(S)-1-[(10R,13S,16S,19S,22R)-19-Benzyl-13-carbamoylmethyl-22-(4-ethoxy-benzyl)-16-isopropyl-12,15,18,21,24-pentaoxo-7,8-dithia-11,14,17,20,23-pentaaza-spiro[5.19]pentacosane-10-carbonyl]-pyrrolidine-2-carboxylic acid (4-amino-butyl)-amide | 99733-17-2

• 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: (S)-1-[(10R,13S,16S,19S,22R)-19-Benzyl-13-carbamoylmethyl-22-(4-ethoxy-benzyl)-16-isopropyl-12,15,18,21,24-pentaoxo-7,8-dithia-11,14,17,20,23-pentaaza-spiro[5.19]pentacosane-10-carbonyl]-pyrrolidine-2-carboxylic acid (4-amino-butyl)-amide
• CAS: 99733-17-2
• 化学式: C₄₉H₇₁N₉O₉S₂
• 分子量: 994.29
• InChiKey: DZFIFGDAEINDGD-BAUGWQFQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  69.0
• 可旋转键数：
  15.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  273.25
• 氢给体数：
  8.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  O-甲基异脲 半硫酸盐 、 (S)-1-[(10R,13S,16S,19S,22R)-19-Benzyl-13-carbamoylmethyl-22-(4-ethoxy-benzyl)-16-isopropyl-12,15,18,21,24-pentaoxo-7,8-dithia-11,14,17,20,23-pentaaza-spiro[5.19]pentacosane-10-carbonyl]-pyrrolidine-2-carboxylic acid (4-amino-butyl)-amide 在 sodium hydroxide 作用下， 以 水 为溶剂， 以64%的产率得到(S)-1-[(10R,13S,16S,19S,22R)-19-Benzyl-13-carbamoylmethyl-22-(4-ethoxy-benzyl)-16-isopropyl-12,15,18,21,24-pentaoxo-7,8-dithia-11,14,17,20,23-pentaaza-spiro[5.19]pentacosane-10-carbonyl]-pyrrolidine-2-carboxylic acid (4-guanidino-butyl)-amide
  参考文献：
  名称：

  Structure-activity relationships of novel vasopressin antagonists containing C-terminal diaminoalkanes and (aminoalkyl)guanidines

  摘要：

  We report the synthesis and biological activity of a series of analogues of the vasopressin antagonists [Pmp1,D-Tyr(Et)2,Val4]arginine-vasopressin (1) and [Pmp1,D-Tyr(Et)2,Val4,desGly9]arginine-vasopressin (2), where part or all of the tripeptide tail has been replaced by a simple alkyldiamine [NH(CH2)nNH2] or (aminoalkyl)guanidine [NH(CH2)nNHC(= NH)NH2] in order to examine the effects that variation of the length and orientation of the tripeptide tail have on renal vasopressin (V2) receptor antagonist activity. The results show that the entire tripeptide tail (Pro-Arg-Gly-NH2) can be replaced by an alkyldiamine or an (aminoalkyl)guanidine, compounds 15 and 16, respectively, indicating that there is no orientational requirement for the basic functional group coming off the cyclic hexapeptide ring. Also, there seems to be an "optimal" distance between the basic functional group and the hexapeptide ring since receptor affinity of the antagonists begins to fall off when the basic functional group is too close (compound 13) or extends too far (compounds 8-10) from the hexapeptide ring. These results suggest all that is necessary for retention of antagonist affinity and potency is a basic functional group, amine or guanidine, extended an optimal distance from the hexapeptide ring.

  DOI：

  10.1021/jm00122a017
• 作为产物：
  描述：

  (S)-1-((R)-2-{(S)-3-Carbamoyl-2-[(S)-2-((S)-2-{(R)-3-(4-ethoxy-phenyl)-2-[2-(1-mercapto-cyclohexyl)-acetylamino]-propionylamino}-3-phenyl-propionylamino)-3-methyl-butyrylamino]-propionylamino}-3-mercapto-propionyl)-pyrrolidine-2-carboxylic acid 在 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 potassium hexacyanoferrate(III) 作用下， 以 水 为溶剂， 反应 116.0h， 生成 (S)-1-[(10R,13S,16S,19S,22R)-19-Benzyl-13-carbamoylmethyl-22-(4-ethoxy-benzyl)-16-isopropyl-12,15,18,21,24-pentaoxo-7,8-dithia-11,14,17,20,23-pentaaza-spiro[5.19]pentacosane-10-carbonyl]-pyrrolidine-2-carboxylic acid (4-amino-butyl)-amide
  参考文献：
  名称：

  Structure-activity relationships of novel vasopressin antagonists containing C-terminal diaminoalkanes and (aminoalkyl)guanidines

  摘要：

  We report the synthesis and biological activity of a series of analogues of the vasopressin antagonists [Pmp1,D-Tyr(Et)2,Val4]arginine-vasopressin (1) and [Pmp1,D-Tyr(Et)2,Val4,desGly9]arginine-vasopressin (2), where part or all of the tripeptide tail has been replaced by a simple alkyldiamine [NH(CH2)nNH2] or (aminoalkyl)guanidine [NH(CH2)nNHC(= NH)NH2] in order to examine the effects that variation of the length and orientation of the tripeptide tail have on renal vasopressin (V2) receptor antagonist activity. The results show that the entire tripeptide tail (Pro-Arg-Gly-NH2) can be replaced by an alkyldiamine or an (aminoalkyl)guanidine, compounds 15 and 16, respectively, indicating that there is no orientational requirement for the basic functional group coming off the cyclic hexapeptide ring. Also, there seems to be an "optimal" distance between the basic functional group and the hexapeptide ring since receptor affinity of the antagonists begins to fall off when the basic functional group is too close (compound 13) or extends too far (compounds 8-10) from the hexapeptide ring. These results suggest all that is necessary for retention of antagonist affinity and potency is a basic functional group, amine or guanidine, extended an optimal distance from the hexapeptide ring.

  DOI：

  10.1021/jm00122a017