌啶衍生物clebopride作为先导化合物，开发了显示出多巴胺受体结合特征的手性类似物，事实证明该手性类似物强烈依赖于立体化学。与D1受体相比，测试化合物对D2类亚型（包括D2（长），D2（短），D3和D4）表现出高选择性。对于顺式-3-氨基-4-甲基吡咯烷3e和对映体ent3e观察到最高的D4和D3亲和力，分别导致K（i）值为0.23和1.8nM。从（S）-天冬氨酸及其非天然旋光对映体开始，以对映纯形式合成3型和5型苯甲酰胺。
• Asymmetric synthesis and properties of the enantiomers of the antibacterial agent 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride
  作者：Terry Rosen、Daniel T. W. Chu、Isabella M. Lico、Prabhavathi B. Fernandes、Linus Shen、Saul Borodkin、Andre G. Pernet

  DOI：10.1021/jm00403a017

  日期：1988.8

  quinolonecarboxylic acid class of antibacterial agents and is currently undergoing clinical evaluation. We have developed efficient asymmetric syntheses of the enantiomers of this agent. The S-(+) enantiomer 1a is 1-2 log2 dilutions more active than the R-(-) enantiomer 1b against aerobic bacteria and 1-2 or more log2 dilutions more active against anaerobic bacteria in vitro. The enantiomer 1a shows

  化合物1 [7-（3-氨基吡咯烷-1-基）-1-（2,4-二氟苯基）-1,4-二氢-6-氟咯-4-羰基-1,8-萘啶-3-羧酸盐酸]是喹诺酮羧酸类抗菌剂的有效成员，目前正在临床评估中。我们已经开发了该试剂的对映异构体的有效不对称合成。在体外，S-（+）对映异构体1a的抗氧性比R-（-）对映异构体1b的活性高1-2个log2稀释，对厌氧菌具有1-2个或更多log2稀释。对映异构体1a在铜绿假单胞菌小鼠保护模型中显示出比消旋体1更好的体内活性。再加上1a相对于消旋体材料的溶解度改善，从临床角度来看，这些特征可能具有实际意义。
• 1-Substituted-3-pyrrolidine derivatives as muscarinic receptor antagonists
  申请人：Mehta Anita

  公开号：US20060194862A1

  公开（公告）日：2006-08-31

  This invention generally relates to the derivatives of 1-substituted-3-pyrroli dines having the structure of Formula (I): The compounds of this invention can function as muscarinic receptor antagonists, and can be used for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to a process for the preparation of the compounds of the present invention. pharmaceutical compositions containing the compounds of the present invention and the methods for treating the diseases mediated through muscarinic receptors.

  本发明通常涉及具有公式（I）结构的1-取代-3-吡咯啉衍生物：本发明的化合物可以作为肌肉型受体拮抗剂，可用于通过肌肉型受体介导的呼吸系统、泌尿系统和胃肠系统的各种疾病的治疗。本发明还涉及制备本发明化合物的方法，含有本发明化合物的制药组合物以及治疗通过肌肉型受体介导的疾病的方法。
• 1-substituted-3-pyrrolidine derivatives as muscarinic receptor antagonists
  申请人：Ranbaxy Laboratories Limited

  公开号：US07465751B2

  公开（公告）日：2008-12-16

  This invention generally relates to the derivatives of 1-substituted-3-pyrroli dines having the structure of Formula (I): The compounds of this invention can function as muscarinic receptor antagonists, and can be used for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to a process for the preparation of the compounds of the present invention. pharmaceutical compositions containing the compounds of the present invention and the methods for treating the diseases mediated through muscarinic receptors.

  本发明一般涉及具有式(I)结构的1-取代-3-吡咯啉啶衍生物：本发明的化合物可以作为毒蕈碱受体拮抗剂，可用于通过毒蕈碱受体介导的呼吸系统、泌尿系统和胃肠道各种疾病的治疗。本发明还涉及制备本发明化合物的方法、含有本发明化合物的制药组合物以及治疗通过毒蕈碱受体介导的疾病的方法。