Siglec ligands, conjugates, and methods of use thereof

A Siglec conjugate of formula (X):

• wherein:
• A1 is absent or alkylene;
• A2 is absent, aryl, heteroaryl, cycloalkyl, or a substituted version thereof;
• R2 is —COOH, —P(O)(OH)2, —OSO2OH, —C(O)NHSO2H, tetrazole, an ester, or a substituted version thereof;
• R3 is H, alkoxy, —S(alkyl), amino, halo, cyano, ester, amide, or a substituted version thereof;
• R4 is hydroxy, alkoxy, amino, amide, or a substituted version thereof;
• R5 is H, amino, ureido, amide, thioamide, oxamide, —NH(cyclobut-3-ene-1,2-dione), sulfonaamide, phosphoramide, alkylamine, triazole, tetrazole, or substituted version thereof;
• R7 is hydroxy or halo;
• X1 is O, S, triazole, —CH(OH)—, —CH2—;
• —CHF—, —NH—, or —CF2—;
• E1 is absent, —(CH2CH2O)g, —(CH2)g—, benzyl, cycloalkyl, or a substituted version thereof, wherein g is an integer ranging from 1 to 10;
• Y is absent, alkylene, phenylene, substituted phenylene, —O—, —NH—, —S—, —C≡C—, —CH2C≡C—, —C(O)—, —OP(O)O—, or —NH-(cyclobut-3-ene-1,2-dione)-NH—, —NHC(O)—, triazole, —(CH2CH2O)g—, —(CH2)g—, wherein g is an integer ranging from 1 to 10;
• X2 is absent, O, —NH—, —C(O)NH—, —C(O)—, —C(O)O—, —NHC(O)—, —NHC(O)O—, —OP(O)(OH)O—, —NHC(O)NH—, —(CH2)g—, —(CH2CH2O)g—, —(CH2CH2O)gNHC(O)—, triazole, or a substituted version thereof, wherein g is an integer ranging from 1 to 10;
• E2 is absent, —(CH2)h—, —(CH2CH2O)h, —(CH2CH2O)hC(O)NH—, -(alkylene)C(O)NH(alkylene)-, (alkylene)C(O)NH(substituted alkylene)-, -(alkylene)C(O)N(substituted alkylene)2-, —C≡C—, or —CH2C≡C—, or a substituted version thereof, wherein h is an integer ranging from 1 to 10;
• and
• Z′ is Z1′ or Z1′-T-Z2′, wherein Z1′ is a diradical group, T is absent or a diradical group, and Z2′ is a diradical group;
• C is absent or a diradical group;
• and
• BAS is a biologically active substance,
• a salt thereof, or a stereoisomer thereof.

A Siglec ligand of formula (XI):

