US 2015/0087635 A1Published application

Substituted pyridyl amide compounds as modulators of the histamine h3 receptor

AssigneeJanssen Pharmaceutica NV

InventorsJohn M. Keith, Michael A. Letavic, Kiev S. Ly, Neelakandha S. Mani, John E. Mills, Chennagiri R. Pandit, Frank J. Villani, Hua Zhong

Life of this patent

Estimating the term…

Abstract

Certain substituted pyridyl amide compounds are histamine H3 receptor modulators useful in the treatment of histamine H3 receptor-mediated diseases.

Claims32

Dependent claims

A compound of Formula (I):

wherein
R1 is —C1-4alkyl or saturated monocyclic cycloalkyl;
m is 1 or 2;
X is N or CH;
Y is N or CRa;
Ra is —H, —Z—Ar, —CH2NRbRc, —CN, —CO2C1-4alkyl, —CO2H, or —CONRbRc;
where Rb and Rc are each independently —H or —C1-4alkyl;
and
R2 is —H or —Z—Ar;
with the proviso that one of X and Y is N and one of Ra and R2 is —Z—Ar;
where Z is O or S;
and
Ar is a phenyl or monocyclic heteroaryl group unsubstituted or substituted with one, two, or three R3 substituents;
where each R3 substituent is independently selected from the group consisting of:
halo, —C1-4alkyl, —OH, —OC1-4alkyl, —SC1-4alkyl, —CN, —CONRdRe, and —NO2;
where Rd and Re are each independently —H or —C1-4alkyl;
or a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutically active metabolite thereof.

14 more elements

A compound selected from the group consisting of:

