Method for treating diseases associated with alterations in cellular integrity using rho kinase inhibitor compounds

A method of treating diabetic nephropathy, malaria, or cancer;

• the method comprises the steps of first identifying a subject suffering from diabetic nephropathy, malaria, or cancer, then administering to the subject an effective amount of a compound of Formula II to treat diabetic nephropathy, malaria, or cancer;
• wherein:
• Q is C═O, SO2, or (CR4R5)n3;
• n1 is 1, 2, or 3;
• n2 is for 2;
• n3 is 0, 1, 2, or 3;
• wherein the ring represented by
• is optionally substituted by alkyl, halo, oxo, OR6, NR6R7, or SR6;
• R2 is R2-1:
• Ar is a monocyclic or bicyclic aryl or heteroaryl ring;
• X is from 1 to 3 substituents on Ar, and each is independently selected from the group consisting of ORB, NR8R9, SR8, SORB, SO2R8, SO2NR8R9, NR8SO2R9, CONR8R9, NR8C(═O)R9, NR8C(═O)OR9, OC(═O)NR8R9, and NR8C(═O)NR9R10,
• R3-R7 are independently H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, or cycloalkylalkynyl, optionally substituted;
• R8 is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, (heterocycle)alkyl, (heterocycle)alkenyl, (heterocycle)alkynyl, or heterocycle;
• optionally substituted by one or more halogen or heteroatom-containing substituents selected from the group consisting of OR11, NR11R12, NO2, SR11, SOR11, SO2R11, SO2NR11R12, NR11SO2R12, OCF3, CONR11R12, NR11C(═O)R12, NR11C(═O)OR12, OC(═O)NR11R12, and NR11C(═O)NR12R13;
• R9 and R10 are independently H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, (heterocycle)alkyl, (heterocycle)alkenyl, (heterocycle)alkynyl, or heterocycle;
• optionally substituted by one or more halogen or heteroatom-containing substituents selected from the group consisting of OR14, NR14R15, NO2, SR14, SOR14, SO2R14, SO2NR14R15, NR14SO2R15, OCF3, CONR14R15, NR14C(═O)R15, NR14C(═O)OR15, OC(═O)NR14R15, and NR14C(═O)NR15R16;
• wherein any two of the groups R8, R9 and R10 are optionally joined with a link selected from the group consisting of bond, —O—, —S—, —SO—, —SO2—, and —NR17— to form a ring;
• R11-R17 are independently H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, (heterocycle)alkyl, (heterocycle)alkenyl, (heterocycle)alkynyl, or heterocycle;
• with the first proviso that if X is acyclic and is connected to Ar by a carbon atom, then X contains at least one nitrogen or sulfur atom,
• with the second proviso that if X is acyclic and is connected to Ar by an oxygen or nitrogen atom, then X contains at least one additional oxygen, nitrogen or sulfur atom.