Nortriptyline compounds for promoting bone growth

A method of treating renal damage, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I:

• R1 and R2 are each independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —C(O)R10, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
• X is selected from the group consisting of O, —NR9, S and —CHR9—;
• R3, R4, R4a, R6, R7, R8 and R9 are each independently selected from the group consisting of H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —OR10, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
• R5 is H or is combined with R4a to form a bond;
• alternatively, R1 is combined with R2, R3 or R4 and the atoms to which each is attached to form a heterocycloalkyl;
• alternatively, R3 replaces the H on the carbon to which it is attached to form a ═O;
• alternatively, when X is —CHR9—, R8 and R9 are combined to form a bond;
• R10 is selected from the group consisting of H and C1-6 alkyl;
• subscript n is from 1-6;
• and
• salts, hydrates, prodrugs and isomers thereof, thereby treating renal damage in the subject.

An orthopedic or periodontal medical device comprising a structural support, wherein an implantable portion of the structural support is adapted to be permanently implanted within a subject, wherein the implantable portion is attached to a bone, the structural support bearing at least a partial external coating comprising a compound of Formula I:

• R1 and R2 are each independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —OR10, —C(O)R10, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
• X is selected from the group consisting of O, —NR9, S and —CHR9—;
• R3, R4, R4a, R6, R7, R8 and R9 are each independently selected from the group consisting of H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —OR10, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
• R5 is H or is combined with R4a to form a bond;
• alternatively, R1 is combined with R2, R3 or R4 and the atoms to which each is attached to form a heterocycloalkyl;
• alternatively, R3 replaces the H on the carbon to which it is attached to form a ═O;
• alternatively, when X is —CHR9—, R8 and R9 are combined to form a bond;
• R10 is selected from the group consisting of H and C1-6 alkyl;
• subscript n is from 1-6;
• and
• salts, hydrates, prodrugs and isomers thereof.

A method of treating cancer, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of Formula I:

• R1 and R2 are each independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —OR10, —C(O)R10, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
• X is selected from the group consisting of O, —NR9, S and —CHR9—;
• R3, R4, R4a, R6, R7, R8 and R9 are each independently selected from the group consisting of H, halogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 hydroxyalkyl, —OR10, cycloalkyl, heterocycloalkyl, aryl and heteroaryl;
• R5 is H or is combined with R4a to form a bond;
• alternatively, R1 is combined with R2, R3 or R4 and the atoms to which each is attached to form a heterocycloalkyl;
• alternatively, R3 replaces the H on the carbon to which it is attached to form a ═O;
• alternatively, when X is —CHR9—, R8 and R9 are combined to form a bond;
• R10 is selected from the group consisting of H and C1-6 alkyl;
• subscript n is from 1-6;
• and
• salts, hydrates, prodrugs and isomers thereof, thereby treating cancer in the subject.