Mitotic kinesin inhibitors and methods of use thereof

A compound of the Formula

• and solvates, resolved enantiomers, diastereomers, racemic mixtures and pharmaceutically acceptable salts thereof, wherein:
• X is S,
• R is Z-NR2R3, Z-OH, or Z-OP(═O)(ORa)(ORa);
• R1 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, saturated or partially unsaturated cycloalkyl, —OR3, —NR4OR5, CRb(═NORc), C(═O)Ra, or —NR4R5, wherein said alkyl, alkenyl, alkynyl, aryl, heteroaryl, and cycloalkyl, are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on said aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —O(C═O)ORd, —NRbSO2Rd, —SO2NRaRb, —C(═O)Ra, —C(═O)ORa, —OC(═O)Ra, —OCH2C(═O)ORa, —NRbC(═O)ORd, —NRdC(═O)Ra, —C(═O)NRaRb, —NRaRb, —NRcC(═O)NRaRb, —NRc(NCN)NRaRb, —ORa, —OP(═O)(ORa)2, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl;
• Ar1 and Ar2 are phenyl, wherein said phenyl is optionally substituted with one or more groups independently selected from F, Cl, Br, I, cyano, nitro, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heteorcycloalkyl, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, ORa, —O(C═O)ORd, —OP(═O)(ORa)(ORa), NRaRb, —NRbSO2Rd, —SO2NRaRb, SR6, SOR6, SO2R6, —C(═O)Ra, —OC(═O)Ra, —OCH2C(═O)ORa, —NRbC(═O)ORd, —NRbC(═O)Ra, —C(═O)NRaRb and —NRcC(═O)NRaRb;
• R2 is hydrogen, —C(═O)R4, —SO2R6, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, wherein said alkyl, alkenyl, alkynyl, and cycloalkyl are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —O(C═O)ORd, —NRbSO2Rd, —SO2NRaRb, —C(═O)Ra, —C(═O)ORa, —OC(═O)Ra, —NRbC(═O)ORd, —NRbC(═O)Ra, —C(═O)NRaRb, —NRaRb, —NRcC(═O)NRaRb, —ORa, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl;
• R3 is hydrogen, —C(═O)R4, alkyl, alkenyl, alkynyl, or saturated or partially unsaturated cycloalkyl, wherein said alkyl, alkenyl, alkynyl, and cycloalkyl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on said aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —O(C═O)ORd, —OP(═O)(ORa)2, —NRbSO2Rd, —SO2NRaRb, —C(═O)Ra, —C(═O)ORa, —OC(═O)Ra, —NRbC(═O)ORd, —NRbC(═O)Ra, —C(═O)NRaRb, —NRaRb, —NRcC(═O)NRaRb, —ORa, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl,
• R4 and R5 are independently H, trifluoromethyl, difluoromethyl, fluoromethyl, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, aryl or heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on said aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —O(C═O)ORd, —NRbSO2Rd, —SO2NRaRb, —C(═O)Ra, —C(═O)ORa, —OC(═O)Ra, —NRbC(═O)ORd, —NRbC(═O)Ra, —C(═O)NRaRb, —NRaRb, —NRcC(═O)NRaRb, —NRcC(NCN)NRaRb, —ORa, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl,
• R6 is alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocycloalkyl, aryl or heteroaryl, wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on said aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —O(C═O)ORd, —NRbSO2Rd, —SO2NRaRb, —C(═O)Ra, —C(═O)ORa, —C(═O)Ra, —NRbC(═O)ORd, —NRbC(═O)Ra, —C(═O)NRaRb, —NRaRb, —NRcC(═O)NRaRb, —NRcC(NCN)NRaRb, —ORa, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl;
• Ra is hydrogen, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or saturated or partially unsaturated heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on said aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —O(C═O)ORh, —NRfSO2Rh, —SO2NReRf, —C(═O)Re, —C(═O)ORe, —OC(═O)Re, —NRfC(═O)ORh, —NRfC(═O)Re, —C(═O)NReRf, —NReRf, —NRgC(═O)NReRf, —NRcC(NCN)NReRf, —ORe, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, saturated or partially unsaturated heterocycloalkyl and heterocyclylalkyl;
• Rb, Rc, Rf and Rg are independently hydrogen or alkyl,
• or Ra and Rb together with the atom to which they are attached form a 4 to 10 membered saturated or partially unsaturated heterocyclic ring which may include 1 to 3 additional heteroatoms, in addition to the nitrogen atom to which said Ra and Rb are attached, selected from N, O and S;
• Rd and Rh are independently trifluoromethyl, alkyl, saturated or partially unsaturated cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocycloalkyl or heterocyclylalkyl;
• Re is hydrogen, trifluoromethyl, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, saturated or partially unsaturated heterocycloalkyl or heterocyclylalkyl;
• and
• Z is alkylene having from 1 to 6 carbons, or alkenylene or alkynylene each having from 2 to 6 carbons, wherein said alkylene, alkenylene and alkynylene are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, —O(C═O)ORd, —NRbSO2Rd, —SO2NRaRb, —C(═O)Ra, —C(═O)ORa, —OC(═O)Ra, —NRbC(═O)ORd, —NRbC(═O)Ra, —C(═O)NRaRb, —NRaRb, —NRcC(═O)NRaRb, —ORa, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl.