(2S)-(acetylthio)(phenyl)ethanoic acid

• 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: (2S)-(acetylthio)(phenyl)ethanoic acid
• 英文别名: (S)-2-(acetylthio)-2-phenylacetic acid；(S)-2-acetylthio-2-phenylacetic acid；(2S)-2-acetylsulfanyl-2-phenylacetic acid
• 化学式: C₁₀H₁₀O₃S
• 分子量: 210.254
• InChiKey: GCBDFXPLCNQIFE-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  左旋苯甘氨酸 在 氢溴酸 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2S)-(acetylthio)(phenyl)ethanoic acid
  参考文献：
  名称：

  Optimal Recognition of Neutral Endopeptidase and Angiotensin-Converting Enzyme Active Sites by Mercaptoacyldipeptides as a Means To Design Potent Dual Inhibitors

  摘要：

  An interesting approach for the treatment of congestive heart failure and chronic hypertension could be to avoid the formation of angiotensin II by inhibiting angiotensin converting enzyme (ACE) and to protect atrial natriuretic factor by blocking neutral endopeptidase 24.11 (NEP). This is support-ed by recent results obtained with potent dual inhibitors of the two zinc metallopeptidases, such as RE 105, HSCH2CH(CH3)PhCONHCH(CH3)COOH (Fournie-Zaluski et rrl. Proc, Natl. Acad. Sci. U.S.A, 1994, 91, 4072-4076), which reduces blood pressure in experimental models of hypertension, independently of the stilt and renin angiotensin system status, In order to develop new dual inhibitors with improved affinities, long duration of action, and/or better bioavailabilities, various series of mercaptoacyldipeptides corresponding to the general formula HSCH(R(1))CONHCH(R(1)')CON(R)CH(R(2)')COOH have been si synthesized. The introduction of well-selected beta-branched chains in positions R(1) and R(1)', associated with a tyrosine or a cyclic amino acid in the C-terminal position, led to potent dual inhibitors of NEP and ACE; such as 21 [N-[(2S)-2-mercapto-3-methylbutanoyl]-Ile-Try] and 22 [N-[(2S)-2-mercapto-3-phenylpropanoyl]Ala-Pro] which have IC50 values in the nanomolar range for NEP and subnanomolar range for ACE, These compounds could have different modes of binding to the two peptidases. In NEP, the dual inhibitors seem to interact only with the S-1' and S-2' subsites, whereas additional interactions with the Si binding subsite of ACE probably account fbr their subnanomolar inhibitory potencies for this enzyme. The localization of the Pro residue of 22 outside the NEP active site is supported by biochemical data using (Arg(102),Glu)NEP and molecular modeling studies with thermolysin used as model of WE:P. One hour after oral administration in mice of a single dose (2.7 x 10(-5) mol/kg, 21 inhibited 80% and 36% of kidney NEP and lung ACE, respectively, while 22 inhibited 40% of kidney NEP and 56% of lung ACE.

  DOI：

  10.1021/jm950590p

文献信息

• Evidence for α-lactone formation in the thioacetylation of some α-hydroxy acids with the aid of <i>Mitsunobu</i> -type reagent
  作者：Bert Strijtveen、Richard M. Kellogg

  DOI：10.1002/recl.19871061006

  日期：——

  (S-Mandelic acid, (S)-lactic acid, and (S)-2-hydroxy-3-phenylpropionic acid react with thioacetic acid in the presence of the salt of diisopropyl azodicarboxylate and triphenylphosphine to give the α-(acetylthio)-substituted products. (S)-Mandelic acid reacts with predominant retention of configuration whereas (S)-lactic acid and (S)-2-hydroxy-3-phenylpropionic acid react predominantly with inversion

  （S-扁桃酸，（S）-乳酸和（S）-2-羟基-3-苯基丙酸在偶氮二羧酸二异丙酯和三苯基膦的盐存在下与硫代乙酸反应生成α-（乙酰硫基）- （S）-扁桃酸主要与构型反应，而（S）-乳酸和（S）-2-羟基-3-苯基丙酸主要与转化反应，α-内酯中间体的参与非常可能。
• Acylmercaptoalkanoyldipeptides, methods of preparation and their therapeutic use
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP0524553A1

  公开（公告）日：1993-01-27

  This invention is directed to a compound of the formula that inhibits simultaneously neutral endopeptidase and peptidyldipeptidase A and is useful in treating hypertension. The invention is also directed to the preparation of the compound, pharmaceutical compositions containing it, and methods for its pharmaceutical use.

  这项发明涉及一种化合物，该化合物能同时抑制中性内肽酶和肽二肽酶A，并可用于治疗高血压。该发明还涉及该化合物的制备，含有该化合物的药物组合物，以及该药物的使用方法。
• STRIJTVEEN, BERT;KELLOGG, RICHARD M., REC. TRAV. CHIM. PAYS-BAS, 106,(1987) N 10, 539-542
  作者：STRIJTVEEN, BERT、KELLOGG, RICHARD M.

  DOI：——

  日期：——
• ACYLMERCAPTOALKANOYLDIPEPTIDES, METHODS OF PREPARATION AND THEIR THERAPEUTIC USE
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP0595878A1

  公开（公告）日：1994-05-11
• PEPTIDYL COMPOUNDS AND THEIR THERAPEUTIC USE AS INHIBITORS OF METALLOPROTEINASES
  申请人：Darwin Discovery Limited

  公开号：EP0728144B1

  公开（公告）日：2000-01-19