Novel 5-aryl-1,3-dihydro-indole-2-thiones. potent, orally active progesterone receptor agonists.
During the course of our studies on 3,3-disubstituted-5-aryloxindoles derived progesterone receptor (PR) antagonists we discovered that changing the amide funtionality to a thio-amide resulted in compounds displaying potent PR agonist activity. In this communication, the synthesis, structure activity relationships (SAR) and in vivo activity of various 5-arylthio-oxindoles will be discussed.
Fensome
Andrew
A
Chemical Sciences, Wyeth Research, Collegeville, PA 19426, USA. fensoma@wyeth.com
Koko
Marci
M
Wrobel
Jay
J
Zhang
Puwen
P
Zhang
Zhiming
Z
Cohen
Jeffrey
J
Lundeen
Scott
S
Rudnick
Kelly
K
Zhu
Yuan
Y
Winneker
Richard
R
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001943:Breast Neoplasms / Q000201:enzymology; D003656:Decidua / Q000187:drug effects; D015195:Drug Design; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D010052:Ovariectomy; D051381:Rats; D011980:Receptors, Progesterone / Q000819:agonists*; D013329:Structure-Activity Relationship; D013871:Thiones / Q000138:chemical synthesis* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007202:Indicators and Reagents; D007211:Indoles; D011980:Receptors, Progesterone; D013871:Thiones; D017258:Medroxyprogesterone Acetate; D000469:Alkaline Phosphatase