Bi- and tricyclic substituted phenyl methanones
The present invention relates to compounds of formula IA wherein R 1 , R 2 , R 3 , and n are as defined in the specification, and to pharmaceutically active acid addition salts thereof. The compounds of the invention are useful in the treatment of neurological and neuropsychiatric disorders.
1. A compound of formula IA
wherein
R 1 is a non aromatic heterocycle, OR′ or N(R″) 2 ;
R′ is lower alkyl, lower alkyl substituted by halogen or —(CH 2 ) n -cycloalkyl;
R″ is lower alkyl;
R 2 is NO 2 , CN or SO 2 R″;
R 3 is hydrogen, halogen, lower alkyl, lower alkoxy, or lower alkyl substituted by halogen;
n is 0, 1 or 2;
or a pharmaceutically active acid addition salt thereof.
2. A compound of claim 1 , selected from the group consisting of
(6-Chloro-3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridin-2-yl)-(2-isopropoxy-5-methanesulfonyl-phenyl)-methanone,
(6-Chloro-3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridin-2-yl)-(5-methanesulfonyl-2-morpholin-4-yl-phenyl)-methanone,
3-(6-chloro-3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-carbonyl)-4-isopropoxy-benzonitrile,
(6-chloro-3,4-dihydro-1H-benzo[4,5]thieno [2,3-c]pyridin-2-yl)-(2-cyclopropylmethoxy-5-methanesulfonyl-phenyl)-methanone and
(6-chloro-3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridin-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone.
3. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula IA
wherein
R 1 is a non aromatic heterocycle, OR′ or N(R″) 2 ;
R′ is lower alkyl, lower alkyl substituted by halogen or —(CH 2 ) n -cycloalkyl;
R″ is lower alkyl;
R 2 is NO 2 , CN or SO 2 R″;
R 3 is hydrogen, halogen, lower alkyl, lower alkoxy, or lower alkyl substituted by halogen;
n is 0, 1 or 2;
or a pharmaceutically active acid addition salt thereof and a pharmaceutically acceptable carrier.
4. A process for preparing a compound of formula IA
wherein
R 1 is a non aromatic heterocycle, OR′ or N(R″) 2 ;
R′ is lower alkyl, lower alkyl substituted by halogen or —(CH 2 ) n -cycloalkyl;
R″ is lower alkyl;
R 2 is NO 2 , CN or SO 2 R″;
R 3 is hydrogen, halogen, lower alkyl, lower alkoxy, or lower alkyl substituted by halogen;
n is 0, 1 or 2;
wherein the process is selected from the group consisting of
a) reacting a compound of formula
with a compound of formula
in the presence of an activating agent to produce a compound of formula
b) reacting a compound of formula
wherein
X is halogen;
with a compound of formula
R 1 H V
in the presence of a base or a catalyst
to produce a compound of formula
c) reacting a compound of formula
wherein
with a compound of formula
R′X VII
to produce a compound of formula
wherein
X is halogen; and
d) reacting a compound of formula
wherein
with a compound of formula
R′OH VIII
under Mitsunobu conditions
to produce a compound of formula
wherein
5. A method of treating a disease selected from the group consisting of schizophrenia, cognitive impairment, and Alzheimer's disease comprising administering to an individual a therapeutically effective amount of a compound of formula I
wherein
R′ is a non aromatic heterocycle, OR′ or N(R″) 2 ;
R′ is lower alkyl, lower alkyl substituted by halogen or —(CH 2 ) n -cycloalkyl;
R″ is lower alkyl;
R 2 is NO 2 , CN or SO 2 R″; R 3 is hydrogen, halogen, lower alkyl, lower alkoxy, or lower alkyl substituted by halogen;
n is 0, 1 or 2;
or a pharmaceutically active acid addition salt thereof.
6. A method of claim 5 , wherein the disease is schizophrenia.
7. The method of claim 5 , wherein the disease is cognitive impairment.
8. The method of claim 5 , wherein the disease is Alzheimer's disease.