BE-18257 A

• 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: BE-18257 A
• 英文别名: cyclo(D-Glu-Ala-D-Val-Leu-D-Trp)；3-[(2R,5S,8R,11S,14R)-14-(1H-indol-3-ylmethyl)-5-methyl-11-(2-methylpropyl)-3,6,9,12,15-pentaoxo-8-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]propanoic acid
• 化学式: C₃₀H₄₂N₆O₇
• 分子量: 598.699
• InChiKey: VKWWONDOCUPZRG-RESQWGQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  199
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  cyclo-(δ-O-tert-butyl-D-glutamyl-L-alanyl-D-valyl-L-leucyl-D-tryptophan) 在 1,2-乙二硫醇 、 三氟乙酸 作用下， 反应 1.0h， 生成 BE-18257 A
  参考文献：
  名称：

  具有高ETA选择性的环状五肽内皮素拮抗剂。增强效力和溶解性的修饰。

  摘要：

  DOI：

  10.1021/jm00089a028

文献信息

• Cyclic peptide surface feature mimics of endothelin
  申请人：Texas Biotechnology Corporation

  公开号：US05736509A1

  公开（公告）日：1998-04-07

  Cyclic peptides and pharmaceutically acceptable salts and esters thereof are provided. The cyclic peptides and pharmaceutically acceptable salts and esters thereof mimic surface features of the C-terminus of endothelin and thereby can be used modulate or alter the activity of the endothelin family of peptides. More particularly, cyclic pentapeptides, cyclic hexapeptides, cyclic heptapeptides and pharmaceutically acceptable derivatives of the peptides that specifically inhibit the activity of endothelin are provided. Among the cyclic peptides are those that have the formula: cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -D-Trp): X.sup.1 is D-Tyr or D-Asp; X.sup.2 is Phe, Ala, Ac.sub.3 c or Pro; X.sup.3 is D-His, D-Ala, D-Val, Gly or .beta.-Ala; and X.sup.4 is His, Ala, .beta.-Ala, Aib, Gly, D-His-gly or Leu; cyclo(X.sup.1 -L-Phe-X.sup.3 -X.sup.4 -X.sup.5) in which X.sup.1 is D-Tyr, D-Asp or D-Glu, X.sup.3 is selected from among D-His, .beta.-Ala-D-His or gly-D-His; X.sup.4 is Ser, Gly or .beta.-Ala, and X.sup.5 is D-Trp or N-Me-D-Trp; cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -L-Trp) in which X.sup.1 is D-Ala, Aib, Gly, D-Val, D-Leu, D-lle, D-Nva, D-Nle, or D-Alle; X.sup.2 is D-Val, D-Leu, D-lle, D-Ala, D-Gln, Gly, Aib, D-Nva, D-Nle, or D-Alle; X.sup.3 is Pro, Gly, Aib, Val, Leu, L-Nva, L-Nle, L-Alle or L-Hyp and X.sup.4 is D-Asp, D-Glu, D-Ser, D-Thr, D-Tyr, D-Cys(O.sub.3 H) or D-Pen(O.sub.3 H); and cyclo(X.sup.1 -X.sup.2 -X.sup.3 -X.sup.4 -L-Trp) in which X.sup.1 is D-Leu, D-Val, D-lle, D-Ala, Gly, Aib, D-Nva, D-Nle or D-Alle; X.sup.2 is Val, lle, Leu, Ala, Gln, Gly, Aib, L-Nva, L-Nle or L-Alle; X.sup.3 is D-Pro, D-Hyp, D-Ala, D-Val, D-lle, Gly, Aib, D-Nva, D-Nle or D-Alle; and X.sup.4 is Asp, Glu, Tyr, Ser, Thr, L-Cys(O.sub.3 H) or L-Pen(O.sub.3 H). Pharmaceutical compositions containing the peptides and methods of modulating the activity of endothelin peptides are also provided.

  本发明提供环肽及其药学上可接受的盐和酯。这些环肽及其药学上可接受的盐和酯模拟内皮素C-末端的表面特征，因此可用于调节或改变内皮素家族肽的活性。特别地，提供了环五肽、环六肽、环七肽和药学上可接受的肽衍生物，它们特异性地抑制内皮素的活性。其中一些环肽具有以下公式：cyclo(X.sup.1-X.sup.2-X.sup.3-X.sup.4-D-Trp)：X.sup.1为D-Tyr或D-Asp；X.sup.2为Phe、Ala、Ac.sub.3 c或Pro；X.sup.3为D-His、D-Ala、D-Val、Gly或.beta.-Ala；X.sup.4为His、Ala、.beta.-Ala、Aib、Gly、D-His-gly或Leu；cyclo(X.sup.1-L-Phe-X.sup.3-X.sup.4-X.sup.5)，其中X.sup.1为D-Tyr、D-Asp或D-Glu，X.sup.3从D-His、.beta.-Ala-D-His或gly-D-His中选出；X.sup.4为Ser、Gly或.beta.-Ala，X.sup.5为D-Trp或N-Me-D-Trp；cyclo(X.sup.1-X.sup.2-X.sup.3-X.sup.4-L-Trp)，其中X.sup.1为D-Ala、Aib、Gly、D-Val、D-Leu、D-lle、D-Nva、D-Nle或D-Alle；X.sup.2为D-Val、D-Leu、D-lle、D-Ala、D-Gln、Gly、Aib、D-Nva、D-Nle或D-Alle；X.sup.3为Pro、Gly、Aib、Val、Leu、L-Nva、L-Nle、L-Alle或L-Hyp，X.sup.4为D-Asp、D-Glu、D-Ser、D-Thr、D-Tyr、D-Cys(O.sub.3 H)或D-Pen(O.sub.3 H)；和cyclo(X.sup.1-X.sup.2-X.sup.3-X.sup.4-L-Trp)，其中X.sup.1为D-Leu、D-Val、D-lle、D-Ala、Gly、Aib、D-Nva、D-Nle或D-Alle；X.sup.2为Val、lle、Leu、Ala、Gln、Gly、Aib、L-Nva、L-Nle或L-Alle；X.sup.3为D-Pro、D-Hyp、D-Ala、D-Val、D-lle、Gly、Aib、D-Nva、D-Nle或D-Alle；X.sup.4为Asp、Glu、Tyr、Ser、Thr、L-Cys(O.sub.3 H)或L-Pen(O.sub.3 H)。还提供了含有这些肽的药物组合物以及调节内皮素肽活性的方法。
• Methods and compositions for emergency contraception using endothelin receptor antagonists
  申请人：THE POPULATION COUNCIL, INC.

  公开号：EP2246062A1

  公开（公告）日：2010-11-03

  Disclosed are methods and compositions containing endothelin receptor antagonists for emergency contraception.

  所公开的是含有内皮素受体拮抗剂的用于紧急避孕的方法和组合物。
• Cyclic Peptide Synthesis with Thioacids
  作者：Kaname Sasaki、David Crich

  DOI：10.1021/ol101201w

  日期：2010.7.16

  C-Terminal amino acid 9-fluorenylmethylthioesters may be carried through Boc chemistry solution phase peptide synthesis sequences. After insertion of the final residue in the form of an Fmoc carbamate, treatment with piperidine releases a seco-peptide as a C-terminal thioacid that on treatment with Sangers reagent undergoes cyclization to a cyclic peptide. Cyclic penta- and hexapeptides have been synthesized in this manner, as has a cyclic glycopeptide. Functional group compatibility with alcohols and carboxylic acids is demonstrated.
• US8173593B2
  申请人：——

  公开号：US8173593B2

  公开（公告）日：2012-05-08