3(S)-[(benzyloxycarbonyl)amino]-5-(carbethoxymethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | 209683-20-5

• 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: 3(S)-[(benzyloxycarbonyl)amino]-5-(carbethoxymethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one
• 英文别名: Ethyl 3-(S)-[(phenylmethoxycarbonyl)amino]-3,4-dihydro-4-oxo-1,5-benzothiazepin-5(2H)-acetate；ethyl 2-[(3S)-4-oxo-3-(phenylmethoxycarbonylamino)-2,3-dihydro-1,5-benzothiazepin-5-yl]acetate
• CAS: 209683-20-5
• 化学式: C₂₁H₂₂N₂O₅S
• 分子量: 414.482
• InChiKey: QGOQSAHOINKITC-MRXNPFEDSA-N

物化性质

• 沸点：
  654.414±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.340±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3(S)-[(benzyloxycarbonyl)amino]-5-(carbethoxymethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one 在 sodium hydroxide 、 氢溴酸 、 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 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：

  Design and Synthesis of Potent Bradykinin Agonists Containing a Benzothiazepine Moiety

  摘要：

  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.

  DOI：

  10.1021/jm9901529
• 作为产物：
  描述：

  四丁基碘化铵 、 溴乙酸乙酯 、 3-(S)-[(phenylmethoxycarbonyl)amino]-2,3-dihydro-1,5-benzothiazepin-4(5H)-one 在 氢氧化钾 作用下， 以 四氢呋喃 为溶剂， 生成 3(S)-[(benzyloxycarbonyl)amino]-5-(carbethoxymethyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one
  参考文献：
  名称：

  Peptide agonists of bradykinin B2 receptor

  摘要：

  本发明涉及一种伪肽化合物，所述伪肽化合物从以下组成的集合中选择：（i）式（I）的化合物：其中：A1代表单键，D-Arg或L-Lys; A2代表L-Pro或trans-4-羟基-L-Pro（4Hyp）; A3代表L-Phe或L-噻氨酸（Thi）; Y代表氢原子或C1-C3烷基; X代表硫或氧原子; 以及（ii）它们的加成盐。本发明还涉及该化合物及其加成盐的制备和在治疗中的应用。

  公开号：

  US06316413B1

文献信息

• US6316413B1
  申请人：——

  公开号：US6316413B1

  公开（公告）日：2001-11-13
• Peptide agonists of bradykinin B2 receptor
  申请人：Fournier Industrie et Sante

  公开号：US06316413B1

  公开（公告）日：2001-11-13

  The invention concerns a pseudopeptide compounds selected among the set constituted by: (i) the compounds of formula (I): in which: A1 represents a single bond, D-Arg or L-Lys; A2 represents L-Pro or trans-4-hydroxy-L-Pro (4Hyp); A3 represents L-Phe or L-thienylalanine (Thi); Y represents a hydrogen atom or a C1-C3 alkyl group; X represents a sulphur or oxygen atom; and, (ii) their additive salts. The invention also concerns the preparation and use of this compound and its additive salts in therapy.

  本发明涉及一种伪肽化合物，所述伪肽化合物从以下组成的集合中选择：（i）式（I）的化合物：其中：A1代表单键，D-Arg或L-Lys; A2代表L-Pro或trans-4-羟基-L-Pro（4Hyp）; A3代表L-Phe或L-噻氨酸（Thi）; Y代表氢原子或C1-C3烷基; X代表硫或氧原子; 以及（ii）它们的加成盐。本发明还涉及该化合物及其加成盐的制备和在治疗中的应用。
• 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.