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.
Chemical Sciences, Wyeth Research, Collegeville, PA 19426, USA. Kernj@wyeth.com
Jeffrey C
JC
Kern
Eugene
E
Terefenko
Eugene
E
Trybulski
Thomas J
TJ
Berrodin
Jeffrey
J
Cohen
Richard C
RC
Winneker
Matthew R
MR
Yudt
Zhiming
Z
Zhang
Yuan
Y
Zhu
Puwen
P
Zhang
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