Solid-Phase Synthesis of a Combinatorial Array of 1,3-Bis(acylamino)-2-butanones, Inhibitors of the Cysteine Proteases Cathepsins K and L
| Autor: | Dennis S. Yamashita, Christopher S. Brook, Lawrence Szewczuk, David G. Tew, Thaddeus A. Tomaszek, Xiaoyang Dong, Daniel F. Veber, Hye-Ja Oh |
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| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular Ketone Stereochemistry Cathepsin L Cathepsin K Cysteine Proteinase Inhibitors Structure-Activity Relationship Solid-phase synthesis Endopeptidases Combinatorial Chemistry Techniques Structure–activity relationship Cathepsin chemistry.chemical_classification biology General Chemistry Cathepsins Cysteine protease Butanones Cysteine Endopeptidases Kinetics chemistry Drug Design biology.protein Cysteine |
| Zdroj: | Journal of Combinatorial Chemistry. 1:207-215 |
| ISSN: | 1520-4774 1520-4766 |
| Popis: | To more rapidly prepare members of the 1,3-bis(acylamino)-2-butanone class of cysteine protease inhibitors, a solid-phase synthesis was developed. 1-Azido-3-amino-2,2-dimethoxybutane (4), which has the two amino groups differentiated and the ketone protected as a a ketal, served as a surrogate for the 1,3-diamino-2-butanone core. Amine (4) was coupled to the BAL-resin-linked carboxylic acids derived from alpha-amino acid esters. Evaluation of a small combinatorial array by measuring inhibition constants (Ki,appS) against cathepsins K, L, and B provided some structure-activity relationship trends with respect to selectivity and potency. Novel, potent inhibitors of cathepsins K and L were identified. |
| Databáze: | OpenAIRE |
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