4,5-cyclicimidazo[1,5-A]quinoxalines

Imidazo[1,5-a]quinoxalines of formula (I)

• where R.sub.3 is
• (A) --COOR.sub.3-1 where R.sub.3-1 is
• (1) --H,
• (2) C.sub.1 -C.sub.9 alkyl,
• (3) C.sub.3 -C.sub.7 cycloalkyl,
• (4) --(CH.sub.2).sub.n6 --O--R.sub.3-3 where n.sub.6 is 2 thru 4 and R.sub.3-3 is --H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.7 cycloalkyl,
• (5) --(CH.sub.2).sub.n6 --NR.sub.3-4 R.sub.3-5 where R.sub.3-4 is --H, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl or --.phi., R.sub.3-5 is --H, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.7 cycloalkyl and where R.sub.3-4 and R.sub.3-5 are taken together with the attached nitrogen atom to fore a heterocyclic ring
• --N.sup.* --(CHR.sub.3-8).sub.nA --(CH.sub.2).sub.n1 --R.sub.3-6 --(CH.sub.2).sub.n2 --(C.sup.* HR.sub.3-9).sub.nB --
• --N.sup.* --(CH.sub.2).sub.n1 --(CHR.sub.3-8).sub.nA --R.sub.3-6 --(CHR.sub.3-9).sub.nB --(C.sup.* H.sub.2).sub.n2 --
• where R.sub.3-8 is --H or C.sub.1 -C.sub.3 alkyl, n.sub.A is 1 or 2, n.sub.1 is 0 thru 2, n.sub.2 is 0 thru 2, R.sub.3-9 is --H or C.sub.1 -C.sub.3 alkyl, n.sub.B is 1 or 2, where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring, with the proviso that the ring not contain more than 5 atom, and where R.sub.3-6 is
• --O--,
• --S--,
• --CO--,
• --CR.sub.3-61 R.sub.3-62 where R.sub.3-61 and R.sub.3-62 are the same or different and are --H or C.sub.1 -C.sub.3 alkyl,
• --NR.sub.3-7 where R.sub.3-7 is
• --H,
• C.sub.1 -C.sub.4 alkyl,
• C.sub.3 -C.sub.7 cycloalkyl,
• --(CH.sub.2).sub.n7 --.phi. where n.sub.7 is 0 thru 4 and .phi. is optionally substituted with 1, 2 or 3 R.sub.3-2 where R3-2 is selected from the group consisting of
• --F,
• --Cl,
• --Br,
• --I,
• --CN,
• --NO.sub.2,
• --O--CO--R.sub.3,2a where R.sub.3,2a is --H, C.sub.1 -C.sub.4
• alkyl or C.sub.3 -C.sub.7 cycloalkyl,
• --(CH.sub.2).sub.n30 --CF.sub.3 where n.sub.30 is 0 thru 3,
• --O--CF.sub.3,
• C.sub.1 --C.sub.6 alkyl,
• C.sub.3 -C.sub.7 cycloalkyl,
• --CH.sub.2 --(C.sub.3 -C.sub.7 cycloalkyl),
• --CH.sub.2 CH(CF.sub.3)CH.sub.3,
• --C(OH)(CH.sub.2 OH)(CH.sub.2 CH.sub.3),
• --C(OH)(CH.sub.2 OH)CH.sub.3,
• --C(CH.sub.3)(OH)(CH.sub.2 OH),
• --CH(OH)(CH.sub.2 OH),
• --CH(OH)(CH.sub.3),
• --CH.sub.2 CH.sub.2 OH,
• --C(CH.sub.3).sub.2 (CH.sub.2 OH),
• --CH(CH.sub.2 OH).sub.2,
• --C(CH.sub.2 --OH).sub.3,
• --C(CH.sub.3).sub.2 --OH,
• --C(CH.sub.3).sub.2 --F,
• --NR.sub.3-2b --CO--R.sub.3-2c where R.sub.3-2b is --H or
• C.sub.1 -C.sub.4 alkyl, and where R.sub.3-2c is
• --H,
• C.sub.1 -C.sub.6 alkyl,
• --.phi.,
• --CH.sub.2 .phi.,
• --(CH.sub.2).sub.n8 --OR.sub.3-2d where n.sub.8 is 0 thru 3 and
• R.sub.3-2d is --H or C.sub.1 -C.sub.4 alkyl,
• --(CH.sub.2).sub.n21 --OH where n.sub.21 is 3 thru 4,
• --(CH.sub.2).sub.n22 --.phi. where n.sub.22 is 0 thru 3 and
• where --.phi. is optionally substituted with --F, --Cl, --Br, --I or C.sub.1 -C.sub.4 alkyl,
• --(CH.sub.2).sub.n8 --N(R.sub.3.2d).sub.2 where n.sub.8 and R.sub.3.2d are as defined above and where the two R.sub.3-2d 's may be taken together with the attached nitrogen atom to form a ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, 4-morpholinyl, and 1-(4-methyl)piperazinyl,
• --S--R.sub.3-2d where R.sub.3-2d is as defined above,
• --SO.sub.2 --N(R.sub.3-2e).sub.2 where R.sub.3-2e is --H or C.sub.1 -C.sub.4 alkyl,
• --CO--N(R.sub.3-2e).sub.2 where R.sub.3-2e is as defined above and where the two R.sub.3-2e 's may be taken together with the attached nitrogen atom to from a ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, 4-morpholinyl, and 1-(4-methyl)piperazinyl,
• --NR.sub.3-2f R.sub.3-2g where R.sub.3-2f and R.sub.3-2g are the same or different and are --H or C.sub.1 -C.sub.4 alkyl and where R.sub.3-2f and R.sub.3-2g may be taken together with the attached nitrogen atom to form a ring, which may contain an additional heteroatom, selected from the group consisting of piperazine, morphine, pyrrolidine and piperidine,
• with the proviso that when R.sub.3-6 is --O--, --S-- or --NR.sub.3-7 --, n.sub.1 and n.sub.2 are 1 or 2,
