Fused heterocyclic compounds as ion channel modulators

Patent metadata

Field	Value
Publication number	US-9695192-B2
Application number	US-201514630519-A
Country	US
Kind code	B2
Filing date	Feb 24, 2015
Priority date	Jul 1, 2011
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

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 Y, Z, n, R 1 and R 3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

First claim

What is claimed is:

1. A compound selected from the group consisting of:

I-1
10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]imidazo[1,2-

d][1,4]oxazepine

I-2
10-(4-(trifluoromethoxy)phenyl)-5,6-dihydrobenzo[f]imidazo[1,2-

d][1,4]oxazepine

I-3
10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f][1,2,4]triazolo-

[4,3-d][1,4]oxazepine

I-4
3-methyl-10-(4-(trifluoromethyl)phenyl)-5,6-

dihydrobenzo[f][1,2,4]triazolo[4,3-d][1,4]oxazepine

I-5
3-cyclopropyl-10-(4-(trifluoromethyl)phenyl)-5,6-

dihydrobenzo[f][1,2,4]triazolo[4,3-d][1,4]oxazepine

I-6
3-methyl-10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]-

imidazo[1,2-d][1,4]oxazepine

I-7
3-(pyrimidin-2-yl)-10-(4-(trifluoromethyl)phenyl)-5,6-

dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

I-8
11-(4-(trifluoromethyl)phenyl)-3,4,6,7-tetrahydro-2H-benzo[f]-

pyrimido[1,2-d][1,4]oxazepine

I-9
3-cyclopropyl-10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo-

[f]imidazo[1,2-d][1,4]oxazepine

I-10
2-(10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo-

[f]imidazo[1,2-d][1,4]oxazepin-3-yl)propan-2-ol

I-11
3-benzyl-10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]-

imidazo[1,2-d][1,4]oxazepine

I-12
3-bromo-10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]-

imidazo[1,2-d][1,4]oxazepine

I-13
3-chloro-10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]-

imidazo[1,2-d][1,4]oxazepine

I-14
2-chloro-3-methyl-10-(4-(trifluoromethyl)phenyl)-5,6-

dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

I-15
1-(10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo-

[f]imidazo[1,2-d][1,4]oxazepin-3-yl)ethanone

I-16
10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]imidazo[1,2-

d][1,4]oxazepine-3-carbonitrile

I-17
3-methyl-10-(4-(trifluoromethoxy)phenyl)-5,6-dihydrobenzo[f]-

imidazo[1,2-d][1,4]oxazepine

I-18
3-cyclopropyl-10-(4-(trifluoromethoxy)phenyl)-5,6-

dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

I-19
2-methyl-10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]-

imidazo[1,2-d][1,4]oxazepine

I-20
2-cyclopropyl-10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo-

[f]imidazo[1,2-d][1,4]oxazepine

I-21
ethyl 10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo-

[f]imidazo[1,2-d][1,4]oxazepine-2-carboxylate

I-22
10-(4-(trifluoromethyl)phenyl)-5,6-dihydrobenzo[f]imidazo[1,2-

d][1,4]oxazepine-2-carboxylic acid

I-23
2-(1-methyl-1H-imidazol-5-yl)-10-(4-(trifluoromethyl)phenyl)-

5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

II-1
5-morpholino-7-(4-(trifluoromethyl)phenyl)-2,3-dihydrobenzo-

[f][1,4]oxazepine

II-2
N-benzyl-7-(4-(trifluoromethyl)phenyl)-2,3-dihydrobenzo-

[f][1,4]oxazepin-5-amine

II-3
5-(pyrrolidin-1-yl)-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepine

II-4
N-cyclopropyl-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepin-5-amine

II-5
N-benzyl-N-methyl-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepin-5-amine

II-6
5-(3,3-difluoropyrrolidin-1-yl)-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepine

II-7
N-(pyrimidin-2-ylmethyl)-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepin-5-amine

II-8
N-cyclopropyl-N-methyl-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepin-5-amine

II-9
N-((3-fluoropyridin-2-yl)methyl)-7-(4-(trifluoromethyl)phenyl)-

2,3-dihydrobenzo[f][1,4]oxazepin-5-amine

II-10
N-(pyridin-2-ylmethyl)-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepin-5-amine

II-11
N-(cyclopropylmethyl)-7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepin-5-amine

II-12
tert-butyl 1-(7-(4-(trifluoromethyl)phenyl)-2,3-dihydrobenzo-

[f][1,4]oxazepin-5-yl)azetidin-3-ylcarbamate

II-13
(S)-tert-butyl 1-(7-(4-(trifluoromethyl)phenyl)-2,3-

dihydrobenzo[f][1,4]oxazepin-5-yl)pyrrolidin-3-ylcarbama

Assignees

• Gilead Sciences Inc

Inventors

• Corkey Britton Kenneth
• Elzein Elfatih
• Jiang Robert H
• Kalla Rao V
• Koltun Dmitry
• Li Xiaofen
• Martinez Ruben
• Parkhill Eric Q
• Perry Thao
• Zablocki Jeff
• Venkataramani Chandrasekar
• Graupe Michael
• Guerrero Juan

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title