US 12,479,825 B2
Melanocortin subtype-2 receptor (MC2R) antagonists and uses thereof
Sangdon Han, San Diego, CA (US); Sun Hee Kim, San Diego, CA (US); and Yunfei Zhu, San Diego, CA (US)
Assigned to CRINETICS PHARMACEUTICALS, INC., San Diego, CA (US)
Appl. No. 17/771,392
Filed by Crinetics Pharmaceuticals, Inc., San Diego, CA (US)
PCT Filed Oct. 30, 2020, PCT No. PCT/US2020/058202
§ 371(c)(1), (2) Date Apr. 22, 2022,
PCT Pub. No. WO2021/091788, PCT Pub. Date May 14, 2021.
Claims priority of provisional application 62/932,306, filed on Nov. 7, 2019.
Prior Publication US 2023/0015914 A1, Jan. 19, 2023
Int. Cl. C07D 401/14 (2006.01); C07D 453/02 (2006.01)
CPC C07D 401/14 (2013.01) [C07D 453/02 (2013.01)] 19 Claims
 
1. A compound of Formula (I), or a pharmaceutically acceptable salt, or solvate thereof:

OG Complex Work Unit Chemistry
wherein:
RA is unsubstituted or substituted phenyl or unsubstituted or substituted monocyclic heteroaryl, wherein if RA is substituted then RA is substituted with Ra, Rb and Rc;
Ra, Rb and Rc are independently selected from the group consisting of hydrogen, halogen, —OR5, —CN, —N(R5)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 monocyclic heteroaryl, wherein any substituted group of Ra, Rb and Rc is substituted with one or more R7 groups;
L is —O—, —C(═O)—, —S—, —SO2—, 5-membered heteroaryl, or a bond;
M is —O—, —C(O)NR4—, —S—, —SO2—, —S(═O)NR4—, 5-membered heteroaryl, or a bond;
RB is unsubstituted or substituted carbocycle, unsubstituted or substituted heterocycle, unsubstituted or substituted C1-C7 alkyl, unsubstituted or substituted C1-C7 fluoroalkyl, or unsubstituted or substituted C1-C6 heteroalkyl, wherein if RB is substituted then RB is substituted with Rd, Re and Rf;
or RB and R4 are taken together with the nitrogen atom to which they are attached to form an unsubstituted or substituted 3- to 7-membered heterocycle, wherein if the 3- to 7-membered heterocycle is substituted then the 3- to 7-membered heterocycle is substituted with Rd, Re and Rf;
Rd, Re and Rf are independently selected from the group consisting of hydrogen, halogen, —OR5, —CN, —N(R5)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 monocyclic heteroaryl, wherein any substituted group of Rd, Re and Rf is substituted with one or more R7 groups;
Y is CR3 or N; wherein when Y is N; L is —C(═O)—, —SO2—, 5-membered heterocycle, or a bond;
Z is CR3 or N;
R1 is an unsubstituted or substituted C1-C6 alkyl or unsubstituted or substituted C3-C6 cycloalkyl, wherein if R1 is substituted then R1 is substituted with hydrogen, —OR6, halogen, —N(R5)2, or —CN;
R2 is hydrogen, unsubstituted or substituted C1-C2 alkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bridged carbocycle, unsubstituted or substituted spirocyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, unsubstituted or substituted bridged heterocycle, unsubstituted or substituted spirocyclic heterocycle, unsubstituted or substituted —(C1-C6 alkyl)-carbocycle, or unsubstituted or substituted —(C1-C6 alkyl)-heterocycle, wherein any substituted group of R2 is substituted with one or more halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted monocyclic heterocycle, —N(R5)2, —OR6, —CN, —CO2R6, —C(═O)N(R5)2, —SR6, —S(═O)R8, —S(═O)2R8, —NR5C(═O)R6, —NR5SO2R8, —SO2R8, or —SO2N(R5)2;
each R3 is independently hydrogen, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C1-C6fluoroalkyl;
R4 is hydrogen, substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;
each R5 is independently hydrogen, substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;
or two R5 on the same nitrogen atom 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 R6 is independently hydrogen, substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;
each R7 is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4alkoxy, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C4fluoroalkoxy, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, —CN, —OH, —CO2R6, —CH2CO2R6, —C(═O)N(R5)2, —C(═O)N(R5) OR6, —CH2C(═O)N(R5)2, —N(R5)2, —CH2N(R5)2, —C(R6)2N(R5)2, —NR5C(═O)R6, —CH2NR5C(═O)R6, —NR5C(═O)N(R6)2, —NR5C(═O)N(R6)2, C(R6)═N(R5)—OR6, —SR6, —S(═O)R8, —SO2R8, or —SO2N(R5)2;
each R8 is independently substituted C1-C6 alkyl, unsubstituted or substituted C3-C6 cycloalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted phenyl, or unsubstituted or substituted heteroaryl;
wherein at least one of L and M is —O—.