Mitotic kinesin inhibitors and methods of use thereof

A compound of the Formula:

• and resolved enantiomers, diastereomers, racemic mixtures and pharmaceutically acceptable salts thereof, wherein:
• R is Z—NR2R3;
• Ar1 is phenyl and Ar2 is imidazolyl, wherein said phenyl and imidazolyl 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, trifluoromethoxy, 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, 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,
• 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 is 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)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;
• 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;
• Rx and Ry are independently H, alkyl, saturated or partially unsaturated cycloalkyl or aryl, wherein said alkyl, cycloalkyl and aryl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on said aryl), 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)NRaRb, —NRaRb, —NRcC(═O)NRaRb, —NRcC(NCN)NRaRb, —ORa, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl,
• or Rx and Ry together with the atom to which they are attached form a saturated or partially unsaturated carbocyclic ring or heterocyclic ring having one or more heteroatoms independently selected from N, O and S, wherein said carbocyclic and heterocyclic rings 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, —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,
• or Ra and Rx 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 oxygen atom to which said Ra is 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)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, cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl;
• Rb, Rc, Rf and Rg are independently hydrogen or alkyl;
• 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 alkenylene 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, heteroarylalkyl, heterocycloalkyl and heterocyclylalkyl.