USRE48334EActiveUtilityPatentIndex 72
Nitrogen-containing heterocyclic compound and use of same
Est. expirySep 19, 2028(~2.2 yrs left)· nominal 20-yr term from priority
C07D 417/08C07D 207/14C07D 409/06C07D 403/06C07D 409/04C07D 403/04C07D 405/06C07D 413/06C07D 413/04C07D 413/08C07D 409/12C07D 403/10C07D 211/58C07D 405/12C07D 401/14C07D 401/12C07D 413/14C07D 401/06C07D 401/04A61P 1/04A61P 25/00A61P 13/10A61P 25/04A61P 29/00A61P 1/00A61P 13/00A61P 1/08A61P 25/22A61P 25/24A61P 43/00
72
PatentIndex Score
1
Cited by
56
References
49
Claims
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.
Claims
exact text as granted — not AI-modifiedThe 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 and R 3 are optionally bonded via an alkylene chain or an alkenylene chain;
R 1 is an alkyl group substituted by a C 1-6 alkoxy group;
or a salt thereof.
19. The compound or salt according to claim 18, wherein R 2 and R 3 are each a hydrogen atom.
20. The compound or salt according to claim 18, wherein ring B is a phenyl ring optionally having substituent(s).
21. The compound or salt according to claim 20, wherein the phenyl ring optionally has 1 to 3 fluorine substituent(s).
22. The compound or salt according to claim 21, wherein the phenyl ring has 1 to 3 fluorine substituent(s).
23. The compound or salt according to claim 18, wherein ring D is an aromatic heterocyclic group substituted by 1 to 3 substituents.
24. The compound or salt according to claim 23, wherein the aromatic heterocyclic group is a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 hetero atoms of one or two kinds selected from a nitrogen atom, an oxygen atom and a sulfur atom.
25. The compound or salt according to claim 24, wherein the aromatic heterocyclic group is selected from the group consisting of furyl, thienyl, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, indolyl, thiazolyl, oxazolyl, thiadiazolyl, triazolyl and tetrazolyl.
26. The compound or salt according to claim 25, wherein ring D is imidazolyl or pyrazolyl optionally substituted by 1 to 3 substituents.
27. The compound or salt according to claim 26, wherein ring D is imidazolyl or pyrazolyl substituted by 1 to 3 substituents.
28. The compound or salt according to claim 23, wherein the aromatic heterocyclic group is a bicyclic fused ring group containing 1 to 4 hetero atoms of one or two kinds selected from a nitrogen atom, an oxygen atom and a sulfur atom.
29. The compound or salt according to claim 28, wherein the aromatic heterocyclic group is a condensation of a 5- to 6-membered aromatic heterocycle and one or two 5- or 6-membered heterocycles containing, besides carbon atoms, 1 to 4 hetero atoms selected from an oxygen atom, a sulfur atom and a nitrogen atom.
30. The compound or salt according to claim 29, wherein the 5- to 6-membered aromatic heterocycle is imidazolyl or pyrazolyl optionally substituted by 1 to 3 substituents.
31. The compound or salt according to claim 29, wherein the 5- to 6-membered aromatic heterocycle is imidazolyl or pyrazolyl substituted by 1 to 3 substituents.
32. A pharmaceutical composition comprising the compound or salt according to claim 18 and a pharmaceutically acceptable carrier.
33. A method of antagonizing an NK1 receptor in a mammal, comprising administering an effective amount of the pharmaceutical composition according to claim 32 to the mammal.
34. The method according to claim 33, wherein the method further antagonizes an NK2 receptor and/or an NK3 receptor.
35. A method of antagonizing an NK2 receptor in a mammal, comprising administering an effective amount of the pharmaceutical composition according to claim 32 to the mammal.
36. The method according to claim 35, wherein the method further antagonizes an NK1 receptor and/or an NK3 receptor.
37. A method for the treatment of vomiting, nausea, depression, anxiety neurosis, or anxiety, comprising administering an effective amount of the compound or salt according to claim 18 to a mammal.
38. A compound represented by the formula
wherein:
ring A is 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, a 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 an alkyl group substituted by a C 1-6 alkoxy group;
m and n are each independently an integer of 0 to 2; and
m+n is an integer of 2;
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); or a salt thereof.
39. The compound or salt according to claim 38, wherein ring B is a phenyl group optionally having substituent(s) or a pyridyl group optionally having substituent(s).
40. The compound or salt according to claim 38, wherein ring B is a phenyl group optionally having substituent(s) or a thienyl group optionally having substituent(s).
41. The compound or salt according to claim 38, wherein ring D is a phenyl group optionally having substituent(s).
42. The compound or salt according to claim 38, wherein R 2 is a hydrogen atom.
43. The compound or salt according to claim 38, wherein L is a group represented by the formula
wherein R 3′ is a hydrogen atom or a C 1-6 alkyl group.
44. The compound or salt according to claim 38, wherein ring D is a 3,5-bis(trifluoromethyl)phenyl group or a 3,5-dichlorophenyl group.
45. A pharmaceutical composition comprising the compound or salt according to claim 38 and a pharmaceutically acceptable carrier.
46. A method of antagonizing an NK1 receptor in a mammal, comprising administering the pharmaceutical composition according to claim 45 to the mammal.
47. The method according to claim 46, wherein the method further antagonizes an NK2 receptor and/or an NK3 receptor.
48. A method of antagonizing an NK2 receptor in a mammal, comprising administering the pharmaceutical composition according to claim 45 to the mammal.
49. The method according to claim 48, wherein the method further antagonizes an NK1 receptor and/or an NK3 receptor.Cited by (0)
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