Novel progesterone receptor modulators: 4-aryl-phenylsulfonamides.
We have developed a new series of progesterone receptor modulators based upon the 4-aryl-phenylsulfonamide. Initial work in the series afforded potent compounds with good properties, however an advanced intermediate proved to be genotoxic in a non-GLP Ames assay following metabolic activation. We subsequently solved this problem and identified advanced leads which demonstrated oral efficacy in rhesus monkey pharmacodynamic and kinetics models.
Chemical Sciences, Drug Safety and Metabolism, Pfizer Global Research and Development, 500 Arcola Road, Collegeville, PA 19426, USA.
Casey
C
McComas
Jeffrey
J
Cohen
Christine
C
Huselton
Michael
M
Marella
Edward
E
Melenski
Cheryl
C
Mugford
Ov
O
Slayden
Richard
R
Winneker
Jay
J
Wrobel
Matthew R
MR
Yudt
Andrew
A
Fensome
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D006207:Half-Life; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011980:Receptors, Progesterone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics
D011980:Receptors, Progesterone; D013449:Sulfonamides; D000469:Alkaline Phosphatase