Document Detail


Synthesis of a novel class of heteroaromatic amino acids and their use in the preparation of analogues of luteinizing hormone-releasing hormone.
MedLine Citation:
PMID:  6366232     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A novel class of heterocyclic aromatic amino acids based on the 3-(2-benzimidazolyl)alanine system has been generated by chiral synthesis from D- or L-aspartic acid. The use of variously substituted o-phenylenediamines for condensation with the beta-carboxyl function of alpha-benzyl N-(benzyloxycarbonyl)-D-aspartate has led to a series of amino acids of graded hydrophobicity with a steric bulk similar to that of tryptophan. In a similar fashion, we have prepared 3-(2-benzothiazolyl)-D-alanine from o-aminothiophenol and 3-(2-benzoxazolyl)-D-alanine from o-aminophenol. Incorporation of these amino acids into the 6-position of luteinizing hormone-releasing hormone (LH-RH) led to a series of very potent agonist analogues (up to 160 times LH-RH potency), active in doses ranging from 0.1 to 0.5 microgram by twice daily injection in a rat estrus cyclicity suppression assay designed to show the paradoxical antifertility effects of these compounds.
Authors:
J J Nestor; B L Horner; T L Ho; G H Jones; G I McRae; B H Vickery
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  27     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1984 Mar 
Date Detail:
Created Date:  1984-04-24     Completed Date:  1984-04-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  320-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Alanine / analogs & derivatives*
Animals
Benzothiazoles
Chemical Phenomena
Chemistry
Estrus / drug effects
Female
Gonadotropin-Releasing Hormone / analogs & derivatives,  chemical synthesis*
Methods
Pregnancy
Rats
Tryptophan
Chemical
Reg. No./Substance:
0/Benzothiazoles; 33515-09-2/Gonadotropin-Releasing Hormone; 56-41-7/Alanine; 73-22-3/Tryptophan; 81440-41-7/3-(2-benzothiazolyl)alanine; 81440-45-1/3-(2-benzimidazolyl)alanine; 88549-23-9/3-(2-benzoxazolyl)alanine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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