1,5-Dihydro-benzo[e][1,4]oxazepin-2(1H)-ones containing a 7-(5'-cyanopyrrol-2-yl) group as nonsteroidal progesterone receptor modulators.
A series of novel 7-(5'-cyanopyrrol-2-yl) substituted benzo[1,4]oxazepin-2-ones were prepared and tested for their progesterone receptor (PR) agonist or antagonist activity in the alkaline phosphatase assay using the human T47D breast carcinoma cell line. Both PR agonists and antagonists were achieved with an appropriate choice of 5-substitution. Several analogs were potent PR agonists (e.g., 12 and 13) or PR antagonists (e.g., 18) with good selectivity over other steroid receptors.
Kern
Jeffrey C
JC
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
Terefenko
Eugene A
EA
Fensome
Andrew
A
Unwalla
Ray
R
Wrobel
Jay
J
Cohen
Jeffrey
J
Zhu
Yuan
Y
Berrodin
Thomas J
TJ
Yudt
Matthew R
MR
Winneker
Richard C
RC
Zhang
Zhiming
Z
Zhang
Puwen
P
D020650:Combinatorial Chemistry Techniques; D006801:Humans; D015394:Molecular Structure; D010077:Oxazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D010077:Oxazepines; D011980:Receptors, Progesterone