US 2025/0026765 A1Published application

Spiroheterocycle derivative having serotonin receptor binding activity

AssigneeShionogi & Co., Ltd.

InventorsTatsuhiko UENO, Rina YASUI

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Abstract

Provided are compounds having a serotonin 5-HT2A receptor antagonism and/or inverse agonism, pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising thereof. A compound represented by Formula (I): wherein R1 is a hydrogen atom or the like; A1 is each independently CR2R2′; A2 is each independently CR3R3′, R2 is each independently a hydrogen atom or the like; R2′ is each independently a hydrogen atom or the like; R3 is each independently a hydrogen atom or the like; R3′ is each independently a hydrogen atom or the like; m and n are each independently 1 or the like; ring B is a ring represented by Formula: or the like wherein R4 is a group represented by Formula: or the like wherein A3 is each independently CR13R13′; A4 is each independently CR14R14′; R13 is each independently a hydrogen atom or the like; R13′ is each independently a hydrogen atom or the like; R14 is each independently a hydrogen atom or the like; R14′ is each independently a hydrogen atom or the like; q and r are each independently 1 or the like; R10 and R11 are each independently substituted or unsubstituted aromatic carbocyclyl or the like; R8 is a hydrogen atom or the like, or a pharmaceutically acceptable salt thereof.

Claims29

Dependent claims

A compound represented by Formula (I):

wherein R1 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;
A1 is each independently CR2R2′;
A2 is each independently CR3R3′;
R2 is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R2′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R3 is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R3′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R2 and R2′ and R3 and R3′ may be taken together with an identical carbon atom to which they are bonded to form a substituted or unsubstituted non-aromatic carbocycle or a substituted or unsubstituted non-aromatic heterocycle;
m and n are each independently 1, 2, or 3;
ring B is a ring represented by Formula:
or
wherein R4 is a group represented by Formula:
wherein A3 is each independently CR13R13′;
A4 is each independently CR14R14′;
R13 is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R13′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R14 is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R14′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
q and r are each independently 0, 1, or 2;
q′ and r′ are each independently 1 or 2;
R10 and R11 are each independently substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;
R12 is a hydrogen atom or substituted or unsubstituted alkyl;
R8 is a hydrogen atom or substituted or unsubstituted alkyl;
R9 is each independently halogen or substituted or unsubstituted alkyl;
p is an integer of any of 0 to 6,
or a pharmaceutically acceptable salt thereof.

23 more elements

A compound represented by Formula (III):

wherein R31 is a hydrogen atom or C1-C3 alkyl;
R32 is each independently a hydrogen atom or substituted or unsubstituted alkyl;
R33 is each independently a hydrogen atom or substituted or unsubstituted alkyl;
R34 is each independently a hydrogen atom, halogen, or substituted or unsubstituted alkyl;
R35 is each independently a hydrogen atom, halogen, or substituted or unsubstituted alkyl;
R32 and R33 and R34 and R35 may be taken together with an identical carbon atom to which they are bonded to form a substituted or unsubstituted non-aromatic carbocycle or a substituted or unsubstituted non-aromatic heterocycle;
ring B′ is a group represented by Formula:
or
wherein R6 is a group represented by Formula:
or
wherein A6 is each independently CR25R25′;
R25 is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R25′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
s is 0 or 1;
s′ is 0, 1, or 2;
R24 is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;
R5 is a hydrogen atom or substituted or unsubstituted alkyl;
R6′ is a group represented by Formula:
wherein A7 is CR27R27′;
R27 is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R27′ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
t is 0 or 1;
R26 is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl;
R7 is a group represented by Formula:
wherein A5 is each independently CR28R28′;
R28 is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
R28′ is each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy;
u is 0, 1, or 2;
R23 is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl,
R21 is a hydrogen atom or substituted or unsubstituted alkyl;
R22 is each independently halogen or substituted or unsubstituted alkyl;
v is 0, 1, or 2,
or a pharmaceutically acceptable salt thereof.

30 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/693,319Filed 21 Sep 2022
Priority: JP 2021-15371522 Sep 2021
Published: 23 Jan 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 498/10
In which the condensed system contains two hetero rings: spiro-condensed systems
A61K 31/438
Having six-membered rings with one nitrogen as the only ring hetero atom: the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings