Cyclocarbamate derivatives as progesterone receptor modulators
View Patent ↗This invention provides compounds of Formula (I): wherein R 1 and R 2 are independent substituents or are fused to form spirocyclic rings; R 3 , R C , and R 4 are as defined herein; and R 5 is a substituted benzene ring or a substituted five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms including O, S, SO, SO 2 or NR 6 ; or pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions and methods using the compounds as antagonists of the progesterone receptor.
1. A compound of formula I:
wherein:
R 1 and R 2 are independently H or CH 3 ;
or R 1 and R 2 are fused to form a carbon-based 3 to 8 membered saturated spirocyclic ring;
R 3 is H or C 1 to C 6 alkyl;
R 4 is H, halogen, or methoxy;
R 5 is selected from the group consisting of (i) and (ii):
(i) a substituted benzene ring having the substituents X, Y and Z as shown below:
wherein:
X is selected from the group consisting of H, halogen, C 1 to C 4 alkoxy, and CN;
Y and Z are independent substituents selected from the group consisting of H, halogen, CN, and C 1 to C 4 alkoxy;
wherein X, Y, and Z are not all H; and
(ii) a five membered ring having in its backbone 1 O heteroatom and containing one or two independent substituents selected from the group consisting of H, C(O)H;
or pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 which is selected from the group consisting of 6-(3-Methoxyphenyl)spiro[4H-3,1-benzoxazine-4,1-cyclobutan]-2(1H)-one; 8-Bromo-6-(3-chloro-4-fluorophenyl)-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; 3-(8-Bromo-4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-5-fluorobenzonitrile; 3-(8-Bromo-4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-5-fluorobenzonitrile; 5-(8-Bromo-4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-2-fluorobenzonitrile; 6-(3-Bromophenyl)-1,4,4-trimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; 6-(3-Fluorophenyl)-4-methyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; 3-(4,4-Dimethyl-8-methoxy-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-5-fluorobenzonitrile; 6-(2,3-Difluoro-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one; 3-(1-Ethyl-4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-fluoro-benzonitrile; 3-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]-oxazin-6-yl)-5-fluoro-phenylacetonitrile; 3-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]-oxazin-6-yl)-4-fluoro-phenylacetonitrile; 4-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-2-fluorophenylacetonitrile; 2-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]-oxazin-6-yl)phenylacetonitrile; 6-(3-Fluoro-4-methoxy-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one; 3-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]-oxazin-6-yl)phenylacetonitrile; and 4-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-furan-2-carbaldehyde; or a pharmaceutically acceptable salt thereof.