Macrolide antibacterial compounds

A compound, or salt, prodrug, or salt of a prodrug thereof, having formula (I)

• 16
• in which
• two of A1, B1, D1, and E1 are hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —CN, —OH, —SH, —C(O)H, —C(O)R1, —C(O)OH, —C(O)OR1, —C(O)NR2R3, or alkyl substituted by one, two, or three substituents independently selected from the group consisting of —CN, —OH, —SH, halo, aryl, heteroaryl, heterocyclyl, —OR2, —SR1, —C(O)H, —C(O)R1, —C(O)OH, —C(O)OR1, —CH═N—OR1, —OC(O)R1, —OC(O)OR1, —C(O)NR2R3, —OC(O)NR2R3, —NR2R3, —N(R4)C(O)H, —N(R4)C(O)R1, —N(R4)C(O)NR2R3, —N(R4)SO2R1, —OR1, —SR1, —S(O)R1, —SO2R1, and —SO2NR2R3, and the remainder are hydrogen;
• or
• A1 and D1, A1 and E1, B1 and D1, or B1 and D1 together are one- to five-membered alkylene or two- to five-membered heteroalkylene, and the remainder are hydrogen;
• or
• A1 and B1 together are one- to seven-membered alkylene or two- to seven-membered heteroalkylene, and D1 and E1 are hydrogen;
• or
• D1 and E1 together are one- to seven-membered alkylene or two- to seven-membered heteroalkylene, and A1 and B1 are hydrogen;
• X1 is hydrogen or fluoride;
• M1 is (E)—CH═CH, (Z)—CH═CH, or C≡C;
• Y1 is arylene or heteroarylene;
• L1 is drawn from left to right and is alkylene, alkenylene, alkynylene, CH═N—O—CH2-(alkenylene), CH2N(R5), CH2N(R5)(CH2)m, C(O)N(R5), N(R5)C(O)N(R6), CH═N—N(R5), CH═N—N(R5)C(O), O, CH═N—O, CH═N—O(CH2)m, C(O)N(R5)(CH2)m, or CH═N—O(CH2)nO,
• in which m is one to four, and n is two to four;
• W1 is hydrogen aryl, heteroaryl, or heterocyclyl;
• R1 is alkyl, aryl, heteroaryl, or heterocyclyl;
• R2 and R3 are independently hydrogen or alkyl;
• or
• R2 and R3 together are 3- to 7-membered alkylene or 3- to 7-membered heteroalkylene;
• R4 is hydrogen or alkyl;
• R5 and R6 are independently hydrogen or alkyl;
• and
• RA is hydrogen or RP in which RP is a hydroxyl protecting moiety;
• in which, for the foregoing,
• each aryl, arylene, heteroaryl, heteroarylene, heterocyclyl, and heterocycloalkylene is unsubstituted or substituted by one, two, three, four, or five substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, halo, —CN, —OH, —SH, —NH2, —NO2, (O), —CF3, —CH2CF3, —CF2CF3, —OCF3, —OCH2CF3, —OCF2CF3, —OR30, —SR30, —S(O)R35, —SO2R35, —C(O)H, —C(O)R35, —C(O)OH, —C(O)OR35, —NH(R35), —N(R35)(R36), —C(O)NH2, —C(O)NH(R35), —C(O)N(R35)(R36), —OC(O)R35, —OC(O)OR35, —OC(O)NH2, —OC(O)NH(R35), —OC(O)N(R35)(R36), —NHC(O)H, —NHC(O)R35, —NHC(O)OR35, —NHC(O)NH2, —NHC(O)NH(R35), —NHC(O)N(R35)(R36), —SO2NH2, —SO2NH(R35), —SO2N(R35)(R36), R40, and alkyl substituted with one or two substituents independently selected from the group consisting of halo, —CN, —OH, —SH, (O), —OR30, —SR30, —C(O)OH, —C(O)OR35, —NH2, —NH(R35), —N(R35)(R36), —C(O)NH2, —C(O)NH(R35), —C(O)N(R35)(R36), —OC(O)R35, —OC(O)NH2, —OC(O)NH(R35), —OC(O)N(R35)(R36), —SO2NH2, —SO2NH(R35), —SO2N(R35)(R36), and R40;
• R30 is alkyl or alkyl substituted with a substituent selected from the group consisting of halo and —OR45;
• R35 and R36 are independently selected alkyl;
• R40 is phenyl, naphthyl, furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, tetrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiomorpholinyl, each of which is unsubstituted or substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, halo, —CN, —OH, —SH, —NO2, (O), —CF3, —CH2CF3, —CF2CF3, —OCF3, —OCH2CF3, —OCF2CF3, —OR45, —SR45, —S(O)R50, —SO2R50, —C(O)H, —C(O)R50, —C(O)OH, —C(O)OR50, —NH2, —NH(R50), —N(R50)(R51), —C(O)NH2, —C(O)NH(R50), —C(O)N(R50)(R51), —OC(O)R50, —OC(O)OR50, —OC(O)NH2, —OC(O)NH(R50), —OC(O)N(R50)(R51), —NHC(O)H, —NHC(O)R50, —NHC(O)OR50, —NHC(O)NH2, —NHC(O)NH(R50), —NHC(O)N(R50)(R51), —SO2NH2, —SO2NH(R50), and —SO2N(R50)(R51);
• R45 is alkyl;
• R50 and R51 are independently selected alkyl.