Capsaicinoid prodrug compounds and their use in treating medical conditions

A compound of Formula I or Formula II, wherein Formula I is represented by:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• R1 represents independently for each occurrence hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C6 aryl, or 3-8 membered heterocycloalkyl;
• or two occurrences of R1 are taken together with the carbon atom to which they are attached to form a 3-6 membered saturated carbocyclic or heterocyclic ring;
• R2 represents independently for each occurrence hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C6 aryl, or 3-8 membered heterocycloalkyl;
• or two occurrences of R2 attached to the same carbon atom are taken together to represent an oxo group;
• or two occurrences of R2 attached to the same carbon atom are taken together with the carbon atom to which they are attached to form a 3-6 membered saturated carbocyclic or heterocyclic ring;
• R3 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-8 membered heterocycloalkyl, or —C(═NH)—NH2;
• wherein C1-6 alkyl, C3-7 cycloalkyl, and 4-8 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxyl, oxo, C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, and C1-4 alkoxyl;
• provided that if R3 is hydrogen, methyl, or ethyl, then at least one of R1 and R2 is not hydrogen;
• and
• R4 is hydrogen, or two occurrences of R4 are taken together with the carbon atoms to which they are attached to form a cis or trans double bond;
• m is 0, 1, 2, or 3;
• and
• n is 0, 1, or 2;
• and
• Formula II is represented by:
• or a pharmaceutically acceptable salt thereof;
• wherein:
• R1 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C6 aryl, or 4-8 membered heterocycloalkyl;
• R2 represents independently for each occurrence hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C6 aryl, or 3-8 membered heterocycloalkyl;
• or two occurrences of R2 are taken together to represent an oxo group;
• or two occurrences of R2 are taken together with the carbon atom to which they are attached to form a 3-6 membered saturated carbocyclic or heterocyclic ring;
• R3 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-8 membered heterocycloalkyl, or —C(═NH)—NH2;
• wherein C1-6 alkyl, C3-7 cycloalkyl, and 4-8 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxyl, oxo, C1-4 alkyl, C1-4 haloalkyl, C3-7 cycloalkyl, and C1-4 alkoxyl;
• R4 is hydrogen, or two occurrences of R4 are taken together with the carbon atoms to which they are attached to form a cis or trans double bond;
• Ring A is one of the following:
• a 3-8 membered heterocyclic ring or a C3-8 saturated or partially unsaturated carbocyclic ring, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxyl, oxo, and C1-4 haloalkoxyl;
• or
• a 6-membered carbocyclic aromatic ring substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, hydroxyl, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C1-4 alkoxyl, and C1-4 haloalkoxyl;
• and
• n is 0 or 1.