Derivatives of benzothiazines, preparation thereof and application thereof as drugs

摘要

The object of the present invention is benzothiazine derivatives having the capability of inhibiting 11β-HSD1 not only at an enzymatic level but also at a cell level. The compounds of the present invention are of general formula (I). Wherein notably R1 represents a hydrogen or OR1 represents an ester or an ether. R2 represents a naphthyl or a 1,2,3,4-tetrahydro-naphthalene or a biphenyl or phenyl pyridine or a substituted phenyl. R3 represents a methyl or ethyl; R4 and R′4 represent a hydrogen.;

主权项

1. Compounds fitting general formula (I):wherein:
R1 represents: hydrogen; C1-C6 alkyl; COR5; SO2R5; CO(CH2)mR6; CO(CH2)mOR6; (CH2)mR6; (CH2)mCONR7R8; (CH2)nNR7R8; (CH2)nOR6; CHR7OR9; or (CH2)mR10, m represents: 1 to 6, n represents: 2 to 6, R2 represents: phenyl substituted with one or more groups selected from a halogen, C1-C6 alkyl, CN, OH, CF3, OCF3, SMe, COMe, CMe(OH)CF3, CH(OH)CF3, COOR7, CONR7R11; a naphthyl, 1,2,3,4-tetrahydro-naphthalene, biphenyl, phenyl pyridine or pyridine in the case where R1, R4 and R′4 represent a hydrogen, either non-substituted or substituted with one or more groups selected from a halogen, C1-C6 alkyl, CN, OH, CF3, OCF3, OMe, SMe; a cycloalkyl either non-substituted or substituted with OH, CONH2, SO2Me, SO2NH2; C1-C6 alkyl aryl or cycloalkyl aryl, wherein R2 is always bound to the carbonyl through a carbon atom and if R2 is phenyl substituted with COOR7, COOR7 is not in position 4 relative to the carbonyl bonded to R2, R3 represents: methyl or ethyl, R4 and R′4, either identical or different, represent: hydrogen; halogen; C1-C6 alkyl; CN; CF3; OCF3; SMe; OMe; NR7R8; SO2Me, R5 represents: C1-C6 alkyl; phenyl either non-substituted or substituted with one or more groups selected from halogen, C1-C6 alkyl, CN, OH, CF3, OCF3, SMe; a naphthyl, either non-substituted or substituted with one or more groups selected from halogen or C1-C6 alkyl, CN, OH, CF3, OCF3, SMe; a cycloalkyl either non-substituted or substituted with a CONH2, SO2Me, SO2NH2, heteroaryl either non-substituted or substituted with one or more groups selected from halogen, C1-C6 alkyl, CN, OH, CF3, OCF3, SMe, R6 represents: hydrogen; C1-C6 alkyl; phenyl either non-substituted or substituted with one or more groups selected from halogen, C1-C6 alkyl, CN, OH, CF3, OCF3, SMe; a naphthyl or heterocycle, either non-substituted or substituted with one or more groups selected from halogen or C1-C6 alkyl, CN, OH, CF3, OCF3, SMe; a cycloalkyl either non-substituted or substituted with CONH2, SO2Me, SO2NH2, R7 represents: hydrogen, C1-C6 alkyl, R8 represents: hydrogen, C1-C6 alkyl, phenyl either non-substituted or substituted with one or more groups selected from halogen, C1-C6 alkyl, CN, OH, CF3, OCF3, SMe; a naphthyl or heterocycle, either non-substituted or substituted with one or more groups selected from halogen, C1-C6 alkyl, CN, OH, CF3, OCF3, SMe; a cycloalkyl either non-substituted or substituted with CONH2, SO2Me, SO2NH2, R7 and R8 taken together may form a cycle of 4 to 6 members with the nitrogen atom to which they are bound and which may contain one or more heteroatoms selected from N, S or O and may either be non-substituted or substituted with one or more groups selected from C1-C6 alkyl, C1-C6 alkyl aryl or aryl, R9 represents: COOMe, COOEt, R10 represents: halogen, COOH, COOR7, and R11 represents: hydrogen, C1-C6 alkyl, C1-C6 alkyl cycloalkyl, cycloalkyl, aryl, C1-C6 alkyl aryl, as well as, stereoisomers and salts thereof acceptable for therapeutic use.