1-(benzothiazol-2-yl)-1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>methanol | 272129-66-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 1-(benzothiazol-2-yl)-1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>methanol
• 英文别名: 2-[(Benzothiazol-2-yl)hydroxymethyl]-1-N-(tert-butoxycarbonyl)-(2S)-pyrrolidine；tert-butyl (2S)-2-[1,3-benzothiazol-2-yl(hydroxy)methyl]pyrrolidine-1-carboxylate
• CAS: 272129-66-5
• 化学式: C₁₇H₂₂N₂O₃S
• 分子量: 334.439
• InChiKey: MWIRBVHDWHQZMG-NBFOIZRFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(benzothiazol-2-yl)-1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>methanol 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 benzothiazol-2-yl-pyrrolidin-2-yl-methanol
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of Peptidyl .alpha.-Keto Heterocycles as Novel Inhibitors of Prolyl Endopeptidase

  摘要：

  The preparation and in vitro prolyl endopeptidase (PEP) inhibitory activity of a series of alpha-keto heterocyclic compounds is described. The design is based on the introduction of alpha-keto heterocycles at the C-terminal end of substrate-like peptides. Many of the compounds including those substituted with thiazole, benzothiazole, benzoxazole, imidazole, and pyridine groups exhibit IC50 potencies of PEP inhibition at nanomolar levels. Structure-activity studies of the C-terminal heterocyclic groups indicate the importance of an sp(2) nitrogen atom at a beta-position from the adjoining ketone carbonyl group. This heterocyclic nitrogen atom would provide a critical hydrogen-bond interaction with the histidine residue of the catalytic triad in PEP. Our inhibitors would extend the generality of the alpha-keto heterocycle design to another serine protease.

  DOI：

  10.1021/jm00047a007
• 作为产物：
  描述：

  tert-butyl (2S)-2-(1,3-benzothiazol-2-ylcarbonyl)-pyrrolidine-1-carboxylate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.67h， 以83%的产率得到1-(benzothiazol-2-yl)-1-<1-(tert-butyloxycarbonyl)-2(S)-pyrrolidinyl>methanol
  参考文献：
  名称：

  Synthesis and activity of pyrrolidinyl- and thiazolidinyl-dipeptide derivatives as inhibitors of the Tc80 prolyl oligopeptidase from Trypanosoma cruzi

  摘要：

  Pyrrolidinyl- and thiazolidinyl- dipeptide derivatives, featuring either a vinyl sulfone-, a 2-ketobenzothiazole-, a nitrile-, or a benzimidazole group at the C-terminus, were designed and synthesized as potential inhibitors of the prolyl-specific Tc80 proteinase from Trypanosoma cruzi, the agent of Chagas' disease. These compounds were evaluated in vitro towards the target enzyme which was classified as a serine protease belonging to the prolyl oligopeptidase family (EC 3.4.21.26). A peptidyl nitrile and two peptidyl alpha-ketobenzothiazoles were shown to be potent reversible and competitive inhibitors of Tc 80 proteinase, with K-i values in the range 38-219 nM, and compared advantageously with some known mammalian prolyl oligopeptidase inhibitors. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00118-5

文献信息

• Peptidyl ketones as inhibitors of DPIV
  申请人：OSI Pharmaceuticals, Inc.

  公开号：US07608577B2

  公开（公告）日：2009-10-27

  The present invention relates to compounds of the general formula 1 and pharmaceutically acceptable salts thereof, to the use of the compounds for the treatment of impaired glucose tolerance, glucosuria, hyperlipidaemia, metabolic acidosis, diabetes mellitus, diabetic neuropathy and nephropathy and of sequelae caused by diabetes mellitus in mammals.

  本发明涉及一般式1的化合物及其药用可接受盐，以及该化合物在哺乳动物中用于治疗糖耐量受损、糖尿病、高脂血症、代谢性酸中毒、糖尿病神经病变和肾病及由糖尿病引起的后遗症的用途。
• US5547978A
  申请人：——

  公开号：US5547978A

  公开（公告）日：1996-08-20
• US7608577B2
  申请人：——

  公开号：US7608577B2

  公开（公告）日：2009-10-27
• Synthesis and Structure-Activity Relationships of Peptidyl .alpha.-Keto Heterocycles as Novel Inhibitors of Prolyl Endopeptidase
  作者：Seiji Tsutsumi、Tsuneo Okonogi、Seiji Shibahara、Shokichi Ohuchi、Emiko Hatsushiba、Arthur A. Patchett、Burton G. Christensen

  DOI：10.1021/jm00047a007

  日期：1994.10

  The preparation and in vitro prolyl endopeptidase (PEP) inhibitory activity of a series of alpha-keto heterocyclic compounds is described. The design is based on the introduction of alpha-keto heterocycles at the C-terminal end of substrate-like peptides. Many of the compounds including those substituted with thiazole, benzothiazole, benzoxazole, imidazole, and pyridine groups exhibit IC50 potencies of PEP inhibition at nanomolar levels. Structure-activity studies of the C-terminal heterocyclic groups indicate the importance of an sp(2) nitrogen atom at a beta-position from the adjoining ketone carbonyl group. This heterocyclic nitrogen atom would provide a critical hydrogen-bond interaction with the histidine residue of the catalytic triad in PEP. Our inhibitors would extend the generality of the alpha-keto heterocycle design to another serine protease.
• Synthesis and activity of pyrrolidinyl- and thiazolidinyl-dipeptide derivatives as inhibitors of the Tc80 prolyl oligopeptidase from Trypanosoma cruzi
  作者：Roger Joyeau、Chanfi Maoulida、Cindy Guillet、François Frappier、Antonio R.L. Teixeira、Joseph Schrével、Jaime Santana、Philippe Grellier

  DOI：10.1016/s0223-5234(00)00118-5

  日期：2000.2

  Pyrrolidinyl- and thiazolidinyl- dipeptide derivatives, featuring either a vinyl sulfone-, a 2-ketobenzothiazole-, a nitrile-, or a benzimidazole group at the C-terminus, were designed and synthesized as potential inhibitors of the prolyl-specific Tc80 proteinase from Trypanosoma cruzi, the agent of Chagas' disease. These compounds were evaluated in vitro towards the target enzyme which was classified as a serine protease belonging to the prolyl oligopeptidase family (EC 3.4.21.26). A peptidyl nitrile and two peptidyl alpha-ketobenzothiazoles were shown to be potent reversible and competitive inhibitors of Tc 80 proteinase, with K-i values in the range 38-219 nM, and compared advantageously with some known mammalian prolyl oligopeptidase inhibitors. (C) 2000 Editions scientifiques et medicales Elsevier SAS.