MEDI 442 |
| We have recently reported that 6-aryl benzoxazinones are progesterone receptor (PR) antagonists (Zhang, et al. J. Med. Chem., 2002, 45(20), 4379). We have also disclosed that replacement of the 6-phenyl moiety with a 7-(5'-cyanopyrrol-2-yl) group on the benzoxazinone scaffold caused the functional activity of this series to switch from PR antagonism to PR agonism in the alkaline phosphatase assay (alk. phos.) using the human T47D breast carcinoma cell line (e.g. 1, Collins, et. al., Bioorg. Med. Chem. Lett. 2004, 14, 2185). In an expansion of this work we decided to examine the SAR of benzoxazin-2-one ring-expansion analogs, i.e the 6-(5'-cyanopyrrol-2-yl) substituted benzo[1,4]oxazepin-2-ones as PR modulators. A number of benzo[1,4]oxazepinones containing 7-(5'-cyanopyrrol-2-yl) group with various substitutions at the 5-position were prepared and evaluated in the T47D cell alkaline phosphatase assay. Interestingly, PR functional activity of these compounds depends upon the 5-substitutions (e.g. 2a and 2b). In this poster, the synthesis and in vitro SAR of 7-pyrrolyl-benzo[1,4]oxazepin-2-ones will be discussed.
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General Poster Session
7:00 PM-9:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Sci-Mix
Division of Medicinal Chemistry |
