Granted Patent B2

US 12,215,099 · App. 17/311,212 · Granted Feb 4, 2025

Inventors: Giles Albert Brown (Cambridge, GB); Miles Stuart Congreve (Cambridge, GB); Benjamin Gerald Tehan (Cambridge, GB); Mark Pickworth (Cambridge, GB)

Assignee: Nxera Pharma UK Limited

C07D413/14C07D471/08

Abstract

Claims (40)

1. A compound of the formula (I):

or a salt thereof, wherein:

R 1 is:

n is 1, 2, 3 or 4;

X 1 is CH 2 or O;

Y is N or CH;

X 2 and X 3 are saturated hydrocarbon groups which together contain a total of four to six carbon atoms and which link together such that the moiety:

represents a monocyclic or bicyclic ring system;

Z is CH 2 or CO;

X 4 is CH 2 or O;

and R 2 is F or H.

2. A compound according to claim 1 of formula (II)

or a salt thereof.

3. A compound according to claim 1 of formula (III)

or a salt thereof.

4. A compound according to claim 1 wherein the ring system formed by the moiety:

is the monocyclic ring system:

or is selected from the bicyclic ring systems A or B:

5. A compound according to claim 1 wherein the ring system formed by the moiety:

is the bicyclic ring system A1:

6. A compound according to claim 1 which is selected from:

1-[3-[4-[2-(4,5-dihydroisoxazol-3-yloxy) ethyl]-1-piperidyl]propyl]-3,4-dihydroquinolin-2-one,

1-[3-[4-[4-(4,5-dihydroisoxazol-3-yloxy) butyl]-1-piperidyl]propyl]-3,4-dihydroquinolin-2-one,

1-[3-[3-[2-(4,5-dihydroisoxazol-3-yloxy) ethyl]-8-azabicyclo [3.2.1]octan-8-yl]propyl]-3,4-dihydroquinolin-2-one,

1-[3-[3-[3-(4,5-dihydroisoxazol-3-yloxy) propyl]-8-azabicyclo [3.2.1]octan-8-yl]propyl]-3,4-dihydroquinolin-2-one,

1-[3-[(1R,5S)-3-[2-(4,5-dihydroisoxazol-3-yloxy) ethoxy]-8-azabicyclo [3.2.1]octan-8-yl]propyl]-3,4-dihydroquinolin-2-one,

1-[3-[3-[3-(4,5-dihydroisoxazol-3-yloxy) propyl]-3,8-diazabicyclo [3.2.1]octan-8-yl]propyl]-3,4-dihydroquinolin-2-one,

4-[3-[4-[2-(4,5-dihydroisoxazol-3-yloxy) ethyl]-1-piperidyl]propyl]-7-fluoro-1,4-benzoxazin-3-one,

4-[3-[4-[4-(4,5-dihydroisoxazol-3-yloxy) butyl]-1-piperidyl]propyl]-7-fluoro-1,4-benzoxazin-3-one,

3-[3-[8-[3-(3,4-dihydro-2H-quinolin-1-yl) propyl]-8-azabicyclo [3.2.1]octan-3-yl]propoxy]-4,5-dihydroisoxazole,

2-[2-[1-[3-(2-oxo-3,4-dihydroquinolin-1-yl) propyl]-4-piperidyl]ethyl]isoxazolidin-3-one,

2-[4-[1-[3-(2-oxo-3,4-dihydroquinolin-1-yl) propyl]-4-piperidyl]butyl]isoxazolidin-3-one,

2-[5-[1-[3-(2-oxo-3,4-dihydroquinolin-1-yl) propyl]-4-piperidyl]pentyl]isoxazolidin-3-one, and

2-[3-[8-[3-(2-oxo-3,4-dihydroquinolin-1-yl) propyl]-8-azabicyclo [3.2.1]octan-3-yl]propyl]isoxazolidin-3-one,

or a salt thereof.

7. A pharmaceutical composition comprising a compound as defined in claim 1 and a pharmaceutically acceptable excipient.

8. A compound according to claim 1 having muscarinic M 1 receptor agonist activity.

9. 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 to a subject in need thereof an effective amount of a compound according to claim 1 .

10. The method according to claim 9 wherein the cognitive disorder is Alzheimers disease.

11. The method according to claim 9 wherein the cognitive disorder is dementia with Lewy bodies.

Assignments (2)

Priority Claims (1)

Continuity (1)

References Cited (249)