Muscarinic M1 receptor agonists

Patent metadata

Field	Value
Publication number	US-9573929-B2
Application number	US-201514941328-A
Country	US
Kind code	B2
Filing date	Nov 13, 2015
Priority date	Nov 18, 2011
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

This invention relates to compounds that are agonists of the muscarinic M1 receptor and which are useful in the treatment of muscarinic M1 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula I, where n is 1 or 2; p is 0, 1 or 2; q is 0, 1 or 2; and R 1 -R 6 are as defined herein.

First claim

The invention claimed is:

1. A compound of the formula:

or a salt thereof, wherein:
R 1 is selected from 2-methylpropyl, tert-butyl, 2-methylbutyl, 2,2-dimethylpropyl, 2-methylbut-2-yl, cyclobutylmethyl, cyclopropylmethyl, cyclopentylmethyl, isopropyl, 1-methylcyclohexyl, 1-methylcyclopentylmethyl, 2-cyclopropylpropyl, 1-methylcyclobutyl, cyclopentyl, 2,3-dimethylbutan-2-yl, 1-ethylcyclobutylmethyl, 1-methylcyclopentyl, 2-cyclopropylpropan-2-yl, cyclobutyl, 1-methylcyclobutylmethyl, 1-(trifluoromethyl)cyclobutyl, 1-ethylcyclobutyl, ( 2 H 3 )methyl( 2 H 6 )propyl and 2-methylpentan-2-yl;
R 2 is selected from hydrogen, methyl, ethyl and isopropyl;
or R 1 and R 2 together with the nitrogen atom to which they are attached form a non-aromatic heterocyclic group of four to nine ring members, wherein the heterocyclic ring may optionally contain a second heteroatom selected from O, N and S and oxidised forms thereof; and wherein the heterocyclic ring may optionally be substituted with one to six more substitutents selected from C 1-2 alkyl; fluorine; and cyano;
R 3 is selected from hydrogen; fluorine; cyano; methoxy and methyl; and
R 4 is selected from methyl, ethyl, ethynyl and 1-propynyl.

2. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

3. A compound of the formula:

or a salt thereof, wherein:
R 1 is selected from 2-methylpropyl, tert-butyl, 2-methylbutyl, 2,2-dimethylpropyl, 2-methylbut-2-yl, cyclobutylmethyl, cyclopropylmethyl, cyclopentylmethyl, isopropyl, 1-methylcyclohexyl, 1-methylcyclopentylmethyl, 2-cyclopropylpropyl, 1-methylcyclobutyl, cyclopentyl, 2,3-dimethylbutan-2-yl, 1-ethylcyclobutylmethyl, 1-methylcyclopentyl, 2-cyclopropylpropan-2-yl, cyclobutyl, 1-methylcyclobutylmethyl, 1-(trifluoromethyl)cyclobutyl, 1-ethylcyclobutyl, ( 2 H 3 )methyl( 2 H 6 )propyl and 2-methylpentan-2-yl;
R 2 is selected from hydrogen, methyl, ethyl and isopropyl;
or R 1 and R 2 together with the nitrogen atom to which they are attached form a non-aromatic heterocyclic group of four to nine ring members, wherein the heterocyclic ring may optionally contain a second heteroatom selected from O, N and S and oxidised forms thereof; and wherein the heterocyclic ring may optionally be substituted with one to six more substitutents selected from C 1-2 alkyl; fluorine; and cyano;
R 3 is selected from hydrogen; fluorine; cyano; methoxy and methyl; and
R 4 is selected from methyl, ethyl, ethynyl and 1-propynyl.

4. A pharmaceutical composition comprising the compound of claim 3 and a pharmaceutically acceptable excipient.

Assignees

• Heptares Therapeutics Ltd

Inventors

• Congreve Miles Stuart
• Brown Giles Albert
• Cansfield Julie Elaine
• Tehan Benjamin Gerald

Classifications

• A61P43/00

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

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title