1.
Bioorg Med Chem Lett
; 21(5): 1299-305, 2011 Mar 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-21315588
RESUMO
A series of benzimidazole pyrrolidinyl amides containing a piperidinyl group were discovered as novel prolylcarboxypeptidase (PrCP) inhibitors. Low-nanomolar IC(50)'s were achieved for several analogs, of which compound 9b displayed modest ex vivo target engagement in eDIO mouse plasma. Compound 9b was also studied in vivo for its effect on weight loss and food intake in an eDIO mouse model and the results will be discussed.
Assuntos
Amidas , Benzimidazóis , Carboxipeptidases/antagonistas & inibidores , Descoberta de Drogas , Inibidores Enzimáticos , Pirrolidinas , Amidas/química , Amidas/farmacologia , Animais , Benzimidazóis/química , Benzimidazóis/farmacologia , Modelos Animais de Doenças , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Pirrolidinas/química , Pirrolidinas/farmacologia , Relação Estrutura-Atividade
2.
Bioorg Med Chem Lett
; 13(3): 427-31, 2003 Feb 10.
Artigo
em Inglês
| MEDLINE
| ID: mdl-12565944
RESUMO
A new class of 4-(aminoheterocycle)piperidine derived 1,3,4 trisubstituted pyrrolidine CCR5 antagonists is reported. Compound 4a is shown to have good binding affinity (1.8 nM) and antiviral activity in PBMC's (IC(95)=50 nM). Compound 4a also has improved PK properties relative to 1.