Nitrogen-containing heterocyclic compound and use of same

Patent metadata

Field	Value
Publication number	US-RE48334-E
Application number	US-200915445251-A
Country	US
Kind code	E1
Filing date	Sep 18, 2009
Priority date	Sep 19, 2008
Publication date	Dec 1, 2020
Grant date	Dec 1, 2020

Abstract

The present invention relates to a compound represented by the formula

wherein ring A is a nitrogen-containing heterocycle;
ring B is an aromatic ring optionally having substituent(s);
ring D is an aromatic ring optionally having substituent(s);
L is a group represented by the formula

R 2 , R 3 , R 4a and R 4b are each independently a hydrogen atom, an optionally halogenated C 1-6 alkyl group or an optionally halogenated C 3-6 cycloalkyl group, or R 2 and R 3 are optionally bonded via an alkylene chain or an alkenylene chain, or R 4a and R 4b are optionally bonded via an alkylene chain or an alkenylene chain;
R 1 is a hydrogen atom or a substituent;
m and n are each independently an integer of 0 to 5;
m+n is an integer of 2 to 5; and
is a single bond or double bond, or a salt thereof; and the like. The compound has a superior tachykinin receptor antagonistic action, and is useful as an agent for the prophylaxis or treatment of various diseases such as lower urinary tract diseases, digestive tract diseases, central neurological disease and the like.

First claim

The invention claimed is:

1. A compound represented by the formula

wherein:
ring A is a piperidine ring or a pyrrolidine ring and each straight line is a single bond and is a single bond;
ring B is an aromatic ring optionally having substituent(s);
ring D is an aromatic ring optionally having substituent(s), wherein 6-quinolyl is excluded;
L is a group represented by the formula

R 2 , R 3 , R 4a and R 4b are each independently a hydrogen atom, an optionally halogenated C 1-6 alkyl group or an optionally halogenated C 3-6 cycloalkyl group, or R 2 and R 3 are optionally bonded via an alkylene chain or an alkenylene chain, or R 4a and R 4b are optionally bonded via an alkylene chain or an alkenylene chain;
R 1 is a hydrogen atom or a substituent;
m and n are each independently an integer of 0 to 3; and
m+n is an integer of 2 to 3;
provided that when L is a group represented by the formula

wherein each of R 4a and R 4b is as defined above, then ring D is an aromatic ring having substituent(s);
excluding: N-[4-(biphenyl-4-yl)piperidin-3-yl]-N′-(naphthalen-2-yl)urea;
or a salt thereof.

2. The compound or salt according to claim 1 , wherein ring B is a phenyl group optionally having substituent(s) or a pyridyl group optionally having substituent(s).

3. The compound or salt according to claim 1 , wherein ring B is a phenyl group optionally having substituent(s) or a thienyl group optionally having substituent(s).

4. The compound or salt according to claim 1 , wherein ring D is a phenyl group optionally having substituent(s).

5. The compound or salt according to claim 1 , wherein R 1 is a hydrogen atom, a hydrocarbon group optionally having substituent(s), an acyl group, a heterocyclic group optionally having substituent(s), or a group represented by —NR 5 R 6 wherein R 5 and R 6 are each independently a hydrogen atom, a hydrocarbon group optionally having substituent(s) or an acyl group, or R 5 and R 6 optionally form, together with the adjacent nitrogen atom, a nitroso group (—N═O).

6. The compound or salt according to claim 1 , wherein R 2 is a hydrogen atom or a C 1-6 alkyl group.

7. The compound or salt according to claim 1 , wherein L is a group represented by the formula

wherein R 3′ is a hydrogen atom or a C 1-6 alkyl group.

