US 2014/0179681 A1 · METHODS AND COMPOSITIONS OF TARGETED DRUG DEVELOPMENT

or a stereoisomer or pharmaceutically acceptable salt thereof;

wherein,

R54 is selected from the group consisting of:

(i) a 5 or 6 membered heterocyclic containing from 1 to 4 N, O, or S atoms or any combination of those atoms with carbon atoms to form a heterocyclic aromatic ring optionally substituted with from 1 to 3 groups selected from:

(a) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(b) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(c) alkoxy —OR10 where R10 is selected from the group consisting of:

(1) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(2) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(d) trifluoromethyl,

(e) trifluoromethoxy,

(f) substituted amino,

(g) nitro;

and

(h) halogen;

R55 is selected from the group consisting of:

hydrogen and straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

R56, R57, R58, and R59 are hydrogen;

R60 is selected from the group consisting of:

(i) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(ii) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

and

(iii) C-1 to C-3 substituted alkyl having at least one substitution group selected from the group consisting of:

(a) carboxyl —COOR10 where R10 is selected from the group consisting of:

(1) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(2) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(b) aryl having an unsubstituted phenyl ring or a phenyl ring substituted at the 2-, 3-, 4-, 5- or 6-position with one or more groups selected from the group consisting of:

(1) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(2) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(3) aryl having phenyl or heteroaryl containing from 1 to 4 N, O, or S atoms;

(4) alkoxy —OR10 where R10 is selected from the group consisting of:

(A) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(B) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(5) trifluoromethyl;

(6) trifluoromethoxy;

(7) difluoromethoxy;

(8) 3,4-methylenedioxy;

(9) 2,3-methylenedioxy;

(10) nitro;

and

(11) halogen;

and

(c) aryloxy (—OAr);

and

Formula (18) excludes a compound of Formula (17):

or a stereoisomer or pharmaceutically acceptable salt thereof;

wherein,

R61, R62, and R64 are independently selected from the group consisting of:

hydrogen and straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

R63 and R65 are independently selected from the group consisting of:

(i) hydrogen;

(ii) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(iii) alkoxy —OR10 where R10 is selected from the group consisting of:

(a) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(b) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

R66 is selected from the group consisting of:

hydrogen and straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

R67, R68, R69, and R70 are hydrogen;

R71 is selected from the group consisting of:

(i) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(ii) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(iii) aryl having an unsubstituted phenyl ring or a phenyl ring substituted at the 2-, 3-, 4-, 5- or 6-position with one or more groups selected from the group consisting of:

(a) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(b) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(c) aryl having phenyl or heteroaryl containing from 1 to 4 N, O, or S atoms;

(d) alkoxy —OR10 where R10 is selected from the group consisting of:

(1) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(2) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(e) trifluoromethyl;

(f) trifluoromethoxy;

(g) difluoromethoxy;

(h) 3,4-methylenedioxy;

(i) 2,3-methylenedioxy;

(j) nitro;

and

(k) halogen;

(iv) C-1 to C-3 substituted alkyl having at least one substitution group selected from the group consisting of:

(a) carboxyl —COOR10 where R10 is selected from the group consisting of:

(1) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(2) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(b) aryl having an unsubstituted phenyl ring or a phenyl ring substituted at the 2-, 3-, 4-, 5- or 6-position with one or more groups selected from the group consisting of:

(1) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(2) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(3) aryl having phenyl or heteroaryl containing from 1 to 4 N, O, or S atoms;

(4) alkoxy —OR10 where R10 is selected from the group consisting of:

(A) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(B) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(5) trifluoromethyl;

(6) trifluoromethoxy;

(7) difluoromethoxy;

(8) 3,4-methylenedioxy;

(9) 2,3-methylenedioxy;

(10) nitro;

and

(11) halogen;

and

(c) aryloxy (—OAr);

(v) heteroaryl containing a heterocyclic ring containing from 1 to 4 N, O, or S atoms optionally substituted with one or more groups selected from the group consisting of:

(a) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(b) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(c) aryl having phenyl or heteroaryl containing from 1 to 4 N, O, or S atoms;

(d) alkoxy —OR10 where R10 is selected from the group consisting of:

(1) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(2) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(e) trifluoromethyl;

(f) trifluoromethoxy;

(g) nitro;

and

(h) halogen;

and

Formula (19) excludes a compound of Formula (17):

or a stereoisomer or pharmaceutically acceptable salt thereof;

wherein, R72 is selected from the group consisting of:

hydrogen and straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

R73 is selected from the group consisting of:

(i) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(ii) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(iii) C-1 to C-3 substituted alkyl having at least one substitution group selected from the group consisting of:

(a) carboxyl —COOR10 where R10 is selected from the group consisting of:

(1) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(2) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(b) aryl having an unsubstituted phenyl ring or a phenyl ring substituted at the 2-, 3-, 4-, 5- or 6-position with one or more groups selected from the group consisting of:

(1) straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(2) C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(3) aryl having phenyl or heteroaryl containing from 1 to 4 N, O, or S atoms;

(4) alkoxy —OR10 where R10 is selected from the group consisting of:

(A) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

and

(B) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

(5) trifluoromethyl;

(6) trifluoromethoxy;

(7) difluoromethoxy;

(8) 3,4-methylenedioxy;

(9) 2,3-methylenedioxy;

(10) nitro;

and

(11) halogen;

and

(c) aryloxy (—OAr);

and

(iv) acyl —COR10 where R10 is selected from the group consisting of:

(a) a straight chain or branched C-1 to C-4 lower alkyl optionally containing unsaturation;

(b) a C-1 to C-6 cycloalkyl optionally containing unsaturation or one oxygen or nitrogen atom;

R74, R75, R76, and R77 are hydrogen;

and

R78 is selected from the group consisting of: