US 2007/0167452 A1Published application

Therapeutic amide derivatives

AssigneePfizer Inc.

InventorsMakoto Kawai, Mitsuhiro Kawamura, Asato Morita, Isao Sakurada

Life of this patent

Estimating the term…

Abstract

The present invention relates to compounds of the formula (I): or a pharmaceutically acceptable salt or solvate thereof, to processes for the preparation of, intermediates used in the preparation of, compositions containing such compounds and the uses of such compounds as antagonists of the NMDA NR2B receptor.

Claims20

Dependent claims

A compound of the formula (I):

or a pharmaceutically acceptable salt or solvate thereof, wherein:
A and B independently represent CH2 or O, with the proviso that A and B are not simultaneously O;
Cy represents one of the following
optionally substituted by one to three groups selected from hydroxy, halogen, C1-6alkyl,
C1-6alkoxy, C1-6 haloalkyl, C1-6alkylamino and amino;
R1 and R2 are independently selected from hydroxy, halogen, C1-6alkyl, C1-6alkoxy,
C1-6haloalkyl and C3-8 cycloalkyl;
n represents an integer from 0-4;
X is hydrogen, hydroxy, halogen or C1-6 alkoxy;
Y is oxy, thio, a 1-4 membered alkylene, a 2-4 membered alkylene ether, 2-4 membered alkylene thioether or an oxyethyleneoxy group, optionally substituted by 1 to 4 groups independently selected from hydroxy, halogen, C1-6alkyl, C1-6alkoxy and C1-6haloalkyl;
Z is CH or N;
and
p represents an integer from 0-5 when Z is CH or 0-4 when Z is N, when p represents 2 or more, two of R2s may be taken together with the carbon atoms to which they are attached to form a 5-8 membered cycloalkyl ring.

10 more elements

A compound of formula (I) selected from the group consisting of:

