US 12,448,384 B2
Diacylglyceride O-acyltransferase 2 inhibitors
Yeon-Hee Lim, South San Francisco, CA (US); Jianming Bao, Princeton, NJ (US); Fa-Xiang Ding, Staten Island, NY (US); Cedric Lorenz Hugelshofer, Oakland, CA (US); Victor W. Mak, South San Francisco, CA (US); James Patrick Roane, Brisbane, CA (US); Jillian R. Sanzone, San Francisco, CA (US); Samantha E. Shockley, San Francisco, CA (US); and Rose Yen, San Francisco, CA (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
Filed on Sep. 12, 2023, as Appl. No. 18/465,497.
Application 18/465,497 is a continuation of application No. 17/319,121, filed on May 13, 2021, granted, now 11,787,810.
Claims priority of provisional application 63/026,263, filed on May 18, 2020.
Prior Publication US 2024/0059700 A1, Feb. 22, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); C07D 231/56 (2006.01); C07D 409/12 (2006.01); C07D 409/14 (2006.01); C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 231/56 (2013.01); C07D 409/12 (2013.01); C07D 409/14 (2013.01); C07D 471/04 (2013.01)] 29 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof wherein:
W is selected from N or C(H);
X is N
Y and Z are independently selected from N or C(R5); and
R1 is
(1) phenyl unsubstituted or substituted with 1, 2, or 3 R6, or
(2) 5- or 6-membered heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted with 1, 2, or 3 R6, or
(3) 8- to 10-membered fused heteroaryl containing 1, 2, 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted with 1, 2, or 3 R6;
R2 is
(1) phenyl optionally mono-substituted or disubstituted with halogen,
(2) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is optionally mono-substituted or disubstituted with halogen, C1-6haloalkyl, C1-6alkyl, C(O)C1-6alkyl, C(O)(OH), or OH,
(3) C1-6alkyl unsubstituted or optionally mono-substituted, disubstituted or trisubstituted with halogen, OH, CF3, —CN, or (C3-6)cycloalkyl,
(4) (C3-6)cycloalkyl unsubstituted or optionally mono-substituted, disubstituted or trisubstituted with C1-6alkyl, halogen, OH, CF3, or —CN,
(5) 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S wherein the heterocyclyl is unsubstituted or substituted by 1, 2, or 3 R7,
(6) —CH2-aryl optionally mono-substituted or disubstituted with halogen,
(7) —CH2-tetrahydropyran, or
(8) —C1-6alkylC(O)NH2;
R3 is
(1) 4- to 7-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S,
(2) —(C1-6)alkyl-heterocyclyl, wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
(3) —(C1-6)alkyl,
(4) —(C3-6)cycloalkyl,
(5) —(C3-6)cycloalkyl-heterocyclyl wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
(6) —(C1-6)hydroxyalkyl,
(7) —(C1-6)cyanoalkyl,
(8) —(C1-6)alkyl-S(O)2—(C1-3)alkyl,
(9) —(C1-6)alkyl-(C3-6)cycloalkyl, or
(10) —C(1-6)alkyl-N(R11)2,
wherein each cycloalkyl or heterocyclyl is unsubstituted or substituted with 1, 2, 3 or 4 R9, and
wherein each alkyl is unsubstituted or substituted with 1, 2, or 3 R10;
R4 is
(1) hydrogen, or
(2) (C1-3)alkyl,
or R3 and R4, together with the nitrogen atom to which they are attached, combine to form a mono- or bicyclic heterocyclyl ring containing 1 N and optionally containing 1 additional heteroatom independently selected from N, O and S, wherein the heterocyclyl ring is unsubstituted or substituted by 1, 2, or 3 R11;
when present, each R5 is selected from
(1) hydrogen,
(2) (C1-3)alkyl,
(3) cyano, or
(4) halogen,
when present, each R6 is independently selected from
(1) cyano,
(2) halogen,
(3) (C1-6)alkyl or OC1-6alkyl wherein the alkyl moiety is optionally substituted with cyano,
(4) (C3-6)cycloalkyl, optionally substituted with halogen, C1-6alkyl, C1-6haloalkyl, cyano, OH or OC1-6alkyl,
(5) —C(O)NH2,
(6) O(C3-6)cycloalkyl wherein the cycloalkyl is optionally substituted with halogen, C1-6alkyl, C1-6haloalkyl, cyano, OH, or OC1-6alkyl,
(7) hydroxy,
(8) —N(R11)2,
(9) (C1-6)haloalkyl-,
(10) OC1-6haloalkyl,
(11) —SO2(C1-6)alkyl, or
(12) —SONH(C1-6)alkyl;
when present, each R7 is independently selected from
(1) (C1-6)alkyl,
(2) halo,
(3) (C1-6)alkoxy-,
(4) (C1-6)haloalkyl-,
(5) (C3-6)cycloalkyl,
(6) hydroxy, or
(7) C(O)C1-6alkyl;
when present, each R9 is independently selected from
(1) (C1-6)alkyl,
(2) (C1-3)haloalkyl-,
(3) oxo,
(4) (C3-6)cycloalkyl,
(5) —N(R11)2
(6) hydroxy,
(7) C1-6alkyl(OH),
(8) cyano,
(9) halo, or
(10) morpholinyl;
when present, R10 is
(1) (C1-3)alkyl,
(2) (C1-3) hydroxy alkyl-,
(3) (C1-3)alkoxy-,
(4) hydroxy,
(5) halogen,
(6) (C1-3)haloalkyl-,
(7) N(R11)2, or
(8) C(O)NH2; and
when present, R11 is independently
(1) hydrogen,
(2) (C1-3)alkyl, or
(3) C(O)C1-6alkyl.