Compositions comprising multiple bioactive agents, and methods of using the same

A composition comprising a compound and at least one other anti-infective agent, wherein the compound is represented by formula I:

• wherein, independently for each occurrence,
• L is alkyl, alkenyl, or cycloalkyl which may be substituted with one or more R1;
• A is a bicyclic heteroaryl ring of 8-12 atoms or a tricyclic ring of 12-16 atoms, wherein the heteroaryl rings contain 1-4 heteroatoms selected from N, S, and O, and wherein the heteroaryl rings are optionally substituted with one or more groups selected from C1-4 alkyl, CH2OH, OR″, SR″, CN, N(R″)2, CH2N(R″)2, NO2, CF3, CO2R″, CON(R″)2, COR″, NR″C(O)R″, F, Cl, Br, I and —S(O)rCF3,
• wherein
• R″ is H, alkyl or alkaryl;
• R1 is H, alkyl, cycloalkyl, aryl, or alkaryl;
• R2 is
• wherein, independently for each occurrence,
• B is C(R1)2 or C═O;
• E is O or S;
• D is C(R1)2, NR1, or C═O providing that the two Ds are different;
• G is O or NR1;
• J is CH2, CH2CH2, or O;
• M is CR1 or N;
• U is O, H2, or CH2;
• X is H, C1-4 alkyl, CH2OH, OR1, SR1, CN, N(R1)2, CH2N(R1)2, NO2, CF3, CO2R1, CON(R1)2, COR1, NR1C(O)R1, F, Cl, Br, I or —S(O)rCF3;
• Z is independently for each occurrence H, C1-4 alkyl, N(R1)2, NHC(O)R1, NHCH2C(O)R1 or NHC(O)CH═CHR1;
• r is 0, 1, or 2;
• R6 is C(O)OR1;
• R1 is as previously defined;
• R3 is alkyl or cycloalkyl;
• and
• b is an integer from 0-4;
• a is an integer from 0-4;
• and
• Y1 is
• wherein,
• R4 is a water solubilizing group;
• R5 is H, alkyl, or cycloalkyl;
• and
• n is an integer from 0 to 4;
• or wherein the compound is represented by formula II:
• wherein, independently for each occurrence:
• A is a bicyclic or tricyclic heteroaryl ring system of 8-12 atoms, wherein said bicyclic or tricyclic heteroaryl ring system contains 1-4 heteroatoms selected from N, S, and O;
• R2 is alkyl or cycloalkyl;
• R3 is one of the following:
• R4 is H or C1-4 alkyl;
• R5 is CH2 when the bond to which it is attached is a double bond;
• or R5 is H or C1-4 alkyl when the bond to which it is attached is a single bond;
• R7 each independently is H, C1-4 alkyl, —C0-6 alkyl-Ar, —(CH2)1-3N(R′)2, or —(CH2)1-3O(R′);
• R8 is H or C1-4 alkyl;
• R10 is C1-4 alkyl, N(R′)2, NHC(O)R′, NHCH2C(O)R′ or NHC(O)CH═CHR′
• indicates that one of two designated bonds is a double bond and the other a single bond;
• Y is independently for each occurrence H, C1-4 alkyl, N(R′)2, NHC(O)R′, NHCH2C(O)R′ or NHC(O)CH═CHR′;
• X is H, C1-4 alkyl, CH2OH, OR′, SR′, CN, N(R′)2, CH2N(R′)2, NO2, CF3, CO2R′, CON(R′)2, COR′, NR′C(O)R′, F, Cl, Br, I or —S(O)rCF3;
• M is CH2, —CH2—CH2—, or O;
• L is CH2 or C(O);
• E is O or NR′;
• R′ is independently for each occurrence H, C1-6 alkyl, —C0-6 alkyl-Het or —C0-6 alkyl-Ar;
• and
• r is 0, 1 or 2;
• or wherein the compound is represented by formula III:
• wherein X1 is
• A is a bicyclic or tricyclic heteroaryl ring system of 8-12 atoms, wherein said bicyclic or tricyclic heteroaryl ring system contains 1-4 heteroatoms selected from N, S, and O;
• R2 is alkyl or cycloalkyl;
• R3 is one of the following:
• R4 is H or C-4 alkyl;
• R7 each independently is H, C1-4 alkyl, —C0-6 alkyl-Ar, —(CH2)1-3N(R′)2, or —(CH2)1-3O(R′);
• R8 is H or C1-4 alkyl;
• R10 is C1-4 alkyl, N(R′)2, NHC(O)R′, NHCH2C(O)R′ or NHC(O)CH═CHR′
• indicates that one of two designated bonds is a double bond and the other a single bond;
• Y is independently for each occurrence H, C1-4 alkyl, N(R′)2, NHC(O)R′, NHCH2C(O)R′ or NHC(O)CH═CHR′;
• X is H, C1-4 alkyl, CH2OH, OR′, SR′, CN, N(R′)2, CH2N(R′)2, NO2, CF3, CO2R′, CON(R′)2, COR′, NR′C(O)R′, F, Cl, Br, I or —S(O)rCF3;
• M is CH2, —CH2—CH2—, or O;
• L is CH2 or C(O);
• E is O or NR′;
• R′ is independently for each occurrence H, C1-6 alkyl —C0-6 alkyl-Het or —C0-6 alkyl-Ar;
• R1 is a water solubilizing group;
• n is an integer in the range 0 to 4;
• r is 0, 1 or 2;
• or pharmaceutically acceptable salts thereof.