1,DCpa²,DLys(atz)^3,6,ILys⁸,DAla¹⁰>GnRH | 134457-33-3

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: 1,DCpa²,DLys(atz)^3,6,ILys⁸,DAla¹⁰>GnRH
• 英文别名: [Ac-DNal¹,DCpa²,DLys(atz)^3,6,ILys⁸,DAla¹⁰]GnRH
• CAS: 134457-33-3
• 化学式: C₇₅H₁₀₇ClN₂₂O₁₃
• 分子量: 1560.27
• InChiKey: APLLXFVHGJVPPA-BKKDQWKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.28
• 重原子数：
  111.0
• 可旋转键数：
  46.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  537.03
• 氢给体数：
  19.0
• 氢受体数：
  22.0

反应信息

• 作为产物：
  描述：

  N-氰基羰亚胺二苯基酯 、 alkaline earth salt of/the/ methylsulfuric acid 生成 1,DCpa²,DLys(atz)^3,6,ILys⁸,DAla¹⁰>GnRH
  参考文献：
  名称：

  Novel gonadotropin-releasing hormone antagonists: peptides incorporating modified N.omega.-cyanoguanidino moieties

  摘要：

  In order to minimize the deleterious effects of histamine release resulting from the administration to rats and humans of some potent gonadotropin-releasing hormone (GnRH) antagonists, various arginine residues were replaced with the less basic N-omega-cyano-N-omega'-alkyl- or -arylhomoarginine, -arginine, or -p-aminophenylalanine and N-omega-triazolyllysine, -ornithine or -p-aminophenylalanine residues in active analogues. These novel analogues were synthesized on a solid-phase support via a two-step modification of the N-omega-NH2 of lysine, ornithine, or p-aminophenylalanine residues in otherwise protected resin bound peptides. Most analogues were tested in the rat antiovulatory assay (AOA) and three in vitro assays: a pituitary cell culture assay, a binding assay to pituitary cell membranes, and a histamine release assay. Introduction of the cyanoguanidino and N-omega-triazolyl moieties into GnRH analogues yielded several water-soluble antagonists which showed a desirable therapeutic ratio (low histamine release activity to high in vivo potency). Among them, ''Azaline'' (10, [Ac-DNal1,DCpa2,DPal3,Lys5(atz),DLys6(atz),ILys8,DAla10]GnRH), inhibited ovulation in the rat by 90% at 2-mu-g/rat with an ED50 in the in vitro histamine release assay comparable to that of GnRH itself.

  DOI：

  10.1021/jm00112a013