Document Detail

Synthesis and biological activity of a series of aspartate transcarbamoylase inhibitors: N-substituted diethyl aspartates and N-substituted-3-oxo-1,4-piperazine-2-acetic acid esters.
MedLine Citation:
PMID:  2352167     Owner:  NLM     Status:  MEDLINE    
Series of N-substituted diethyl aspartates and N-substituted-3-oxo-1,4-piperazine-2-acetic acid esters were synthesized as potential inhibitors of aspartate transcarbamoylase. The aspartates were obtained by addition of substituted alkyl amines to diethyl maleate, or conversion of the hydroxy ethyl amino adduct to other functions. The 3-oxo-1,4-piperazine-2-acetic acid esters were prepared by addition of ethylene diamine to diethyl maleate, followed by cyclization. Addition of 1,2-diamino-2-methylpropane gave the corresponding 5,5-dimethyl-3-oxo-1,4-piperazine-2-acetic acid ester. N-Acyl derivatives in each series were obtained using the bromoacyl chlorides. A majority of the compounds in each series showed antimicrobial activity against five representative microorganisms, as well as significant activity against aspartate transcarbamoylase. Four of the compounds were found to have significant specificity against several tumor cell lines. A distance of two carbons between N and a reactive function was found to give the best activity for either antimicrobial, antienzyme, or tumor cell specificity activities, in either the open chain aspartates or cyclic piperazines. Little difference in anti-enzyme activity was found between the aspartates and piperazines, but introduction of the planar phenyl substituents lowered inhibitory activity.
P L Dutta; W O Foye
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  79     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  1990 May 
Date Detail:
Created Date:  1990-07-16     Completed Date:  1990-07-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  447-52     Citation Subset:  IM    
Samuel M. Best Research Laboratory, Massachusetts College of Pharmacy and Allied Health Sciences, Boston, MA 02115.
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MeSH Terms
Aspartate Carbamoyltransferase / antagonists & inhibitors*
Aspartic Acid / analogs & derivatives*,  pharmacology
Chemistry, Physical
Drug Screening Assays, Antitumor
Microbial Sensitivity Tests
Phosphonoacetic Acid / analogs & derivatives*,  pharmacology
Physicochemical Phenomena
Reg. No./Substance:
4408-78-0/Phosphonoacetic Acid; 51321-79-0/NSC 224131; 56-84-8/Aspartic Acid; EC Carbamoyltransferase

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

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