Mitragynine analogs and uses thereof

A compound of the formula:

• or a pharmaceutically acceptable salt or tautomer thereof,
• wherein:
• is a single bond or double bond;
• each of R1, R2, R3, and R4 is independently selected from the group consisting of hydrogen, halogen, —CN, —NO2, —N3, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —ORA, —N(RB)2, —SRA, —SeRA, —C(═O)RC, —C(═O)ORA, —C(═O)N(RB)2, —OC(═O)RC, —OC(═O)N(RB)2, —NRBC(═O)RC, —NRBC(═O)ORA, —NRBC(═O)N(RB)2, —S(═O)RC, —SO2RC, —NRBSO2RC, and —SO2N(RB)2;
• R5 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)RC, —C(═O)ORA, —C(═O)N(RB)2, —S(═O)RC, —SO2RC, —SO2N(RB)2, or a nitrogen protecting group;
• R6 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —ORA, —N(RB)2, —SRA, —C(═O)RC, —C(═O)ORA, —C(═O)N(RB)2, —OC(═O)RC, —OC(═O)N(RB)2, —NRBC(═O)RC, —NRBC(═O)ORA, —NRBC(═O)N(RB)2, —S(═O)RC, —SO2RC, —NRBSO2RC, or —SO2N(RB)2;
• or R5 and R6 are absent and
• is a double bond;
• provided that
• (i) R2 is optionally substituted heteroaryl, and R7 is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —ORA, —OC(═O)RC, —C(═O)RC, —C(═O)ORA, —OC(═O)N(RB)2, —C(═O)N(RB)2, —S(═O)RC, —SO2RC, or —SO2N(RB)2;
• or
• (ii) at least one of R1, R2, R3, and R4 is independently optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted, monocyclic or bicyclic heterocyclyl, or optionally substituted heteroaryl, and R7 is —OH;
• each of R10, R11, R12, and R13 is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —ORA, —N(RB)2, and —SRA;
• or R12 and R13 are taken together to form an optionally substituted alkenyl moiety;
• R14 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or an oxygen protecting group;
• each of R15 and R16 is independently selected from the group consisting of hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —CN, —N3, —ORA, —N(RB)2, and —SRA;
• each of R17 and R18 is independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —ORA, —N(RB)2, and —SRA;
• or R17 and R18 are taken together to form
• each instance of RA is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, an oxygen protecting group when attached to oxygen, a sulfur protecting group when attached to sulfur, or a selenium protecting group when attached to selenium;
• each instance of RB is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted acyl, or a nitrogen protecting group, or two RB groups are taken together with their intervening atoms to form an optionally substituted heterocyclic ring;
• and
• each instance of RC is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl.