Pyrazine and triazine derivatives of 1,2,4,5-tetrahydro-Benzo or Thieno [d] azepine
AssigneeHoffman-La Roche Inc.
InventorsAlfred Binggeli, Hans-Peter Maerki, Vincent Mutel, Maurice Wilhelm, Wolfgang Wostl
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Abstract
The invention relates to compounds which are represented by the formula wherein R1, R2, R3, R4, X and Y are as defined in the specification, as well as pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing these compounds and to a process for their preparation. The compounds possess affinity towards metabotropic glutamate receptors and are therefore useful in the treatment or prevention of acute and/or chronic neurological disorders.
Claims24
A compound of the formula
- wherein
- R1 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, or unsubstituted phenyl or phenyl substituted in meta or para positions with at least one substituent selected from the group consisting of lower alkyl, lower alkoxy or halogen;
- or is absent, when X is —N═ or ═N—;
- R2 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, —O, —S-lower alkyl, —SO2-lower alkyl or —OR, —O(CHRa)m+1—ORb, NRc2, —NH—NRd2, —N(Re)(CHRf)m+1—ORg, —N(Rh)(CHRi)m-pyridino, —N(Ri)(CHRk)n—(C3-C6)cycloalkyl, —N(Rl)(CHRm)m(CRn2)—NRo2, or —N(Rp)(CHRq)m+1—NH—C(O)—O-lower alkyl;
- m is 1, 2, 3, 4, 5 or 6;
- n is 0, 1, 2, 3, 4 or 5;
- R, Ra-q are each independently selected from the group consisting of hydrogen, lower alkyl or lower alkenyl;
- X is selected from the group consisting of —N═, ═N—, >O═ or ═O<;
- the dotted line is a bond when R2 is ═O, or lower alkenyl,
- Y is selected from the group consisting of —CH═CH—, —CH═OR3—, —OR3═CH—, CR3═CR4— or S;
- and
- R3, R4 are, independently, selected form the group consisting of hydrogen, lower alkyl, lower alkoxy or halogen with the proviso, that when Y represents a vinylene group, only one group R3 and one group R4 may be present in the resultant benzene ring;
- or a pharmaceutically acceptable salt thereof in racemic and optically active form.
A process for the manufacture of compounds of formula I-3 or a pharmaceutically acceptable salt thereof, which process comprises reacting a compound of the formula
- wherein R22 signifies alkyl, with the compound of formula
- to obtain a compound of formula
- wherein
- Y is selected from the group consisting of —CH═CH—, —CH═CR3—, —CR3═CH—, —CR3═CR4— or S;
- R3, R4 are, independently, selected form the group consisting of hydrogen, lower alkyl, lower alkoxy or halogen with the proviso, that when Y represents a vinylene group, only one group R3 and one group R4 may be present in the resultant benzene ring and, converting a compound of formula I-3 into a pharmaceutically acceptable salt.
A process for the manufacture of compounds of formula I-4 or a pharmaceutically acceptable salt thereof, which process comprises reacting a compound of the formula
- wherein
- R1 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, or unsubstituted phenyl or phenyl substituted in meta or para positions with at least one substituent selected from the group consisting of lower alkyl, lower alkoxy or halogen,
- R2 is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, ═O, —S-lower alkyl, —SO-lower alkyl or —OR, —O(CHRa)m+1—ORb, —NRc2, NH—NRd2, —N(Re)(CHRf)m(CRn2)NRo2, or —N(Rp)(CHRq)m+1—NH—C(O)—O-lower alkyl;
- m is 1, 2, 3, 4, 5 or 6;
- n is 0, 1, 2, 3, 4 or 5;
- R, Ra-q are independently selected from the group consisting of hydrogen, lower alkyl or lower alkenyl;
- X is selected from the group consisting of —N═, ═N—, >C═ or ═C<;
- the dotted line is a bond when R2 is ═O, or lower alkenyl,
- Y is selected from the group consisting of —CH═CH—, —CH═CR3—, —CR3═CH—, —CR3═CR4— or S;
- and
- R3, R4 are, independently, selected form the group consisting of hydrogen, lower alkyl, lower alkoxy or halogen with the proviso, that when Y represents a vinylene group, only one group R3 and one group R4 may be present in the resultant benzene ring;
- R5 signifies halogen,
- with the compound of formula
- to obtain a compound of formula
- and converting a compound of formula I-4 into a pharmaceutically acceptable salt.
Dependencies are inferred from the claim text.