• wherein:
• A1 is absent or alkylene;
• A2 is absent, alkyl, aryl, heteroaryl, cycloalkyl, or a substituted version thereof;
• R2 is —COOH, —P(O)(OH)2, —OSO2OH, —C(O)NHSO2H, tetrazole, an ester, or a substituted version thereof;
• R3 is H, alkyl, alkoxy, —S(alkyl), amino, halo, cyano, ester, amide, or a substituted version thereof;
• R4 is hydroxy, alkoxy, amino, amide, or a substituted version thereof;
• R5 is H, amino, ureido, amide, thioamide, oxamide, —NH(cyclobut-3-ene-1,2-dione), sulfonaamide, phosphoramide, alkylamine, triazole, tetrazole, or substituted version thereof;
• R7 is hydroxy or halo;
• XX1 is S, triazole, —CH(OH)—, —CH2—, —CHF—, —NH—, or —CF2—;
• EE1 is absent, —(CH2CH2O)f—, —(CH2)g—, benzyl, cycloalkyl, or a substituted version thereof, wherein f and g are each independently an integer ranging from 1 to 10;
• Y is absent, alkylene, phenylene, substituted phenylene, —O—, —NH—, —S—, —C≡C—, —CH2C≡C—, —C(O)—, —OP(O)O—, —NH-(cyclobut-3-ene-1,2-dione)-NH—, —NHC(O)—, triazole, —(CH2CH2O)g—, —(CH2)g—, wherein g is an integer ranging from 1 to 10;
• X2 is absent, O, —NH—, —C(O)NH—, —C(O)—, —C(O)O—, —NHC(O)—, —NHC(O)O—, —OP(O)(OH)O—, —NHC(O)NH—, —(CH2)g—, —(CH2CH2O)g—, —(CH2CH2O)gNHC(O)—, triazole, or a substituted version thereof, wherein g is an integer ranging from 1 to 10;
• EE2 is absent, —(CH2)h—, -(alkylene)C(O)NH(alkylene)-, (alkylene)C(O)NH(substituted alkylene)-, -(alkylene)C(O)N(substituted alkylene)2-, —C≡C—, —CH2C≡C—, —(CH2CH2O)i— or —(CH2CH2O)hC(O)NH—, wherein h and i are each independently selected from an integer ranging from 1 to 10;
• and
• Z is Z1 or Z1′-T-Z2, wherein Z1 is a chemoselective functional group, wherein Z1′ is a diradical group, T is absent or a diradical group, and Z2 is a chemoselective functional group,
• a salt thereof, or a stereoisomer thereof.

A Siglec conjugate of formula (XII):

• wherein:
• A1 is absent or alkylene;
• A2 is absent, alkyl, aryl, heteroaryl, cycloalkyl, or a substituted version thereof;
• R2 is —COOH, —P(O)(OH)2, —OSO2OH, —C(O)NHSO2H, tetrazole, an ester, or a substituted version thereof;
• R3 is H, alkyl, alkoxy, —S(alkyl), amino, halo, cyano, ester, amide, or a substituted version thereof;
• R4 is hydroxy, alkoxy, amino, amide, or a substituted version thereof;
• R5 is H, amino, ureido, amide, thioamide, oxamide, —NH(cyclobut-3-ene-1,2-dione), sulfonaamide, phosphoramide, alkylamine, triazole, tetrazole, or substituted version thereof;
• R7 is hydroxy or halo;
• XX1 is S, triazole, —CH(OH)—, —CH2—, —CHF—, —NH—, or —CF2—;
• EE1 is absent, —(CH2CH2O)f—, —(CH2)g—, benzyl, cycloalkyl, or a substituted version thereof, wherein f and g are each independently an integer ranging from 1 to 10;
• Y is absent, alkylene, phenylene, substituted phenylene, —O—, —NH—, —S—, —C≡C—, —CH2C≡C—, —C(O)—, —OP(O)O—, —NH-(cyclobut-3-ene-1,2-dione)-NH—, —NHC(O)—, triazole, —(CH2CH2O)g—, —(CH2)g—, wherein g is an integer ranging from 1 to 10;
• X2 is absent, O, —NH—, —C(O)NH—, —C(O)—, —C(O)O—, —NHC(O)—, —NHC(O)O—, —OP(O)(OH)O—, —NHC(O)NH—, —(CH2)g—, —(CH2CH2O)g—, —(CH2CH2O)gNHC(O)—, triazole, or a substituted version thereof, wherein g is an integer ranging from 1 to 10;
• EE2 is absent, —(CH2)h—, -(alkylene)C(O)NH(alkylene)-, (alkylene)C(O)NH(substituted alkylene)-, -(alkylene)C(O)N(substituted alkylene)2-, —C≡C—, —CH2C≡C—, —(CH2CH2O)i—, —(CH2CH2O)hC(O)NH—, or a substituted version thereof, wherein h and i are each independently selected from an integer ranging from 1 to 10;
• and
• Z′ is Z1′ or Z1′-T-Z2′, wherein Z1′ is a diradical group, T is absent or a diradical group, and Z2′ is a diradical group;
• C is absent or a diradical group;
• and
• BAS is a biologically active substance,
• a salt thereof, or a stereoisomer thereof.