Imidazo Compounds
The application relates to novel heterocyclic compounds of the general formula (I) and salts, preferably pharmaceutically acceptable salts, thereof, in which R, R 1 , R 2 , Q, m and n have the meanings explained in detail in the description and * designates an asymmetric carbon atom, a process for their preparation and the use of these compounds as medicaments, in particular as aromatase inhibitors.
1 - 9 . (canceled)
10 . A compound of the general formula
in which
R is deuterium, halogen or hydrogen;
R 1 is aryl-C 0 -C 4 -alkyl or heterocyclyl-C 0 -C 4 -alkyl, which radicals are unsubstituted or substituted by 1-4 C 1 -C 8 alkoxy, C 1 -C 8 alkoxycarbonyl, C 1 -C 8 alkyl, C 0 -C 8 alkylcarbonyl, C 1 -C 8 alkylsulphonyl, optionally substituted aryl, aryl-C 0 -C 4 alkoxycarbonyl, cyano, halogen, optionally substituted heterocyclyl, hydroxy, nitro, oxide, oxo, tri-C 1 -C 4 -alkylsilyl, trifluoromethoxy or trifluoromethyl;
R 2 is a) deuterium, halogen, hydroxy, cyano or hydrogen; or
b) C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkoxy, C 1 -C 4 alkoxycarbonyl-C 1 -C 4 alkyl, C 1 -C 8 alkyl, C 0 -C 4 alkylcarbonyl, aryl-C 0 -C 4 alkyl, carboxy-C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl or heterocyclyl-C 0 -C 4 alkyl, which radicals may be substituted by 1-4 C 1 -C 8 alkoxy, C 1 -C 8 alkoxycarbonyl, C 1 -C 8 alkyl, C 0 -C 8 alkylcarbonyl, C 1 -C 9 alkylsulphonyl, optionally substituted aryl, aryl-C 0 -C 4 alkoxycarbonyl, cyano, halogen, optionally substituted heterocyclyl, hydroxy, nitro, oxide, oxo, tri-C 1 -C 4 alkylsilyl, trifluoromethoxy or trifluoromethyl;
Q is oxygen or sulphur;
m is a number 0, 1 or 2;
n is a number 0, 1 or 2; and
* designates an asymmetric carbon atom; and
where
m and n are not simultaneously 0;
or a salt, preferably a pharmaceutically acceptable salt, thereof
and which compound shows an aromatase inhibitory activity at least 10 times higher, than the compound of the formula (I) with the opposite configuration around the asymmetric carbon atom labelled “*”.
11 . A compound according to claim 10 , which compound shows an aromatase inhibitory activity at least 40 times higher, than the compound of the formula (I) with the opposite configuration around the asymmetric carbon atom labelled “*”.
12 . A compound according to claim 10 , where R is deuterium or hydrogen.
13 . A compound according to claim 10 , where R 1 is optionally mono-, di- or tri-substituted phenyl or optionally mono-, di- or tri-substituted benzofuranyl, benzo[b]thiophenyl, benzoimidazolyl, benzo[d]isothiazolyl, benzo[d]isoxazolyl, benzo[b]thiophenyl, imidazolyl, indazolyl, oxazolyl, pyridyl, pyrrolyl, thiazolyl or thiophenyl.
14 . A compound according to claim 10 , where R 2 is C 1 -C 8 alkoxy, hydroxy, C 1 -C 8 alkyl, aryl-C 0 -C 4 alkyl, deuterium, halogen, cyano or hydrogen.
15 . A compound according to claim 10 , where Q is oxygen.
16 . A method for the prevention, for delaying the progression or for the treatment of a disease or condition which responds to aromatase inhibition, where a therapeutically effective amount of a compound of the general formula (I) or a pharmaceutically acceptable salt thereof according to claim 10 is used.
17 . A method for the prevention, for delaying the progression or for the treatment of a proliferative disease or condition which responds to aromatase inhibition, where a therapeutically effective amount of a compound of the general formula (I) or a pharmaceutically acceptable salt thereof according to claim 16 is used.
18 . A pharmaceutical composition comprising a compound of the general formula (I) or a pharmaceutically acceptable salt thereof according to claim 10 , and conventional excipients.