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Design, synthesis, and biological evaluation of novel, centrally-acting thyrotropin-releasing hormone analogues.

Abstract：

:Novel, metabolically stable and centrally acting TRH analogues with substituted pyridinium moieties replacing the [His(2)] residue of the endogenous peptide were prepared by solid-phase Zincke reaction. The 1,4-dihydropyridine prodrugs of these analogues obtained after reducing the pyridinium moiety were able to reach the brain and maintain a sustained concentration of the charged, degradation-resistant analogues formed after enzymatic oxidation of the prodrug, as manifested by the analeptic action measured in mice. Among the four analogues reported, compound 2a showed the highest potency and longest duration of action in reducing the pentobarbital-induced sleeping time compared to the parent TRH. No binding to the endocrine TRH-receptor was measured for 2a; thus, this compound emerged as a potent, centrally acting TRH analogue.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Prokai-Tatrai K,Perjési P,Zharikova AD,Li X,Prokai L

doi

10.1016/s0960-894x(02)00368-2

subject

Has Abstract

pub_date

2002-08-19 00:00:00

pages

2171-4

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960894X02003682

journal_volume

12

pub_type

杂志文章

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