Pharmaceutical compounds
This invention relates to compounds that are agonists of the muscarinic M 1 and/or M 4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M 1 and M 4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula where Y, R 1 , R 2 and R 4 are as defined herein.
1. A compound of the formula (1):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is CONR 8 R 9 ;
R 2 is selected from hydrogen; fluorine; cyano; hydroxy; amino; and a C 1-3 non-aromatic hydrocarbon group which is optionally substituted with one to six fluorine atoms and wherein one of the carbon atoms of the hydrocarbon group may optionally be replaced by a heteroatom selected from O, N and S and oxidized forms thereof;
R 4 is H or a C 1-6 non-aromatic hydrocarbon group which is optionally substituted with one to six fluorine atoms and wherein one or two, but not all, carbon atoms of the hydrocarbon group may optionally be replaced by a heteroatom selected from O, N and S and oxidised forms thereof;
R 8 is hydrogen, a non-aromatic C 1-6 hydrocarbon group optionally substituted with one or more fluorine atoms, or R 8 can be joined together with R 9 to form an optionally substituted monocyclic or bicyclic ring containing 0, 1, 2 or 3 heteroatoms selected from O, N and S and oxidized forms thereof, and
R 9 is a non-aromatic C 1-6 hydrocarbon group optionally substituted with one or more fluorine atoms, or R 9 can be joined together with R 8 to form an optionally substituted monocyclic or bicyclic ring containing 0, 1, 2 or 3 heteroatoms selected from O, N and S and oxidized forms thereof.
2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H.
3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is H or methyl.
4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydrogen and R 1 is selected from the group consisting of:
5. The compound according to claim 1 , which is selected from the group consisting of:
Ethyl 7-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate;
Ethyl 7-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate;
Ethyl 7-{4-[(cyclobutylmethyl)carbamoyl]piperidin-1-yl}-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate;
Ethyl 7-[4-(azepan-1-ylcarbonyl)piperidin-1-yl]-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate;
Methyl 7-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate;
Methyl 7-{4-[(2-methylpropyl)carbamoyl]piperidin-1-yl}-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate;
Methyl 7-{4-[(cyclobutylmethyl)carbamoyl]piperidin-1-yl}-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate; and
Methyl 7-[4-(azepan-1-ylcarbonyl)piperidin-1-yl]-3-oxa-9-azabicyclo[3.3.1]nonane-9-carboxylate;
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
7. A method of treating a cognitive disorder or psychotic disorder or for the treatment or lessening the severity of acute, chronic, neuropathic, or inflammatory pain comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.
8. The method according to claim 7 , wherein the cognitive disorder is Alzheimer's disease.
9. The method according to claim 7 , wherein the cognitive disorder is dementia with Lewy bodies.
10. The method according to claim 7 , wherein the cognitive disorder is schizophrenia.