新型生长激素促分泌素活性系列

New active series of growth hormone secretagogues.

作者信息

Guerlavais Vincent, Boeglin Damien, Mousseaux Delphine, Oiry Catherine, Heitz Annie, Deghenghi Romano, Locatelli Vittorio, Torsello Antonio, Ghé Corrado, Catapano Filomena, Muccioli Giampiero, Galleyrand Jean-Claude, Fehrentz Jean-Alain, Martinez Jean

机构信息

Laboratoire des Aminoacides, Peptides et Protéines (LAPP), UMR 5810, Université Montpellier I et II, B.P. 14491, Faculté de Pharmacie, 15 Avenue Charles Flahaut, 34093 Montpellier Cédex 5, France.

出版信息

J Med Chem. 2003 Mar 27;46(7):1191-203. doi: 10.1021/jm020985q.

DOI:10.1021/jm020985q

PMID:12646029

Abstract

New growth hormone secretagogue (GHS) analogues were synthesized and evaluated for growth hormone releasing activity. This series derived from EP-51389 is based on a gem-diamino structure. Compounds that exhibited higher in vivo GH-releasing potency than hexarelin in rat (subcutaneous administration) were then tested per os in beagle dogs and for their binding affinity to human pituitary GHS receptors and to hGHS-R 1a. Compound 7 (JMV 1843, H-Aib-(d)-Trp-(d)-gTrp-formyl) showed high potency in these tests and was selected for clinical studies.(1)

摘要

合成了新型生长激素促分泌素（GHS）类似物，并对其生长激素释放活性进行了评估。该系列化合物源自EP - 51389，基于偕二氨基结构。然后，在大鼠（皮下给药）体内表现出比六肽促生长素更高的生长激素释放效力的化合物，在比格犬中进行口服测试，并测试它们与人垂体GHS受体和hGHS - R 1a的结合亲和力。化合物7（JMV 1843，H - Aib - (d) - Trp - (d) - gTrp - 甲酰基）在这些测试中表现出高效力，并被选用于临床研究。(1)