Benzodiazepine derivatives that inhibit rock
The present invention relates to dihydrobenzodiazepine derivatives, compositions and medicaments containing the same, as well as processes for the preparation and use of such compounds, compositions and medicaments. Such dihydrobenzodiazepine derivatives are useful in the treatment of diseases associated with inappropriate ROCK kinase.
1. A compound of Formula (I):
wherein
the dotted line represents a bond or is absent;
R 1 represents pyrazolyl, pyridinyl, pyrimidinyl optionally substituted by NH 2 , or indazolyl;
R 2 represents phenyl optionally substituted by one or more substituents selected from C 1-6 alkyl, CN, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, NO 2 , halogen; or a 5-membered heteroaryl group containing one or more heteroatoms selected from O, N or S optionally substituted by a 5-membered heteroaryl group;
R 3 and R 4 independently represent H or C 1-6 alkyl;
or a salt thereof.
2. A compound selected from the group consisting of:
Structure
Name
5-(2-fluorophenyl)-7-(4-pyridinyl)-2,3-dihydro-1H-1,4- benzodiazepine
5-(2-fluorophenyl)-7-(4-pyridinyl )-2,3,4,5-tetrahydro- 1H-1,4-benzodiazepine
(3S)-5-(2-fluorophenyl)-3-methyl-7-(4-pyridinyl)-2,3- dihydro-1H-1,4-benzodiazepine
7-(4-pyridinyl)-5-(3-thienyl)-2,3-dihydro-1H-1,4- benzodiazepine
5-(2,2′-bithien-5-yl)-7-(4-pyridinyl)-2,3-dihydro-1H- 1,4-benzodiazepine
7-(4-pyridinyl)-2,3-dihydro-1H-1,4-benzodiazepine
5-(3-nitrophenyl)-7-(4-pyridinyl)-2,3-dihydro-1H-1,4- benzodiazepine
5-[3-(methyloxy)phenyl]-7-(4-pyridinyl)-2,3-dihydro- 1H-1,4-benzo-diazepine
5-phenyl-7-(4-pyridinyl)-2,3-dihydro-1H-1,4- benzodiazepine
7-(4-pyridinyl)-5-[2-(trifluoromethyl)phenyl]-2,3- dihydro-1H-1,4-benzodiazepine
5-(2-nitrophenyl)-7-(4-pyridinyl)-2,3-dihydro-1H-1,4- benzodiazepine
-(5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-7-yl)-2- pyrimidinamine
5-phenyl-7-(1H-pyrazol-4-yl)-2,3-dihydro-1H-1,4- benzodiazepine
[2-fluoro-5-(1H-indazol-5- yl)phenyl](phenyl)methanone
4-[7-(4-pyridinyl)-2,3-dihydro-1H-1,4-benzodiazepin- 5-yl]benzonitrile
5-(4-chlorophenyl)-7-(4-pyridinyl)-2,3-dihydro-1H-1,4- benzodiazepine
and salts thereof.
3. A compound of Formula (I):
wherein
the dotted line represents a bond or is absent;
R 1 represents pyrazolyl, pyridinyl optionally substituted by halo, pyrimidinyl optionally substituted by NH 2 , or indazolyl;
R 2 represents phenyl optionally substituted by one or more substituents selected from C 1-6 alkyl, CN, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, NO 2 , halogen; or a 5-membered heteroaryl group containing one or more heteroatoms selected from O, N or S optionally substituted by a 5-membered heteroaryl group;
R 3 and R 4 independently represent H or C 1-6 alkyl;
or a salt or thereof.
4. The compound:
7-(3-fluoropyridin-4-yl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine
or a salt thereof.
5. A pharmaceutical composition comprising a therapeutically effective amount of a compound as claimed in claim 1 , or a salt thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.
6. A pharmaceutical composition comprising a therapeutically effective amount of a compound as claimed in claim 2 or a salt thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.
7. A pharmaceutical composition comprising a therapeutically effective amount of a compound as claimed in claim 3 or a salt thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.
8. A pharmaceutical composition comprising a therapeutically effective amount of a compound as claimed in claim 4 or a salt thereof and one or more of pharmaceutically acceptable carriers, diluents and excipients.