Patent ID: 6734176
Filing Date: 2004-05-11
Classification: A61P,C07D

Abstract:
A method of treating order a disorder that responds to treatment with cannabinoid antagonists comprising administering to a mammal in need of such treatment an effective amount to treat said disorder of a compound of formula (1): in whichR1 represents a radical â€”NHCOR4 or â€”N(R5)â€”Yâ€”R6, Y is CO or SO2; R2 and R3, which are identical or different, represent either an aromatic radical selected from phenyl, naphthyl and indenyl, these aromatic radicals being unsubstituted or substituted with one or more halogen atoms or alkyl, alkoxy, formyl, hydroxyl, trifluoromethyl, trifluoro-methoxy, â€”CO-alk, cyano, â€”COOH, â€”COOalk, â€”CONR7R8, â€”COâ€”NHâ€”NR9R10, alkylsulfanyl, alkylsulfinyl, alkyl-sulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, hydroxyalkyl or -alk-NR7R8radicals; or a heteroaromatic radical selected from beuzofuryl, benzothiazolyl, benzothlenyl, benzoxazolyl, chromanyl, 2,3-dihydrobenzofuryl, 2,3-dihydrobenzothienyl, pyrimidinyl, furyl, imidazolyl, isochromanyl, isoquinolyl, pyrrolyl, pyridyl, quinolyl, 1,2.3,4-tetrahydroisoquinolyl, thiazolyl and thienyl rings, it being possible for these heteroaromatic radicals to be unsubsututed or substituted with a halogen atom or an alkyl, alkoxy, hydroxyl, trifluoromethyl, trifluoromethoxy, cyano, â€”COOH, â€”COOalk, â€”COâ€”NHâ€”NR9R10, â€”CONR7R8, -alk-NR9R10, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl or hydroxyalkyl radical; R4 represents a radical -alk-SO2â€”R11, -alk-SO2â€”CH&boxH;CHâ€”R11, Met substituted with â€”SO2â€”R11 or phenyl substituted with â€”SO2â€”R11 or -alk-SO2â€”R11; R5 represents a hydrogen atom or an alkyl radical; R6 represents a phenylalkyl, Met or Ar radical; R7 and R8 which are identical or different, represent a hydrogen atom or an alkyl radical or alternatively R7 and R8 together form with the nitrogen atom to which they are attached a 3- to 10-membered saturated mono- or bicyclic heterocycle, optionally further having another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl radicals; R9 and R10, which are identical or different, represent a hydrogen atom or an alkyl, â€”COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radical or alternatively R9 and R10 together form with the nitrogen atom to which they ate attached a 3- to 10-membered saturated or unsaturated mono- or bicyclic heterocycle, optionally further having another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl, â€”COalk, â€”COOalk, â€”COâ€”NHalk, â€”CSâ€”NHalk, oxo, hydroxyalkyl, -alk-O-alk or â€”COâ€”NH2 radicals; R11 represents an alkyl, Ar or Het radical; Ar represents a phenyl, naphthyl or indenyl radical, these radicals being optionally substituted with one or more halogen atoms or alkyl, alkoxy, cyano, â€”CO-alk, â€”COOH, â€”COOalk, â€”CONR12R13, â€”COâ€”NHâ€”NR14R15, alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, -alk-NR14R15, â€”NR14R15, alkylthioalkyl, formyl, hydroxyl, hydroxyalkyl, Het, â€”O-alk-NH-cycloalkyl, OCF3, CF3, â€”NHâ€”CO-alk, â€”SO2NH2, â€”NHâ€”COCH3, â€”NHâ€”COOalk or Het radicals or alternatively, a fused ring containing a 3-10 membered Het radical is formed on 2 adjacent carbon atoms, with a dioxymethylene, said Het being an unsaturated or saturated mono- or bicyclic heterocycle having one or more heteroatoms selected from oxygen, sulfur and nitrogen optionally substituted with one or more halogen atoms or alkyl, alkoxy, vinyl, alkoxycarbonyl, oxo, hydroxyl, OCF3 or CF3 radicals, the nitrogen-containing heterocycles being optionally in their N-oxidized form; R12 and R13, which are identical or different, represent a hydrogen atom or an alkyl radical or, alternatively, R12 and R13 together with the nitrogen atom to which they are attached form a 3- to 10-membered saturated mono- or bicyclic heterocycle, optionally further having another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl radicals; R14 and R15, which are identical or different, represent a hydrogen atom or an alkyl, â€”COOalk, cycloalkyl, alkylcycloalkyl, -alk-O-alk or hydroxyalkyl radical or alternatively R14 and R15 together form with the nitrogen atom to which they are attached a 3- to 10-membered saturated or unsaturated mono- or bicyclic heterocycle, optionally further having another heteroatom selected from oxygen, sulfur and nitrogen and being optionally substituted with one or more alkyl, â€”COalk, â€”COOalk, â€”COâ€”NHalk, â€”CS-NHalk, oxo, hydroxyalkyl, -alk-O-alk or â€”COâ€”NH2 radicals; alk represents an alkyl or alkylene radical; the alkyl and alkylene radicals and portions and the alkoxy radicals and portions are in the form of a straight or branched chain having 1 to 6 carbon atoms and the cycloalkyl radicals have 3 to 10 carbon atoms; or the optical isomers thereof or pharmaceutically acceptable salts thereof.