Granted Patent B2

US 12,637,443 · App. 18/269,692 · Granted May 26, 2026

Inventor: Kenji Nakahara (Osaka, JP)

Assignee: SHIONOGI & CO., LTD.

C07D401/12C07D403/12C07D405/12C07D405/14C07D409/12C07D413/12C07D417/12C07D471/08

Abstract

Claims (55)

1 . A compound represented by Formula (I):

wherein R 1 is substituted or unsubstituted 5-membered aromatic heterocyclyl or substituted or unsubstituted 6-membered aromatic heterocyclyl;

R 2 is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

R 3 is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

n is 1 or 2;

a combination of (L 1 , L 2 ) is (NH, N) or (CH 2 , N);

R 4 is a group represented by Formula:

wherein p and q are each 2;

p″ and q″ are each independently 1 or 2;

R a is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted non-aromatic carbocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;

R a″ is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted non-aromatic carbocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;

X b is each independently CR b R b′ ;

X c is each independently CR c R c′ ;

R b is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

R b′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

R c is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

R c′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

R b″ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

R c″ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

X d is CR d or N;

X d″ is CR d or N;

R d is a hydrogen atom, halogen, cyano, substituted or unsubstituted alkyl, or substituted or unsubstituted carbamoyl;

R b and R b′ and R c and R c′ may be taken together with the same carbon atom to which they are bonded to form a substituted or unsubstituted non-aromatic carbocycle or a substituted or unsubstituted non-aromatic heterocycle;

R a , and R b bonded to a carbon atom adjacent to a nitrogen atom to which R a is bonded may be taken together with the nitrogen atom to which R a is bonded and the carbon atom to which R b is bonded to form a substituted or unsubstituted non-aromatic heterocycle; or

R a , and R c bonded to a carbon atom adjacent to a nitrogen atom to which R a is bonded may be taken together with the nitrogen atom to which R a is bonded and the carbon atom to which R c is bonded to form a substituted or unsubstituted non-aromatic heterocycle;

R b and R o may be taken together to form a (C1-C3) bridge, wherein one of the carbon atoms constituting the bridge may be replaced with an oxygen atom;

R a and R d may be taken together to form a (C1-C3) bridge, wherein one of the carbon atoms constituting the bridge may be replaced with an oxygen atom;

R 5 and R 6 are each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; or

R 5 and R 6 may be taken together with the same carbon atom to which they are bonded to form a substituted or unsubstituted non-aromatic carbocycle;

R 7 is a group represented by Formula:

wherein A is CR 11 or N;

R 9 is substituted or unsubstituted alkyloxy, substituted or unsubstituted amino, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted alkyl, substituted or unsubstituted non-aromatic carbocyclyl, or cyano;

R 10 is a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy; or

R 9 and R 10 may be taken together to form a substituted or unsubstituted non-aromatic carbocycle or a substituted or unsubstituted non-aromatic heterocycle;

R 11 is each independently a hydrogen atom, halogen, hydroxy, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;

provided that the following compounds are excluded:

or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 , wherein A is CR 11 , or a pharmaceutically acceptable salt thereof.

3 . The compound according to claim 1 , wherein A is CH, or a pharmaceutically acceptable salt thereof.

4 . The compound according to claim 1 , wherein X d is CR 4 , and R d is a hydrogen atom or substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof.

5 . The compound according to claim 1 , wherein X d is CH, or a pharmaceutically acceptable salt thereof.

6 . The compound according to claim 1 , wherein R 2 is each independently a hydrogen atom or substituted or unsubstituted alkyl, and R 3 is each independently a hydrogen atom or substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof.

7 . The compound according to claim 1 , wherein R 5 and R 6 are each independently a hydrogen atom or substituted or unsubstituted alkyl, or a pharmaceutically acceptable salt thereof.

8 . The compound according to claim 1 , wherein R 1 is substituted or unsubstituted 5-membered aromatic heterocyclyl, substituted or unsubstituted pyridin-2-yl, substituted or unsubstituted pyridin-3-yl, substituted or unsubstituted pyridazin-3-yl, substituted or unsubstituted pyrimidin-4-yl, or substituted or unsubstituted pyrazinyl, or a pharmaceutically acceptable salt thereof.

9 . The compound according to claim 1 , wherein R 1 is substituted or unsubstituted 5-membered aromatic heterocyclyl, or a pharmaceutically acceptable salt thereof.

10 . The compound according to claim 1 , wherein the compound is selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

11 . A pharmaceutical composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

12 . The pharmaceutical composition according to claim 11 , wherein the pharmaceutical composition is a serotonin 5-HT2A receptor antagonist and/or inverse agonist.

13 . The pharmaceutical composition according to claim 11 , wherein the pharmaceutical composition is a serotonin 5-HT2A receptor antagonist and/or inverse agonist and a 5-HT2C receptor antagonist and/or inverse agonist.

14 . A method for treating and/or preventing a disease related to a serotonin 5-HT2A receptor comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

15 . A method for treating and/or preventing a disease related to serotonin 5-HT2A and 5-HT2C receptors comprising administering an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

16 . A pharmaceutical composition comprising the compound according to claim 10 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.

17 . A method for treating and/or preventing a disease related to a serotonin 5-HT2A receptor comprising administering an effective amount of the compound according to claim 10 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

18 . The compound according to claim 1 , wherein R 1 is substituted or unsubstituted pyrazolyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted triazolyl, substituted or unsubstituted isoxazolyl, or substituted or unsubstituted thiazolyl, or a pharmaceutically acceptable salt thereof.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (41)