(S)-3-boc-氨基-5-(羧基甲基)-2,3-二氢-1,5-苯并硫杂-4(5h)-酮 | 250349-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 中文名称: (S)-3-boc-氨基-5-(羧基甲基)-2,3-二氢-1,5-苯并硫杂-4(5h)-酮
• 英文名称: Boc-D-BT-OH
• 英文别名: (S)-2-(3-((tert-Butoxycarbonyl)amino)-4-oxo-3,4-dihydrobenzo[b][1,4]thiazepin-5(2H)-yl)acetic acid；2-[(3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-2,3-dihydro-1,5-benzothiazepin-5-yl]acetic acid
• CAS: 250349-13-4
• 化学式: C₁₆H₂₀N₂O₅S
• 分子量: 352.411
• InChiKey: BNDWQYMZOLVICH-SNVBAGLBSA-N

物化性质

• 沸点：
  622.4±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-3-boc-氨基-5-(羧基甲基)-2,3-二氢-1,5-苯并硫杂-4(5h)-酮 在 N-甲基吗啉 、 氯甲酸异丁酯 、 ammonium hydroxide 作用下， 以100%的产率得到Boc-DBT-NH2
  参考文献：
  名称：

  Structural elucidation of the β-turn inducing (S)-[3-amino-4-oxo-2,3-dihydro-5H-benzo[b][1,4]thiazepin-5-yl] acetic acid (DBT) motif

  摘要：

  X-ray diffraction analysis of Boc-DBT-NH2 (DBT = (S-[amino]-5-carbethoxymethyl-2,3-dihydro-1,5-benzothiazepine-4(5H)-one) showed that this constrained dipeptide mimetic adopts a type II' beta-turn in the solid state. IR and NMR studies indicated that the folded conformation is retained in solution. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.03.134
• 作为产物：
  描述：

  (3S)-3-[[叔丁氧羰基]氨基]-3,4-二氢-4-氧代-1,5-苯并硫氮杂卓-5(2H)-乙酸乙酯 在 sodium hydroxide 、 水 作用下， 以 1,4-二氧六环 为溶剂， 生成 (S)-3-boc-氨基-5-(羧基甲基)-2,3-二氢-1,5-苯并硫杂-4(5h)-酮
  参考文献：
  名称：

  设计，合成和生物评价1，5-苯并硫氮杂-4-酮衍生物靶向因子VIIa /组织因子

  摘要：

  1，5-苯并硫氮杂-4-酮骨架被证明可以提供有效的蛋白酶抑制剂。在这项贡献中，我们描述了其在因子VIIa /组织因子抑制剂设计中的用途。一系列在其芳基部分包含未取代的支架的化合物导致化合物20的IC 50为2.16μM。在对该化合物进行分子建模研究之后，制备了第二个化合物，需要合成受保护的7-或8-取代的1,5-苯并噻氮杂-4-酮衍生物。

  DOI：

  10.1016/j.bmcl.2009.01.039

文献信息

• Synthesis and Characterization of Bradykinin B₂ Receptor Agonists Containing Constrained Dipeptide Mimics
  作者：Muriel Amblard、Isabelle Daffix、Gilbert Bergé、Monique Calmès、Pierre Dodey、Didier Pruneau、Jean-Luc Paquet、Jean-Michel Luccarini、Pierre Bélichard、Jean Martinez

  DOI：10.1021/jm9901531

  日期：1999.10.1

  study, we have investigated the effects of replacement of the D-Tic-Oic moiety by various constrained dipeptide mimetics. The resulting compounds were tested for their binding affinity toward the cloned human B(2) receptor and for their functional interaction with the bradykinin-induced contraction of isolated human umbilical vein. Subsequently, we have designed novel bradykinin B(2) receptor agonists

