Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof

A compound having Formula III:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• Y is oxygen or sulfur;
• R1 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
• R21, R22 and R23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R21, is defined as above, and R22 and R23 together with the nitrogen atom to which they are attached form a heterocycle selected from the group consisting of piperidine, piperazine and morpholine;
• A1 is pyridinyl, pyrimidinyl, 1,3,5-triazinyl, quinolinyl, 3,4-methylenedioxyphenyl, 3,4-ethylenedioxyphenyl, indanyl, tetrahydronaphthyl, or naphthyl,
• any of which is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, saturated or partially unsaturated heterocycle, cycloalkyl, heteroaryl, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxyalkyl, nitro, amino, ureido, cyano, acylamino, thiol, acyloxy, azido, alkoxy, carboxy, aminocarbonyl, and alkylthiol;
• X is one of O, S, or SO;
• and
• R8, R9, R10, R11 and R12 independently are hydrogen, halo, haloalkyl, cycloalkyl, saturated or partially unsaturated heterocycle, heteroaryl, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxyalkyl, nitro, amino, ureido, cyano, acylamido, hydroxy, thiol, acyloxy, azido, alkoxy, carboxy, carbonylamido or alkylthiol;
• or
• one of R8 and R9, or R9 and R10, or R10 and R11, or R11 and R12 form a carbocycle or heterocycle selected from the group consisting of —OCH2O—, OCF2O—, —(CH2)3—, —(CH2)4—, —OCH2CH2O—, —CH2N(R7)CH2—, —CH2CH2N(R7)CH2—, —CH2N(R7)CH2CH2— and —CH═CH—CH═CH—;
• where R7 is hydrogen, alkyl or cycloalkyl.

A compound having the Formula VII:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• Y is oxygen or sulfur;
• R1 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
• R21, R22 and R23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R21, is defined as above, and R22 and R23 together with the nitrogen atom to which they are attached form a heterocycle selected from the group consisting of piperidine, piperazine and morpholine;
• B1 is cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl or piperidinyl, any of which is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, heterocycle, cycloalkyl, saturated or partially unsaturated heteroaryl, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxyalkyl, nitro, amino, ureido, cyano, acylamino, thiol, acyloxy, azido, alkoxy, carboxy, aminocarbonyl, and alkylthiol;
• R3, R4, R5 and R6 independently are hydrogen, halo, haloalkyl, cycloalkyl, saturated or partially unsaturated heterocycle, heteroaryl, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxyalkyl, nitro, amino, ureido, cyano, acylamido, hydroxy, thiol, acyloxy, azido, alkoxy, carboxy, carbonylamido or alkylthiol;
• or
• R3 and R4 or R5 and R6 form a bridge selected from the group consisting of —OCH2O—, —OCF2O—, —(CH2)3—, —(CH2)4—, —OCH2CH2O—, —CH2N(R7)CH2—, —CH2CH2N(R7)CH2—, —CH2N(R7)CH2CH2— and —CH═CH—CH═CH—;
• where R7 is hydrogen, alkyl or cycloalkyl;
• and
• X is one of O, S, or SO.

A compound having the Formula VIII:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• Y is oxygen or sulfur;
• R1 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
• R21, R22 and R23 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R21, is defined as above, and R22 and R23 together with the nitrogen atom to which they are attached form a heterocycle selected from the group consisting of piperidine, piperazine and morpholine;
• B2 is cyclopentyl, cyclohexyl, cycloheptyl, tetrahydrofuranyl, tetrahydropyrariyl, pyrrolidinyl or piperidinyl, any of which is optionally substituted with one or more substituents selected from the group consisting of halo, haloalkyl, heterocycle, cycloalkyl, saturated or partially unsaturated heteroaryl, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxyalkyl, nitro, amino, ureido, cyano, acylamino, thiol, acyloxy, azido, alkoxy, carboxy, aminocarbonyl, and alkylthiol;
• R8, R9, R10, R11, and R12 independently are hydrogen, halo, haloalkyl, cycloalkyl, saturated or partially unsaturated heterocycle, heteroaryl, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, cycloalkylalkyl, heterocycloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, alkoxyalkyl, nitro, amino, ureido, cyano, acylamido, hydroxy, thiol, acyloxy, azido, alkoxy, carboxy, carbonylamido or alkylthiol;
• or
• one of R8 and R9, or R9 and R10, or R10 and R11, or R11 and R12 form a carbocycle or heterocycle selected from the group consisting of —OCH2O—, —OCF2O—, —(CH2)3—, —(CH2)4—, —OCH2CH2O—, —CH2N(R7)CH2—, —CH2CH2N(R7)CH2—, —CH2N(R7)CH2CH2— and —CH═CH—CH═CH—;
• where R7 is hydrogen, alkyl or cycloalkyl;
• and
• X is one of O, S, or SO.