IP Library Granted Patent US 10,822,335
Granted Patent B2
US 10,822,335 · App. 16/371,896 · Granted Nov 3, 2020

N1-pyrazolospiroketone acetyl-CoA carboxylase inhibitors

Inventors: Mary Theresa Didiuk (Madison, CT); Robert Lee Dow (Quincy, MA); David Andrew Griffith (Sudbury, MA)
Assignee: Pfizer Inc.
C07D471/10A61K31/435A61K31/438A61K31/519A61K45/06C07D487/10C07D491/20C07D519/00
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Quick Facts
Patent No.
US 10,822,335
App. No.
16/371,896
Granted
Nov 3, 2020
Kind
B2
Abstract

The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of the compound, wherein R 1 , R 2 , R 3 , Z, A 1 , L and A 2 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.

Claims (14)

1. A method for treating nonalcoholic fatty liver disease (NAFLD) in a human comprising the step of administering to the human in need of such treatment a therapeutically effective amount of a compound of Formula (I)

or a pharmaceutically acceptable salt thereof; wherein

R 1 is (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, tetrahydrofuranyl or oxetanyl; wherein said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from (C 1 -C 3 )alkoxy, hydroxy, fluoro, phenyl, tetrahydrofuranyl or oxetanyl;

R 2 is hydrogen, halo, (C 1 -C 3 )alkyl, or cyano;

R 3 are each independently hydrogen or (C 1 -C 3 )alkyl;

L is a direct bond or a (C 1 -C 6 )alkylene wherein one carbon of the (C 1 -C 6 )alkylene is optionally replaced by —C(O)—, —C(O)NH—, —NHC(O)—, —O—, —S—, NH or N(C 1 -C 3 )alkyl;

Z is CH 2 or O;

A 1 and A 2 are each independently (C 6 -C 10 )aryl, 5 to 12 membered heteroaryl or 8 to 12 membered fused heterocyclicaryl; wherein said (C 6 -C 10 )aryl, 5 to 12 membered heteroaryl or 8 to 12 membered fused heterocyclicaryl are each optionally substituted with one to three substituents independently selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo, amino, (C 1 -C 3 )alkylamino, di(C 1 -C 3 )alkylamino, hydroxy, cyano and amido wherein the alkyl portion of the (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkylamino and di(C 1 -C 3 )alkylamino are optionally substituted with one to five fluoro; and wherein one of A 1 or A 2 is substituted by CO 2 R 4 , (C 1 -C 6 )CO 2 R 4 ; and

R 4 is H.

2. The method of claim 1 wherein R 1 is isopropyl or t-butyl; R 2 is hydrogen; each R 3 is hydrogen; A 1 is phenyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyrimidinyl, indolyl, benzopyrazinyl, benzoimidazolyl, benzoimidazolonyl, pyrrolopyridinyl, pyrrolopyrimidinyl, pyrazolopyridinyl, pyrazolopyrimidinyl, indazolyl, indolinonyl, naphthyridinyl, quinolinyl, quinolinonyl, dihydroquinolinonyl, oxo-dihydroquinolinonyl, isoquinolinyl, isoquinolinonyl, dihydroisoquinonyl or oxo-dihydroisoquinonyl, wherein A 1 is optionally substituted with one to three substituents independently selected from fluoro, chloro, methyl, methoxy, amino, methylamino, dimethylamino, amido or cyano; and L is a direct bond or O; or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 wherein R 1 is isopropyl or t-butyl; R 2 is hydrogen; each R 3 is hydrogen; A 1 is phenyl, pyridinyl, indazolyl, indolyl, benzoimidazolyl, pyrrolopyridinyl or pyrrolopyrimidinyl, wherein A 1 is optionally substituted with one methyl, methoxy, methylamino or dimethylamino; and L is a direct bond or O; or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 wherein R 1 is isopropyl or t-butyl; R 2 is hydrogen; each R 3 is hydrogen; A 1 is phenyl, pyridinyl, indazolyl, indolyl, benzoimidazolyl, pyrrolopyridinyl or pyrrolopyrimidinyl, wherein A1 is optionally substituted with one methyl, methoxy, methylamino or dimethylamino; L is a direct bond, and A 2 is phenyl substituted with CO 2 H; or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 wherein R 1 is isopropyl or t-butyl; R 2 is hydrogen; each R 3 is hydrogen; A 1 is pyridinyl optionally substituted with methylamino or dimethylamino; L is a direct bond, and A 2 is phenyl substituted with CO 2 H; or a pharmaceutically acceptable salt thereof.

6. A method for treating nonalcoholic fatty liver disease (NAFLD) in a human comprising the step of administering to the human in need of such treatment a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, diluent, or carrier.

Assignments (1)
ASSIGNEE ADDRESS CORRECTION Recorded Mar 20, 2023
From: PFIZER INC.
To: PFIZER INC.
Reel/Frame 063119/0087 →