Abstract：
:The design, synthesis, and evaluation of a series of novel inhibitors of aspartate transcarbamoylase (ATCase) are reported. Several submicromolar phosphorus-containing inhibitors are described, but all-carboxylate compounds are inactive. Compounds were synthesized to probe the postulated cyclic transition-state of the enzyme-catalyzed reaction. In addition, the associated role of the protonation state at the phosphorus acid moiety was evaluated using phosphinic and carboxylic acids. Although none of the synthesized inhibitors is more potent than N-phosphonacetyl-l-aspartate (PALA), the compounds provide useful mechanistic information, as well as the basis for the design of future inhibitors and/or prodrugs.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Coudray L,Pennebaker AF,Montchamp JLdoi
10.1016/j.bmc.2009.09.045subject
Has Abstractpub_date
2009-11-15 00:00:00pages
7680-9issue
22eissn
0968-0896issn
1464-3391pii
S0968-0896(09)00897-9journal_volume
17pub_type
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更新日期：2018-11-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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