• (6) aryl, where aryl is
• --.phi. optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 1-naphthyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-naphthyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-imidazolyl optionally substituted with one or two R.sub.3-2 and R.sub.3-12 where R.sub.3-2 and R.sub.3-12 are as defined above,
• 4-imidazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above and where R.sub.3-12 is --H, C.sub.1 -C.sub.4 alkyl or --CHO,
• 3-isoxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 4-isoxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 5-isoxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 3-pyrazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-12 and R.sub.3-2 are as defined above,
• 4-pyrazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-12 and R.sub.3-2 are as defined above,
• 5-pyrazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-12 and R.sub.3-2 are as defined above,
• 2-oxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 4-oxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-thiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 4-thiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-furanyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 3-furanyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-thienyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 3-thienyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-pyrrolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-12 and R.sub.3-2 are as defined above,
• 3-pyrrolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-12 and R.sub.3-2 are as defined above,
• 1,2,4-oxadiazol-3-yl optionally substituted with one R.sub.3-2 where R.sub.3-2 is as defined above,
• 1,2,4-oxadiazol-5-yl optionally substituted with one R.sub.3-2 where R.sub.3-2 is as defined above,
• 1,2,4-thiadiazol-3-yl optionally substituted with one R.sub.3-2 where R.sub.3-2 is as defined above,
• 1,2,4-thiadiazol-5-yl optionally substituted with one R.sub.3-2 where R.sub.3-2 is as defined above,
• 1,2,4-triazol-3-yl optionally substituted with one or two R.sub.3-2 where R.sub.3-12 and R.sub.3-2 are as defined above,
• 1,2,4-triazol-5-yl optionally substituted with one R.sub.3-2 where R.sub.3-12 and R.sub.3-2 are as defined above,
• 1,2,3,4-tetrazol-5-yl substituted with R.sub.3-12 where R.sub.3-12 is as defined above,
• 5-oxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 5-thiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• (B) --CO--NR.sub.3-10 R.sub.3-11 where R.sub.3-10 and R.sub.3-11 are the same or different and are C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl or --.phi.,
• (C) --CN,
• (D) aryl, where aryl is as defined above,
• (E) --C.ident.C--R.sub.3-1 where R.sub.3-1 is as defined above,
• (F) --CO--R.sub.3-1 where R.sub.3-1 is as defined above,
• (G) --CS--R.sub.3-1 where R.sub.3-1 is as defined above,
• (H) --CO--R.sub.3-13 where R.sub.3-13 is selected from the group consisting of
• 1-imidazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 1-pyrrolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 1-pyrazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 1,2,3-triazol-1-yl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 1,2,4-triazol-1-yl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 1-tetrazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-furanyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 3-furanyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-thienyl optionally substituted with one or two or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 3-thienyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-oxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 4-oxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 5-oxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 3-isoxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 4-isoxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 5-isoxazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 2-thiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 4-thiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 5-thiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 3-isothiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 4-isothiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above,
