Abstract:
:We report structure-activity investigations in a series of tripeptide amide inhibitors of thrombin, and the development of a series of highly potent active site directed alpha-keto carbonyl inhibitors having the side chain of lysine at P1. Compounds of this class are unstable by virtue of reactivity at the electrophilic carbonyl and racemization at the adjacent carbon (CH). Modifications of prototype alpha-keto-ester 8a have afforded analogs retaining nanomolar Ki. Optimal potency and stability have been realized in alpha-keto-amides 11b (Ki = 2.8 nM) and 11c (Ki = 0.25 nM).
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Brady SF,Sisko JT,Stauffer KJ,Colton CD,Qiu H,Lewis SD,Ng AS,Shafer JA,Bogusky MJ,Veber DFdoi
10.1016/0968-0896(95)00105-psubject
Has Abstract,Author List Incompletepub_date
1995-08-01 00:00:00pages
1063-78issue
8eissn
0968-0896issn
1464-3391pii
096808969500105Pjournal_volume
3pub_type
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