(D)-3-(benzoylthio)-2-methylpropanoic acid chloride | 76740-20-0

• 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: (D)-3-(benzoylthio)-2-methylpropanoic acid chloride
• 英文别名: (+/-)-S-benzoyl-3-mercapto-2-methylpropanoyl chloride；S-benzoyl-3-mercapto-2-methylpropanoyl chloride；3-(benzoylthio)-2-methylpropionyl chloride；3-benzoylthio-2-methylpropionyl chloride；(S)-3-(benzoylthio)-2-methyl propanoyl chloride；D-3-(benzoylthio)-2-methyl-propionyl chloride；(1)-S-(3-Chloro-2-methyl-3-oxopropyl) benzenecarbothioate；S-(3-chloro-2-methyl-3-oxopropyl) benzenecarbothioate
• CAS: 76740-20-0
• 化学式: C₁₁H₁₁ClO₂S
• 分子量: 242.726
• InChiKey: MJZHAVYNYFDSMZ-UHFFFAOYSA-N

物化性质

• 沸点：
  326.5±34.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  59.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (D)-3-(benzoylthio)-2-methylpropanoic acid chloride 在 Sodium tetraborate decahydrate 、 sodium hydroxide 作用下， 反应 10.0h， 生成 (2S)-2-(3-(benzoylthio)-2-methylpropanamido)-3-(3,4-bis(benzoyloxy)phenyl)propanoic acid
  参考文献：
  名称：

  Thiol compounds. III. Synthesis and antihypertensive activity of mercaptoacylamino acids.

  摘要：

  报道了一系列含有酪氨酸、多巴和α-甲基多巴结构的巯基乙酰氨基酸，并讨论了其结构-活性关系。这些化合物被测试了抗高血压活性，其中一些化合物对血管紧张素I转化酶表现出抑制活性。N-(2-巯基丙酰)-L-酪氨酸-b (6b) 的效力被发现是N-(2-巯基丙酰)-L-苯丙氨酸-a (Ia) 的5倍。

  DOI：

  10.1248/cpb.29.1203
• 作为产物：
  描述：

  3-苯甲酰硫基-2-甲基丙酸 在 氯化亚砜 作用下， 反应 2.0h， 生成 (D)-3-(benzoylthio)-2-methylpropanoic acid chloride
  参考文献：
  名称：

  Sulfur-containing acylamino acids. I. Syntheses and angiotensin I converting enzyme-inhibitory activities of sulfur-containing N-mercaptoalkanoyl amino acids.

  摘要：

  含硫氨基酸的N-巯基烷酰基衍生物被合成并检验了它们对从兔肺提取的血管紧张素I转化酶（ACE）的抑制作用。ACE的抑制作用是通过采用高脯酰-L-组氨酰-L-亮氨酸作为底物的光谱测定法确定的。在合成的含硫化合物中，N-(2-苄基-3-巯基丙酰基)-S-甲基-L-半胱氨酸（13a）和N-(2-苄基-3-巯基丙酰基)-S-乙基-L-半胱氨酸（13c）对ACE活性显示了最强大的抑制作用。13a和13c对ACE活性的IC50值分别为0.028和0.020 μM。

  DOI：

  10.1248/cpb.35.2382

文献信息

• 1-mercaptoalkanoylindoline-2-carboxylic acids
  申请人：Ciba-Geigy Corporation

  公开号：US04599357A1

  公开（公告）日：1986-07-08

  1-Mercaptoalkanoylindoline-2-carboxylic acids, e.g., those of the formula ##STR1## and functional derivatives thereof, are antihypertensive and cardioactive agents.

  1-巯基烷酰吲哚-2-羧酸，例如，具有公式##STR1##的化合物及其功能性衍生物，是抗高血压和心脏活性剂。
• Mercaptoacyl derivatives of substituted prolines
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04316906A1

  公开（公告）日：1982-02-23

  New mercaptoacyl derivatives of substituted prolines which have the general formula ##STR1## are useful as hypotensive agents.

  新的取代脯氨酸巯基酰衍生物具有一般公式##STR1##，可用作降压剂。
• Angiotensin converting enzyme inhibitors: N-Substituted monocyclic and bicyclic amino acid derivatives
  作者：James L. Stanton、Norbert Gruenfeld、Joseph E. Babiarz、Michael H. Ackerman、Robert C. Friedmann、Andrew M. Yuan、William Macchia

  DOI：10.1021/jm00363a011

  日期：1983.9

  (14a-x),- N-arylalanines (15a,b),-N-cycloalkylglycines (16a-k), and -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids (17a-d), -1,2,3,4-tetrahydroquinoline-2-carboxylic acids (18a-f), and -indoline-2-carboxylic acids (19a-k) is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound, and the structure--activity relationship for each series is discussed. The

