Cereblon modulators and uses thereof

A small molecule modulator of Formula (I*), or a pharmaceutically acceptable salt or solvate thereof:

• wherein,
• A is N or C(R2);
• B is N or C(R3);
• D is N or C(R4);
• E is H or
• F is N or C(R5);
• X is absent, —O—, —NR6—, or —S—,
• Y is H, halogen, —OR6, substituted or unsubstituted C1-C6alkyl, or substituted or unsubstituted C1-C6haloalkyl;
• L is —C(═O)—, —S(═O)—, or —S(═O)2—;
• Z1 is —C(R7)2—CR8R9— or —CR7=CR8—;
• R2 is H, halogen, —CN, —N(R12)2, —OR6, —CH(OR6)R12, —C(═O)R12, —C(═O)N(R12)2, —S(═O)2R12, —S(═O)2N(R12)2, —N(R12)C(O)R12, —N(R12)S(═O)2R12, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6haloalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C5heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R3 is H, halogen, —CN, —N(R12)2, —OR6, —CH(OR6)R12, —C(═O)R12, —C(O)N(R12)2, —S(═O)2R12, —S(═O)2N(R12)2, —N(R12)C(═O)R12, —N(R12)S(═O)2R12, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6haloalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C2-C5heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R4 is H, halogen, —CN, —N(R12)2, —C(═O)R12, —C(═O)N(R12)2, —S(═O)2R12, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6haloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• R5 is H, halogen, —CN, —N(R12)2, —OR6, —C(═O)R12, —C(═O)N(R12)2, —N(R12)C(═O)R12, —S(═O)2R12, —N(R12)S(═O)2R12, —S(═O)2N(R12)2, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6haloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• each R6 is independently H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6haloalkyl, or substituted or unsubstituted C1-C10 heteroalkyl;
• R7 is H, —CN, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C3-C6cycloalkyl, or substituted or unsubstituted aryl;
• R8 is H, —NR10R11, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6aminoalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C1-6 alkylene-C6-10 aryl, or substituted or unsubstituted C2-C6heterocycloalkyl;
• R9 is H or substituted or unsubstituted C1-C6alkyl,
• R10 and R11 are each independently H, substituted or unsubstituted C1-C6alkyl, or substituted or unsubstituted C1-C8heteroalkyl;
• or
• R10 and R11 are taken together with the nitrogen to which they are attached to form a substituted or unsubstituted C2-C9heterocycloalkyl;
• each R12 is independently H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, or substituted or unsubstituted aryl;
• or
• two R12 on the same nitrogen are taken together with the nitrogen to which they are attached to form a substituted or unsubstituted C2-C9heterocycloalkyl;
• each R13 is independently halogen, —CN, —OR6, —C(═O)N(R12)2, —N(R12)C(═O)R12, —N(R12)S(═O)2R12, —N(S(═O)2R12)2, —S(═O)2R12, —S(═O)2N(R12)2, —(CH2)p—(OCH2CH2)q-substituted CM alkyl, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6haloalkyl, or substituted or unsubstituted C1-C20heteroalkyl;
• R14 is H or substituted or unsubstituted C1-C6alkyl;
• each R15, R16, R17, and R18 is independently selected from the group consisting of H, F, —OR6, and substituted or unsubstituted C1-C6alkyl;
• m is 0, 1, or 2,
• n is 0 or 1;
• each p is independently 0,1, 2, or 3;
• p is 1-6,
• S represents the sulfur atom of a cysteine residue C287 as set forth in SEQ ID NO:
• 1, or cysteine residue C286 as set forth in SEQ ID NO:
• 2 or 3;
• and
• CP represents the cereblon polypeptide set forth in SEQ ID NO:
• 1, 2, or 3.