• 5-isothiazolyl optionally substituted with one or two R.sub.3-2 where R.sub.3-2 is as defined above;
• (I) --C.sup.* .dbd.N--C(R.sub.3-14).sub.2 --[C(R.sub.3-15).sub.2 ].sub.n23 --R.sup.*.sub.3-16 where the atoms marked with an asterisk (*) are bonded to each other resulting in the formation of a ring,
• where the R.sub.3-14 's are the same or different and are --H or C.sub.1 -C.sub.3 alkyl,
• where n.sub.23 is 1 thru 3,
• where the R.sub.3-15 's are the same or different and are --H or C.sub.1 -C.sub.3 alkyl,
• where R.sub.3-16 is --O--, --S--, --C(R.sub.3-14).sub.2 --, --NR.sub.3-12 where R.sub.3-12 and R.sub.3-14 are as defined above,
• (J) --CH(OH)R.sub.3-1 where R.sub.3-1 is as defined above,
• (K) --CH.sub.2 --O--R.sub.3-1 where R.sub.3-1 is as defined above,
• (L) --CH.sub.2 --NR.sub.3-4 R.sub.3-5 where R.sub.3-4 and R.sub.3-5 are as defined above;
• 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 and the other of R.sub.4-1 and R.sub.4-2 is taken together with R.sub.5 to form a ring of the formula
• (R.sub.5 end)--CO--R.sub.45-1 --(CH.sub.2).sub.n3 --(R.sub.4 end)
• where n.sub.3 is 0 thru 3 and R.sub.45-1 is
• --O--,
• --CO--,
• --S--,
• --CH.dbd.CH--,
• --C(R.sub.3-17).sub.2 -- where the R.sub.3-17 's are the same or different and are --H or C.sub.1 -C.sub.4 alkyl,
• --NR.sub.45-2 where R.sub.45-2 is
• --H,
• C.sub.1 -C.sub.6 alkyl,
• --(CH.sub.2).sub.n9 --.phi. where n.sub.9 is 0 thru 4 and --.phi. is optionally substituted with --F, --Cl, --Br, --I or C.sub.1 -C.sub.4 alkyl,
• --(CH.sub.2).sub.n10 --NR.sub.45-3 R.sub.45-4 where n.sub.10 is 2 thru 6, where R.sub.45-3 is
• --H,
• C.sub.1 -C.sub.4 alkyl,
• --.phi. and where R.sub.45-4 is --H or C.sub.1 -C.sub.3 alkyl, and
• where R.sub.6 is --H,
• --F,
• --Cl,
• --Br,
• --I,
• --CN,
• --NO.sub.2,
• --O--CO--R.sub.6-1 where R.sub.6-1 is --H, C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.7 cycloalkyl,
• --CF.sub.3,
• --O--CF.sub.3,
• C.sub.1 -C.sub.6 alkyl,
• C.sub.3 -C.sub.7 cycloalkyl,
• --CH.sub.2 CH.sub.2 OH,
• --NR.sub.6-2 --CO--R.sub.6-3 where R.sub.6-2 is --H or C.sub.1 -C.sub.4 alkyl, and where R.sub.6-3 is
• --H,
• C.sub.1 -C.sub.6 alkyl,
• --.phi. optionally substituted with --F, --Cl, --Br, --I or C.sub.1 -C.sub.4 alkyl, --CH.sub.2 --.phi.,
• --(CH.sub.2).sub.n24 --OR.sub.6-4 where n.sub.24 is 0 thru 3 and R.sub.6-4 is C.sub.1 -C.sub.4 alkyl,
• --(CH.sub.2).sub.n25 --OH where n.sub.25 is 2 thru 4,
• --(CH.sub.2).sub.n26 --.phi. where n.sub.26 is 0 thru 3,
• --(CH.sub.2).sub.n24 --N(R.sub.6-4).sub.2 where n.sub.24 and R.sub.6-4 are as defined above,
• --S--R.sub.6-4 where R.sub.6-4 is as defined above,
• --SO.sub.2 --N(R.sub.6-5).sub.2 where R.sub.6-5 is --H or C.sub.1 -C.sub.4 alkyl,
• --CO--N(R.sub.6-5).sub.2 where R.sub.6-5 is as defined above,
• --CO.sub.2 --R.sub.6-4 where R.sub.6-4 is as defined above,
• --NR.sub.6-6 R.sub.6-7 where R.sub.6-6 and R.sub.6-7 are the same or different and are --H or C.sub.1 -C.sub.4 alkyl and where R.sub.6-6 and R.sub.6-7 may be taken together with the attached nitrogen atom to form a ring, which may contain an additional heteroatom, selected from the group consisting of piperazine, morpholine, pyrrolidine and piperidine;
• where W.sub.6 is --CR.sub.6 .dbd. where R.sub.6 is as defined above;
• where W.sub.7 is --CR.sub.7 .dbd. where R.sub.7 is as defined for R.sub.6, the R.sub.6, R.sub.7, R.sub.8 and R.sub.9 may be the same or different;
• where W.sub.8 is --CR.sub.8 .dbd. where R.sub.8 is as defined for R.sub.6, the R.sub.6, R.sub.7, R.sub.8 and R.sub.9 may be the same or different;
• where W.sub.9 is --CR.sub.9 .dbd. where R.sub.9 is as defined for R.sub.6, the R.sub.6, R.sub.7, R.sub.8 and R.sub.9 may be the same or different;
• or a pharmaceutically acceptable salt thereof where such exist.