  N-（3-巯基丙酰基）-N-芳基甘氨酸（14a-x），-N-芳基丙氨酸（15a，b），-N-环烷基甘氨酸（16a-k）和-1,2,3,4-的合成描述了四氢异喹啉-3-羧酸（17a-d），-1,2,3,4-四氢喹啉-2-羧酸（18a-f）和-二氢吲哚-2-羧酸（19a-k）。报道了每种化合物对血管紧张素转化酶（ACE）的体外抑制作用，并讨论了每个系列的结构-活性关系。讨论了ACE的体内抑制作用和各系列代表性化合物的降压作用。最有效的化合物19d的体外ACE IC50为2.6 X 10（-9）M，并且以10 mg / kg po的剂量在85 mm的自发性高血压大鼠中降低了血压。
• Synthesis and antihypertensive activity of N-(mercaptoacyl)-thiazolidinecarboxylic acids.
  作者：MASAYUKI OYA、TOSHIO BABA、EISHIN KATO、YOICHI KAWASHIMA、TOSHIO WATANABE

  DOI：10.1248/cpb.30.440

  日期：——

  The synthesis and antihypertensive activity of a new series of N-(mercaptoacyl)-thiazolidinecarboxylic acids (VIIa-d) are described. Antihypertensive activity was evaluated in terms of angiotensin I-converting enzyme (ACE) inhibitory activity. The activities of these compounds were compared with that of (2S)-1-[(2S)-3-mercapto-2-methylpropanoyl] proline, SQ 14225, and many of them were found to be relatively potent inhibitors of ACE. The most potent was (4R)-2-(2-hydroxyphenyl)-3-(3-mercaptopropanoyl)-4-thiazolidinecarboxylic acid (62). Structure-activity relationships among the thiazolidines and some related compounds are discussed.

  报道了一系列新型N-(巯基乙酰基)-噻唑烷羧酸(VIIa-d)的合成及其抗高血压活性。抗高血压活性通过血管紧张素I转化酶(ACE)抑制活性来评估。这些化合物的活性与(2S)-1-[(2S)-3-巯基-2-甲基丙酰基]脯氨酸(SQ 14225)进行了比较，发现其中许多化合物是相对强效的ACE抑制剂。其中最有效的是(4R)-2-(2-羟基苯基)-3-(3-巯基丙酰基)-4-噻唑烷羧酸(62)。讨论了噻唑烷及其相关化合物的结构-活性关系。
• Studies on angiotensin-converting enzyme inhibitors. I. Syntheses and angiotensinconverting enzyme inhibitory activity of 2-(3-mercaptopropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives.
  作者：KIMIAKI HAYASHI、YASUHIKO OZAKI、KENICHI NUNAMI、TOMOFUMI UCHIDA、JYOJI KATO、KEIZO KINASHI、NAOTO YONEDA

  DOI：10.1248/cpb.31.570

  日期：——

  (3S)-2-[(2S)-3-Mercapto-2-methylpropionyl]-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid [(3S), (2S)-6a] was prepared by the reaction of (3S)-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester [(3S)-2a] or benzyl ester [(3S)-2b] with 3-benzoylthio-2-methylpropionyl chloride (3a), followed by fractional crystallization and removal of the protective group. The absolute configuration of (3S), (2S)-6a was confirmed by X-ray diffraction analysis of the thiazepino [4, 3-b] isoquinoline compound (7) derived from 6a. Resolution of 3-benzoylthio-2-methylpropionic acid (8) was completed by using optically active phenylalanine amide as a resolving agent. The other optical isomers of (3S), (2S)-6a were prepared by the reaction of (3S)- or (3R)-2b with optically active 3a. The in vitro ACE inhibitory activity of each isomer of 6a was evaluated. Among them, (3S), (2S)-6a was found to be the most potent inhibitor with an IC50 value of 8.6×10-9M. Compound (3S), (2S)-6a induced a dose-dependent inhibition of the pressor response to angiotensin I after oral administration to normotensive anesthetized rats. Moreover, (3S), (2S)-6a markedly reduced the systolic blood pressure in renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). The in vivo ACE inhibitory activity and the hypotensive effects of (3S), (2S)-6a were comparable to those of captopril.

  (3S)-2-[(2S)-3-巯基-2-甲基丙酰基]-1, 2, 3, 4-四氢异喹啉-3-羧酸[(3S), (2S)-6a]是通过(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸叔丁基酯[(3S)-2a]或苄基酯[(3S)-2b]与3-苯甲酰硫-2-甲基丙酰氯(3a)反应制备而成，随后通过分馏结晶去除保护基团。通过对由6a衍生的噻唑烯[4, 3-b]异喹啉化合物(7)进行X射线衍射分析，确认了(3S), (2S)-6a的绝对构型。使用光学活性的苯丙氨酸酰胺作为分解剂完成了3-苯甲酰硫-2-甲基丙酸(8)的分解。通过(3S)-或(3R)-2b与光学活性3a反应制备了(3S), (2S)-6a的其他光学异构体。评估了每种6a异构体的体外ACE抑制活性。其中，(3S), (2S)-6a被发现是最有效的抑制剂，IC50值为8.6×10^-9M。化合物(3S), (2S)-6a在该显混合型麻醉大鼠口服给药后，诱导了对血管紧张素I的加压反应的剂量依赖性抑制。此外，(3S), (2S)-6a显著降低了肾性高血压大鼠(RHR)和自发性高血压大鼠(SHR)的收缩压。(3S), (2S)-6a的体内ACE抑制活性和降压效果与卡托普利相当。