4-Hydroxy-N-{[cis-4-(phenoxymethyl)cyclohexyl]methyl}benzamide;
4-Hydroxy-N-({cis-4-[(4-methoxyphenoxy)methyl]cyclohexyl}methyl)benzamide;
N-{[cis-4-(Benzyloxy)cyclohexyl]methyl}-4-hydroxybenzamide;
N-({cis-4-[(4-Chlorobenzyl)oxy]cyclohexyl}methyl)-4-hydroxybenzamide;
N-({cis-4-[(3-Chlorobenzyl)oxy]cyclohexyl}methyl)-4-hydroxybenzamide;
4-Hydroxy-N-{[cis-4-(4-methoxyphenoxy)cyclohexyl]methyl}benzamide;
N-{[cis-4-(4-Chlorophenoxy)cyclohexyl]methyl}-4-hydroxybenzamide;
4-Hydroxy-N-{[1-hydroxy-4-(phenoxymethyl)cyclohexyl]methyl}benzamide;
N-({trans-4-[(4-Fluorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[(3-Fluorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[(2-Fluorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[(2,6-Difluorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[(3,5-Difluorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[(3-Chlorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[(4-Chlorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
4-Hydroxy-N-({trans-1-hydroxy-4-[(2-methylphenoxy)methyl]cyclohexyl}methyl)benzamide;
4-Hydroxy-N-({trans-1-hydroxy-4-[(3-methylphenoxy)methyl]cyclohexyl}methyl)benzamide;
4-Hydroxy-N-({trans-1-hydroxy-4-[(4-methylphenoxy)methyl]cyclohexyl}methyl)benzamide;
N-({trans-4-[(Benzyloxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-[(trans-4-{[(2-Fluorobenzyl)oxy]methyl}-1-hydroxycyclohexyl)methyl]-4-hydroxybenzamide;
N-[(trans-4-{[(4-Fluorobenzyl)oxy]methyl}-1-hydroxycyclohexyl)methyl]-4-hydroxybenzamide;
4-Hydroxy-N-{[trans-1-hydroxy-4-(2-phenoxyethyl)cyclohexyl]methyl}benzamide;
N-({trans-4-[2-(2-Fluorophenoxy)ethyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[2-(3-Fluorophenoxy)ethyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-({trans-4-[2-(4-Fluorophenoxy)ethyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
N-{[trans-4-(Benzyloxy)-1-hydroxycyclohexyl]methyl}-4-hydroxybenzamide;
N-{[trans-4-(4-Chlorophenoxy)-1-hydroxycyclohexyl]methyl}-4-hydroxybenzamide;
N-{[cis-4-(4-Chlorophenoxy)-1-hydroxycyclohexyl]methyl}-4-hydroxybenzamide;
N-{[trans-4-(4-Chlorophenoxy)-1-hydroxycyclohexyl]methyl}-3-fluoro-4-hydroxybenzamide;
N-{[cis-4-(4-Chlorophenoxy)-1-hydroxycyclohexyl]methyl}-3-fluoro-4-hydroxybenzamide;
(+)-4-hydroxy-N-{[5S-(phenoxymethyl)tetrahydro-2H-pyran-2S-yl]methyl}benzamide;
(−)-4-hydroxy-N-{[5R-(phenoxymethyl)tetrahydro-2H-pyran-2R-yl]methyl}benzamide;
4-hydroxy-N-{[5S-(benzyloxymethyl)tetrahydro-2H-pyran-2S-yl]methyl}benzamide;
4-hydroxy-N-{[5R-(benzyloxymethyl)tetrahydro-2H-pyran-2R-yl]methyl}benzamide;
(−)-4-Hydroxy-N-{[(3R,6S)-6-(phenoxymethyl)tetrahydro-2H-pyran-3-yl]methyl}benzamide;
(+)-4-Hydroxy-N-{[(3S,6R)-6-(phenoxymethyl)tetrahydro-2H-pyran-3-yl]methyl}benzamide;
N-({trans-4-[(2-Fluorobenzyl)oxy]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
3-Fluoro-N-({trans-4-[2-(2-fluorophenoxy)ethyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
trans - N-{[4-(4-chlorophenoxy)cyclohexyl]methyl}-3-fluoro-4-hydroxybenzamide;
cis- N-{[4-(4-chlorophenoxy)cyclohexyl]methyl}-3-fiuoro-4-hydroxybenzamide;
N-{[cis-4-(4-Fluorophenoxy)cyclohexyl]methyl}-4-hydroxybenzamide;
3-Fluoro-N-{[cis-4-(4-fluorophenoxy)cyclohexyl]methyl}-4-hydroxybenzamide;
N-({trans-4-[2-(2-Fluorophenoxy)ethyl]-1-hydroxycyclohexyl}methyl)-1H-pyrazole-4-carboxamide;
4-hydroxy-N-{[cis-4-(2-phenylethoxy)cyclohexyl]methyl}benzamide;
2-fluoro-4-hydroxy-N-{[trans-1-hydroxy-4-(phenoxymethyl)cyclohexyl]methyl}benzamide;
N-({trans-4-[(benzyloxy)methyl]-1-hydroxycyclohexyl}methyl)-3-fluor6-4-hydoxybenzamide;
N-({cis-4-[(Benzyloxy)methyl]cyclohexyl}methyl)-4-hydroxybenzamide
3-Fluoro-4-hydroxy-N-{[trans-1-hydroxy-4-(phenoxymethyl)cyclohexyl]methyl}benzamide;
3-Fluoro-4-hydroxy-N-{[trans-1-hydroxy-4-(2-phenoxyethyl)cyclohexyl]methyl}benzamide;
3-Fluoro-N-[(trans-4-{[(4-fluorobenzyl)oxy]methyl}-1-hydroxycyclohexyl)methyl]-4-hydroxybenzamide;
3-Fluoro-N-({trans-4-[(2-fluorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
3-Fluoro-N-({trans-4-[(4-fluorophenoxy)methyl]-1-hydroxycyclohexyl}methyl)-4-hydroxybenzamide;
4-Hydroxy-N-[(trans-1-hydroxy-4-{[(5-methylpyridin-2-yl)oxy]methyl}cyclohexyl)methyl]benzamide;
N-[(trans-4-Benzyl-1-hydroxycyclohexyl)methyl]-4-hydroxybenzamide;
3-fluoro-N-[(trans-4-{[(2-fluorobenzyl)oxy]methyl}-1-hydroxycyclohexyl)methyl]-4-hydroxybenzamide;
6-Hydroxy-N-{[cis-4-(2-phenethoxy)cyclohexyl]methyl}nicotinamide;
N-{[cis-4-(2-Phenylethoxy)cyclohexyl]methyl}-1H-pyrazole-4-carboxamide;
N-{[cis-4-(Phenoxymethyl)cyclohexyl]methyl}-1H-pyrazole-4-carboxamide;
N-{[cis-4-(2-Phenoxyethyl)cyclohexyl]methyl}-1H-pyrazole-4-carboxamide;
N-({cis-4-[(3-Fluorophenoxy)methyl]cyclohexyl}methyl)-1H-pyrazole-4-carboxamide;
N-({cis-4-[(4-Fluorophenoxy)methyl]cyclohexyl}methyl)-1H-pyrazole-4-carboxamide;
N-({(2R,5R)-5-[(4-Fluorophenoxy)methyl]tetrahydro-2H-pyran-2-yl}methyl)- H-pyrazole-4-carboxamide;
N-{[cis-4-(4-Methoxybenzyl)cyclohexyl]methyl}-1H-pyrazole-4-carboxamide;
3-Amino-N-[(cis-4-benzylcyclohexyl)methyl]-1H-pyrazole-4-carboxamide;
N-({(2R,5R)-5-[(4-Chlorophenoxy)methyl]tetrahydro-2H-pyran-2-yl}methyl)-1H-pyrazole-4-carboxamide;
3-Amino-N-({(2R,5R)-5-[(4-fluorophenoxy)methyl]tetrahydro-2H-pyran-2-yl}methyl)-1H-pyrazole-4-carboxamide;
3-Amino-N-({(2R5R)-5-[(4-chlorophenoxy) methyl]tetrahydro-2H-pyran-2-yl}methyl)-1H-pyrazole-4-carboxamide;
and
3-Amino-N-({(2R,5R)-5-[(4-ethylphenoxy)methyl]tetrahydro-2H-pyran-2-yl}methyl)-1H-pyrazole-4-carboxamide;
or a pharmaceutically acceptable salt or solvate thereof.

67 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/597,868Filed 1 Feb 2005
Priority: 11 Feb 2004
Published: 19 Jul 2007
Term ends: Not estimatedThe source records don’t support an estimate.

Classification29 codes

C07C 235/48
With carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring:…
A61P 25/16
For treating abnormal movements, e.g. chorea, dyskinesia: anti-Parkinson drugs
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
C07D 207/34
Having two double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having three…

Family

Application60/544,258Us provisional application · filed 11 Feb 2004
US 2007/0167452 A1This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

Facts

Application

10/597,868Filed 1 Feb 2005

Priority

11 Feb 2004

Published

19 Jul 2007

Term ends

Not estimatedThe source records don’t support an estimate.

Classification29 codes

C07C 235/48
With carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring:…
A61P 25/16
For treating abnormal movements, e.g. chorea, dyskinesia: anti-Parkinson drugs
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…
C07D 207/34
Having two double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having three…