Patent ID: 6133446
Filing Date: 2000-10-17
Classification: A61K,A61P,C07C,C07D,C07F

Abstract:
An aromatic bicyclic amines of formula (I) where m is 0 or 1;where n is 0 or 1;where R.sub.1 (1) is .alpha.-R.sub.1-1 :.beta.-R.sub.1-2 where one of R.sub.1-1 or R.sub.1-2 is --H or C.sub.1 -C.sub.6 alkyl and the other of R.sub.1-1 or R.sub.1-2 is --CR.sub.10-1 R.sub.10-2 --CR.sub.11 --R.sub.2 --Ar/Hetwhere R.sub.10-1 and R.sub.10-2 are the same or different and are --H or C.sub.1 -C.sub.6 alkyl,where R.sub.11 is .dbd.O or R.sub.11-1 :R.sub.11-2 where R.sub.11-1 and R.sub.11-2 are the same or different and are --H or C.sub.1 -C.sub.6 alkyl;where R.sub.2 is ##STR17## where R.sub.2-4 is: --H,C.sub.1 -C.sub.6 alkyl,C.sub.3 -C.sub.7 cycloalkyl,--C.sub.1 -C.sub.3 alkyl-[C.sub.3 -C.sub.7 cycloalkyl],where s is 1;where R.sub.3 is --O-- or --S--;where R.sub.4 is .alpha.-R.sub.4-1 :.beta.-R.sub.4-2 where one of R.sub.4-1 and R.sub.4-2 is:--H,C.sub.1 -C.sub.6 alkyl, and where the other of R.sub.4-1 or R.sub.4-2 is--H,C.sub.1 -C.sub.6 alkyl,--.phi.,--OH,--O--(C.sub.1 -C.sub.3)alkyl;where R.sub.5 is .alpha.-R.sub.5-1 :.beta.-R.sub.5-2 where one of R.sub.5-1 and R.sub.5-2 is:--H,--C.sub.1 -C.sub.6 alkyl, and where the other of R.sub.5-1 or R.sub.5-2 is;--H,C.sub.1 -C.sub.6 alkyl,--.phi.,--OH,--O--(C.sub.1 -C.sub.3)alkyl;and when n is 1, one of R.sub.4-1 or R.sub.4-2 and one of R.sub.5-1 or R.sub.5-2 can be taken together with the carbon atoms to which they are attached to form a carbon ring of 5-, 6- or 7-members;where R.sub.6 is--H--F,--Cl,--Br,--I,--CO--NR.sub.6-1 R.sub.6-2 where R.sub.6-1 and R.sub.6-2 are the same or different and are--H,C.sub.1 -C.sub.6 alkyl,C.sub.3 -C.sub.7 cycloalkyl,--C.sub.1 -C.sub.3 alkyl-[C.sub.3 -C.sub.7 cycloalkyl],--SO--NR.sub.6-1 R.sub.6-2 where R.sub.6-1 and R.sub.6-2 are as defined above,--CF.sub.3,--.phi. optionally substituted with one or two--F,--Cl,--Br,--I,--CO--NR.sub.6-1 R.sub.6-2 where R.sub.6-1 and R.sub.6-2 are as defined above,--NR.sub.6-1 R.sub.6-2 where R.sub.6-1 and R.sub.6-2 are as defined above,--NO.sub.2,--C.tbd.N,--N(R.sub.6-1)--CO--R.sub.6-2 where R.sub.6-1 and R.sub.6-2 are as defined above,--O--SO.sub.2 --CF.sub.3,C.sub.1 -C.sub.4 alkyl,--Si(CH.sub.3).sub.3,and where R.sub.6 and one of R.sub.5-1 or R.sub.5-2 are taken together with the carbon atoms to which they are attached to form a carbon ring of 5-, 6- or 7-members;where R.sub.7 is--H--F,--Cl,--Br,--I,--CO--NR.sub.7-1 R.sub.7-2 where R.sub.7-1 and R.sub.7-2 are the same or different and are--H,C.sub.1 -C.sub.6 alkyl,C.sub.3 -C.sub.7 cycloalkyl.,--C.sub.1 -C.sub.3 alkyl-[C.sub.3 -C.sub.7 cycloalkyl],--SO--NR.sub.7-1 R.sub.7-2 where R.sub.7-1 and R.sub.7-2 are as defined above,--CF.sub.3,.phi. optionally substituted with one or two--F,--Cl,--Br,--I,--CO--NR.sub.7-1 R.sub.7-2 where R.sub.7-1 and R.sub.7-2 and R.sub.7-2 are as defined above,--NR.sub.7-1 R.sub.7-2 where R.sub.7-1 and R.sub.7-2 are as defined above,--NO.sub.2,--C.tbd.N,--N(R.sub.7-1)--CO--R.sub.7-2 where R.sub.7-1 and R.sub.7-2 are as defined above,--O--SO.sub.2 --CF.sub.3,C.sub.1 -C.sub.4 alkyl,--Si(CH.sub.3).sub.3 ;where R.sub.8 is--H--F,--Cl,--Br,--I,--CO--NR.sub.8-1 R.sub.8-2 where R.sub.8-1 and R.sub.8-2 are the same or different and are--H,C.sub.1 -C.sub.6 alkyl,C.sub.3 -C.sub.7 cycloalkyl,--C.sub.1 -C.sub.3 alkyl-[C.sub.3 -C.sub.7 cycloalkyl],--SO--NR.sub.8-1 R.sub.8-2 where R.sub.8-1 and R.sub.8-2 are as defined above,--CF.sub.3,--.phi. optionally substituted with one or two--F,--Cl,--Br,--I,--CO--NR.sub.8-1 R.sub.8-2 where R.sub.8-1 and R.sub.8-2 are as defined above,--NR.sub.8-1 R.sub.8-2 where R.sub.8-1 and R.sub.8-2 are as defined above,--NO.sub.2,--C.tbd.N,--N(R.sub.8-1)--CO--R.sub.8-2 where R.sub.8-1 and R.sub.8-2 are as defined above,--O--SO.sub.2 --CF.sub.3,C.sub.1 -C.sub.4 alkyl,--Si(CH.sub.3).sub.3 ;where R.sub.9 is--H--F,--Cl,--Br,--I,--CO--NR.sub.9-1 R.sub.9-2 where R.sub.9-1 and R.sub.9-2 are the same or different and are--H,C.sub.1 -C.sub.6 alkyl,C.sub.3 -C.sub.7 cycloalkyl,--C.sub.1 -C.sub.3 alkyl-[C.sub.3 -C.sub.7 cycloalkyl],--SO--NR.sub.9-1 R.sub.9-2 where R.sub.9-1 and R.sub.9-2 are as defined above,--CF.sub.3,--.phi. optionally substituted with one or two--F,--Cl,--Br,--I,--CO--NR.sub.9-1 R.sub.9-2 where R.sub.9-1 and R.sub.9-2 are as defined above,--NR.sub.9-1 R.sub.9-2 where R.sub.9-1 and R.sub.9-2 are as defined above,--NO.sub.2,--C.tbd.N,--N(R.sub.9-1)--CO--R.sub.9-2 where R.sub.9-1 and R.sub.9-2 are as defined above,--O--SO.sub.2 --CF.sub.3,C.sub.1 -C.sub.4 alkyl,--Si(CH.sub.3).sub.3 ;with the proviso that not more than two of R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are other than --H;where Ar/Het is --.phi. optionally substituted with one or two R.sub.Ar/Het-1 where R.sub.Ar/Het-1 is selected from the group consisting of--F,--Cl,--Br,--I,--CO--NR.sub.Ar/Het-2 R.sub.Ar/Het-3 where R.sub.Ar/Het-2 and R.sub.Ar/Het-3 are the same or different and are:--H,C.sub.1 -C.sub.6 alkyl,C.sub.3 -C.sub.7 cycloalkyl,--C.sub.1 -C.sub.3 alkyl-[C.sub.3 -C.sub.7 cycloalkyl],--SO.sub.2 --NR.sub.Ar/Het-2 R.sub.Ar/Het-3 where R.sub.Ar/Het-2 and R.sub.Ar/Het-3 are as defined above,--OH,--SH,C.sub.1 -C.sub.6 alkyl,C.sub.3 -C.sub.6 cycloalkyl,--O--R.sub.Ar/Het-4 where R.sub.Ar-Het-4 is--C.sub.1 -C.sub.6 alkyl,--CH.sub.2 --(C.sub.3 -C.sub.6 cycloalkyl),--CH.sub.2 --.phi.,--(C.sub.3 -C.sub.6 cycloalkyl),--SO.sub.2 --CF.sub.3,--CH.sub.2 --CF.sub.3,--CF.sub.3,--CO--R.sub.Ar/Het-2 where R.sub.Ar/Het-2 is as defined above,--CO--OR.sub.Ar/Het-2 where R.sub.Ar/Het-2 is as defined above,--C.tbd.N,--NO.sub.2,--NR.sub.Ar/Het-2 --CO--R.sub.Ar/Het-3 where R.sub.Ar/Het-2 and R.sub.Ar/Het-3 are as defined above,--S--(C.sub.1 -C.sub.6 alkyl),--NR.sub.Ar/Het-2 R.sub.Ar/Het-3 where R.sub.Ar/Het-2 and R.sub.Ar/Het-3 are as defined above,2-, 3- and 4-pyridinyl optionally substituted with one or two R.sub.Ar/Het-1 where R.sub.Ar/Het-1 is as defined above.2-, 4-, 5-pyrimidinyl optionally substituted with one or two R.sub.Ar/Het-1 where R.sub.Ar/Het-1 is as defined above, and enantiomers and diastereomers thereof where such exist and pharmaceutically acceptable salts thereof.