US 10,947,222 B2Granted

Indole derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2

AssigneeMerck Sharp & Dohme Corp.

InventorsDong-Ming Shen, Thomas H. Graham, Jinlong Jiang, Fa-Xiang Ding, Clare Tudge

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Abstract

The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, nonalcoholic steatohepatitis (NASH), cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.

Claims13

Dependent claims

A compound having structural Formula I:

or a pharmaceutically acceptable salt thereof wherein:
R1 is
(1) aryl unsubstituted or substituted by 1-3 R5, or
(2) 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted by 1-3 R5, or
(3) 8- to 10-membered fused heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted by 1-3 R5;
R2 is
R3 is
(1) —(C1-6)alkyl-O—(C1-3)alkyl,
(2) 4- to 7-membered monocyclic or 6- to 10-membered bicyclic heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O, and S, wherein the heterocyclyl is unsubstituted or substituted by 1-3 R7,
(3) —(C1-6)alkyl-heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O, and S, and wherein the heterocyclyl is a 5- to 7-membered ring, or
(4) —(C1-6)alkyl-pyridinyl, wherein the pyridinyl is unsubstituted or substituted with (C1-3)alkyl or halo(C1-3)alkyl, and wherein the alkyl is unsubstituted or substituted with a hydroxy;
R4 is
(1) hydrogen,
(2) (C1-3)alkyl, or
(3) CN;
each R5 is
(1) halo,
(2) (C1-3)alkyl,
(3) halo(C1-3)alkyl,
(4) (C3-6)cycloalkyl,
(5) —C(O)NH2,
(6) —C(O)O(C1-3)alkyl,
(7) (C1-3)alkoxy,
(8) halo(C1-3)alkoxy,
(9) hydroxy,
(10) phenyl,
(11) —NHC(O)CH3,
(12) 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted by 1-2 (C1-3)alkyl, or hydroxy,
(13) CN,
(14) hydroxy(C1-3)alkyl, or
(15) (C1-3)alkyl-heterocyclyl, wherein the heterocyclyl contains 1 or 2 heteroatoms independently selected from N, O, or S, and wherein the heterocyclyl is a 5- to 7-membered ring;
each R6 is
(1) hydrogen, or
(2) halo;
each R7 is
(1) oxo, or
(2) (C1-3)alkyl;
X is CH or N;
Y is CH or N;
n is 1 or 2.

37 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/461,880Filed 13 Nov 2017 · us provisional application
Priority: 18 Nov 2016
Published: US 2019/0276443 A112 Sep 2019
Granted: 16 Mar 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07D 409/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61K 31/404
Condensed with carbocyclic rings, e.g. carbazole: indoles, e.g. pindolol
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings