5-Aryl indanones and derivatives as non-steroidal progesterone receptor modulators.
Novel 5-aryl indanones, inden-1-one oximes, and inden-1-ols were synthesized and evaluated as progesterone receptor (PR) modulators using the T47D cell alkaline phosphatase assay. Both PR agonists and antagonists were achieved with appropriate 3- and 5-substitution from indanones and inden-1-ols while inden-1-one oximes provided only PR antagonists. Several compounds such as 10 and 11 demonstrated potent in vitro PR agonist potency similar to that of steroidal progesterone (1). In addition, a number of compounds (e.g., 12, 13, 17, 18) showed potent PR antagonist activity indicating the indanones and derivatives are promising PR modulator templates.
Kern
Jeffrey C
JC
Chemical Sciences, Wyeth Research, Collegeville, PA 19426, USA. Kernj@wyeth.com
Terefenko
Eugene
E
Trybulski
Eugene
E
Berrodin
Thomas J
TJ
Cohen
Jeffrey
J
Winneker
Richard C
RC
Yudt
Matthew R
MR
Zhang
Zhiming
Z
Zhu
Yuan
Y
Zhang
Puwen
P
D015195:Drug Design; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011980:Receptors, Progesterone / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007189:Indans; D011980:Receptors, Progesterone