US 12,630,510 B2Granted

EP2 antagonist

AssigneeOno Pharmaceutical Co., Ltd.

InventorsAkio Watanabe, Atsushi Yoshida, Yasuo Hirooka, Michael G. Yang, Ning Li

Life of this patent

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Abstract

A drug containing, as an active ingredient, a compound having an antagonistic activity against an EP2 receptor in the prevention and/or treatment of a disease associated with the activation of an EP2 receptor, of formula (I-A): wherein all symbols have the same meanings as those described in the specification, or a pharmaceutically acceptable salt thereof.

Claims14

Dependent claims

A compound of formula (I-1):

wherein:
R38 and R40 each independently represent (1) a hydrogen atom, (2) a halogen atom, or (3) a C1-4 alkyl group;
the C1-4 alkyl group in each of R38 and R40 may be independently substituted by a halogen atom;
L2 represents (1) a bond, (2) a C1-8 alkylene group, (3) a C2-8 alkenylene group, or (4) a C2-8 alkynylene group, wherein one or two carbon atoms in the C1-8 alkylene group, the C2-8 alkenylene group and the C2-8 alkynylene group may be independently replaced by an oxygen atom or a sulfur atom that may be oxidized, and each of the C1-8 alkylene group, the C2-8 alkenylene group and the C2-8 alkynylene group may be substituted by 1 to 8 halogen atoms;
Y represents (1) a bond, (2) an oxygen atom, or (3) a sulfur atom that may be oxidized;
R1 represents (1) COOR10;
R10 represents (1) a hydrogen atom or (2) a C1-4 alkyl group;
R2 represents (1) a hydrogen atom or (2) a C1-4 alkyl group;
R3 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) a (3- to 6-membered cyclic group)-O—, or (8) a (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
each of the groups (2) to (8) in R3 may be substituted by 1 to 9 R16s;
when there are a plurality of R3s, the plurality of R3s may be the same as or different from each other;
R16 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR17R18;
when there are a plurality of R16s, the plurality of R16s may be the same as or different from each other;
R17 and R18 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
R4 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) (3- to 6-membered cyclic group)-O—, or (8) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
each of the groups (2) to (8) in R4 may be substituted by 1 to 9 R19s;
when there are a plurality of R4s, the plurality of R4s may be the same as or different from each other;
R19 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR20R21;
R20 and R21 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R19s, the plurality of R19s may be the same as or different from each other;
R5 represents (1) a hydrogen atom, (2) a C3-10 carbocyclic ring, or (3) a 3- to 10-membered heterocyclic ring, wherein each of the C3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring may be substituted by 1 to 5 R22s;
when L2 represents a bond, R5 is not a hydrogen atom;
R22 represents (1) a C1-6 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a C3-6 cycloalkyl group, (5) a C1-6 alkoxy group, (6) a C3-6 cycloalkyloxy group, (7) a C2-6 acyl group, (8) a C2-6 acyloxy group, (9) a C1-6 alkylthio group, (10) a C3-6 cycloalkylthio group, (11) a C1-6 alkylsulfinyl group, (12) a C3-6 cycloalkylsulfinyl group, (13) a C1-6 alkylsulfonyl group, (14) a C3-6 cycloalkylsulfonyl group, (15) a C1-6 alkoxycarbonyl group, (16) a 5- to 6-membered cyclic group, (17) (5- to 6-membered cyclic group)-(C1-4 alkylene)-, (18) a (5- to 6-membered cyclic group)-(C1-4 alkylene)-O— group, (19) a (5- to 6-membered cyclic group)-C1-4 acyl group, (20) a halogen atom, (21) a hydroxyl group, (22) a nitro group, (23) a cyano group, (24) —NR23R24, (25) —CONR25R26 or (26) —SO2NR27R28,
R23, R24, R25, R26, R27 and R28 each independently represent (1) a hydrogen atom, (2) a C1-6 alkyl group, (3) a C2-6 acyl group or (4) a C1-6 alkylsulfonyl group;
each of the groups (1) to (19) in R22 may be substituted by 1 to 9 R29s;
when there are a plurality of R22s, the plurality of R22s may be the same as or different from each other;
R29 represents (1) a C1-4 alkyl group, (2) a C1-4 alkoxy group, (3) a C2-6 acyl group, (4) a C3-6 cycloalkyl group, (5) a hydroxyl group, (6) —NR30R31 or (7) a halogen atom;
R30 and R31 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R29s, the plurality of R29s may be the same as or different from each other;
X represents (1) CR6 or (2) NR7;
R6 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) (3- to 6-membered cyclic group)-O—, or (8) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
each of the groups (2) to (8) in R6 may be substituted by 1 to 9 R32s;
R32 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR33R34;
R33 and R34 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R32s, the plurality of R32s may be the same as or different from each other;
R7 represents (1) a C1-6 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a 3- to 6-membered cyclic group, or (5) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
R7 may be substituted by 1 to 9 R35s;
R35 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR36R37,
R36 and R37 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R35s, the plurality of R35s may be the same as or different from each other;
the ring A represents (1) a benzene ring, or (2) a 5- to 6-membered nitrogen-containing aromatic heterocyclic ring;
the symbol
in the ring A represents a single bond or a double bond;
n represents an integer of 1 to 4;
m represents an integer of 0 to 3;
and
p represents an integer of 1 to 4,
or a pharmaceutically acceptable salt thereof.

