Inhibitors of cytosolic phospholipase A2

A method of treating a disease or disorder in a mammal, or preventing progression of symptoms of such a disease or disorder, wherein the disease or disorder is selected from the group consisting of stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, and central nervous system damage resulting from trauma, the method comprising administering to a mammal in need thereof a pharmaceutically acceptable amount of a compound having the Formula I:

• wherein:
• n1, is 1 or 2;
• n2 is 1 or 2;
• n3 is 1 or 2;
• n5 is 0, 1 or 2;
• X2 is a bond, O, —CH2- or SO2;
• each R5 is independently H or C1-3 alkyl;
• R6 is H or C1-6 alkyl;
• R7 is selected from the group consisting of OH, benzyloxy, CH3, CF3, OCF3, C1-3alkoxy, halogen, COH, CO(C1-3alkyl), CO(OC1-3alkyl), quinoline-5-yl, quinoline-8-yl, 3,5-dimethylisoxazol-4-yl, thiophene-3-yl, pyridin-4-yl, pyridine-3-yl, —CH2-Q, and phenyl optionally substituted by from one to three independently selected R30 groups;
• R8 is selected from the group consisting of H, OH, NO2, CF3, OCF3, C1-3 alkoxy, halogen, CO(C1-3 alkyl), CO(OC1-3 alkyl), quinoline-5-yl, quinoline-8-yl, 3,5-dimethylisoxazol -4-yl, thiophene-3-yl, —CH2-Q, and phenyl substituted by from one to three independently selected R30 groups;
• Q is OH, dialkylamino,
• R20 is selected from the group consisting of H, C1-3 alkyl and CO(C1-3 alkyl);
• and
• R30 is selected from the group consisting of dialkylamino, CN and OCF3;
• provided that:
• a) when each R5 is H, R6 is H, n5 is 0, and R8 is H, then R7 cannot be chlorine;
• b) when each R5 is H, R6 is H, n5 is 0, X2 is O or CH2-, and R8 is H, then R7 cannot be CH3;
• c) when each R5 is H, and R6 is H, then R7 and R8 cannot both be fluorine;
• d) when each R5 is H, R6 is H, and X2 is O, then R7 and R8 cannot both be chlorine;
• e) when each R5 is H, R6 is H, X2 is O, and R8 is NO2, then R7 cannot be fluorine;
• and
• f) when each R5 is H, R6 is H, X2 is SO2, and R8 is H, then R7 cannot be fluorine or chlorine;
• or a pharmaceutically acceptable salt thereof.

A method for treating venous or arterial thrombosis in a mammal, or preventing progression of a symptom of said thrombosis, the method comprising administering to a mammal in need thereof a pharmaceutically acceptable amount of a compound having the Formula I:

• wherein:
• n1, is 1 or 2;
• n2 is 1 or 2;
• n3 is 1 or 2;
• n5 is 0, 1 or 2;
• X2 is a bond, O, —CH2- or SO2;
• each R5 is independently H or C1-3 alkyl;
• R6 is H or C1-6 alkyl;
• R7 is selected from the group consisting of OH, benzyloxy, CH3, CF3, OCF3, C1-3alkoxy, halogen, COH, CO(C1-3 alkyl), CO(OC1-3 alkyl), quinoline-5-yl, quinoline-8-yl, 3,5-dimethylisoxazol-4-yl, thiophene-3-yl, pyridin-4-yl, pyridine-3-yl, —CH2-Q, and phenyl optionally substituted by from one to three independently selected R30 groups;
• R8 is selected from the group consisting of H, OH, NO2, CF3, OCF3, C1-3 alkoxy, halogen, CO(C1-3 alkyl), CO(OC1-3 alkyl), quinoline-5-yl, quinoline-8-yl, 3,5-dimethylisoxazol -4-yl, thiophene-3-yl, —CH2-Q, and phenyl substituted by from one to three independently selected R30 groups;
• Q is OH, dialkylamino,
• R20 is selected from the group consisting of H, C1-3 alkyl and CO(C1-3 alkyl);
• and
• R30 is selected from the group consisting of dialkylamino, CN and OCF3;
• provided that:
• a) when each R5 is H, R6 is H, n5 is 0, and R8 is H, then R7 cannot be chlorine;
• b) when each R5 is H, R6 is H, n5 is 0, X2 is O or —CH2-, and R8 is H, then R7 cannot be CH3;
• c) when each R5 is H, and R6 is H, then R7 and R8 cannot both be fluorine;
• d) when each R5 is H, R6 is H, and X2 is O, then R7 and R8 cannot both be chlorine;
• e) when each R5 is H, R6 is H, X2 is O, and R8 is NO2, then R7 cannot be fluorine;
• and
• f) when each R5 is H, R6 is H, X2 is SO2, and R8 is H, then R7 cannot be fluorine or chlorine;
• or a pharmaceutically acceptable salt thereof.