8. The compound or salt according to claim 1 , wherein A compound represented by the formula

wherein:
ring A is a piperidine ring or a pyrrolidine ring and each straight line is a single bond and is a single bond;
ring B is an aromatic ring optionally having substituent(s);
ring D is a 3,5-bis(trifluoromethyl)phenyl group or a 3,5-dichlorophenyl group;
L is a group represented by the formula

R 2 , R 3 , R 4a and R 4b are each independently a hydrogen atom, an optionally halogenated C 1-6 alkyl group or an optionally halogenated C 3-6 cycloalkyl group, or R 2 and R 3 are optionally bonded via an alkylene chain or an alkenylene chain, or R 4a and R 4b are optionally bonded via an alkylene chain or an alkenylene chain;
R 1 is a hydrogen atom or a substituent;
m and n are each independently an integer of 0 to 3; and
m+n is an integer of 2 to 3.

9. Methyl 4-{[(3S,4R)-3-[{[3,5-bis(trifluoromethyl)phenyl](methyl)carbamoyl}(methyl)amino]-4-(4-fluorophenyl)pyrrolidin-1-yl]carbonyl}piperidine-1-carboxylate, or a salt thereof.

10. 1-[(3S,4R)-4-(4-Chlorophenyl)-1-{[4-(methylsulfonyl)piperazin-1-yl]carbonyl}pyrrolidin-3-yl]-3-(3,5-dichlorophenyl)-1,3-dimethylurea, or a salt thereof.

11. 1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(3S,4R)-4-(5-fluoropyridin-2-yl)-1-({trans-4-[5-(trifluoromethyl)-1H-tetrazol-1-yl]cyclohexyl}carbonyl)pyrrolidin-3-yl]-1,3-dimethylurea, or a salt thereof.

12. A pharmaceutical composition comprising the compound or salt according to claim 1 and a pharmaceutically acceptable carrier.

13. A method of antagonizing an NK1 receptor in a mammal, comprising administering the pharmaceutical composition according to claim 12 to the mammal.

14. The method according to claim 13 , wherein the method further antagonizes an NK2 receptor and/or an NK3 receptor.

15. A method of antagonizing an NK2 receptor in a mammal, comprising administering the pharmaceutical composition according to claim 12 to the mammal.

16. The method according to claim 15 , wherein the method further antagonizes an NK1 receptor and/or an NK3 receptor.

17. A method for the treatment of vomiting, nausea, depression, anxiety neurosis, or anxiety, comprising administering an effective amount of the a compound represented by the formula

or salt according to claim 1 thereof to a mammal,
wherein:
ring A is a piperidine ring or a pyrrolidine ring and each straight line is a single bond and is a single bond;
ring B is an aromatic ring optionally having substituent(s);
ring D is an aromatic ring optionally having substituent(s), wherein 6-quinolyl is excluded;
L is a group represented by the formula

R 2 , R 3 , R 4a and R 4b are each independently a hydrogen atom, an optionally halogenated C 1-6 alkyl group or an optionally halogenated C 3-6 cycloalkyl group, or R 2 and R 3 are optionally bonded via an alkylene chain or an alkenylene chain, or R 4a and R 4b are optionally bonded via an alkylene chain or an alkenylene chain;
R 1 is a hydrogen atom or a substituent;
m and n are each independently an integer of 0 to 3; and
m+n is an integer of 2 to 3;
provided that when L is a group represented by the formula

wherein each of R 4a and R 4b is as defined above, then ring D is an aromatic ring having substituent(s);
excluding: N-[4-(biphenyl-4-yl)piperidin-3-yl]-N′-(naphthalen-2-yl)urea.

18. A compound represented by the formula

wherein:
ring B is an aromatic ring optionally having substituent(s);
ring D is a phenyl optionally having substituent(s) or an aromatic heterocyclic group optionally having substituent(s), wherein 6-quinolyl is excluded;
R 2 and R 3 are each independently a hydrogen atom, a halogenated C 1-6 alkyl group or an optionally halogenated C 3-6 cycloalkyl group, or R 2

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Shirai Junya
• Sugiyama Hideyuki
• Kamei Taku
• Maezaki Hironobu

Classifications

• C07D417/08

  linked by a carbon chain containing alicyclic rings · CPC title

• C07D207/14

  Nitrogen atoms not forming part of a nitro radical · CPC title

• C07D409/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D403/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D409/04

  directly linked by a ring-member-to-ring-member bond · CPC title