1,DCpa²,DPal³,Lys(atz)⁵,DLys(atz)⁶,ILys⁸,DAla¹⁰>GnRH | 134457-26-4

• 分子结构分类: 有机化合物 - 有机聚合物 - 多肽
• 英文名称: 1,DCpa²,DPal³,Lys(atz)⁵,DLys(atz)⁶,ILys⁸,DAla¹⁰>GnRH
• 英文别名: azaline A；[Ac-DNal¹,DCpa²,DPal³,Lys(atz)⁵,DLys(atz)⁶,ILys⁸,DAla¹⁰]GnRH；(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-6-[(5-amino-1H-1,2,4-triazol-3-yl)amino]hexanoyl]amino]-6-[(5-amino-1H-1,2,4-triazol-3-yl)amino]hexanoyl]amino]-4-methylpentanoyl]amino]-6-(propan-2-ylamino)hexanoyl]-N-[(2R)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide
• CAS: 134457-26-4
• 化学式: C₇₄H₁₀₆ClN₂₃O₁₂
• 分子量: 1545.26
• InChiKey: APYKABCXCKNQMG-PPTOZNKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  110
• 可旋转键数：
  46
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  530
• 氢给体数：
  18
• 氢受体数：
  22

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,DPal³,Lys(atz)⁵,DLys(atz)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

文献信息

• Novel gonadotropin-releasing hormone antagonists: peptides incorporating modified N.omega.-cyanoguanidino moieties
  作者：Paula Theobald、John Porter、Catherine Rivier、Anne Corrigan、Marilyn Perrin、Wylie Vale、Jean Rivier、William Hook、Reuben Siraganian

  DOI：10.1021/jm00112a013

  日期：1991.8

  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.