Modified polysaccharide polymers and related compositions and methods thereof

An alginate comprising a mannuronate or guluronate monomer, wherein the mannuronate or guluronate monomer has having a structure of Formula (I-a):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is O, NR6, or S;
• R1 is absent, C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C1-6 heteroalkylene, C1-6 haloalkylene, —N(R7a)—, —O—, —C(O)—, —C(O)O—, —C(O)N(RC)—, or —N(RC)C(O)—, wherein alkylene, alkenylene, alkynylene, heteroalkylene, and haloalkylene is optionally substituted by one or more R8;
• R2 and R3 are each independently hydrogen, C1-6 alkylene-S(O)2—C2-6 alkenyl, or C1-6 alkylene-S(O)2—R9, C1-6 heteroalkylene-S(O)2—R9, C(O)—C1-6 alkylene-S(O)2—R9, or C(O)—C1-6 heteroalkylene-S(O)2—R9, wherein each alkylene or alkenyl is optionally substituted by one or more R10, and each of R2 and R3 is not both hydrogen;
• each R4 is absent, C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, C1-6 heteroalkylene, C1-6 haloalkylene, —N(R7a)—, —O—, —C(O)—, —C(O)O—, —C(O)N(RC)—, or —N(RC)C(O)—, wherein each alkylene, alkenylene, alkynylene, heteroalkylene, and is optionally substituted by one or more R8;
• R5 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 heteroalkyl, C1-6 haloalkyl, N(R7a)(R7b), ORA, C(O)RB, C(O)ORA, C(O)N(RC)(RD), N(RC)C(O)RB, halogen, cyano, azido, aryl, heteroaryl, cycloalkyl, heterocyclyl, an afibrotic compound, or a peptide, wherein alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally substituted by one or more R8;
• R6 is hydrogen, C1-6 alkyl, C1-6 heteroalkyl, or C1-6 haloalkyl, wherein alkyl, heteroalkyl, and haloalkyl is optionally substituted by one or more R10;
• R7a and R7b are each independently hydrogen, C1-6 alkyl, cycloalkyl, or heterocyclyl, wherein alkyl, cycloalkyl, or heterocyclyl is optionally substituted by one or more R10;
• each R8 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, halogen, oxo, cyano, azido, aryl, heteroaryl, cycloalkyl, heterocyclyl, ORA, N(RC)(RD), C(O)ORA, C(O)RB, C(O)N(RC)(RD), or N(RC)C(O)RB, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl is substituted by 0-12 R11;
• RA is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, an afibrotic compound, or a peptide, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl is substituted by 0-12 R11;
• RB, RC, and RD are C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, halogen, aryl, heteroaryl, cycloalkyl, heterocyclyl, an afibrotic compound, or a peptide;
• wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, and is optionally substituted by one or more R11;
• or
• RB and RC are taken together with the atoms to which they are attached to form a 3-10 membered heterocyclyl or heteroaryl ring, each of which is optionally substituted with one or more R10;
• R9 is a peptide or afibrotic compound;
• each R10 is independently C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, halogen, oxo, ORA, N(RC)(RD), C(O)ORA, C(O)RB, C(O)N(RC)(RD), or N(RC)C(O)RB, wherein each alkyl, heteroalkyl, and haloalkyl is optionally substituted by one or more R11;
• and
• each R11 is independently C1-6 alkyl, halogen, oxo, cycloalkyl, or heterocyclyl.