45 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/621,137Filed 26 Jun 2020
Priority: JP 2019-12207728 Jun 2019
Published: US 2022/0388955 A18 Dec 2022
Granted: 19 May 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification59 codes

C07D 207/34
Having two double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having three…
C07D 213/643
Attached in position 2 or 6: 2-Phenoxypyridines; Derivatives thereof
A61K 31/145
Amines: having sulfur, e.g. thiurams , Sulfinylamines , Sulfonylamines
A61K 31/167
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the nitrogen of a carboxamide group directly attached to the aromatic ring,…

Family

US 2022/0388955 A1Pre-grant publication · published 8 Dec 2022
US 12,630,510 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula (I-1):

wherein:
R38 and R40 each independently represent (1) a hydrogen atom, (2) a halogen atom, or (3) a C1-4 alkyl group;
the C1-4 alkyl group in each of R38 and R40 may be independently substituted by a halogen atom;
L2 represents (1) a bond, (2) a C1-8 alkylene group, (3) a C2-8 alkenylene group, or (4) a C2-8 alkynylene group, wherein one or two carbon atoms in the C1-8 alkylene group, the C2-8 alkenylene group and the C2-8 alkynylene group may be independently replaced by an oxygen atom or a sulfur atom that may be oxidized, and each of the C1-8 alkylene group, the C2-8 alkenylene group and the C2-8 alkynylene group may be substituted by 1 to 8 halogen atoms;
Y represents (1) a bond, (2) an oxygen atom, or (3) a sulfur atom that may be oxidized;
R1 represents (1) COOR10;
R10 represents (1) a hydrogen atom or (2) a C1-4 alkyl group;
R2 represents (1) a hydrogen atom or (2) a C1-4 alkyl group;
R3 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) a (3- to 6-membered cyclic group)-O—, or (8) a (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
each of the groups (2) to (8) in R3 may be substituted by 1 to 9 R16s;
when there are a plurality of R3s, the plurality of R3s may be the same as or different from each other;
R16 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR17R18;
when there are a plurality of R16s, the plurality of R16s may be the same as or different from each other;
R17 and R18 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
R4 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) (3- to 6-membered cyclic group)-O—, or (8) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
each of the groups (2) to (8) in R4 may be substituted by 1 to 9 R19s;
when there are a plurality of R4s, the plurality of R4s may be the same as or different from each other;
R19 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR20R21;
R20 and R21 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R19s, the plurality of R19s may be the same as or different from each other;
R5 represents (1) a hydrogen atom, (2) a C3-10 carbocyclic ring, or (3) a 3- to 10-membered heterocyclic ring, wherein each of the C3-10 carbocyclic ring and the 3- to 10-membered heterocyclic ring may be substituted by 1 to 5 R22s;
when L2 represents a bond, R5 is not a hydrogen atom;