  先前我们已经证明了D-Tic-Oic二肽被（3S）-[氨基] -5-（羰基甲基）-2,3-二氢-1，5-苯并噻唑啉-4（5H）-一个（D -BT）缓激肽B（2）受体拮抗剂HOE 140中的部分导致了完全有效和选择性的缓激肽B（2）受体激动剂（H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT- Arg-OH，JMV1116）对人受体具有高亲和力（K（i）0.7 nM）。在本研究中，我们研究了各种约束的二肽模拟物替代D-Tic-Oic部分的影响。测试了所得化合物对克隆的人B（2）受体的结合亲和力以及与缓激肽诱导的孤立人脐静脉收缩的功能相互作用。后来，我们设计了新型缓激肽B（2）受体激动剂，它们可能对内肽酶的酶促裂解具有抗性，并且可能代表了有趣的新药理学工具。为了增加化合物JMV1116的效力，其N端部分和D-BT部分都被修饰。D-精氨酸残基被L-赖氨酸残基取代导致更有效的
• AN IMPROVED SYNTHESIS OF (S)- OR (R)-N-BcE-PROTECTED 1,5-BENZOTHIAZEPINE DERIVATIVES
  作者：Muriel Amblard、Monique Calmès、Virginie Roques、Samuel Tabet、Albert Loffet、Jean Martinez

  DOI：10.1080/00304940209458076

  日期：2002.8.1
• WO2007/101347
  申请人：——

  公开号：——

  公开（公告）日：——
• Design and Synthesis of Potent Bradykinin Agonists Containing a Benzothiazepine Moiety
  作者：Muriel Amblard、Isabelle Daffix、Philippe Bedos、Gilbert Bergé、Didier Pruneau、Jean-Luc Paquet、Jean-Michel Luccarini、Pierre Bélichard、Pierre Dodey、Jean Martinez

  DOI：10.1021/jm9901529

  日期：1999.10.1

  A bradykinin analogue (H-Arg-Pro-Pro-Gly-Phe-Ser-D-BT-Arg-OH, 3) in which the Pro-Phe dipeptide was replaced by the (3S)[amino]-5-(carbonylmethyl)-2,3-dihydro-1,5-benzothiazepin 4(5K)-one (D-BT) moiety has been synthesized. The same modification was performed on the potent bradykinin Bz receptor antagonist HOE 140 (H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH), in which the -D-Tic-Oic- moiety was replaced by D-BT to yield H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-Arg-OH, 1 (JMV111G). These compounds were examined in vitro for their binding affinity toward bradykinin B-1 and B-2 receptors as well as for their ability to interfere with bradykinin-induced contraction of both human umbilical vein and rat uterus. The two compounds 3 and 1 competed with [H-3]bradykinin binding to the human cloned B-2 receptor giving K-i values of 13 +/- 2 and 0.7 +/- 0.1 nM, respectively. Unexpectedly, both compounds were full bradykinin B-2 receptor agonists on the human umbilical vein (pD(2) = 6.60 +/- 0.07 for 3 and 6.80 +/- 0.08 for 1) and rat uterus (pD(2) = 7.20 +/- 0.09 for 3 and 7.50 +/- 0.09 for 1) preparations with the same efficacy as bradykinin. In addition 1 induced a concentration-dependent phosphoinositide production in CHO cells expressing the human cloned B-2 receptor. These data provide evidence for a bioactive conformation of bradykinin constrained at the dipeptide Pro-Phe.
• Design, synthesis, and biological evaluation of 1,5-benzothiazepine-4-one derivatives targeting factor VIIa/tissue factor
  作者：Erwan Ayral、Philippe Gloanec、Gilbert Bergé、Guillaume de Nanteuil、Philippe Mennecier、Alain Rupin、Tony J. Verbeuren、Pierre Fulcrand、Jean Martinez、Jean-François Hernandez

  DOI：10.1016/j.bmcl.2009.01.039

  日期：2009.3

  the design of factor VIIa/tissue factor inhibitors. A series containing a scaffold non-substituted on its aryl part led to compound 20 with an IC50 of 2.16 μM. Following molecular modelling studies of this compound, a second series was prepared, which necessitated the synthesis of protected 7- or 8-substituted 1,5-benzothiazepine-4-one derivatives.

  1，5-苯并硫氮杂-4-酮骨架被证明可以提供有效的蛋白酶抑制剂。在这项贡献中，我们描述了其在因子VIIa /组织因子抑制剂设计中的用途。一系列在其芳基部分包含未取代的支架的化合物导致化合物20的IC 50为2.16μM。在对该化合物进行分子建模研究之后，制备了第二个化合物，需要合成受保护的7-或8-取代的1,5-苯并噻氮杂-4-酮衍生物。