1-<2(S)-<<(1,1-dimethylethoxy)carbonyl>amino>-4-(methylthio)-1-oxobutyl>morpholine | 156757-45-8

• 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
• 英文名称: 1-<2(S)-<<(1,1-dimethylethoxy)carbonyl>amino>-4-(methylthio)-1-oxobutyl>morpholine
• 英文别名: tert-butyl N-[(2S)-4-methylsulfanyl-1-morpholin-4-yl-1-oxobutan-2-yl]carbamate
• CAS: 156757-45-8
• 化学式: C₁₄H₂₆N₂O₄S
• 分子量: 318.437
• InChiKey: OXGMPBMKCRSRGR-NSHDSACASA-N

物化性质

• 沸点：
  499.9±45.0 °C(predicted)
• 密度：
  1.143±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  93.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-<2(S)-<<(1,1-dimethylethoxy)carbonyl>amino>-4-(methylthio)-1-oxobutyl>morpholine 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 N-<2(S)-amino-4-(methylthio)-1-oxobutyl>morpholine hydrochloride
  参考文献：
  名称：

  Mercaptoacyl aminoacid inhibitors of atriopeptidase. 1. Structure-activity relationship studies of methionine and S-alkylcysteine derivatives

  摘要：

  A broad series of N-(3-mercaptoacyl) amino acid derivatives was evaluated for their ability to inhibit atriopeptidase (neutral endopeptidase, EC 3.4.24.11) in vitro and in vivo. Structural parameters studied were (i) the substituent on the 2-position of the 3-mercaptopropionyl moiety, (ii) the amino acid component, (iii) the S-terminal derivative, and (iv) the C-terminal derivative. Optimum activity was observed for derivatives of methionine and S-alkylcysteines. N-[3-Mercapto-2(S)-[(2-methylphenyl)methyl]-1-oxopropyl]-L-methionine was identified as a highly effective inhibitor of atriopeptidase meriting evaluation as a potential cardiovascular therapeutic agent.

  DOI：

  10.1021/jm00041a026
• 作为产物：
  描述：

  吗啉 、 Boc-L-蛋氨酸 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以82%的产率得到1-<2(S)-<<(1,1-dimethylethoxy)carbonyl>amino>-4-(methylthio)-1-oxobutyl>morpholine
  参考文献：
  名称：

  Mercaptoacyl aminoacid inhibitors of atriopeptidase. 1. Structure-activity relationship studies of methionine and S-alkylcysteine derivatives

  摘要：

  A broad series of N-(3-mercaptoacyl) amino acid derivatives was evaluated for their ability to inhibit atriopeptidase (neutral endopeptidase, EC 3.4.24.11) in vitro and in vivo. Structural parameters studied were (i) the substituent on the 2-position of the 3-mercaptopropionyl moiety, (ii) the amino acid component, (iii) the S-terminal derivative, and (iv) the C-terminal derivative. Optimum activity was observed for derivatives of methionine and S-alkylcysteines. N-[3-Mercapto-2(S)-[(2-methylphenyl)methyl]-1-oxopropyl]-L-methionine was identified as a highly effective inhibitor of atriopeptidase meriting evaluation as a potential cardiovascular therapeutic agent.

  DOI：

  10.1021/jm00041a026

文献信息

• FARNESYL TRANSFERASE INHIBITORS
  申请人：AstraZeneca UK Limited

  公开号：EP1054865A1

  公开（公告）日：2000-11-29
• [EN] FARNESYL TRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS DE LA FARNESYLE TRANSFERASE
  申请人：ASTRAZENECA UK LIMITED

  公开号：WO1999041235A1

  公开（公告）日：1999-08-19

  (EN) The present invention relates to a compound of formula (1) wherein A is of formula (2), (3), (4), B is phenyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, thienyl, thiazolyl, furyl or oxazolyl, the ring being substituted on ring carbon atoms by R1 and -(CH2)nR2; or B is pyrrolyl, pyrazolyl or imidazolyl, and when A is of formula (2) or (3), B can also be naphthyl substituted by R1 and -(CH2)nR2; R1 is of the formula -CONHCH(R10)R11 wherein R11 is of the formula -CH2OR13, -COR14 or -CH2COR14 or R11 is morpholinoC1-4alkyl, pyrrolidin-1-ylC1-4alkyl or piperidin-1-ylC1-4alkyl; or R11 is phenyl-1-hydroxyC1-4alkyl; or heteroaryl-1-hydroxyC1-4alkyl; R2 is phenyl or heteroaryl; and n is 0, 1 or 2; or a prodrug, solvate or pharmaceutically-acceptable salt thereof. Processes for their preparation, their use as therapeutic agents and pharmaceutical compositions containing them. A particular use is in cancer therapy.(FR) La présente invention concerne un composé de la formule (1) dans laquelle A correspond à la formule (2), (3) ou (4), et dans laquelle B représente phényle, pyridyle, pyridazinyle, pyrimidyle, pyrazinyle, thiényle, thiazolyle, furyle ou oxazolyle, le noyau étant substitué sur les atomes de carbone du cycle par R1 et -(CH2)nR2; ou bien B représente pyrrolyle, pyrazolyle ou imidazolyle, et lorsque A correspond à la formule (2) ou (3), B peut également représenter naphtyle substitué par R1 et -(CH2)nR2; R1 correspond à la formule -CONHCH(R10)R11 dans laquelle R11 correspond à la formule -CH2OR13, -COR14 ou -CH2COR14, ou bien R11 représente morpholino-alkyle C1-4, pyrrolidin-1-yl-alkyle C1-4, ou pipéridin-1-yl-alkyle C1-4; ou bien R11 représente phényl-1-hydroxy-alkyle C1-4, ou hétéroaryl-1-hydroxy-alkyle C1-4; R2 représente phényle ou hétéroaryle, et n vaut 0, 1 ou 2. L'invention concerne également un promédicament, un solvate ou sel de ce composé, acceptable sur le plan pharmacologique. Elle concerne encore des procédés de préparation de ces composés, leur utilisation en tant qu'agents thérapeutiques, ainsi que des compositions pharmaceutiques les contenant. On utilise notamment ces composés dans la thérapie du cancer.
• Mercaptoacyl aminoacid inhibitors of atriopeptidase. 1. Structure-activity relationship studies of methionine and S-alkylcysteine derivatives
  作者：Bernard R. Neustadt、Elizabeth M. Smith、Terry L. Nechuta、Alan A. Bronnenkant、Martin F. Haslanger、Robert W. Watkins、Caroline J. Foster、Edmund J. Sybertz

  DOI：10.1021/jm00041a026

  日期：1994.7

  A broad series of N-(3-mercaptoacyl) amino acid derivatives was evaluated for their ability to inhibit atriopeptidase (neutral endopeptidase, EC 3.4.24.11) in vitro and in vivo. Structural parameters studied were (i) the substituent on the 2-position of the 3-mercaptopropionyl moiety, (ii) the amino acid component, (iii) the S-terminal derivative, and (iv) the C-terminal derivative. Optimum activity was observed for derivatives of methionine and S-alkylcysteines. N-[3-Mercapto-2(S)-[(2-methylphenyl)methyl]-1-oxopropyl]-L-methionine was identified as a highly effective inhibitor of atriopeptidase meriting evaluation as a potential cardiovascular therapeutic agent.