1.
Bioorg Med Chem Lett
; 19(1): 21-6, 2009 Jan 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-19028424
RESUMO
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
Assuntos
Antineoplásicos/química , Receptores ErbB/antagonistas & inibidores , Pirimidinas/farmacologia , Pirrolidinas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Administração Oral , Animais , Camundongos , Farmacocinética , Pirimidinas/síntese química , Pirrolidinas/síntese química , Relação Estrutura-Atividade
2.
Bioorg Med Chem Lett
; 19(6): 1694-7, 2009 Mar 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-19237286
RESUMO
A series of thiophene PLK1 inhibitors was optimized for increased solubility and reduced protein binding through the appendage of basic amine functionality. Interesting selectivity between PLK1 and PLK3 was also obtained through these modifications.