R22 represents (1) a C1-6 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a C3-6 cycloalkyl group, (5) a C1-6 alkoxy group, (6) a C3-6 cycloalkyloxy group, (7) a C2-6 acyl group, (8) a C2-6 acyloxy group, (9) a C1-6 alkylthio group, (10) a C3-6 cycloalkylthio group, (11) a C1-6 alkylsulfinyl group, (12) a C3-6 cycloalkylsulfinyl group, (13) a C1-6 alkylsulfonyl group, (14) a C3-6 cycloalkylsulfonyl group, (15) a C1-6 alkoxycarbonyl group, (16) a 5- to 6-membered cyclic group, (17) (5- to 6-membered cyclic group)-(C1-4 alkylene)-, (18) a (5- to 6-membered cyclic group)-(C1-4 alkylene)-O— group, (19) a (5- to 6-membered cyclic group)-C1-4 acyl group, (20) a halogen atom, (21) a hydroxyl group, (22) a nitro group, (23) a cyano group, (24) —NR23R24, (25) —CONR25R26 or (26) —SO2NR27R28,
R23, R24, R25, R26, R27 and R28 each independently represent (1) a hydrogen atom, (2) a C1-6 alkyl group, (3) a C2-6 acyl group or (4) a C1-6 alkylsulfonyl group;
each of the groups (1) to (19) in R22 may be substituted by 1 to 9 R29s;
when there are a plurality of R22s, the plurality of R22s may be the same as or different from each other;
R29 represents (1) a C1-4 alkyl group, (2) a C1-4 alkoxy group, (3) a C2-6 acyl group, (4) a C3-6 cycloalkyl group, (5) a hydroxyl group, (6) —NR30R31 or (7) a halogen atom;
R30 and R31 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R29s, the plurality of R29s may be the same as or different from each other;
X represents (1) CR6 or (2) NR7;
R6 represents (1) a halogen atom, (2) a C1-6 alkyl group, (3) a C2-6 alkenyl group, (4) a C2-6 alkynyl group, (5) a C1-6 alkoxy group, (6) a 3- to 6-membered cyclic group, (7) (3- to 6-membered cyclic group)-O—, or (8) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
each of the groups (2) to (8) in R6 may be substituted by 1 to 9 R32s;
R32 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR33R34;
R33 and R34 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R32s, the plurality of R32s may be the same as or different from each other;
R7 represents (1) a C1-6 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a 3- to 6-membered cyclic group, or (5) (3- to 6-membered cyclic group)-(C1-4 alkylene)-;
R7 may be substituted by 1 to 9 R35s;
R35 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C2-6 acyl group, (5) a C3-6 cycloalkyl group, (6) a hydroxyl group, or (7) —NR36R37,
R36 and R37 each independently represent (1) a hydrogen atom or (2) a C1-4 alkyl group;
when there are a plurality of R35s, the plurality of R35s may be the same as or different from each other;
the ring A represents (1) a benzene ring, or (2) a 5- to 6-membered nitrogen-containing aromatic heterocyclic ring;
the symbol
in the ring A represents a single bond or a double bond;
n represents an integer of 1 to 4;
m represents an integer of 0 to 3;
and
p represents an integer of 1 to 4,
or a pharmaceutically acceptable salt thereof.

45 more elements

Facts

Application

17/621,137Filed 26 Jun 2020

Priority

JP 2019-12207728 Jun 2019

Published

US 2022/0388955 A18 Dec 2022

Granted

19 May 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification59 codes

C07D 207/34
Having two double bonds between ring members or between ring members and non-ring members: with hetero atoms or with carbon atoms having three…
C07D 213/643
Attached in position 2 or 6: 2-Phenoxypyridines; Derivatives thereof
A61K 31/145
Amines: having sulfur, e.g. thiurams , Sulfinylamines , Sulfonylamines
A61K 31/167
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the nitrogen of a carboxamide group directly attached to the aromatic ring,…