Muscarinic agonists
This invention relates to compounds that are agonists of the muscarinic M 1 receptor and/or M4 receptor and which are useful in the treatment of muscarinic M 1 /M 4 receptor mediated diseases. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds include those according to formula 1 or a salt thereof, wherein q, r, s, Q, R 1 , R 2′ , R 2″ , R 3 and R 4 are as defined herein.
1. A compound of the formula (1):
or a salt thereof, wherein
q is 1;
r is 1 or 2;
s is 0 or 1 where the total of r and s is 1 or 2;
Q is an azetidine linked to the adjacent six-membered ring by the nitrogen atom of the azetidine ring;
R 1 is selected from hydrogen; methyl; ethyl; fluorine; oxo; and COOMe;
R 2′ and R 2″ are independently selected from hydrogen; fluorine; and a C 1-6 non-aromatic hydrocarbon group;
R 3 is hydrogen;
R 4 is hydrogen or a C 1-6 non-aromatic hydrocarbon group which is optionally substituted with one to six fluorine atoms
and the dotted line indicates a single bond.
2. The compound according to claim 1 wherein R 4 is selected from hydrogen and methyl.
3. The compound according to claim 1 which is
Ethyl2-[4-(3,3-difluoroazetidin-1-yl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate;
Ethyl2-{4-[(2R)-2-(methoxycarbonyl)azetidin-1-yl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate;
Ethyl2-[4-(2-oxoazetidin-1-yl)piperidin-1-yl]-6-azaspiro[3.4]octane-6-carboxylate;
Ethyl2-{4-[(2S)-2-methyl-4-oxoazetidin-1-yl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate;
Ethyl2-{4-[(2S)-2-ethyl-4-oxoazetidin-1-yl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate;
Ethyl2-{4-[(2R)-2-methyl-4-oxoazetidin-1-yl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate;
Ethyl2-{4-[(2R)-2-ethyl-4-oxoazetidin-1-yl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate;
or a salt thereof.
4. A pharmaceutical composition comprising the compound as defined in claim 1 and a pharmaceutically acceptable excipient.
5. The compound according to claim 1 wherein the moiety:
is selected from:
6. The compound according to claim 1 wherein the moiety:
is selected from: