Glycopeptide phosphonate derivatives

A glycopeptide of formula I:

• wherein:
• R1 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and —Ra—Y—Rb—(Z)x;
• or R1 is a saccharide group optionally substituted with —Ra—Y—Rb—(Z)x, Rf, —C(O)Rf, or —C(O)—Ra—Y—Rb—(Z)x;
• R2 is hydrogen or a saccharide group optionally substituted with —Ra—Y—Rb—(Z)x, Rf, —C(O)Rf, or —C(O)—Ra—Y—Rb—(Z)x;
• R3 is —ORc, —NRcRc, —O——Ra—Y—Rb—(Z)x, —NRc—Ra—Y—Rb—(Z)x, —NRcRe, or —O—Re;
• or R3 is a nitrogen-linked, oxygen-linked, or sulfur-linked substituent that comprises one or more phosphono groups;
• R4 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —Ra—Y—Rb—(Z)x, —C(O)Rd and a saccharide group optionally substituted with —Ra—Y—Rb—(Z)x, Rf, or —C(O)—Ra—Y—Rb—(Z)x, or R4 and R5 can be joined, together with the atoms to which they are attached, to form a heterocyclic ring optionally substituted with —NRc—Ra—Y—Rb—(Z)x;
• R5 is selected from the group consisting of hydrogen, halo, —CH(Rc)—NRcRc, —CH(Rc)—NRcRe, —CH(Rc)—NRc—Ra—Y—Rb—(Z)x, —CH(Rc)—Rx, —CH(Rc)—NRc—Ra—C(═O)—Rx, and a substituent that comprises one or more phosphono groups;
• R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —Ra—Y—Rb—(Z)x, —C(O)Rd and a saccharide group optionally substituted with —Ra—Y—Rb—(Z)x, Rf, —C(O)Rf, or —C(O)—Ra—Y—Rb—(Z)x, or R5 and R6 can be joined, together with the atoms to which they are attached, to form a heterocyclic ring optionally substituted with —NRc—Ra—Y—Rb—(Z)x;
• R7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, —Ra—Y—Rb—(Z)x, and —C(O)Rd;
• R8 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
• R9 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
• R10 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
• or R8 and R10 are joined to form —Ar1—O—Ar2—, where Ar1 and Ar2 are independently arylene or heteroarylene;
• R11 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic, or R10 and R11 are joined, together with the carbon and nitrogen atoms to which they are attached, to form a heterocyclic ring;
• R12 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic, —C(O)Rd, —C(NH)Rd, —C(O)NRcRc, —C(O)ORd, —C(NH)NRcRc, —Ra—Y—Rb—(Z)x, and —C(O)—Ra—Y—Rb—(Z)x, or R11 and R12 are joined, together with the nitrogen atom to which they are attached, to form a heterocyclic ring;
• R13 is selected from the group consisting of hydrogen or —OR14;
• R14 is selected from hydrogen, —C(O)Rd and a saccharide group;
• each Ra is independently selected from the group consisting of alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene;
• each Rb is independently selected from the group consisting of a covalent bond, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene and substituted alkynylene, provided Rb is not a covalent bond when Z is hydrogen;
• each Rc is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic and —C(O)Rd;
• each Rd is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl and heterocyclic;
• Re is a saccharide group;
• each Rf is independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, or heterocyclic;
• Rx is an N-linked amino saccharide or an N-linked heterocycle;
• X1, X2 and X3 are independently selected from hydrogen or chloro;
• each Y is independently selected from the group consisting of oxygen, sulfur, —S—S—, —NRc—, —S(O)—, —SO2, —NRcC(O)—, —OSO2—, —OC(O)—, —NRcSO2—, —C(O)NRc—, —C(O)O—, —SO2NRc, —SO2O—, —P(O)(ORc)O—, —P(O)(ORc)NRc—, —OP(O)(ORc)O—, —OP(O)(ORc)NRc—, —OC(O)O—, —NRcC(O)O—, —NRcC(O)NRc—, —OC(O)NRc, —C(═O)—, and —NRcSO2NRc—;
• each Z is independently selected from hydrogen, aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocyclic;
• n is 0, 1 or 2;
• and
• x is 1 or2;
• or a pharmaceutically acceptable salt, stereoisomer, or prodrug thereof;
• provided at least one of R3 and R5 is a substituent comprising one or more phosphono groups.