甲基(4S)-4-苯氧基-L-脯氨酸酯 | 113949-37-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 甲基(4S)-4-苯氧基-L-脯氨酸酯
• 英文名称: cis-4-phenoxy-L-propline
• 英文别名: L-Proline, 4-phenoxy-, (4S)-；(2S,4S)-4-phenoxypyrrolidine-2-carboxylic acid
• CAS: 113949-37-4
• 化学式: C₁₁H₁₃NO₃
• 分子量: 207.229
• InChiKey: RWSHAZYNUOFZMI-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甲基(4S)-4-苯氧基-L-脯氨酸酯 在 氨 、 sodium carbonate 作用下， 以 水 为溶剂， 反应 3.0h， 生成 (2S,4S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]-4-phenoxypyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines

  摘要：

  Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.

  DOI：

  10.1021/jm00401a014
• 作为产物：
  描述：

  dibenzyl (2S,4S)-4-phenoxypyrrolidine-1,2-dicarboxylate 生成 甲基(4S)-4-苯氧基-L-脯氨酸酯
  参考文献：
  名称：

  KRAPCHO, JOHN;TURK, CHESTER;CUSHMAN, DAVID W.;POWELL, JAMES R.;DEFORREST,+, J. MED. CHEM., 31,(1988) N 6, C. 1148-1160

  摘要：

  DOI：

文献信息

• [EN] PROLINE DERIVATIVES HAVING AFFINITY FOR THE CALCIUM CHANNEL ALPHA-2-DELTA SUBUNIT<br/>[FR] DERIVES DE PROLINE PRESENTANT UNE AFFINITE POUR LA SOUS-UNITE ALPHA-2-DELTA DU CANAL DE CALCIUM
  申请人：PFIZER LTD

  公开号：WO2004039367A1

  公开（公告）日：2004-05-13

  The compounds of formula (I) or a pharmaceutically acceptable salt, solvate or pro-drug thereof, are proline derivatives useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, fibromyalgia, arthritis, neuropathalogical disorders, sleep disorders, visceral pain disorders and gastrointestinal disorders. Processes for the preparation of the final products and intermediates useful in the process are included. Pharmaceutical compositions containing one or more of the compounds are also included. Wherein either X is O, S, NH or CH2 and Y is CH2 or a direct bond, or Y is O, S or NH and X is CH2; and R is a 3-12 membered cycloalkyl, 4-12 membered heterocycloalkyl, heteroaryl or aryl, where any ring may be optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, nitro, amino, hydroxycarbonyl, Cl-C6 alkyl, Cl-C6 alkenyl, CI-C6 alkynyl, Cl-C6 alkoxy, hydroxyC,-C6 alkyl, Cl-C6 alkoxyC,-C6 alkyl, perfluoro Cl-C6 alkyl, perfluoroC,-C6 alkoxy, Cl-C6 alkylamino, di- C1-C6 alkylamino, aminoC1-C6 alkyl, Cl-C6 alkylaminoC,-C6 alkyl, di-Cl-C6 alkylaminoC,-C6 alkyl, CI-C6acyl, C1-C6acyloxy, Cl-C6acyloxyC,-C6 alkyl, Cl-C6 acylamino, Cl-C6 alkylthio, C1-C6 alkylthiocarbonyl, C1-C6 alkylthioxo, C1-C6 alkoxycarbonyl, Cl-C6 alkylsulfonyl, C1-C6 alkylsulfonylamino, aminosulfonyl, Cl-C6 alkylaminosulfonyl, di-Cl-C6 alkylaminosulfonyl, 3-8 membered cycloalkyl, 4-8 membered heterocycloalkyl, phenyl and monocyclic heteroaryl; or a pharmaceutically acceptable salt, solvate or pro-drug thereof.

