| 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. | |
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MedLine Citation:
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PMID: 2352167 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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P L Dutta; W O Foye |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 79 ISSN: 0022-3549 ISO Abbreviation: J Pharm Sci Publication Date: 1990 May |
Date Detail:
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Created Date: 1990-07-16 Completed Date: 1990-07-16 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 447-52 Citation Subset: IM |
Affiliation:
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Samuel M. Best Research Laboratory, Massachusetts College of Pharmacy and Allied Health Sciences, Boston, MA 02115. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aspartate Carbamoyltransferase
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antagonists & inhibitors* Aspartic Acid / analogs & derivatives*, pharmacology Chemistry, Physical Drug Screening Assays, Antitumor Microbial Sensitivity Tests Phosphonoacetic Acid / analogs & derivatives*, pharmacology Physicochemical Phenomena |
| Chemical | |
Reg. No./Substance:
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4408-78-0/Phosphonoacetic Acid; 51321-79-0/NSC 224131; 56-84-8/Aspartic Acid; EC 2.1.3.2/Aspartate Carbamoyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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