title: 5-Alkylated thiazolidinones as follicle-stimulating hormone (FSH) receptor agonists.
abstract: We prepared analogs of potent thiazolidinone-based follicle-stimulating hormone (FSH) agonists 1, that is, 3 that contained an additional 5-alkyl substituent. This extra substituent was added to reduce synthetic problems that arose during preparation of analogs of 1. These compounds (3) were evaluated in a Chinese hamster ovary (CHO) cell line that expressed recombinant human FSH receptor (FSHR) and a luciferase reporter gene regulated by a cAMP response element (CRE). Selected compounds were also tested on a CHO-cell line that over expressed the FSHR for the ability to induce cAMP production. When the 5-alkyl substituent was a methyl group as in analog 16a, similar FSH activity (i.e., EC(50) = 51 nM, 100% efficacy relative to hFSH) to the analogous 5-hydrogen series compound (e.g., 2) was observed; thus, proving that a small 5-alkyl substituent was well tolerated. New derivatives of 3, in which the potentially hydrolytically labile secondary amide function of 1 (-CONH-) was modified to other moieties (e.g., -CH(2)NH-, -CH(2)S-, and -CH(2)OCONH-), were also prepared and evaluated. These congeners (namely 21, 22, and 24) also displayed good potency in the CRE-luciferase assay.
authors: Chemical and Screening Sciences, Wyeth Research, Collegeville, PA 19426, USA. wrobelj@wyeth.com
authors: Jay
authors: J
authors: Wrobel
authors: James
authors: J
authors: Jetter
authors: Wenling
authors: W
authors: Kao
authors: John
authors: J
authors: Rogers
authors: Li
authors: L
authors: Di
authors: Jamin
authors: J
authors: Chi
authors: M Claudia
authors: MC
authors: Peréz
authors: Gi-Chung
authors: GC
authors: Chen
authors: Emily S
authors: ES
authors: Shen