1.
J Med Chem
; 62(17): 8164-8177, 2019 09 12.
Artigo
em Inglês
| MEDLINE
| ID: mdl-31408339
RESUMO
Recent efforts to identify new highly potent arginase inhibitors have resulted in the discovery of a novel family of (3R,4S)-3-amino-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid analogues with up to a 1000-fold increase in potency relative to the current standards, 2-amino-6-boronohexanoic acid (ABH) and N-hydroxy-nor-l-arginine (nor-NOHA). The lead candidate, with an N-2-amino-3-phenylpropyl substituent (NED-3238), example 43, inhibits arginase I and II with IC50 values of 1.3 and 8.1 nM, respectively. Herein, we report the design, synthesis, and structure-activity relationships for this novel series of inhibitors, along with X-ray crystallographic data for selected examples bound to human arginase II.
Assuntos
Arginase/antagonistas & inibidores , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Pirrolidinas/farmacologia , Arginase/metabolismo , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Pirrolidinas/síntese química , Pirrolidinas/química , Relação Estrutura-Atividade
2.
Angew Chem Int Ed Engl
; 40(19): 3627-3629, 2001 Oct 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-11592202