Opioid receptor modulators

A method of treating a disease or condition in a subject, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I):

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• R1 is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, three, four, or five R7;
• R2 is selected from C6-10aryl and C1-9heteroaryl, wherein C6-10aryl and C1-9heteroaryl are optionally substituted with one, two, three, four, or five R8;
• R3 is —X-R3a,
• X is a bond;
• R3a is C3-8cycloalkyl substituted with one, two, three, four, or five R9;
• R4 is hydrogen, C1-C6alkyl, or C1-C6haloalkyl;
• R5 and R6 are each independently selected from hydrogen, C1-C6alkyl, and C1-C6haloalkyl;
• or R5 and R6 are combined to form an azetidinyl, pyrrolidinyl, piperidinyl, or piperazinyl ring;
• each R7 is independently selected from halogen, —CN, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, —OR10, —SR10, —C(O)OR10, —OC(O)N(R10)(R11), —N(R12)C(O)N(R10)(R11), —N(R12)C(O)R13, —N(R12)C(O)OR13, —N(R12)S(O);
• R13, —C(O)R13, —OC(O)R13, —C(O)N(R10)(R11), —C(O)C(O)N(R10)(R11), —S(O)R13, —S(O)2R13, and —S(O);
• N(R10)(R11), wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, —CN, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, —OR14, —SR14, —C(O)OR14, —OC(O)N(R14)(R15), —N(R16)C(O)N(R14)(R15), —N(R16)C(O)R17, —N(R16)C(O)OR17, —N(R16)S(O)2R17, —C(O)R17, —OC(O)R17, —C(O)N(R14)(R15), —C(O)C(O)N(R14)(R15), —S(O)R17, —S(O)2R17, and —S(O)2N(R14)(R15);
• or two R7 are combined to form a heterocycloalkyl ring optionally substituted with oxo;
• or R7 and R6 are combined to form a heterocycloalkyl ring;
• each R8 and each R9 are each independently selected from halogen, —CN, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, —OR10, —SR10, —C(O)OR10, —OC(O)N(R10)(R11), —N(R12)C(O)N(R10)(R11), —N(R12)C(O)R13, —N(R12)C(O)OR13, —N(R12)S(O)2R13, —C(O)R13, —OC(O)R13, —C(O)N(R10)(R11), —C(O)C(O)N(R10)(R11), —S(O)R13, —S(O), R13, and —S(O)2N(R10)(R11), wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, —CN, C1-6alkyl, C1-9haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, C1-9heteroaryl, —OR14, —SR14, —C(O)OR14, —OC(O)N(R14)(R15), —N(R16)C(O)N(R14)(R15), —N(R16)C(O)R17, —N(R16)C(O)OR17, —N(R16)S(O);
• R17, —C(O)R17, —OC(O)R17, —C(O)N(R14)(R15), —C(O)C(O)N(R14)(R15), —S(O)R17, —S(O)2R17, and —S(O)2N(R14)(R15);
• each R10 is independently selected from hydrogen, C1-6alkyl, C1-6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• each R11 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• each R12 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• each R13 is independently selected C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• each R14 is independently selected from hydrogen, C1-6alkyl, C1-6 haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• each R15 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• each R16 is independently selected from hydrogen, C1-6alkyl, and C1-6haloalkyl;
• and
• each R17 is independently selected C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl are optionally substituted with one, two, or three groups selected from halogen, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C3-6cycloalkyl, C2-9heterocycloalkyl, C6-10aryl, and C1-9heteroaryl;
• wherein the disease or condition is pain, opioid overdose, depression, obsessive compulsive disorder, opioid use disorder, addiction, or a combination thereof.