Larsson L E, Lindeberg G, Melin P, Pliska V
J Med Chem. 1978 Apr;21(4):352-6. doi: 10.1021/jm00202a008.
[Mpa1,Tyr(Et)2]-LVP (1-deamino-2-O-ethyltyrosine-8-lysine-vasopressin), [Mpa1,Tyr(n-Pr)2]-LVP, [Tyr(n-Bu)2]-LVP, [Mpa1,Tyr(n-Bu)2]-LVP, and [Mpa1,Tyr(n-hexyl)2]-LVP were synthesized in solution by the p-nitrophenyl ester method. The previously prepared [Tyr(Et)2]-LVP was resynthesized. All compounds possessed weak agonistic properties in both antidiuretic (0.5-2.0 IU/mumol) and pressor (0.5-3.0 IU/mumol) assays. In the rat none of the analogues inhibited the antidiuretic action of LVP when the two substances were given together in a single injection. However, when administered in low subthreshold doses, most of the deamino compounds suppressed the antidiuresis induced by a continuous infusion of LVP. Complete inhibition was obtained with [Mpa1,Tyr(Et)2]-LVP. The antagonistic potency seemed to decrease with increasing size of the alkyl substituent and [Mpa1,Tyr(n-hexyl)2]-LVP showed no antagonism. The molar inhibitor-LVP ratio for maximal inhibition was well below 100. Neither of the two amino analogues showed a clear-cut antagonism in the antidiuretic assay. Furthermore, none of the reported compounds was antagonistic to LVP in the rat pressor assay.
采用对硝基苯酯法在溶液中合成了[Mpa1,Tyr(Et)2]-LVP（1-脱氨基-2-O-乙基酪氨酸-8-赖氨酸-加压素）、[Mpa1,Tyr(n-Pr)2]-LVP、[Tyr(n-Bu)2]-LVP、[Mpa1,Tyr(n-Bu)2]-LVP和[Mpa1,Tyr(n-己基)2]-LVP。对先前制备的[Tyr(Et)2]-LVP进行了重新合成。所有化合物在抗利尿（0.5 - 2.0 IU/μmol）和升压（0.5 - 3.0 IU/μmol）试验中均具有较弱的激动活性。在大鼠中，当两种物质单次注射合用时，没有一种类似物能抑制LVP的抗利尿作用。然而，当以低阈下剂量给药时，大多数脱氨基化合物能抑制由持续输注LVP诱导的抗利尿作用。[Mpa1,Tyr(Et)2]-LVP可实现完全抑制。拮抗效力似乎随着烷基取代基尺寸的增加而降低，[Mpa1,Tyr(n-己基)2]-LVP未表现出拮抗作用。最大抑制时的摩尔抑制剂-LVP比值远低于100。在抗利尿试验中，这两种氨基类似物均未表现出明显的拮抗作用。此外，在大鼠升压试验中，所报道的化合物均未对LVP产生拮抗作用。