[6-(3,4-Dichloro-phenoxy)-pyridin-3-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
(4-Isopropyl-piperazin-1-yl)-[6-(pyridin-3-yloxy)-pyridin-3-yl]-methanone;
(4-Isopropyl-piperazin-1-yl)-[6-(4-methylsulfanyl-phenoxy)-pyridin-3-yl]-methanone;
[6-(3-Chloro-phenoxy)-pyridin-3-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
(4-Isopropyl-piperazin-1-yl)-(6-phenoxy-pyridin-3-yl)-methanone;
[6-(4-Chloro-3-methyl-phenoxy)-pyridin-3-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
3-[5-(4-Isopropyl-piperazine-1-carbonyl)-pyridin-2-yloxy]-benzonitrile;
[6-(4-Chloro-phenoxy)-pyridin-3-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(3,4-dichloro-phenoxy)-pyridin-3-yl]-methanone;
[6-(4-Chloro-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-[1,4]diazepan-1-yl)-methanone;
3-[5-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-pyridin-2-yloxy]-benzonitrile;
[6-(4-Chloro-3-methyl-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-(6-phenoxy-pyridin-3-yl)-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(3,4-dichloro-phenoxy)-pyridin-3-yl]-methanone;
[6-(3,4-Dichloro-phenoxy)-pyridin-3-yl]-(4-isopropyl-[1,4]diazepan-1-yl)-methanone;
[6-(4-Chloro-3-methyl-phenoxy)-pyridin-3-yl]-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone;
[6-(4-Chloro-3-methyl-phenoxy)-pyridin-3-yl]-(4-isopropyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone;
3-[5-(4-Cyclobutyl-[1,4]diazepane-1-carbonyl)-pyridin-2-yloxy]-benzonitrile;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-(6-phenoxy-pyridin-3-yl)-methanone;
(4-Cyclopropyl-piperazin-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone;
[6-(3-Chloro-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-[1,4]diazepan-1-yl)-methanone;
[6-(3-Chloro-phenoxy)-pyridin-3-yl]-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone;
[6-(4-Chloro-phenoxy)-pyridin-3-yl]-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(3,4-difluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(3,4-difluoro-phenoxy)-pyridin-3-yl]-methanone;
[6-(3,4-Difluoro-phenoxy)-pyridin-3-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(2-fluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(2,4-difluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(2-fluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(2,4-difluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(3,5-dichloro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(2,5-difluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(3,5-dichloro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(3,5-difluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(3-fluoro-phenoxy)-pyridin-3-yl]-methanone;
[6-(3-Fluoro-phenoxy)-pyridin-3-yl]-(4-isopropyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(3-fluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(3-methyl-4-methylsulfanyl-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(3-methyl-4-methylsulfanyl-phenoxy)-pyridin-3-yl]-methanone;
(4-Isopropyl-[1,4]diazepan-1-yl)-[6-(3-methyl-4-methylsulfanyl-phenoxy)-pyridin-3-yl]-methanone;
[6-(3,4-Dichloro-phenoxy)-pyridin-2-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[6-(3,4-dichloro-phenoxy)-pyridin-2-yl]-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(3,4-dichloro-phenoxy)-pyridin-2-yl]-methanone;
[6-(3,4-Dichloro-phenoxy)-pyridin-2-yl]-(4-isopropyl-[1,4]diazepan-1-yl)-methanone;
[6-(4-Chloro-3-methyl-phenoxy)-pyridin-2-yl]-(4-cyclopropyl-[1,4]diazepan-1-yl)-methanone;
[6-(4-Chloro-3-methyl-phenoxy)-pyridin-2-yl]-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone;
[6-(4-Chloro-3-methyl-phenoxy)-pyridin-2-yl]-(4-isopropyl-[1,4]diazepan-1-yl)-methanone;
[5-(3,4-Dichloro-phenoxy)-pyridin-2-yl]-(4-isopropyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[5-(3,4-dichloro-phenoxy)-pyridin-2-yl]-methanone;
(4-Cyclopropyl-[1,4]diazepan-1-yl)-[5-(3,4-dichloro-phenoxy)-pyridin-2-yl]-methanone;
3-(3,4-Dichloro-phenoxy)-6-(4-isopropyl-piperazine-1-carbonyl)-pyridine-2-carbonitrile;
3-(3,4-Dichloro-phenoxy)-6-(4-isopropyl-piperazine-1-carbonyl)-pyridine-2-carboxylic acid amide;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(4-methylsulfanyl-phenoxy)-pyridine-2-carbonitrile;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(pyridin-3-yloxy)-pyridine-2-carbonitrile;
3-(4-Chloro-3-methyl-phenoxy)-6-(4-cyclopropyl-[1,4]diazepane-1-carbonyl)-pyridine-2-carbonitrile;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(3,4-dichloro-phenoxy)-pyridine-2-carbonitrile;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(4-fluoro-phenoxy)-pyridine-2-carbonitrile;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(3-fluoro-phenoxy)-pyridine-2-carbonitrile;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(2-fluoro-phenoxy)-pyridine-2-carbonitrile;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(4-methylsulfanyl-phenoxy)-pyridine-2-carboxylic acid amide;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-(pyridin-3-yloxy)-pyridine-2-carboxylic acid amide;
[6-Aminomethyl-5-(3,4-dichloro-phenoxy)-pyridin-2-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
(4-Cyclopentyl-[1,4]diazepan-1-yl)-(6-phenoxy-pyridin-3-yl)-methanone;
(4-Cyclopentyl-[1,4]diazepan-1-yl)-[6-(3,4-dichloro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclopentyl-[1,4]diazepan-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone;
[5-(4-Chloro-phenoxy)-pyridin-2-yl]-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[5-(4-fluoro-phenoxy)-pyridin-2-yl]-methanone;
[5-(3-Chloro-phenoxy)-pyridin-2-yl]-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[5-(3-fluoro-phenoxy)-pyridin-2-yl]-methanone;
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[5-(2-fluoro-phenoxy)-pyridin-2-yl]-methanone;
[6-(2-Chloro-phenoxy)-pyridin-3-yl]-(4-cyclobutyl-[1,4]diazepan-1-yl)-methanone;
(4-Cyclopentyl-piperazin-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone;
[6-(2-Chloro-phenoxy)-pyridin-3-yl]-(4-isopropyl-piperazin-1-yl)-methanone;
[6-(2-Chloro-phenoxy)-pyridin-3-yl]-(4-cyclopentyl-piperazin-1-yl)-methanone;
[6-(4-Chloro-phenoxy)-pyridin-3-yl]-(4-cyclopentyl-piperazin-1-yl)-methanone;
(4-Cyclopentyl-piperazin-1-yl)-[6-(2-fluoro-phenoxy)-pyridin-3-yl]-methanone;
(4-Cyclobutyl-piperazin-1-yl)-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone;
[1,4]Diazepan-1-yl-[6-(4-fluoro-phenoxy)-pyridin-3-yl]-methanone;
[6-(4-Fluoro-phenoxy)-pyridin-3-yl]-(4-methyl-[1,4]diazepan-1-yl)-methanone;
6-(4-Cyclopropyl-[1,4]diazepane-1-carbonyl)-3-phenoxy-pyridine-2-carbonitrile;
6-(4-Cyclobutyl-[1,4]diazepane-1-carbonyl)-3-(4-fluoro-phenoxy)-pyridine-2-carbonitrile;
and
(4-Cyclobutyl-[1,4]diazepan-1-yl)-[6-(4-fluoro-phenylsulfanyl)-pyridin-3-yl]-methanone;
and pharmaceutically acceptable salts thereof.

83 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/561,156Filed 4 Dec 2014
Priority: 30 May 2006
Published: 26 Mar 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification23 codes

C07D 213/82
Amides; Imides: in position 3
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 11/00
Drugs for disorders of the respiratory system
A61P 15/00
Drugs for genital or sexual disorders

Family

Application60/803,407Us provisional application · filed 30 May 2006
Application60/823,108Us provisional application · filed 22 Aug 2006
Application11/753,607Continuation · filed 25 May 2007
Application12/828,883Continuation · filed 1 Jul 2010
Application14/132,354Continuation · filed 18 Dec 2013
Application14/561,156Continuation
US 2007/0281923 A1Published application
US 2010/0267701 A1Published application
US 2014/0107105 A1Published application
US 7,777,031 B2Related patent
US 8,637,520 B2Related patent
US 8,940,731 B2Related patent
US 9,321,729 B2Related patent
US 2015/0087635 A1This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Back to results