Spiro-oxindole mdm2 antagonists

A compound having Formula I:

• wherein:
• R1a, R1b, R1c, and R1d are independently selected from the group consisting of hydrogen, halogen, hydroxy, amino, nitro, cyano, alkoxy, aryloxy, optionally substituted alkyl, haloalkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted cycloalkenyl, optionally substituted aryl, optionally substituted heteroaryl, carboxamido, and sulfonamido;
• R2 is selected from the group consisting of optionally substituted aryl and optionally substituted heteroaryl;
• R3 is selected from the group consisting of optionally substituted alkyl, optionally substituted (cycloalkyl)alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted cycloalkenyl, optionally substituted aryl, and optionally substituted heteroaryl;
• R4 is selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl;
• R5 is selected from the group consisting of:
• wherein:
• each R6a and R6b is independently selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl;
• R7 is selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted cycloalkyl;
• R8a and R8b are each independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted cycloalkyl;
• or
• R8a and R8b taken together with the carbon that they are attached form a 3- to 8-membered optionally substituted cycloalkyl;
• W1 is selected from the group consisting of —OR9a and —NR9bR9e;
• R9a is hydrogen;
• R9b is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —SO2R9d, and —CONR9eR9f;
• R9e is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• or
• R9b and R9c taken together with the nitrogen atom to which they are attached form a 4- to 8-membered optionally substituted heterocyclo;
• R9d is selected from the group consisting of optionally substituted alkyl and optionally substituted cycloalkyl;
• R9e and R9f are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, and optionally substituted cycloalkyl;
• or
• R9e and R9f taken together with the nitrogen atom to which they are attached form a 4- to 8-membered optionally substituted heterocyclo;
• W2 is selected from the group consisting of —OR10 and —NR11aR11b;
• R10 is hydrogen;
• or
• one of R9a and R10 is hydrogen and the other is a metabolically cleavable group;
• with the proviso that when W1 is —OR9a and W2 is —OR10 then at least one of R7, R8a, and R8b is other than hydrogen;
• R11a is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —SO2R11c, and —CONR11dR11e;
• R11b is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• or
• R11a and R11b taken together with the nitrogen atom to which they are attached form a 4- to 8-membered optionally substituted heterocyclo;
• R11c is selected from the group consisting of optionally substituted alkyl and optionally substituted cycloalkyl;
• R11d and R11e are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, and optionally substituted cycloalkyl;
• or
• R11d and R11e together with the nitrogen atom to which they are attached form a 4- to 8-membered optionally substituted heterocyclo;
• n is 1, 2, 3, 4, or 5;
• each R12a, R12b, R12c and R12d is independently selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl;
• R13 is selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl;
• R14 is selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted cycloalkyl;
• Z is selected from the group consisting of —OR15 and —NR16aR16b;
• Z and R14 taken together form a carbonyl group;
• R15 is selected from the group consisting of hydrogen and metabolically cleavable group;
• R16a is selected from the group consisting of —SO2R16e and —CONR16dR16e;
• R16b is selected from the group consisting of hydrogen and optionally substituted alkyl;
• R16c is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• R16d and R16e are each independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
• or
• R16d and R16e taken together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocyclo;
• o is 1, 2, or 3;
• p is 0, 1, 2, or 3;
• each R17a, R17b, R17c and R17d is independently selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl;
• R18 is selected from the group consisting of hydrogen and optionally substituted C1-C6 alkyl;
• R19 is selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted cycloalkyl;
• R20 is selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted cycloalkyl;
• R21a and R21b are each hydrogen;
• or
• one of R21a and R21b is hydrogen and the other is metabolically cleavable group;
• q is 0, 1, 2, or 3;
• r is 1, 2, or 3;
• X is selected from the group consisting of O, S, and NR′;
• Y is selected from the group consisting of O, S, and NR″;
• R′ is selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, and optionally substituted cycloalkyl;
• R″ is selected from the group consisting of hydrogen, optionally substituted alkyl, aralkyl, and optionally substituted cycloalkyl;
• and
• represents a single or a double bond,
• or a pharmaceutically acceptable salt, solvate, or prodrug thereof.