| Autor: |
Wang S; Department of Medicinal Chemistry, Department of Pharmacology, Analytical Department, Xenova Ltd., 957 Buckingham Avenue, Slough, Berkshire SL1 4NL,UK. swang@trigen.co.uk, Wan NC, Harrison J, Miller W, Chuckowree I, Sohal S, Hancox TC, Baker S, Folkes A, Wilson F, Thompson D, Cocks S, Farmer H, Boyce A, Freathy C, Broadbridge J, Scott J, Depledge P, Faint R, Mistry P, Charlton P |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2004 Mar 11; Vol. 47 (6), pp. 1339-50. |
| DOI: |
10.1021/jm0310129 |
| Abstrakt: |
In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