  化学式（I）的化合物或其药学上可接受的盐、溶剂化合物或前药是脯氨酸衍生物，在治疗癫痫、晕厥发作、运动减退、颅内疾病、神经退行性疾病、抑郁症、焦虑、恐慌、疼痛、纤维肌痛、关节炎、神经病理性疾病、睡眠障碍、内脏疼痛疾病和胃肠疾病的治疗中有用。包括制备最终产品和在过程中有用的中间体的方法。还包括含有一种或多种该化合物的药物组合物。其中X为O、S、NH或CH2，Y为CH2或直接键，或Y为O、S或NH，X为CH2；R为3-12环状烷基、4-12环状杂环烷基、杂芳基或芳基，其中任何环都可以选择性地用一个或多个取代基独立选择自卤素、羟基、氰基、硝基、氨基、羟基羰基、Cl-C6烷基、Cl-C6烯基、Cl-C6炔基、Cl-C6烷氧基、羟基C1-C6烷基、Cl-C6烷氧基C1-C6烷基、全氟Cl-C6烷基、全氟C1-C6烷氧基、Cl-C6烷基氨基、二-Cl-C6烷基氨基、氨基C1-C6烷基、Cl-C6烷基氨基C1-C6烷基、二-Cl-C6烷基氨基C1-C6烷基、Cl-C6酰基、C1-C6酰氧基、Cl-C6酰氧基C1-C6烷基、Cl-C6酰胺基、Cl-C6烷基硫基、C1-C6烷基硫羰基、C1-C6烷基硫氧基、C1-C6烷氧羰基、Cl-C6烷基磺基、C1-C6烷基磺酰胺基、氨基磺基、Cl-C6烷基氨基磺基、二-Cl-C6烷基氨基磺基、3-8环状烷基、4-8环状杂环烷基、苯基和单环杂芳基；或其药学上可接受的盐、溶剂化合物或前药。
• Macrocyclic prolinyl acyl guanidines as inhibitors of β-secretase (BACE)
  作者：Kenneth M. Boy、Jason M. Guernon、Yong-Jin Wu、Yunhui Zhang、Joe Shi、Weixu Zhai、Shirong Zhu、Samuel W. Gerritz、Jeremy H. Toyn、Jere E. Meredith、Donna M. Barten、Catherine R. Burton、Charles F. Albright、Andrew C. Good、James E. Grace、Kimberley A. Lentz、Richard E. Olson、John E. Macor、Lorin A. Thompson

  DOI：10.1016/j.bmcl.2015.10.031

  日期：2015.11

  The synthesis, evaluation, and structure-activity relationships of a class of acyl guanidines which inhibit the BACE-1 enzyme are presented. The prolinyl acyl guanidine chemotype (7c), unlike compounds of the parent isothiazole chemotype (1), yielded compounds with good agreement between their enzymatic and cellular potency as well as a reduced susceptibility to P-gp efflux. Further improvements in

  介绍了抑制BACE-1酶的一类酰基胍的合成，评估和构效关系。与母体异噻唑化学类型（1）的化合物不同，脯氨酰基酰基胍化学类型（7c）产生的化合物在其酶促和细胞效能之间具有良好的一致性，并且对P-gp外排的敏感性降低。通过大环化策略实现了效力和P-gp比的进一步提高。给出了野生型小鼠体内的概况和大环类似物21c的P-gp效应。
• LABELED MOLECULAR IMAGING AGENTS AND METHODS OF USE
  申请人：General Electric Company

  公开号：US20150202333A1

  公开（公告）日：2015-07-23

  Imaging agents are described that comprise labeled substrates capable of being introduced into cells via the cystine/glutamate antiporter. The substrates may be used for imaging or detecting oxidative stress in cells by introducing the labeled agents into cells via the cystine/glutamate antiporter and subsequent detection.

