Compounds and methods for treatment of cancer and modulation of programmed cell death for melanoma and other cancer cells

A compound having formula:

• and salts thereof;
• where:
• n and m, independently, are integers ranging from 1 to 6;
• R4 of the —NR4— group is a hydrogen or an alkyl group;
• a —CH2—CH2— group of one or both of the —(CH2)n— or —(CH2)m— groups is replaced with a —CR4═CR4— group, where each R4 group therein is, independently, a hydrogen or an alkyl group having 1-3 carbon atoms;
• A and B, independently, are selected from C or D where:
• C is a straight-chain alkyl group substituted with one or more optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms or combinations of such substituents;
• or
• C is an alkyl group substituted with one, two or three optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms, or combinations of such substituents;
• D is an optionally substituted aromatic group having one or two carbon rings which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms, or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl and alkoxyl groups may be substituted with one or more halogens;
• and
• wherein only one of A or B can be C.

A compound having formula:

• and salts thereof;
• where:
• n and m, independently, are integers ranging from 1 to 6;
• R4 of the —NR4— group is a hydrogen or an alkyl group;
• a —CH2—CH2— group of one or both of the —(CH2)n— or —(CH2)m— groups is replaced with a −CR4═CR4— group, where each R4 group therein is, independently, a hydrogen or an alkyl group having 1-3 carbon atoms;
• A and B, independently, are selected from C or D where:
• C is a straight-chain alkyl group substituted with one or more optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms or combinations of such substituents;
• or
• C is an alkyl group substituted with one, two or three optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms, or combinations of such substituents;
• D is an optionally substituted aromatic group having one or two carbon rings, which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms, or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl and alkoxyl groups may be substituted with one or more halogens;
• wherein only one of A or B can be C;
• and
• wherein the R4 group of the —CR4═CR4— group is hydrogen.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound having formula:

• and salts thereof;
• where:
• n and m, independently, are zeroes or integers ranging from 1 to 6;
• R4 of the —NR4— group is an alkyl group;
• one of the CH2 groups of the —(CH2)n— or —(CH2)m— groups that is not linked to —CO—, or —NR4— can be replaced with an oxygen atom;
• one or more of the carbons of the —(CH2)n— or —(CH2)m— groups can be substituted with one or two non-hydrogen substituents selected from halogens, alkyl groups having 1 to 3 carbon atoms, or alkoxy groups having from 1 to 3 carbon atoms;
• a —CH2—CH2— group of either or both of the —(CH2)n— or —(CH2)m— groups can be replaced with a —CR4═CR4— group, where each R4 group therein is, independently, a hydrogen or an alkyl group;
• A and B, independently, are selected from C or D where:
• C is a straight-chain alkyl group substituted with one or more optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms, or combinations of such substituents;
• or
• C is an alkyl group substituted with one, two or three optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms, or combinations of such substituents;
• D is an optionally substituted aromatic group having one or two carbon rings, which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl and alkoxy groups may be substituted with one or more halogens;
• and
• wherein only one of A or B can be C.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound having formula:

• and salts thereof;
• where:
• n and m, independently, are zeroes or integers ranging from 1 to 6;
• R4 of the —NR4— group is an alkyl group;
• a —CH2—CH2— group of either or both of the —(CH2)n— or —(CH2)m— groups is optionally replaced with a —CR4═CR4— group, where each R4 group therein is, independently, a hydrogen or an alkyl group;
• A and B, independently, are selected from C or D where:
• C is a straight-chain alkyl group substituted with one or more optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms or combinations of such substituents;
• or
• C is an alkyl group substituted with one, two or three optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms or combinations of such substituents;
• D is an optionally substituted aromatic group having one or two carbon rings, which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms, or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl or alkoxy groups may be substituted with one or more halogens;
• and
• wherein only one of A or B can be C.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound having formula:

• and salts thereof;
• where:
• m and n are 2;
• R4 is a hydrogen or an alkyl group;
• one of the CH2 groups of the —(CH2)n— or —(CH2)m— groups that is not linked to —CO, or can be replaced with an oxygen atom;
• one or more of the carbons of the —(CH2)n— or —(CH2)m— groups can be substituted with one or two non-hydrogen substituents selected from halogens, alkyl groups having 1 to 3 carbon atoms, or alkoxy groups having from 1 to 3 carbon atoms;
• a —CH2—CH2— group of either or both of the —(CH2)n— or —(CH2)m— groups can be replaced with a —CR4═CR4— group, where each R4 group therein is independently, a hydrogen or an alkyl group;
• A and B, independently, are selected from C or D where:
• C is a straight-chain alkyl group substituted with one or more optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms, or combinations of such substituents;
• or
• C is an alkyl group substituted with one, two or three optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms or combinations of such substituents;
• D is an optionally substituted aromatic group having one or two carbon rings, which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms, or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl and alkoxy groups may be substituted with one or more halogens;
• and
• wherein only one of A or B can be C.

A compound having formula:

• and salts thereof;
• where:
• n and m, independently, are zeroes or integers ranging from 1 to 6;
• R4 of the —NR4— group is an alkyl group;
• one of the CH2 groups of the —(CH2)n— or —(CH2)m— groups that is not linked to —CO, or —NR4— can be replaced with an oxygen atom;
• one or more of the carbons of the —(CH2)n— or —(CH2)m— groups can be substituted with one or two non-hydrogen substituents selected from halogens, alkyl groups having 1 to 3 carbon atoms, or alkoxy groups having from 1 to 3 carbon atoms;
• a —CH2—CH2— group of either or both of the —(CH2)n— or —(CH2)m— groups can be replaced with a —CR4═CR4— group, where each R4 group therein is, independently, a hydrogen or an alkyl group;
• A and B, independently, are selected from C or D where:
• C is a straight-chain alkyl group substituted with one or more optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms, or combinations of such substituents;
• or
• C is an alkyl group substituted with one, two or three optionally substituted phenyl rings, wherein the phenyl rings are optionally substituted with one or more halogens, one or more alkyl groups having 1 to 3 carbon atoms, one or more alkoxy groups having from 1 to 3 carbon atoms, or combinations of such substituents;
• D is an optionally substituted aromatic group having one or two carbon rings, which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms, or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl and alkoxy groups may be substituted with one or more halogens;
• wherein only one of A or B can be C;
• and
• wherein the R4 group of —NR4— or the R4 group of —CR4═CR4— is an alkyl group having 1-3 carbon atoms.

A compound having formula:

• and salts thereof;
• where:
• n and m, independently, are zeroes or integers ranging from 1 to 6;
• R4 of the —NR4— group is an alkyl group;
• one of the CH2 groups of the —(CH2)m— or —(CH2)m— groups that is not linked to —CO, or —NR4— can be replaced with an oxygen atom;
• one or more of the carbons of the —(CH2)n— or —(CH2)m— groups can be substituted with one or two non-hydrogen substituents selected from halogens, alkyl groups having 1 to 3 carbon atoms, or alkoxy groups having from 1 to 3 carbon atoms;
• a —CH2—CH2— group of either or both of the —(CH2)n— or —(CH2)m— groups can be replaced with a —CR4═CR4— group, where each R4 group therein is, independently, a hydrogen or an alkyl group;
• A and B, independently, are selected from C or D where:
• C is a triphenyl methyl group;
• and
• D is an optionally substituted aromatic group having one or two carbon rings, which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl and alkoxy groups may be substituted with one or more halogens;
• and
• wherein only one of A or B can be C.

A compound having formula:

• and salts thereof;
• where:
• n and m, independently, are zeroes or integers ranging from 1 to 6;
• R4 of the —NR4— group is an alkyl group;
• one of the CH2 groups of the —(CH2)n— or —(CH2)m— groups that is not linked to —CO, or —NR4— can be replaced with an oxygen atom;
• one or more of the carbons of the —(CH2)n— or —(CH2)m— groups can be substituted with one or two non-hydrogen substituents selected from halogens, alkyl groups having 1 to 3 carbon atoms, or alkoxy groups having from 1 to 3 carbon atoms;
• a —CH2—CH2— group of either or both of the —(CH2)n— or —(CH2)m— groups can be replaced with a —CR4═CR4— group, where each R4 group therein is, independently, a hydrogen or an alkyl group;
• A is a triphenyl methyl group and B is D, where
• D is an optionally substituted aromatic group having one or two carbon rings, which may be fused aromatic rings, wherein one or more carbons of the one or two aromatic rings are optionally substituted with one or more halogens, one or more alkyl groups having from 1 to 3 carbon atoms, or one or more alkoxy groups having from 1 to 3 carbons, wherein the alkyl and alkoxy groups may be substituted with one or more halogens.