US 2015/0175595 A1Published application

Fused heterocyclic compounds as ion channel modulators

AssigneeGilead Sciences, Inc.

InventorsRao Kalla, Thao Perry, Jeff Zablocki

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Abstract

The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein n, R1, R2, R2′, R3, R4, R5, R6 and R7 are as described herein, and to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Claims39

Dependent claims

A compound of Formula I:

wherein
R1 is a 5 or 6 membered aryl, heteroaryl or heterocyclic group wherein each heteroaryl or heterocyclic group contains from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur;
and wherein the aryl, heteroaryl or heterocyclic group is optionally substituted with 1 or 2 groups independently selected from the group consisting of —C1-C6 alkyl, —C3-C6 cycloalkyl, C1-C6 alkylC3-C6 cycloalkyl, halogen, —C1-C6 haloalkyl, —OC1-C6 alkyl, —OC1-C6 haloalkyl, and —C(O)C1-C6 alkyl;
R2 and R2′ are at each occurrence independently H or —C1-C6 alkyl;
or one set of R2 and R2′ combine with the carbon atom to which they are both attached to form a C3-C6 cycloalkyl group;
R3 is H, —C1-C6 alkyl or C3-C6 cycloalkyl,
R4 is H, —C1-C6 alkyl, —OC1-C6 alkyl, —OC1-C6haloalkyl, —C3-C6 cycloalkyl, or halo;
R5 is a 5 or 6 membered aryl, heteroaryl or heterocyclic group optionally substituted with one, two or three groups independently selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkylC3-C6 cycloalkyl, —C1-C6haloalkyl, —OC1-C6 alkyl, —OC1-C6haloalkyl, —O-aryl, and halo;
wherein the cycloalkyl group is optionally substituted with —C1-C6 alkyl or —C1-C6 haloalkyl;
and
wherein the substituent —O-aryl group is optionally substituted with —C1-C6 alkyl, halo, C1-C6 haloalkyl, —OC1-C6 alkyl, or —OC1-C6 haloalkyl;
and wherein two substituents on the aryl, heteroaryl, or heterocyclic ring of R5 optionally combine to form a 8-12 membered bicyclic ring optionally containing one or two oxygen atoms;
and wherein the bicyclic ring is optionally substituted with 1 or 2 groups independently selected from the group consisting of —C1-C6 alkyl, —C1-C6 haloalkyl, —OC1-C6 alkyl, —OC1-C6 haloalkyl, —C3-C6 cycloalkyl, and halo;
R6 is H, —C1-C6 alkyl, —C1-C6haloalkyl, —OC1-C6 alkyl, —OC1-C6haloalkyl, or halo;
or R6 combines with the aryl, heteroaryl or heterocyclic ring of R5 to form a tetracyclic ring optionally substituted with 1 or 2 groups independently selected from C1-C6 alkyl, —C1-C6 haloalkyl, —OC1-C6 alkyl, —OC1-C6 haloalkyl, —C3-C6 cycloalkyl, and halo;
R7 is H, —C1-C6 alkyl, —C1-C6 haloalkyl, —OC1-C6 alkyl, —C1-C6 haloalkyl, or halo;
n=1-4;
or a pharmaceutically acceptable salt thereof.

15 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/573,854Filed 17 Dec 2014
Priority: 19 Dec 2013
Published: 25 Jun 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07D 417/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/04
Drugs for disorders of the cardiovascular system: inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Family

Application61/918,247Us provisional application · filed 19 Dec 2013
US 9,416,128 B2Related patent
US 2015/0175595 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula I:

wherein
R1 is a 5 or 6 membered aryl, heteroaryl or heterocyclic group wherein each heteroaryl or heterocyclic group contains from 1 to 3 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur;
and wherein the aryl, heteroaryl or heterocyclic group is optionally substituted with 1 or 2 groups independently selected from the group consisting of —C1-C6 alkyl, —C3-C6 cycloalkyl, C1-C6 alkylC3-C6 cycloalkyl, halogen, —C1-C6 haloalkyl, —OC1-C6 alkyl, —OC1-C6 haloalkyl, and —C(O)C1-C6 alkyl;
R2 and R2′ are at each occurrence independently H or —C1-C6 alkyl;
or one set of R2 and R2′ combine with the carbon atom to which they are both attached to form a C3-C6 cycloalkyl group;
R3 is H, —C1-C6 alkyl or C3-C6 cycloalkyl,
R4 is H, —C1-C6 alkyl, —OC1-C6 alkyl, —OC1-C6haloalkyl, —C3-C6 cycloalkyl, or halo;
R5 is a 5 or 6 membered aryl, heteroaryl or heterocyclic group optionally substituted with one, two or three groups independently selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 alkylC3-C6 cycloalkyl, —C1-C6haloalkyl, —OC1-C6 alkyl, —OC1-C6haloalkyl, —O-aryl, and halo;
wherein the cycloalkyl group is optionally substituted with —C1-C6 alkyl or —C1-C6 haloalkyl;
and
wherein the substituent —O-aryl group is optionally substituted with —C1-C6 alkyl, halo, C1-C6 haloalkyl, —OC1-C6 alkyl, or —OC1-C6 haloalkyl;
and wherein two substituents on the aryl, heteroaryl, or heterocyclic ring of R5 optionally combine to form a 8-12 membered bicyclic ring optionally containing one or two oxygen atoms;
and wherein the bicyclic ring is optionally substituted with 1 or 2 groups independently selected from the group consisting of —C1-C6 alkyl, —C1-C6 haloalkyl, —OC1-C6 alkyl, —OC1-C6 haloalkyl, —C3-C6 cycloalkyl, and halo;
R6 is H, —C1-C6 alkyl, —C1-C6haloalkyl, —OC1-C6 alkyl, —OC1-C6haloalkyl, or halo;
or R6 combines with the aryl, heteroaryl or heterocyclic ring of R5 to form a tetracyclic ring optionally substituted with 1 or 2 groups independently selected from C1-C6 alkyl, —C1-C6 haloalkyl, —OC1-C6 alkyl, —OC1-C6 haloalkyl, —C3-C6 cycloalkyl, and halo;
R7 is H, —C1-C6 alkyl, —C1-C6 haloalkyl, —OC1-C6 alkyl, —C1-C6 haloalkyl, or halo;
n=1-4;
or a pharmaceutically acceptable salt thereof.

15 more elements

Facts

Application

14/573,854Filed 17 Dec 2014

Priority

19 Dec 2013

Published

25 Jun 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification18 codes

C07D 417/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/04
Drugs for disorders of the cardiovascular system: inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure