Lipopeptides as antibacterial agents

A compound having the formula (I):

• and salts thereof;
• wherein R is:
• wherein X′ and X″ are independently C═O, C═S, C═NH, C═NRX, S═O or SO2;
• wherein n is 0 or 1;
• wherein RX is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, hydroxyl, alkoxy, carboxy or carboalkoxy;
• wherein B is X″RY, H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl;
• wherein RY is hydrido, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or hydroxyl;
• wherein A is H, NH2, NHRA, NRARB, alkyl, alkenyl, alkynyl, alkoxy, aryloxy, aryl, heteroaryl, cycloalkyl or heterocyclyl;
• wherein RA and RB are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or carboalkoxy;
• wherein when n is 0, then A is additionally:
• wherein each of R50-R53 is independently C1-C15 alkyl;
• alternatively, wherein B and A together form a 5-7 membered heterocyclic or heteroaryl ring;
• wherein R1 is
• wherein X′ and X′″ are independently C═O, C═S, C═NH, C═NRX′, S═O or SO2;
• wherein m is 0 or 1;
• wherein RX′ is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heteorcyclyl, hydroxyl, alkoxy, carboxy or carboalkoxy;
• wherein B′ is X′″RY′, H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl;
• wherein RY′ is hydrido, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or hydroxyl;
• wherein A′ is unsubstituted alkyl, alkenyl, alkynyl, alkoxy, aryloxy;
• or alkyl wherein one or more hydrogen atoms is replaced by a substituent group selected from acyl, amino, acylamino, acyloxy, carboalkoxy, carboxy, carboxyamido, cyano, halo, hydroxyl, nitro, thio, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, aryloxy, sulfinyl, sulfonyl, oxo, guanidino, and formyl;
• provided that when B′ is H then (X′)m-A′ is other than
• (a) —C(O)(C1-C16 unsubstituted alkyl)-NH2;
• (b) —C(O)(C1-C10 unsubstituted alkyl)-NHC(O)RD, wherein RD is —C1-C18 unsubstituted alkyl, or —C1-C18 selected substituted alkyl wherein one proton is replaced by a hydroxyl, carboxyl or C1-C3 alkoxy, or one to three protons is replaced by a halo substituent;
• (c) —C(O)C1-C18 unsubstituted alkyl;
• (d) —C(O)C4-C18 unsubstituted alkenyl;
• wherein R54 is selected from C1-C17-unsubstituted alkyl or C2-C17-unsubstituted alkenyl;
• wherein R55 is selected from hyroxyethyl, hydroxymethyl, mercaptomethyl, mercaptoethyl, methylthioethyl, 2-thienyl, 3-indolemthyl, phenyl optionally substituted with a group selected from halo, nitro, C1-C3-unsubstituted alkyl, hydroxy, C1-C3-unsubstituted alkoxy, C1-C3-unsubstituted alkylthio, carbamyl or C1-C3 unsubstituted alkylcarbamyl;
• or benzyl optionally substituted with a group selected from halo, nitro, C1-C3-unsubstituted alkyl, hydroxy, C1-C3-unsubstituted alkoxy, C1-C3-unsubstituted alkylthio, carbamyl or C1-C3 unsubstituted alkylcarbamyl;
• wherein t is 0 or 1 and wherein u is an integer from 1-3;
• (f) —C(O)C1-C18 selected unsubstituted alkyl wherein one proton is replaced by a hydroxyl, carboxyl or C1-C3 alkoxy, or one to three protons is replaced by a halo substituent;
• and
• (g) an amino protecting group;
• and
• wherein when B′ is H and m is 0, then A′ is other than C4-C14 unsubstituted alkyl;
• wherein R2 is
• wherein K and K′ together form a C3-C7 cycloalkyl or heterocyclyl ring or a C5-C10 aryl or heteroaryl ring;
• wherein J is hydrido, amino, NHRJ, NRJRK, alkyl, alkenyl, alkynyl, alkoxy, aryloxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, alkylamino, hydroxyl, thio, alkylthio, alkenylthio, sulfinyl, sulfonyl, azido, cyano, halo,
• wherein each of R24, R25, and R26 is independently alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl;
• or R24 and R25 together form a 5-8 membered heterocyclyl ring;
• wherein RJ and RK are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl;
• or
• alternatively, wherein J together with R17, forms a 5-8 membered heterocyclyl or cycloalkyl ring;
• or
• alternatively, wherein J, together with both R17 and R18, forms a 5-8 membered aryl, cycloalkyl, heterocyclyl or heteroaryl ring;
• and
• wherein each of R17 and R18 is independently hydrido, halo, hydroxyl, alkoxy, amino, thio, sulfinyl, sulfonyl or
• wherein R17 and R18 taken together can form a ketal, thioketal,
• wherein each of R22 and R23 is independently hydrido or alkyl.