1-Methyl-1H-pyrrole-2-carbonitrile containing tetrahydronaphthalene derivatives as non-steroidal progesterone receptor antagonists.
Non-steroidal 1-methyl-1H-pyrrole-2-carbonitrile containing tetrahydronaphthalenes and acyclic derivatives were evaluated as novel series of progesterone receptor (PR) antagonists using the T47D cell alkaline phosphatase assay. Moderate to potent PR antagonists were achieved with these scaffolds. Several compounds (e.g., 15 and 20) demonstrated low nanomolar PR antagonist potency and good selectivity versus other steroid receptors.
Kern
Jeffrey C
JC
Chemical Sciences, Pfizer Global Research and Development, 500 Arcola Road, Collegeville, PA 19426, USA. Jkern75@hotmail.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
D000469:Alkaline Phosphatase / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D011758:Pyrroles / Q000737:chemistry*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D011758:Pyrroles; D011980:Receptors, Progesterone; D013764:Tetrahydronaphthalenes; D000469:Alkaline Phosphatase