Pyrimidine, quinazoline, pteridine and triazine derivatives
This invention is concerned with compounds of the formula wherein A, R 1 to R 5 and G are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, to a process for their preparation and to their use for the treatment and/or prevention of diseases which are associated with the modulation of SST receptors subtype 5.
1. A compound of formula I:
wherein
A is —O— or —NH—;
R 1 is selected from the group consisting of hydrogen, C 1-7 -alkoxy and halogen;
R 2 is selected from the group consisting of C 2-7 -alkyl, C 2-7 -alkenyl, halogen-C 1-7 -alkyl, C 1-7 -alkoxy-C 1-7 -alkyl, and benzyl, or, in case R 3 and R 4 form a ring, R 2 can also be methyl;
R 3 is selected from the group consisting of phenyl substituted by halogen,
R 4 is selected from the group consisting of hydrogen, hydroxy, C 1-7 -alkoxy, amino, nitro, hydroxy-C 1-7 -alkoxy, C 1-7 -alkoxy-C 1-7 -alkoxy, and —O-benzyl;
or R 3 and R 4 are bonded to each other to form a ring together with the carbon atoms they are attached to and R 3 and R 4 together are —CH═CH—CH═CH— or —O—C(CH 3 ) 2 —CH═CH—;
R 5 is selected from the group consisting of hydrogen, halogen, C 1-7 -alkoxy and C 1-7 -alkoxy-C 1-7 -alkoxy;
G is
wherein
R 10 is selected from the group consisting of hydrogen, C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, unsubstituted phenyl, phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, halogen, halogen-C 1-7 -alkyl and —COOH, —OR 26 , wherein R 26 is selected from the group consisting of hydrogen, C 1-7 -alkyl, unsubstituted phenyl and phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy and halogen, —C(O)OR 27 , wherein R 27 is C 1-7 -alkyl, thiazolyl, thienyl, and azetidinyl, or, in case R 11 is cyano, R 10 can also be amino;
R 11 is selected from the group consisting of hydrogen, C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, cyano, nitro, —COOH, —CONHR 28 , wherein R 28 is selected from the group consisting of hydrogen, C 1-7 -alkyl, unsubstituted phenyl and phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, halogen and halogen-C 1-7 -alkoxy, —OR 30 , wherein R 30 is selected from the group consisting of hydroxy-C 1-7 -alkyl, cyano-C 1-7 -alkyl, C 1-7 -alkylsulfonyl and —CH 2 —CONH 2 , unsubstituted phenyl, phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, halogen, halogen-C 1-7 -alkyl, —COOH and —CONH 2 , and pyridyl;
R 12 is selected from the group consisting of hydrogen, C 1-7 -alkyl, C 1-7 -alkoxy, halogen, halogen-C 1-7 -alkyl, —COOR 28 , wherein R 28 is hydrogen or C 1-7 -alkyl, and hydroxy-C 1-7 -alkylamino;
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein A is O.
3. The compound according to claim 1 , wherein R 1 is hydrogen or halogen.
4. The compound according to claim 1 , wherein R 2 is selected from the group consisting of C 2-7 -alkyl, C 2-7 -alkenyl, halogen-C 1-7 -alkyl, C 1-7 -alkoxy-C 1-7 -alkyl and benzyl.
5. The compound according to claim 1 , wherein R 2 is selected from the group consisting of ethyl, propyl, isopropyl, allyl, 2-fluoroethyl, methoxymethyl, butyl, isobutyl and benzyl.
6. The compound according to claim 1 , wherein R 4 is selected from the group consisting of hydrogen, hydroxy, C 1-7 -alkoxy, nitro, C 1-7 -alkoxy-C 1-7 -alkoxy, and —O-benzyl.
7. The compound according to claim 1 , wherein R 5 is hydrogen.
8. The compound according to claim 1 , wherein G is
and wherein
R 10 is selected from the group consisting of hydrogen, C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, unsubstituted phenyl, phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, halogen, halogen-C 1-7 -alkyl and —COOH, —OR 26 , wherein R 26 is selected from the group consisting of hydrogen, C 1-7 -alkyl, unsubstituted phenyl and phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy and halogen, —C(O)OR 27 , wherein R 27 is C 1-7 -alkyl, thiazolyl, thienyl, and azetidinyl, or, in case R 11 is cyano, R 10 can also be amino;
R 11 is selected from the group consisting of hydrogen, C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, cyano, nitro, —COOH, —CONHR 28 , wherein R 28 is selected from the group consisting of hydrogen, C 1-7 -alkyl, unsubstituted phenyl and phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, halogen and halogen-C 1-7 -alkoxy, —OR 30 , wherein R 30 is selected from the group consisting of hydroxy-C 1-7 -alkyl, cyano-C 1-7 -alkyl, C 1-7 -alkylsulfonyl and —CH 2 —CONH 2 , unsubstituted phenyl, phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, halogen, halogen-C 1-7 -alkyl, —COOH and —CONH 2 , and pyridyl;
R 12 is selected from the group consisting of hydrogen, C 1-7 -alkyl, C 1-7 -alkoxy, halogen, halogen-C 1-7 -alkyl, —COOR 28 , wherein R 28 is hydrogen or C 1-7 -alkyl, and hydroxy-C 1-7 -alkylamino.
9. The compound according to claim 1 , wherein
R 10 is hydrogen or C 1-7 -alkyl;
R 11 is selected from the group consisting of hydrogen, C 1-7 -alkyl, —COOH, —CONH 2 , unsubstituted phenyl, phenyl substituted by one to three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, halogen, halogen-C 1-7 -alkyl, —COOH and —CONH 2 , and pyridyl; and
R 12 is hydrogen or C 1-7 -alkyl.
10. The compound according to claim 1 , selected from the group consisting of
[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-yl]-(5-ethyl-pyrimidin-2-yl)-amine,
[1-(4-chloro-3,5-diethoxy-benzyl)-piperidin-4-yl]-(4,6-dimethyl-pyrimidin-2-yl)-amine,
[1-(4-chloro-3,5-diethoxy-benzyl)-piperidin-4-yl]-pyrimidin-2-yl-amine,
2-[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-ylamino]-pyrimidine-5-carboxylic acid,
2-[1-(4-chloro-3,5-diethoxy-benzyl)-piperidin-4-ylamino]-pyrimidine-5-carboxylic acid,
[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-yl]-(5-phenyl-pyrimidin-2-yl)-amine,
[1-(4-chloro-3,5-diethoxy-benzyl)-piperidin-4-yl]-(5-phenyl-pyrimidin-2-yl)-amine,
[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-yl]-[5-(4-methoxy-phenyl)-pyrimidin-2-yl]-amine,
[1-(4-chloro-3,5-diethoxy-benzyl)-piperidin-4-yl]-[5-(4-methoxy-phenyl)-pyrimidin-2-yl]-amine,
[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-yl]-(5-pyridin-3-yl-pyrimidin-2-yl)-amine,
[1-(3,5-diethoxy-4-fluoro-benzyl)-piperidin-4-yl]-(5-pyridin-3-yl-pyrimidin-2-yl)-amine,
[1-(4-chloro-3,5-diethoxy-benzyl)-piperidin-4-yl]-(5-pyridin-3-yl-pyrimidin-2-yl)-amine,
4-{2-[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-ylamino]-pyrimidin-5-yl}-benzamide,
or a pharmaceutically acceptable salt thereof.
11. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 as well as a pharmaceutically acceptable carrier and/or adjuvant.