(R)-benzyl 2-(benzyloxycarbonylamino)-3-(chlorosulfonyl)propanoate | 64957-08-0

• 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: (R)-benzyl 2-(benzyloxycarbonylamino)-3-(chlorosulfonyl)propanoate
• 英文别名: (R)-2-benzyloxycarbonylamino-3-chlorosulfonyl-propionic acid benzyl ester；(R)-2-Benzyloxycarbonylamino-3-chlorsulfonyl-propionsaeure-benzylester；benzyl (2R)-3-chlorosulfonyl-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 64957-08-0
• 化学式: C₁₈H₁₈ClNO₆S
• 分子量: 411.863
• InChiKey: MXWGFBQDTUWBFL-INIZCTEOSA-N

物化性质

• 沸点：
  571.8±50.0 °C(Predicted)
• 密度：
  1.384±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  98.77
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (R)-benzyl 2-(benzyloxycarbonylamino)-3-(chlorosulfonyl)propanoate 以 氯仿 为溶剂， 生成 benzyl ((benzyloxy)carbonyl)((2-(4-(fluorosulfonyl)benzoyl)hydrazineyl)sulfonyl)-D-alaninate
  参考文献：
  名称：

  Potential inhibitors of L-asparagine biosynthesis. 4. Substituted sulfonamide and sulfonylhydrazide analogs of L-asparagine

  摘要：

  Several N-substituted sulfonamides and N'-substituted sulfonylhydrazides have been prepared as sulfur analogues of L-asparagine with the potential of acting as inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma). L-Cysteine was converted in known steps to N-carboxy-3-(sulfonylchloro)-L-alanine dibenzyl ester (1). Condensation of 1 with O-benzylhydroxylamine, p-(fluorosulfonyl)benzylamine, or monoethyl fumarylhydrazide (9), followed by deblocking with HF, gave 3-(hydroxysulfamoyl)-L-alanine (3a), 3-[p-(fluorosulfonylbenzyl)]sulfamoyl-L-alanine (3c), and 3-sulfo-L-alanine S-[2-[(E)-3-(ethoxycarbonyl)acryloyl]hydrazide] (3e), respectively. Similarly, 1 with 2-chloroethylamine and deblocking with H2-Pd gave 3-[(2-chloroethyl)sulfamoyl]-L-alanine (3b). tert-Butyl carbazate was allowed to react with 1 and the tert-butyl group was removed with HCl. The resulting sulfonylhydrazide 7 was condensed with p-(fluorosulfonyl)benzoyl chloride and then deblocked with HF to give 3-sulfo-L-alanine S-[2-[P-(fluorosulfonyl)benzoyl]hydrazide] (3d). The inhibition of ASase by 3a-e at 2 mM was 97, 0, 30, 43, and 37%, respectively, and 3a was competitive with L-aspartic acid. Neither 3a nor 3e was effective in increasing the life span of mice bearing P-388 lymphocytic leukemia.

  DOI：

  10.1021/jm00199a008
• 作为产物：
  描述：

  N,N'-二(苄氧羰基)-L-胱氨酸 在 盐酸 、 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.17h， 生成 (R)-benzyl 2-(benzyloxycarbonylamino)-3-(chlorosulfonyl)propanoate
  参考文献：
  名称：

  Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors

  摘要：

  Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.

  DOI：

  10.1021/acs.jmedchem.0c00949

文献信息

• Notes: 2-Amino-2-carboxyethanesulfonamide
  作者：Donald Ross、Charles Skinner、William Shive

  DOI：10.1021/jo01091a627

  日期：1959.9
• Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors
  作者：Markus Schade、Beatrix Merla、Bernhard Lesch、Markus Wagener、Simone Timmermanns、Katrien Pletinckx、Torsten Hertrampf

  DOI：10.1021/acs.jmedchem.0c00949

  日期：2020.10.22

  Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.
• Potential inhibitors of L-asparagine biosynthesis. 4. Substituted sulfonamide and sulfonylhydrazide analogs of L-asparagine
  作者：Steven Brynes、Gilbert J. Burckart、Michael Mokotoff

  DOI：10.1021/jm00199a008

  日期：1978.1

  Several N-substituted sulfonamides and N'-substituted sulfonylhydrazides have been prepared as sulfur analogues of L-asparagine with the potential of acting as inhibitors of L-asparagine synthetase (ASase, from Novikoff hepatoma). L-Cysteine was converted in known steps to N-carboxy-3-(sulfonylchloro)-L-alanine dibenzyl ester (1). Condensation of 1 with O-benzylhydroxylamine, p-(fluorosulfonyl)benzylamine, or monoethyl fumarylhydrazide (9), followed by deblocking with HF, gave 3-(hydroxysulfamoyl)-L-alanine (3a), 3-[p-(fluorosulfonylbenzyl)]sulfamoyl-L-alanine (3c), and 3-sulfo-L-alanine S-[2-[(E)-3-(ethoxycarbonyl)acryloyl]hydrazide] (3e), respectively. Similarly, 1 with 2-chloroethylamine and deblocking with H2-Pd gave 3-[(2-chloroethyl)sulfamoyl]-L-alanine (3b). tert-Butyl carbazate was allowed to react with 1 and the tert-butyl group was removed with HCl. The resulting sulfonylhydrazide 7 was condensed with p-(fluorosulfonyl)benzoyl chloride and then deblocked with HF to give 3-sulfo-L-alanine S-[2-[P-(fluorosulfonyl)benzoyl]hydrazide] (3d). The inhibition of ASase by 3a-e at 2 mM was 97, 0, 30, 43, and 37%, respectively, and 3a was competitive with L-aspartic acid. Neither 3a nor 3e was effective in increasing the life span of mice bearing P-388 lymphocytic leukemia.