title: Novel pyrrole-containing progesterone receptor modulators.
abstract: A series of 1,4-dihydro-2H-[d][3,1]-benzoxazin-2-one and 1,3-dihydro-[3H]-indol-2-one containing 6- or 5-, respectively, appended substituted pyrrole moieties were synthesized and evaluated for their ability to modulate the activity of the progesterone receptor (PR). Key structural changes to the pyrrole moieties of these molecules were shown to have a predictive influence as to whether the compounds behaved as PR agonists or antagonists. Compounds with the 5(')-cyano-2(')-pyrrole moiety (e.g., 32, 33, and 38) were shown to be potent PR agonists (EC(50)'s of 1.1, 1.8, and 2.8 nM, respectively). Compounds with the 5(')-nitro-2(')-pyrrole moiety (e.g., 34 and 36) were shown to be PR antagonists (IC(50)'s of 180 and 36 nM, respectively).
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Collins
authors.forename: Valerie
authors.initials: V
authors.lastname: Hudak
authors.forename: Reinhold
authors.initials: R
authors.lastname: Bender
authors.forename: Andrew
authors.initials: A
authors.lastname: Fensome
authors.forename: Puwen
authors.initials: P
authors.lastname: Zhang
authors.forename: Lori
authors.initials: L
authors.lastname: Miller
authors.forename: Richard C
authors.initials: RC
authors.lastname: Winneker
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Cohen
authors.forename: Rayomond J
authors.initials: RJ
authors.lastname: Unwalla
authors.forename: Jay
authors.initials: J
authors.lastname: Wrobel
mesh_terms: D048588:Benzoxazines / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry*; D011980:Receptors, Progesterone / Q000187:drug effects*
chemical_list: D048588:Benzoxazines; D007211:Indoles; D011758:Pyrroles; D011980:Receptors, Progesterone