Spirocyclic piperidine melanocortin subtype-2 receptor (mc2r) antagonists and uses thereof

A method for treating a disease or condition in a mammal that would benefit from the modulation of melanocortin subtype-2 receptor (MC2R) activity, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof:

• wherein:
• RA is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl, wherein if RA is substituted then RA is substituted with 1, 2, 3 or 4 groups selected from Ra, Rb, and Rc;
• Ra, Rb, and Rc are independently selected from the group consisting of hydrogen, halogen, —OR4, —CN, —N(R4)2, —C(═O)R7, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C2-C7 heterocycloalkyl, unsubstituted or substituted phenyl, and unsubstituted or substituted heteroaryl, wherein any substituted group of Ra, Rb, and Rc is substituted with one or more R6 groups;
• wherein, if Ra, Rb, or Rc is attached to the N atom of a heteroaryl, then it is hydrogen, —C(═O)R7, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, or unsubstituted or substituted C2-C7 heterocycloalkyl;
• RB is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl, wherein if RB is substituted then RB is substituted with 1, 2, 3 or 4 groups selected from Rd, Re and Rf;
• Rd, Re, and Rf are independently selected from the group consisting of hydrogen, halogen, —OR4, —CN, —N(R4)2, —C(═O)R7, —C(═O)N(R4)2, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C2-C7 heterocycloalkyl, unsubstituted or substituted phenyl, and unsubstituted or substituted heteroaryl, wherein any substituted group of Rd, Re, and Rf is substituted with one or more R6 groups;
• wherein, if Rd, Re, or Rf is attached to the N atom of a heteroaryl, then it is hydrogen, —C(═O)R7, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, or unsubstituted or substituted C2-C7 heterocycloalkyl;
• X1 is CR11 or N;
• X3 is CR13 or N;
• X4 is CR14 or N;
• R11, R13, and R14 are each independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6cycloalkyl, —CN, —OR4, —SR4, —CO2R4, —C(═O)N(R4)2, or —N(R4)2;
• W is absent, —C(R3)2—, —C(R3)2—C(R3)2—, —C(═O)—, #—C(═O)—O—, #—C(═O)—C(R3)2—, or #—C(═O)NR2—;
• wherein # indicates the attachment point to the N atom of the ring;
• Y is absent, —(C═O)—, *—O(C═O)—, *—NR2—(C═O)—, —(SO2)—, or *—NR2—(SO2)—;
• wherein * indicates the attachment point to R1;
• R1 is unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C2-C7 heterocycloalkyl, unsubstituted or substituted —(C1-C6 alkyl)-(C3-C6 cycloalkyl), or unsubstituted or substituted —(C1-C6 alkyl)-(C2-C7 heterocycloalkyl), wherein any substituted group of R1 is substituted with one or more halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted monocyclic heterocycle, —N(R4)2, —OR5, —CN, —CO2R5, —C(═O)N(R4)2, —SR5, —S(═O)R7, —S(═O)2R7, —NR4C(═O)R5, —NR4SO2R7, —SO2R7, or —SO2N(R4)2;
• each R2 is independently hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, or unsubstituted or substituted C2-C7 heterocycloalkyl;
• each R3 is independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, or unsubstituted or substituted C2-C7 heterocycloalkyl;
• each R4 is independently selected from the group consisting of hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl;
• or two R4 are taken together with the nitrogen atom to which they are attached to form an unsubstituted or substituted 3- to 6-membered monocyclic heterocycle;
• each R5 is independently selected from the group consisting of hydrogen, substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl;
• each R6 is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4alkoxy, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4fluoroalkoxy, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, —CN, —OH, —CO2R5, —CH2CO2R5, —C(═O)N(R4)2, —C(═O)N(R4)OR5, —CH2C(═O)N(R4)2, —N(R4)2, —CH2N(R4)2, —C(R5)2N(R4)2, —NR4C(═O)R5, —CH2NR4C(═O)R5, —NR4C(═O)N(R5)2, —NR4C(═O)N(R4)2, —C(R5)═N(R4)—OR5, —SR5, —S(═O)R7, —SO2R7, or —SO2N(R4)2;
• and
• each R7 is independently selected from the group consisting substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted phenyl, and unsubstituted or substituted heteroaryl.