Antimicrobial compositions for treating microbial infections

An antimicrobial pharmaceutical formulation for topical administration comprising:

• (a) at least one squalene synthase inhibitor,
• (b) at least one antimicrobial;
• and
• (c) a pharmaceutically acceptable carrier,
• wherein the at least one squalene synthase inhibitor is or comprises a compound represented by formula I:
• wherein:
• m is 0, 1, 2 or 3;
• n is an integer between 1 and 10 inclusive;
• each D and E are each independently selected from the group consisting of. H, aryl, substituted aryl, alkyl, substituted alkyl, carboxyl, aminocarbonyl, alkylsulfonylaminocarboxyl, alkoxycarbonyl, and halo;
• M1, M2, and M3 are each independently selected from the group consisting of metals, ammonium and esters thereof;
• R1 is selected from the group consisting of. H, aryl, substituted aryl, alkyl, substituted alkyl, carboxyl, aminocarbonyl, alkylsulfonylaminocarboxyl, alkoxycarbonyl, and halo, or R1 and R2, together with the carbons to which they are bound, can be joined to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring;
• R2 is selected from the group consisting of. H, aryl, substituted aryl, alkyl, substituted alkyl, carboxyl, aminocarbonyl, alkylsulfonylaminocarboxyl, alkoxycarbonyl, and halo, or R2 and R1, together with the carbons to which they are bound, can be joined to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring, or R2 and R3, together with the carbons to which they are bound, can be joined to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring;
• R3 is selected from the group consisting of. H, aryl, substituted aryl, alkyl, substituted alkyl, carboxyl, aminocarbonyl, alkylsulfonylaminocarboxyl, alkoxycarbonyl, and halo, or R3 and R2, together with the carbons to which they are bound, can be joined to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring, or R3 and R4, together with the carbons to which they are bound, can be joined to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring;
• R4 is selected from the group consisting of. H, aryl, substituted aryl, alkyl, substituted alkyl, carboxyl, aminocarbonyl, alkylsulfonylaminocarboxyl, alkoxycarbonyl, and halo, or R4 and R3, together with the carbons to which they are bound, can be joined to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring;
• R5, R6, R7, R8, and R9 are each independently selected from the group consisting of:
• H, aryl, substituted aryl, alkyl, substituted alkyl, carboxyl, aminocarbonyl, alkylsulfonylaminocarboxyl, alkoxycarbonyl, and halo;
• L1 is —S—, —SO—, —SO2—, —O—, —N(R19)—, or —C(R20)(R21)—;
• wherein R19, R20 and R21 are each independently selected from the group consisting of. H, aryl, substituted aryl, alkyl, substituted alkyl, carboxyl, aminocarbonyl, alkylsulfonylaminocarboxyl, alkoxycarbonyl, and halo;
• and the antimicrobial pharmaceutical formulation is formulated for topical administration.