Preparation of methanoimidazopyridinones, methanoimidazopyrazinones, and related compounds as modulators of nuclear hormone receptor function.

Abstract

Title compds. [I; G = (substituted)aryl, heterocyclyl; E = C:Z2, CR7CR71, SO2, P:OR2, P:OOR2; Z1, Z2 = O, S, NH, NR6; A1, A2 = CR7, N; Y = JJ1J2; J = (CR7R7)n; n = 0-3; J1 = bond, O, S, SO, SO2, NH, NR6, CO, O2C, NR1C:O, CR7R71, C:CR1R8, R2P:O, OPO2, OSO2, C:N, NHNH, NHNR6, NR6NH, N:N, (substituted) cycloalkyl, cycloalkenyl, heterocyclyl, aryl; J2 = (CR7R71)n; n = 0-3; Y is not a bond; W = CR7R71CR7R71, CRS:CR8, CR7R7CO, NR9CR7R7, N:CR8, N:N, NR9R91, (substituted) cycloalkyl, cycloalkenyl, heterocyclyl, aryl; Q = H, (substituted) alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, arylalkyl, alkynyl, aryl, heterocyclyl, halo, CN, R10CO, R4CO, R5R6NC, HOCR7R71, NO2, R10CH2, R10, NH2, C:OSR1, SO2R1, NR4R5; M = bond, O, CR7R71, NR10; M1 = bond, NR10; ≥1 of M, M1 must = bond; L = bond, (CR7R71)n, NH, NR5, N(CR7R71)n; R1 = H, R2; R2 = (substituted) alkyl, cycloalkyl , cycloalkenyl, heterocyclyl, cycloalkylalkyl, cycloalkenylalkyl, heterocycloalkyl, aryl, arylalkyl; R3 = R1, halo, cyano, etc.; R4 = R1, R1CO, R1NHCO etc.; R5 = R2, R1CO, R1NHCO, etc.; R6 = R2, CN, OH, OR1, R1CO, R1NHCO, etc.; R7, R71 = R1, halo, CN, nitro, amino, alkylthio, etc.; R8, R81 = R1, nitro, halo, CN, amino, alkylthio, etc.; R9, R91 = R1, CN, OH, etc.; R10 = CN, OH, OR1, R1CO, etc.; with provisos; and salts thereof] were prepd. as modulators of nuclear hormone receptor function (no data). Thus, 2-azabicyclo[2.2.1]hept-5-ene-3-carboxylic acid Et ester in toluene was treated with 3-(trifluoromethylphenyl)isocyanate followed by heating at 70 °C for 3 h to give the urea deriv. which was heated at 80° with DBU in PhMe to give (5α,8α,8aα)-8,8a-dihydro-2-[3-(trifluoromethyl)phenyl]-5,8-methanoimidazo[1,5-a]pyridine-1,3(2H,5H)-dione II. I and pharmaceutical compns. thereof are useful in the treatment of nuclear hormone receptor-assocd. conditions, such as cancer and immune disorders (no data). [on SciFinder(R)]