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;
• R1 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocycloalkyl, —OR3, —NR4OR5, CRb(═NORc), C(═O)Ra, or —NR4R5, wherein said alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl 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, —NRbC(═O)Ra, —C(═O)NRa Rb, —NRaRb, —NRcC(═O)NRaRb, —NRcC(NCN)NRaRb, —ORa,—OP(═O)(ORa)2, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl;
• Arl is phenyl and Ar2 is pyridyl, wherein said pyridinyl and phenyl are 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, trifluorornethoxy, ORa, —O(C═O)ORd, —OP(═O)(ORa)(ORa), NRaRb, —NRbSO2Rd, —SO2NRaRb, SR6, SOR6, SO2R6, —C(═O)Ra, —C(═O)ORa, —/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, a natural or unnatural amino acid, or a polypeptide of two or more amino acids independently selected from natural and unnatural amino acids, 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, —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, 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,
• or R2 and R3 together with the nitrogen atom to which they are attached form a saturated or partially unsaturated heterocyclic ring which may include 1 to 3 additional heteroatoms, in addition to the nitrogen atom to which said R2 and R3 are attached, selected from N, O and S, wherein said heterocyclic ring is 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, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl;
• R4 and R5 are independently H trifluoromethyl, difluoromethyl, fluoromethyl, alkyl, alkenyl, alkynyl, saturated or partially unsaturated cycloalkyl, saturated or partially unsaturated heterocycloalkyl, aryl or heteroaryl, wherein said alkyl, alkenyl, alkynyl, 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, —OC(═O)Ra, —NRbC(═O)Rd, —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,
• or R4 and R5 together with the atoms to which they are attached form a saturated or partially unsaturated heterocyclic ring which may include 1 to 3 additional heteroatoms, in addition to the heteroatoms to which said R4 and R5 are attached, selected from N, O and S, wherein said heterocyclic ring is 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(═)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, heteroarylalkyl, heterocycloalkyl and heterocyclyialkyl;
• 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, —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, 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 heterocyclylakl, 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, 13 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, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl.