US 12,421,193 B2
GPR52 modulators and methods of use
Juan Pablo Cueva-Garcia, San Diego, CA (US); Neil J. Ashweek, San Diego, CA (US); and Collin Regan, San Diego, CA (US)
Assigned to Neurocrine Biosciences, Inc., San Diego, CA (US)
Appl. No. 17/919,483
Filed by Neurocrine Biosciences, Inc., San Diego, CA (US)
PCT Filed Apr. 21, 2021, PCT No. PCT/US2021/028394
§ 371(c)(1), (2) Date Oct. 17, 2022,
PCT Pub. No. WO2021/216705, PCT Pub. Date Oct. 28, 2021.
Claims priority of provisional application 63/013,862, filed on Apr. 22, 2020.
Prior Publication US 2023/0234925 A1, Jul. 27, 2023
Int. Cl. C07D 213/56 (2006.01); C07D 213/68 (2006.01); C07D 213/69 (2006.01); C07D 213/84 (2006.01); C07D 239/26 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01)
CPC C07D 213/56 (2013.01) [C07D 213/68 (2013.01); C07D 213/69 (2013.01); C07D 213/84 (2013.01); C07D 239/26 (2013.01); C07D 401/12 (2013.01); C07D 405/12 (2013.01)] 21 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
X, Y1 and Y2 are independently N (nitrogen) or CH;
Z is N or CR1, where at least one of Z, X, Y1 and Y2 is N (nitrogen);
Z1 is

OG Complex Work Unit Chemistry
Z2 is

OG Complex Work Unit Chemistry
Q1 is N (nitrogen) or CR4;
Q2 is N (nitrogen) or CR5;
R1 is hydrogen, halogen, C1-C6alkyl or haloC1-C6alkyl;
R2 is hydrogen, halogen, C1-C6alkyl, haloC1-C6alkyl, or —ORA;
R3 is hydrogen, halogen, C1-C6alkyl, or haloC1-C6alkyl;
i) R4, R5, R6, and R7, are independently hydrogen, halogen, —(CH2)n—CN, nitro, haloC1-C6alkyl, C3-C8cycloalkyl, —NHC(═O)RB, —ORB, —S(O)mRB, —(CH2)mC(═O)RB, —S(O)pN(RBRC), or C1-C6alkyl optionally substituted with hydroxyl; or
ii) R4 and R5, together with the carbon atoms to which they are attached, form a 6 membered aryl group, a 5-6 membered heteroaryl group optionally substituted with C1-C6alkyl, a 5-6 membered cycloalkyl group optionally substituted with ═O, or a 5-6 membered heterocyclyl group, and R6 and R7 are independently hydrogen, halogen, —(CH2)n—CN, nitro, C1-C6alkyl optionally substituted with hydroxyl, haloC1-C6alkyl, C3-C8cycloalkyl, —NHC(═O)RB, —ORB, —S(O)mRB, —(CH2)mC(═O)RB or —S(O)pN(RBRC); or
iii) R5 and R6, together with the carbon atoms to which they are attached, form a 6 membered aryl group, a 5-6 membered heteroaryl group optionally substituted with C1-C6alkyl, a 5-6 membered cycloalkyl group optionally substituted with ═O, or a 5-6 membered heterocyclyl group, and R4 and R7, are independently hydrogen, halogen, —(CH2)n—CN, nitro, C1-C6alkyl optionally substituted with hydroxyl, haloC1-C6alkyl, C3-C8cycloalkyl, —NHC(═O)RB, —ORB, —S(O)mRB, —(CH2)mC(═O)RB or —S(O)pN(RBRC); or
iv) R6 and R7, together with the carbon atoms to which they are attached, form a 6 membered aryl group, a 5-6 membered heteroaryl group optionally substituted with C1-C6alkyl, a 5-6 membered cycloalkyl group optionally substituted with ═O, or a 5-6 membered heterocyclyl group, and R4 and R5, are independently hydrogen, halogen, —(CH2)n—CN, nitro, C1-C6alkyl optionally substituted with hydroxyl, haloC1-C6alkyl, C3-C8cycloalkyl, —NHC(═O)RB, —ORB, —S(O)mRB, —(CH2)mC(═O)RB or —S(O)pN(RBRC);
one of R8 and R9 is —(CH2)nC(═O)N(RERF) and the other of R8 and R9 is hydrogen, halogen, C1-C6alkyl, haloC1-C6alkyl, —C(═O)RD, or —ORE; or
R8 and R9 together with the carbon atom to which they are attached, form a 5-6 membered heterocyclyl group, said 5-6 membered heterocyclyl group optionally substituted with ═O, with the proviso that the heterocyclic group formed is not a 1,3-dioxolanyl ring when Y1 and Z are each N and X and Y2 are each CH;
R10 is hydrogen, halogen, C1-C6alkyl, haloC1-C6alkyl, —C(═O)RD, or —ORE;
each RA, RB, RC, is independently hydrogen, C1-C6alkyl, or haloC1-C6alkyl;
each RD is independently hydrogen, C1-C6alkyl, haloC1-C6alkyl, —NH2, or —NH(CH2)qOH;
each RE, and RF, is independently hydrogen, C1-C6alkyl, or haloC1-C6alkyl; or
RE and RF, together with the nitrogen atom to which they are attached, form a 5-6 membered heterocyclyl group;
each m is independently 0, 1, 2 or 3;
each n is independently 0, 1, 2 or 3;
each p is independently 1 or 2; and
each q is independently 2, 3 or 4.