1.
J Med Chem
; 62(17): 8164-8177, 2019 09 12.
Artículo
en Inglés
| MEDLINE
| ID: mdl-31408339
RESUMEN
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.
Asunto(s)
Arginasa/antagonistas & inhibidores , Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , Pirrolidinas/farmacología , Arginasa/metabolismo , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estructura Molecular , Pirrolidinas/síntesis química , Pirrolidinas/química , Relación Estructura-Actividad
2.
Angew Chem Int Ed Engl
; 40(19): 3627-3629, 2001 Oct 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-11592202