(S)-(2-tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide | 150417-15-5

• 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: (S)-(2-tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
• 英文别名: (S)-2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide；(3S)-3-Carbamoyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester；tert-butyl (3S)-3-carbamoyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
• CAS: 150417-15-5
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: CDNXESHBZDXBQT-LBPRGKRZSA-N

物化性质

• 沸点：
  467.2±45.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-(2-tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (3S)-1,2,3,4-四氢-3-异喹啉甲酰胺
  参考文献：
  名称：

  DPP-IV的β-苯乙胺抑制剂的反向结合：X射线结构以及新型片段和精细抑制剂的特性。

  摘要：

  与DPP-IV结合的β-苯乙胺片段抑制剂5的共晶体结构表明苯环占据了酶的脯氨酸口袋。该发现为基于β-苯乙胺的DPP-IV抑制剂的反向结合模式的一般假设提供了基础。从而消除了类似底物的结构-活性关系（SAR）的新型抑制剂设计概念得以实现，并发现了新型有效的抑制剂。

  DOI：

  10.1016/j.bmcl.2005.11.103
• 作为产物：
  描述：

  N-叔丁氧羰基-(S)-1,2,3,4-四氢异喹啉-3-羧酸 在 N,N-二异丙基乙胺 氨 、 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 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-(2-tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  DPP-IV的β-苯乙胺抑制剂的反向结合：X射线结构以及新型片段和精细抑制剂的特性。

  摘要：

  与DPP-IV结合的β-苯乙胺片段抑制剂5的共晶体结构表明苯环占据了酶的脯氨酸口袋。该发现为基于β-苯乙胺的DPP-IV抑制剂的反向结合模式的一般假设提供了基础。从而消除了类似底物的结构-活性关系（SAR）的新型抑制剂设计概念得以实现，并发现了新型有效的抑制剂。

  DOI：

  10.1016/j.bmcl.2005.11.103

文献信息

• The reversed binding of β-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors
  作者：Sonja Nordhoff、Silvia Cerezo-Gálvez、Achim Feurer、Oliver Hill、Victor G. Matassa、Günther Metz、Christian Rummey、Meinolf Thiemann、Paul J. Edwards

  DOI：10.1016/j.bmcl.2005.11.103

  日期：2006.3

  beta-phenethylamine fragment inhibitor 5 bound to DPP-IV revealed that the phenyl ring occupied the proline pocket of the enzyme. This finding provided the basis for a general hypothesis of a reverse binding mode for beta-phenethylamine-based DPP-IV inhibitors. Novel inhibitor design concepts that obviate substrate-like structure-activity relationships (SAR) were thereby enabled, and novel, potent inhibitors were

  与DPP-IV结合的β-苯乙胺片段抑制剂5的共晶体结构表明苯环占据了酶的脯氨酸口袋。该发现为基于β-苯乙胺的DPP-IV抑制剂的反向结合模式的一般假设提供了基础。从而消除了类似底物的结构-活性关系（SAR）的新型抑制剂设计概念得以实现，并发现了新型有效的抑制剂。
• DPP-IV INHIBITORS
  申请人：Graffinity Pharmaceuticals Aktiengesellschaft

  公开号：EP1541148A1

  公开（公告）日：2005-06-15

  The invention relates to compounds of formula (I) wherein a dotted line indicates an optionally present double bond and wherein Z, R1 - R8, n, X1, X2, Y and T have the meaning as cited in the description and the claims. Said compounds are useful as DPP-IV inhibitors. The invention also relates to the preparation of such compounds as well as the production and use thereof as medicament.

  该发明涉及式(I)的化合物，其中虚线表示可能存在的双键，Z、R1 - R8、n、X1、X2、Y 和 T 的含义如描述和权利要求中所述。所述化合物可用作DPP-IV抑制剂。该发明还涉及制备这种化合物以及将其作为药物的生产和使用。
• Highly Potent Cyclic Disulfide Antagonists of Somatostatin
  作者：Simon J. Hocart、Rahul Jain、William A. Murphy、John E. Taylor、David H. Coy

  DOI：10.1021/jm9806289

  日期：1999.6.1

  The search for synthetic analogues of somatostatin (SRIF) which exhibit selective affinities for the five known receptor subtypes (sst(1-5)) has generated a large number of potent agonist analogues. Many of these agonists display good subtype selectivities and affinities for the subtypes 2, 3, and 5, with very few selective for sst(1) or sst(4). Until the recent report by Bass and co-workers (Mol. Pharmacol. 1996, 50, 709-715; erratum Mel. Pharmacol. 1997, 51, 170), no true antagonists of somatostatin had been discovered, let alone any displaying differential receptor subtype selectivity. In this present study, we further explore the effect of this putative L,D-5(6) antagonist motif on somatostatin octapeptide analogues with a cyclic hexapeptide core. The most potent antagonist found to date is H-Cpa-cyclo[DCys-Tyr-DTrp-Lys-Thr-Cys]-Nal-NH2, PRL-2970 (21), which has an IC50 Of 1.1 nM in a rat pituitary growth hormone in vitro antagonist assay versus SRIF (1 nM). This analogue bound to cloned human somatostatin subtype 2 receptors with a K-i of 26 nM. The highest hsst(2) affinity analogue was H-Cpa-cyclo[DCys-Pal-DTrp-Lys-Tle-Cys]-Nal-NH2, PRL-2915 (15), with a K-i of 12 nM (IC50 = 1.8 nM). This analogue was also selective for hsst(2) over hsst(3) and hsst(5) by factors of 8 and 40, respectively, and had no agonist activity when tested alone at concentrations up to 10 mu M. Regression analysis of the binding affinities versus the observed antagonist potencies revealed high correlations for hsst(2) (r = 0.65) and hsst(3) (r = 0.52) with a less significant correlation to hsst5 (r = 0.40). This is quite different from the somatostatin agonist analogues which show a highly significant correlation to hsst(2) (r > 0.9). Receptor-selective somatostatin antagonists should provide valuable tools for characterizing the many important physiological functions of this neuropeptide.
• Synthesis and Characterization of N-Substituted (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxamides and Thioamides as Organocatalysts for Asymmetric Aldol Reaction
  作者：Pavel Drabina、Ladislav Androvič、Illia Panov、Lydie Harmand、Zdeňka Padělková、Miloš Sedlák

  DOI：10.3987/com-14-13029

  日期：——
• Optimized synthesis of tetrahydroisoquinoline-hydantoins
  作者：Julie Charton、Amaury Cazenave Gassiot、Patricia Melnyk、Sophie Girault-Mizzi、Christian Sergheraert

  DOI：10.1016/j.tetlet.2004.07.112

  日期：2004.9

  Several methods have been developed and compared for the solution synthesis of tetrahydroisoquinoline-hydantoin (Tichydantoin) derivatives. Starting materials were Tic-OH and amines readily available from commercial sources. The best yields were observed when the imidazolidine-2,4-dione ring was synthesized in two steps: (1) reaction of Tic-OH with the appropriate amine and (2) cyclization with 1,1'-carbonyldiimidazole. (C) 2004 Elsevier Ltd. All rights reserved.