  描述了包含标记底物的成像剂，这些底物能够通过半胱氨酸/谷氨酸抗转运体引入细胞中。这些底物可用于通过通过半胱氨酸/谷氨酸抗转运体将标记的剂量引入细胞并进行后续检测，从而成像或检测细胞中的氧化应激。
• Therapeutic proline derivatives
  申请人：——

  公开号：US20040132801A1

  公开（公告）日：2004-07-08

  The compounds of formula (I) or a pharmaceutically acceptable salt, solvate or pro-drug thereof, are proline derivatives useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, fibromyalgia, arthritis, neuropathalogical disorders, sleep disorders, visceral pain disorders and gastrointestinal disorders. Processes for the preparation of the final products and intermediates useful in the process are included. Pharmaceutical compositions containing one or more of the compounds are also included. 1 wherein either X is O, S, NH or CH 2 and Y is CH 2 or a direct bond, or Y is O, S or NH and X is CH 2 ; and R is a 3-12 membered cycloalkyl, 4-12 membered heterocycloalkyl, heteroaryl or aryl, where any ring may be optionally substituted with one or more substituents independently selected from halogen, hydroxy, cyano, nitro, amino, hydroxycarbonyl, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, C 1 -C 6 alkynyl, C 1 -C 6 alkoxy, hydroxyC 1 -C 6 alkyl, C 1 -C 6 alkoxyC 1 -C 6 alkyl, perfluoro C 1 -C 6 alkyl, perfluoroC 1 -C 6 alkoxy, C 1 -C 6 alkylamino, di-C 1 -C 6 alkylamino, aminoC 1 -C 6 alkyl, C 1 -C 6 alkylaminoC 1 -C 6 alkyl, di-C 1 -C 6 alkylaminoC 1 -C 6 alkyl, C 1 -C 6 acyl, C 1 -C 6 acyloxy, C 1 -C 6 acyloxyC 1 -C 6 alkyl, C 1 -C 6 acylamino, C 1 -C 6 alkylthio, C 1 -C 6 alkylthiocarbonyl, C 1 -C 6 alkylthioxo, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 alkylsulfonylamino, aminosulfonyl, C 1 -C 6 alkylaminosulfonyl, di-C 1 -C 6 alkylaminosulfonyl, 3-8 membered cycloalkyl, 4-8 membered heterocycloalkyl, phenyl and monocyclic heteroaryl; or a pharmaceutically acceptable salt, solvate or pro-drug thereof.

  公式（I）的化合物或其药学上可接受的盐、溶剂合物或前药是脯氨酸衍生物，可用于治疗癫痫、晕厥发作、低动力症、头颅疾病、神经退行性疾病、抑郁症、焦虑症、惊恐症、疼痛、纤维肌痛、关节炎、神经病理学疾病、睡眠障碍、内脏疼痛疾病和胃肠疾病的治疗。包括用于制备最终产品和在过程中有用的中间体的过程。还包括含有一种或多种化合物的制药组合物。其中，X为O、S、NH或CH2，Y为CH2或直接键，或Y为O、S或NH，X为CH2；R为3-12环烷基、4-12杂环烷基、杂环芳基或芳基，其中任何环都可以选择地用一个或多个取代基独立地选择自卤素、羟基、氰基、硝基、氨基、羟基羰基、C1-C6烷基、C1-C6烯基、C1-C6炔基、C1-C6烷氧基、羟基C1-C6烷基、C1-C6烷氧基C1-C6烷基、全氟C1-C6烷基、全氟C1-C6烷氧基、C1-C6烷基氨基、二C1-C6烷基氨基、氨基C1-C6烷基、C1-C6烷基氨基C1-C6烷基、二C1-C6烷基氨基C1-C6烷基、C1-C6酰基、C1-C6酰氧基、C1-C6酰氧基C1-C6烷基、C1-C6酰氨基、C1-C6烷硫基、C1-C6烷硫酰基、C1-C6烷基磺酰氨基、氨基磺酰基、C1-C6烷基氨基磺酰基、二C1-C6烷基氨基磺酰基、3-8环烷基、4-8杂环烷基、苯基和单环杂芳基；或其药学上可接受的盐、溶剂合物或前药。
• KRAPCHO, JOHN;TURK, CHESTER;CUSHMAN, DAVID W.;POWELL, JAMES R.;DEFORREST,+, J. MED. CHEM., 31,(1988) N 6, C. 1148-1160
  作者：KRAPCHO, JOHN、TURK, CHESTER、CUSHMAN, DAVID W.、POWELL, JAMES R.、DEFORREST,+

  DOI：——

  日期：——