Muscarinic agonists

Patent metadata

Field	Value
Publication number	US-10738029-B2
Application number	US-201615749957-A
Country	US
Kind code	B2
Filing date	Aug 3, 2016
Priority date	Aug 3, 2015
Publication date	Aug 11, 2020
Grant date	Aug 11, 2020

Abstract

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.

First claim

The invention claimed is:

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:

Assignees

• Heptares Therapeutics Ltd

Inventors

• Brown Giles Albert
• Cansfield Julie
• Pickworth Mark
• Tehan Benjamin Gerald
• Teobald Barry John

Classifications

• A61P25/18

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

• C07D401/14 Primary

  containing three or more hetero rings · 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