Hydrophobically tagged small molecules as inducers of protein degradation

A compound of Formula (II):

• or a pharmaceutically acceptable salt thereof;
• wherein:
• Ring A is substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each occurrence of RB is independently hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group, or two RB groups are joined to form an substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• each instance of RC is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORC1, —N(RC1)2, —SRC1, —C(═O)RC1, —C(═O)ORC1, —C(═O)SRC1, —C(═O)N(RC1)2, —NRC1C(═O)RC1, —NRC1C(═O)ORC1, —NRC1C(═O)SRC1, or —NRC1C(═O)N(RC1)2, wherein each occurrence of RC1 is independently hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two RC1 groups are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• a is 0, 1, 2, 3, or 4;
• b is 1;
• L1 represents a linker of 4 to 20, inclusive, consecutive, covalently bonded atoms in length, selected from the group consisting of substituted and unsubstituted alkylene;
• substituted and unsubstituted alkenylene;
• substituted and unsubstituted alkynylene;
• substituted and unsubstituted heteroalkylene;
• substituted and unsubstituted heteroalkenylene;
• substituted and unsubstituted heteroalkynylene;
• substituted and unsubstituted heterocyclylene;
• substituted and unsubstituted carbocyclylene;
• substituted and unsubstituted arylene;
• substituted and unsubstituted heteroarylene;
• and combinations thereof;
• L2 represents a bond or a linker selected from the group consisting of substituted and unsubstituted alkylene;
• substituted and unsubstituted alkenylene;
• substituted and unsubstituted alkynylene;
• substituted and unsubstituted heteroalkylene;
• substituted and unsubstituted heteroalkenylene;
• substituted and unsubstituted heteroalkynylene;
• substituted and unsubstituted heterocyclylene;
• substituted and unsubstituted carbocyclylene;
• substituted and unsubstituted arylene;
• substituted and unsubstituted heteroarylene;
• and combinations thereof;
• RH represents a hydrophobic group selected from the group consisting of substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted carbocyclyl, substituted and unsubstituted heterocyclyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroarylalkyl, substituted and unsubstituted carbocycylalkyl, and substituted and unsubstituted heterocyclylalkyl;
• wherein the hydrophobic group refers to a group comprising zero hydrogen bond donors;
• and
• RD is of formula:
• wherein:
• RD1 is hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —CN, —NO2, —ORD1a, —N(RD1a)2, —SRD1a, —CH2ORD1a, —CH2N(RD1a)2, —CH2SRD1a, —C(═O)RD1a, —C(═O)ORD1a, —C(═O)SRD1a, —C(═O)N(RD1a)2, —C(═S)RD1a, —C(═S)ORD1a, —C(═S)SRD1a, —C(═S)N(RD1a)2, —C(═NRD1a)RD1a, —C(═NRD1a)ORD1a, —C(═NRD1a)SRD1a, or —C(═NRD1a)N(RD1a)2, wherein each occurrence of RD1a is independently hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two RD1a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• RD2 is hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —CN, —NO2, —ORD2a, —N(RD2a)2, —SRD2a, —CH2ORD2a, —CH2N(RD2a)2, —CH2SRD2a, —C(═O)RD2a, —C(═O)ORD2a, —C(═O)SRD2a, —C(═O)N(RD2a)2, —C(═S)RD2a, —C(═S)ORD2a, —C(═S)SRD2a, —C(═S)N(RD2a)2, —C(═NRD2a)RD2a, —C(═NRD2a)ORD2a, —C(═NRD2a)SRD2a, or —C(═NRD2a)N(RD2a)2, wherein each occurrence of RD2a is independently hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two RD2a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• RD3 is hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORD3a, —N(RD3a)2, —SRD3a, —CH2ORD3a, —CH2N(RD3a)2, —CH2SRD3a, —C(═O)RD3a, —C(═O)ORD3a, —C(═O)SRD3a, —C(═O)N(RD3a)2, —C(═S)RD3a, —C(═S)ORD3a, —C(═S)SRD3a, —C(═S)N(RD3a)2, —C(═NRD3a)RD3a, —C(═NRD3a)ORD3a, —C(═NRD3a)SRD3a, or —C(═NRD3a)N(RD3a)2 wherein eachoccurrence each occurrence of RD3a is independently hydrogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or two RD3a groups are joined to form an substituted or unsubstituted heterocyclic ring;
• optionally RD1 and RD3, or RD2 and RD3, or RD1 and RD2 are joined to form an substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring;
• RD4 is a leaving group selected from the group consisting of —Br, —Cl, —I, and —OS(═O)wRD4a, wherein w is 1 or 2, and RD4a is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• X1 is a bond or NRD5, wherein RD5 is hydrogen, C1-6 alkyl, or a nitrogen protecting group;
• each instance of Y is independently O, S, or NRD6, wherein RD6 is hydrogen, C1-6 alkyl, or a nitrogen protecting group;
• and
• z is 0, 1, 2, 3, 4, 5, or 6.