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 (1) wherein X 1 ; X 2 ; R 1 and R 4 are as defined herein.
1. A compound of formula (4):
or a salt thereof, wherein:
R 1 is CONR 5 R 6 ;
R 4 is H or a C 1-6 non-aromatic hydrocarbon group which is optionally substituted with one to six fluorine atoms; and
R 5 and R 6 are independently selected from hydrogen and a non-aromatic C 1-6 hydrocarbon group optionally substituted with one or more fluorine atoms or R 5 and R 6 are joined together to form a monocyclic or bicyclic ring.
2. The compound according to claim 1 , or a salt thereof, wherein R 1 is selected from the group consisting of:
3. The compound according to claim 1 , or a salt thereof, wherein R 1 is:
4. The compound according to claim 1 , or a salt thereof, wherein R 4 is H or methyl.
5. The compound according to claim 1 , or a salt thereof, wherein R 4 is H.
6. The compound according to claim 1 which is selected from the group consisting of:
ethyl 2-{(1R,5S,6r)-6-[(2-methylpropyl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-{(1R,5S,6r)-6-[(cyclobutylmethyl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-{(1R,5S,6r)-6-[(1-methylcyclobutyl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-{(1R,5S,6r)-6-[ethyl(methyl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-[(1R,5S,6r)-6-(diethylcarbamoyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
methyl 2-[(1R,5S,6r)-6-(diethylcarbamoyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-{(1R,5S,6r)-6-[methyl(propan-2-yl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-{(1R,5S,6r)-6-[ethyl(propan-2-yl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
methyl 2-{(1R,5S,6r)-6-[ethyl(propan-2-yl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-{(1R,5S,6r)-6-[cyclopropyl(ethyl)carbamoyl]-3-azabicyclo[3.1.0]hex-3-yl}-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-[(1R,5S,6r)-6-(pyrrolidin-1-ylcarbonyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-[(1R,5S,6r)-6-(piperidin-1-ylcarbonyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-[(1R,5S,6r)-6-(azepan-1-ylcarbonyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-[(1R,5S,6r)-6-(2-azaspiro[3.3]hept-2-ylcarbonyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-[(1R,5S,6r)-6-(4-azaspiro[2.3]hex-4-ylcarbonyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
ethyl 2-[(1R,5S,6r)-6-(1-azaspiro[3.3]hept-1-ylcarbonyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro [3.4]octane-6-carboxylate;
methyl 2-[(1R,5S,6r)-6-(1-azaspiro [3.3]hept-1-ylcarbonyl)-3-azabicyclo [3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate; and
ethyl 2-[(1R,5S,6r)-6-(6-oxa-1-azaspiro[3.3]hept-1-ylcarbonyl)-3-azabicyclo[3.1.0]hex-3-yl]-6-azaspiro[3.4]octane-6-carboxylate;
or a salt thereof.
7. A method of treating Alzheimer's disease, dementia with Lewy bodies or schizophrenia in a subject, comprising administering to the subject an effective amount of a compound according to claim 1 , or a salt thereof.
8. A method of treating Alzheimer's disease in a subject, comprising administering to the subject an effective amount of a compound according to claim 1 , or a salt thereof.
9. A method of treating dementia with Lewy bodies in a subject, comprising administering to the subject an effective amount of a compound according to claim 1 , or a salt thereof.
10. A method of treating schizophrenia in a subject, comprising administering to the subject an effective amount of a compound according to claim 1 , or a salt thereof.