Substituted phenanthridinones and methods of use thereof

A method of enhancing the vascular function of a transplanted organ, the method comprising:

• contacting an organ ex vivo with a compound of Formula I:
• or a pharmaceutically acceptable base or acid addition salt, hydrate, ester, solvate, or a mixture thereof, wherein:
• X is C═O;
• Q is NHCO;
• R1, R3, R4, R5, R7, R8, R9, R10, are, independently, hydrogen or lower alkyl;
• Y1 and Y2 are hydrogen;
• n is 0 to 10;
• and
• Z1 and Z2 are, independently:
• hydrogen, alkylhalo, alkylhydroxy, C1-C10 straight or branched chain alkyl, C2-C10 straight or branched chain alkenyl group, C2-C10 straight or branched chain alkynyl group, aryl, benzyl, alkylamino, alkylcarboxy, alkylester, arylalkyl, or Z1 or Z2 taken together form a fused ring, wherein said ring has 4-8 ring members;
• and
• introducing said organ into a subject,
• the compound being in an amount effective for enhancing the vascular function of the organ.

A method for prolonging the function of a transplanted organ in a subject, the method comprising administering to said subject a compound of Formula I:

• or a pharmaceutically acceptable base or acid addition salt, hydrate, ester, solvate, or a mixture thereof, wherein:
• X is C═O;
• Q is NHCO;
• R1, R3, R4, R5, R7, R8, R9, R10, are, independently, hydrogen or lower alkyl;
• Y1 and Y2 are hydrogen;
• n is 0 to 10;
• and
• Z1 and Z2 are, independently:
• hydrogen, alkylhalo, alkylhydroxy, C1-C10 straight or branched chain alkyl, C2-C10 straight or branched chain alkenyl group, C2-C10 straight or branched chain alkynyl group, aryl, benzyl, alkylamino, alkylcarboxy, alkylester, arylalkyl, or Z1 or Z2 taken together form a fused ring, wherein said ring has 4-8 ring members,
• the compound being in an amount effective for prolonging the function of a transplanted organ in said subject.

A method for enhancing the endothelial function of a transplanted organ in a subject, the method comprising administering to said subject a compound of Formula I:

• or a pharmaceutically acceptable base or acid addition salt, hydrate, ester, solvate, or a mixture thereof, wherein:
• X is C═O;
• Q is NHCO;
• R1, R3, R4, R5, R7, R8, R9, R10, are, independently, hydrogen or lower alkyl;
• Y1 and Y2 are hydrogen;
• n is 0 to 10;
• and
• Z1 and Z2 are, independently:
• hydrogen, alkylhalo, alkylhydroxy, C1-C10 straight or branched chain alkyl, C2-C10 straight or branched chain alkenyl group, C2-C10 straight or branched chain alkynyl group, aryl, benzyl, alkylamino, alkylcarboxy, alkylester, arylalkyl, or Z1 or Z2 taken together form a fused ring, wherein said ring has 4-8 ring members;
• the compound being in an amount effective for enhancing the endothelial function of a transplanted organ in said subject.

A method of enhancing the endothelial function of a transplanted organ, the method comprising:

• contacting an organ ex vivo with a compound of Formula I:
• or a pharmaceutically acceptable base or acid addition salt, hydrate, ester, solvate, or a mixture thereof, wherein:
• X is C═O;
• Q is NHCO;
• R1, R3, R4, R5, R7, R8, R9, R10, are, independently, hydrogen or lower alkyl;
• Y1 and Y2 are hydrogen;
• n is 0 to 10;
• and
• Z1 and Z2 are, independently:
• hydrogen, alkylhalo, alkylhydroxy, C1-C10 straight or branched chain alkyl, C2-C10 straight or branched chain alkenyl group, C2-C10 straight or branched chain alkynyl group, aryl, benzyl, alkylamino, alkylcarboxy, alkylester, arylalkyl, or Z1 or Z2 taken together form a fused ring, wherein said ring has 4-8 ring members;
• and
• introducing said organ into a subject,
• the compound being in an amount effective for enhancing the endothelial function of a transplanted organ in said subject.

A method for prolonging the function of a transplanted organ, the method comprising:

• contacting said organ ex vivo with a compound of Formula I:
• or a pharmaceutically acceptable base or acid addition salt, hydrate, ester, solvate, or a mixture thereof, wherein:
• X is C═O;
• Q is NHCO;
• R1, R3, R4, R5, R7, R8, R9, R10, are, independently, hydrogen or lower alkyl;
• Y1 and Y2 are hydrogen;
• n is 0 to 10;
• and
• Z1 and Z2 are, independently:
• hydrogen, alkylhalo, alkylhydroxy, C1-C10 straight or branched chain alkyl, C2-C10 straight or branched chain alkenyl group, C2-C10 straight or branched chain alkynyl group, aryl, benzyl, alkylamino, alkylcarboxy, alkylester, arylalkyl, or Z1 or Z2 taken together form a fused ring, wherein said ring has 4-8 ring members,
• the compound being in an amount effective for prolonging the function of the organ.