N-((S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-L-cysteine methyl ester | 1034535-49-3

• 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: N-((S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-L-cysteine methyl ester
• 英文别名: N-(3S-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-L-cysteine methyl ester；Boc-Tic-Cys-OMe；tert-butyl (3S)-3-[[(2R)-1-methoxy-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 1034535-49-3
• 化学式: C₁₉H₂₆N₂O₅S
• 分子量: 394.492
• InChiKey: AFIRCYLMZHOMEV-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-((S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-L-cysteine methyl ester 在 盐酸 、 三乙胺 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 241.5h， 生成 (R)-2-((S)-3,3-dimethyl-1-oxo-10,10a-dihydroimidazo[1,5-b]isoquinolin-2(1H,3H,5H)-yl)-3-mercaptopropanoic acid methyl ester
  参考文献：
  名称：

  2-Substituted (S)-2-(3,3-dimethyl-1-oxo-10,10a-dihydroimidazo[1,5-b]isoquinolin-2(1H,3H,5H)-yl)acetic acids: Conformational prediction, synthesis, anti-thrombotic and vasodilative evaluation

  摘要：

  (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid (TIC) can inhibit thrombosis by inhibiting platelet aggregation. The investigation of amino acids modified TIC reveals that a stretching conformation is critical for high anti-thrombotic activity. The conformational modeling shows that introducing a ring into amino acid modified TIC results in a desirable stretching conformation. According to this hypothesis, we synthesized seventeen novel 2-substituted (S)-2-(3,3-dimethyl-1-oxo-10,10a-dihydroimidazo[1,5-b] isoquinolin-2(1H,3H,5H)-yl)acetic acids (5a-q). In the in vitro anti-platelet aggregation assay, for ADP-induced platelet aggregation the IC50 values of 5a-q are 1.8-3.4-folds lower than that of TIC. In the in vivo anti-thrombotic assay, the effective dose of 5a-q was 167-folds lower than that of TIC. The vessel strip assay showed that 5a-q had mild vasorelaxation activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.005
• 作为产物：
  描述：

  L-苯丙氨酸 在 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 氯仿 、 水 为溶剂， 反应 70.0h， 生成 N-((S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-L-cysteine methyl ester
  参考文献：
  名称：

  2-Substituted (S)-2-(3,3-dimethyl-1-oxo-10,10a-dihydroimidazo[1,5-b]isoquinolin-2(1H,3H,5H)-yl)acetic acids: Conformational prediction, synthesis, anti-thrombotic and vasodilative evaluation

  摘要：

  (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid (TIC) can inhibit thrombosis by inhibiting platelet aggregation. The investigation of amino acids modified TIC reveals that a stretching conformation is critical for high anti-thrombotic activity. The conformational modeling shows that introducing a ring into amino acid modified TIC results in a desirable stretching conformation. According to this hypothesis, we synthesized seventeen novel 2-substituted (S)-2-(3,3-dimethyl-1-oxo-10,10a-dihydroimidazo[1,5-b] isoquinolin-2(1H,3H,5H)-yl)acetic acids (5a-q). In the in vitro anti-platelet aggregation assay, for ADP-induced platelet aggregation the IC50 values of 5a-q are 1.8-3.4-folds lower than that of TIC. In the in vivo anti-thrombotic assay, the effective dose of 5a-q was 167-folds lower than that of TIC. The vessel strip assay showed that 5a-q had mild vasorelaxation activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.005

文献信息

• A class of novel N-(3S-1,2,3,4-tetrahydroisoquinoline-3-carbonyl)-l-amino acid derivatives: their synthesis, anti-thrombotic activity evaluation, and 3D QSAR analysis
  作者：Shenling Cheng、Xiaoyi Zhang、Wei Wang、Ming Zhao、Meiqing Zheng、Heng Wei Chang、Jianghui Wu、Shiqi Peng

  DOI：10.1016/j.ejmech.2009.08.002

  日期：2009.12

  To find new anti-thrombotic agents, a natural amino acid was introduced into the 3-position of anti-platelet aggregation active 3S-tetrahydroisoquinoline-3-carboxylic acid (THIQA), and 20 novel dipeptide derivatives, 3S-tetrahydroisoquinoline-3-carboxyamino acids (6a–t), targeting the intestinal peptide transport system were provided. In vitro anti-platelet aggregation assay of 6a–t indicated that

  为了找到新的抗血栓形成剂，将天然氨基酸引入了抗血小板聚集活性3 S-四氢异喹啉-3-羧酸（THIQA）的3位，以及20种新型二肽衍生物3 S-四氢异喹啉-3提供了靶向肠肽转运系统的-羧基氨基酸（6a - t）。6a - t的体外抗血小板凝集试验表明，它们抑制二磷酸腺苷（ADP），花生四烯酸（AA），血小板活化因子（PAF）和凝血酶（TH）诱导的血小板凝集的效力高于THIQA和6a – t的体内抗血栓形成测定提示它们在大鼠中抑制血栓形成的能力也高于THIQA。根据基于MFA的Cerius2 QSAR模块，使用训练/测试集6a，b，d，g – p / 6c，e，f，q和训练/测试集6a – p / 6q – t，两个方程式（r， 0.984和0.996）建立了与6a - t的体内或体外活性相关的结构。