Antimicrobial compounds and methods of making and using the same

A compound of Formula (A):

• or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer
• wherein:
• is a single or a double bond;
• X is —NHC(NH)NH2, —CH2NH2, —CH2NHC(NH)NH2, —CH2NHCH2C(O)CH3, —CH2NHC(NH)(C1-C4)alkyl, —CH2NHC(NH)(C3-C7)cycloalkyl, —CH2NHC(NH)heteroaryl, heteroaryl, —CH2heteroaryl, —NHCH2heteroaryl, —CH2NHheteroaryl, —CH(OH)heteroaryl, —CH2heterocycloalkyl, —NHCH2heterocycloalkyl, or —CH2NHheterocycloalkyl, wherein the (C1-C4)alkyl, cycloalkyl, heterocycloalkyl and heteroaryl are optionally substituted with one or more R7;
• Z is O, CH2, NR11, or S(O)p;
• W is N(R5) or C(R5)(R5′);
• R1 is H, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C3)alkoxy, (C1-C3)haloalkyl, —O(C1-C3)haloalkyl, heterocycloalkyl, halogen, —NO2, wherein the (C1-C4)alkyl, (C2-C4)alkenyl, and heterocycloalkyl are optionally substituted with one or more R12;
• or
• R1 and R2 together with the carbon atoms to which they are attached form a (C3-C7)cycloalkyl or heterocycloalkyl;
• R2 is —F, —Cl, —CF3, —SCF3, or —OCF3;
• R3 is H or —NO2;
• R4 is H, (C1-C3)alkyl, (C2-C3)alkenyl, halogen, or —NO2;
• R5 is H or —CH3;
• R5′ is H;
• or
• R6 is H, (C1-C3)alkyl, (C2-C3)alkenyl, (C1-C3)haloalkyl, CH2NHC(NH)NH2, —CH2NHC(NH)(C1-C3)alkyl, —(CH2)nOH, —CH2S(O)pNH2, —CH2NH(C1-C3)alkyl, —CH2C(O)NH2, —(CH2)nNH2, —CH2heterocycloalkyl, —CH2NHheterocycloalkyl, —(CH2)nheteroaryl, or —CH2NHheteroaryl, wherein the heteroaryl and heterocycloalkyl is optionally substituted with one or more R8;
• or
• R5 and R6 together with the carbon atoms to which they are attached and the Z atom connecting said two carbon atoms, form a (C5-C6)cycloalkyl or a 5- to 6-membered heterocycloalkyl ring containing 1-3 heteroatoms optionally substituted with one or more R9;
• or
• when W is N(R5), R6 and W together with the Z atom connecting W and the carbon atom to which R6 is attached, form a 5- to 6-membered heterocycloalkyl ring containing 1-3 heteroatoms optionally substituted with one or more R9;
• at least one of R5 and R6 is not H;
• each R7 is independently (C1-C3)alkyl, halogen, oxo, —OH, or —NH2;
• each R8 is independently (C1-C3)alkyl, (C1-C3)alkoxy, halogen, oxo, —NH2, or —NHR10;
• each R9 is independently (C1-C3)alkyl, (C2-C4)alkenyl, —NH2, —NHC(NH)NH2, —NHC(NH)(C1-C3)alkyl,_CH2heteroaryl, —NHheterocycloalkyl, or —NHheteroaryl, wherein the (C1-C3)alkyl is optionally substituted with one or more substituents independently selected from —NHC(NH)NH2, —OH and —NH2;
• each R10 is independently —CH2aryl optionally substituted with (C1-C3)alkoxy or halogen;
• R11 is H, —NHC(NH)NH2, —C(O)H, —C(O)(C1-C4)alkyl, —C(O)O(C1-C4)alkyl, (C1-C4)alkyl, (C3-C6)cycloalkyl, or heterocycloalkyl, wherein the (C1-C4)alkyl is optionally substituted with one or more substituents independently selected from —OH, (C1-C3)alkoxy, —NH2, and —NHC(NH)NH2;
• each R12 is independently selected from (C1-C3)alkoxy, (C1-C3)haloalkyl, (C1-C3) hydroxyalkyl, halogen, —OH, —NH2, —NH(C1-C4)alkyl, —N((C1-C4)alkyl)2, and oxo;
• R13 is —CH3, —CH═CH2, —CF3, —CH2F, or —CH2OH;
• R13′ is H or —CH3;
• n is 1 or 2;
• each p is independently 0, 1, or 2;
• and
• provided that when Z is NH, X is —CH2NHC(NH)NH2 or —CH2NH2, R1 is H or F, R3 is H, R5 is methyl, and R6 is H, then R4 is (C1-C3)alkyl, (C2-C3)alkenyl, F, I, or —NO2;
• provided that when Z is NH, W is not CH(CH3), and X is not CH2NHC(NH)NH2, and R2 is not Cl, and R13 is not CH3, and R6, R1, R3, R4, and R13′ are not H.