Estrogen receptor beta-subtype selective tetrahydrofluorenones: use of a fused pyrazole as a phenol bioisostere

R R Wilkening; R W Ratcliffe; A K Fried; D Meng; W Sun; L Colwell; S Lambert; M Greenlee; S Nilsson; A Thorsell; M Mojena; C Tudela; K Frisch; W Chan; E T Birzin; S P Rohrer; M L Hammond

doi:10.1016/j.bmcl.2006.05.036

Estrogen receptor beta-subtype selective tetrahydrofluorenones: use of a fused pyrazole as a phenol bioisostere

Bioorg Med Chem Lett. 2006 Aug 1;16(15):3896-901. doi: 10.1016/j.bmcl.2006.05.036. Epub 2006 May 30.

Authors

R R Wilkening¹, R W Ratcliffe, A K Fried, D Meng, W Sun, L Colwell, S Lambert, M Greenlee, S Nilsson, A Thorsell, M Mojena, C Tudela, K Frisch, W Chan, E T Birzin, S P Rohrer, M L Hammond

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800-B116 Rahway, NJ 07065, USA. robert_wilkening@merck.com

PMID: 16730987
DOI: 10.1016/j.bmcl.2006.05.036

Abstract

Synthesis of a series of fused pyrazole tetrahydrofluorenone analogs which are potent, ERbeta subtype selective ligands is described. Analogs possessing subnanomolar ERbeta binding, greater than 100-fold ERbeta-selectivity, and oral bioavailability are reported.

MeSH terms

Animals
Area Under Curve
Biological Availability
Cyclization
Estrogen Receptor beta / drug effects*
Estrogen Receptor beta / metabolism
Fluorenes / blood
Fluorenes / chemistry*
Fluorenes / metabolism
Pyrazoles / chemistry*
Rats

Substances

Estrogen Receptor beta
Fluorenes
Pyrazoles