Nitrogen containing heterocyclic compounds and medicines containing the same

1. A compound represented by the following formula:

wherein X 2 represents methylene, 1,2-ethylene or 1,1-ethylene;

wherein -X 3 -X 4 - is methylene, oxygen, a single bond or a group represented by the formula;

wherein X 40 represents (1) methylene having between 0 and 2 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano, (2) oxygen, (3) -CO- , (4) -S-, (5) -S(O)- or (6) -S(O) 2 -;

X 41 represents methylene having between 0 and 2 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano;

R 34 represents C 1-6 alkyl;

R 41 represents (1) phenyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano,

(2) phenyl-C 1-6 alkyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano or (3) C 1-6 alkyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkoxy, and cyano; and

R 42 represents (1) C 1-6 alkyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkoxy, and cyano or (2) hydrogen;

wherein A 2 is phenyl having between 0 and 3 substituents selected from Substituent Group A below, 1-naphthyl having between 0 and 3 substituents selected from Substituent Group A below, 2-naphthyl having between 0 and 3 substituents selected from Substituent Group A below, an aromatic ring having 5 to 10 atoms in the ring and containing one or more hetero atoms among the atoms of the ring and having between 0 and 3 substituents selected from Substituent Group A below, or a 9- to 11-membered benzene fused ring group having between 0 and 3 substituents selected from Substituent Group A below;

wherein Substituent Group A is the group consisting of C 1-6 alkyl having between 0 and 3 substituents selected from Substituent Group B below, C 1-6 alkoxy having between 0 and 3 substituents selected from Substituent Group B below, halogen, C 3-8 cycloalkyl, C 2-7 alkoxycarbonyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, cyano, nitro, phenyl, pyridyl, ethylenedioxy, methylenedioxy, a group represented by the formula:

wherein t1 and t2 each independently represents zero or an integer from 1 to 3, and R 80 represents hydrogen, C 1-6 alkyl or C 3-8 cycloalkyl,

and a group represented by the formula:

wherein R 73 and R 74 each independently represents hydrogen, C 1-6 alkyl, C 2-7 acyl, C 1-6 alkylsulfonyl, —CO—NR 75 R 76 or —CS—NR 75 R 76 , and R 75 and R 76 each independently represents hydrogen or C 1-6 alkyl;

wherein Substituent Group B is the group consisting of halogen, C 1-6 alkoxy, cyano, hydroxyl, and C 3-8 cycloalkyl;

wherein A 1 represents a group represented by the formula:

wherein R 21 represents hydrogen or C 1-6 alkyl, and R 61a and R 62a each independently represents hydrogen, halogen, C 1-6 alkoxy, C 1-6 alkyl or cayno; and

wherein R 51 , R 53 , R 54 , R 55 and R 57 each independently represents (1) hydrogen, (2) halogen, (3) cyano, (4) hydroxyl, (5) C 2-7 alkoxycarbonyl, (6) C 1-6 alkyl having between 0 to 4 substituents selected from the group consisting of hydroxyl, C 1-6 alkoxy, and halogen, (7) C 1-6 alkoxy having between 0 and 4 substituents selected from the group consisting of hydroxyl, C 1-6 alkoxy, and halogen, (8) 2-methylphenyloxymethyl or (9) 2-fluorophenyloxymethyl, a salt thereof or a hydrate of the foregoing.

2. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein R 51 , R 53 , R 54 , R 55 and R 57 each independently represents (1) hydrogen, (2) hydroxyl, (3) halogen, (4) alkyl, (5) cyano or (6) hydroxymethyl.

3. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein at least one of R 51 , R 53 , R 54 , R 55 and R 57 is not hydrogen.

4. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein at least four of R 51 , R 53 , R 54 , R 55 and R 57 are hydrogen.

5. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein all of R 51 , R 53 , R 54 , R 55 and R 57 are hydrogen.

6. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein —X 3 —X 4 — is a group represented by the formula:

wherein X 42 represents (1) methylene having 0 or 1 substituent selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano, (2) oxygen, (3) —CO—, (4) —S—, (5) —S(O)—, (6) —S(O) 2 — or (7) —CF 2 —, and

R 43 represents either methylene having 0 or 1 substituent selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano, or —CF 2 —.

7. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein —X 3 —X 4 — is a group represented by the formula:

wherein X 45 represents either methylene having 0 or 1 substituent selected from the group consisting of fluorine, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano, or —CF 2 —.

8. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein —X 3 —X 4 — is a group represented by the formula:

9. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein A 2 is a monovalent group derived by removing a hydrogen atom from a compound represented by the formula:

and A 2 has between 0 and 3 substituents selected from Substituent Group A, wherein Substituent Group A is the group consisting of C 1-6 alkyl having between 0 and 3 substituents selected from Substituent Group B below, C 1-6 alkoxy having between 0 and 3 subsuituents selected from Substituent Group B below, halogen, C 3-8 cycloalkyl, C 2-7 alkoxycarbonyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, cyano, nitro, phenyl, pyridyl, ethylenedioxy, methylenedioxy, a group represented by the formula:

wherein t1 and t2 each independently represents zero or an integer from 1 to 3, and R 80 represents hydrogen, C 1-6 alkyl or C 3-8 cycloalkyl, and a group represented by the formula:

wherein R 73 and R 74 each independently represents hydrogen, C 1-6 alkyl, C 2-7 acyl, C 1-6 alkylsulfonyl, —CO—NR 75 R 76 or —CS—NR 75 R 76 , and R 75 and R 76 each independently represents hydrogen or C 1-6 alkyl;

wherein Substituent Group B is the group consisting of halogen, C 1-6 alkoxy, cyano, hydroxyl, and C 3-8 cycloalkyl.

10. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein Substituent Group A is the group consisting of halogen, C 1-6 alkyl having between 0 and 3 substituents selected from Substituent Group B, C 1-6 alkoxy having between 0 and 3 substituents selected from Substituent Group B, C 3-8 cycloalkyl, C 1-6 alkylthio, and a group represented by the formula:

wherein t1 and t2 each independently represents zero or an integer from 1 to 3, and R 80 represents hydrogen, C 1-6 alkyl or C 3-8 cycloalkyl.

11. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein A 2 is a group represented by the formula:

wherein R 81 represents (1) C 1-6 alkyl having between 0 and 3 substituents selected from the group consisting of halogen, C 3-8 cycloalkyl, and C 1-6 alkoxy, (2) C 1-6 alkoxy having between 0 and 3 substituents selected from the group consisting of halogen, C 3-8 cycloalkyl, and C 1-6 alkoxy, (3) hydrogen, (4) C 1-6 alkylthio having between 0 and 3 substituents selected from the group consisting of halogen, C 3-8 cycloalkyl, and C 1-6 alkoxy or (5) halogen.

12. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein A 2 is a group represented by the formula:

13. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein A 1 is a group represented by the formula:

14. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein R 21 is hydrogen.

15. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein R 61a and R 62a are hydrogen.

16. A compound according to claim 1 , a salt of the compound or a hydrate of the foregoing, wherein the compound is a compound selected from the group consisting of:

6-[2-[4-(2-fluorophenoxymethyl)piperidino]ethyl]-1H-pyrazin-2-one,

(E)-3-[4-[2-(3-methyl-2-thienyl)vinyl]piperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-(2,3-dihydrobenzofuran-7-yl)ethyl]piperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-(2-fluorophenyl)acetyl]piperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-(2-methylphenyl)acetyl]piperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-(2-methoxyphenyl)acetyl]piperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-[2-(trifluoromethyl)phenyl]acetyl]piperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-[2-fluoro-6-(trifluoromethyl)phenyl]acetyl]piperidino]methyl-1H-pyrazin-2-one,

cis-3-[4-[2-(2-fluorophenyl)acetyl]-2-methylpiperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-(2-fluorophenyl)acetyl]-4-methylpiperidino]methyl-1H-pyrazin-2-one,

3-[4-methyl-4-[2-[2-(trifluoromethyl)phenyl]acetyl]piperidino]methyl-1H-pyrazin-2-one,

3-[1-[4-[2-(2-fluorophenyl)acetyl]piperidino]ethyl]-1H-pyrazin-2-one,

3-[1-[4-[2-[2-(trifluoromethyl)phenyl]acetyl]piperidino]ethyl]-1H-pyrazin-2-one,

3-[4-(2-fluorophenoxymethyl)piperidino]methyl-1H-pyrazin-2-one,

3-[4-(2-methoxyphenoxymethyl)piperidino]methyl-1H-pyrazin-2-one,

3-[4-(2-methylphenoxymethyl)piperidino]methyl-1H-pyrazin-2-one,

3-[4-[2-(2-ethoxyphenyl)acetyl]piperidino]methyl-1H-pyrazin-2-one, and

3-[4-[2-[2-(methylthio)phenyl]acetyl]piperidino]methyl-1H-pyrazin-2-one.

17. A method for treating neuralgia, comprising administering to a patient a pharmacologically effective dose of a compound according to claim 1 , a salt thereof or a hydrate of the foregoing.

18. A method for treating diabetic neuralgia, HIV neuralgia, postherpetic neuralgia, trigemical neuralgia, stump pain, post spinal injury pain, thalamic pain or post-stroke pain, comprising administering to a patient a pharmacologically effective dose of a compound according to claim 1 , a salt thereof or a hydrate of the foregoing.

19. A method for treating low back pain, inflammatory pain, arthralgia, postoperative pain or cancer pain, comprising administering to a patient a pharmacologically effective dose of a compound according to claim 1 , a salt thereof or a hydrate of the foregoing.

20. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

21. The pharmaceutical composition of claim 20 , wherein the composition is formulated for parenteral administration.

22. The pharmaceutical composition of claim 20 , wherein the composition is formulated for oral administration.

23. A compound represented by the following formula:

wherein X 2 represents methylene, 1,2-ethylene or 1,1-ethylene;

wherein —X 3 —X 4 — is methylene, oxygen, a single bond or a group represented by the formula:

wherein X 40 represents (1) methylene having between 0 and 2 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano, (2) oxygen, (3) —CO—, (4) —S—, (5) —S(O)— or (6) —S(O) 2 —;

X 41 represents methylene having between 0 and 2 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano;

X 34 represents C 1-6 alkyl;

X 41 represents (1) phenyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano, (2) phenyl-C 1-6 alkyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl, C 1-6 alkoxy, and cyano or (3) C 1-6 alkyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkoxy, and cyano; and

R 42 represents (1) C 1-6 alkyl having between 0 and 3 substituents selected from the group consisting of halogen, hydroxyl, C 1-6 alkoxy, and cyano or (2) hydrogen;

wherein A 2 a monovalent group derived by removing a hydrogen atom from a compound represented by the formula:

and A 2 has between 0 and 3 substituents selected from Substituent Group A,

wherein Substituent Group A is the group consisting of C 1-6 alkyl having between 0 and 3 substituents selected from Substituent Group B below, C 1-6 alkoxy having between 0 and 3 substituents selected from Substituent Group B below, halogen, C 3-8 cycloalkyl, C 2-7 alkoxycarbonyl, C 2-7 acyl, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, cyano, nitro, phenyl, pyridyl, ethylenedioxy, methylenedioxy, a group represented by the formula:

wherein t1 and t2 each independently represents zero or an integer from 1 to 3, and R 80 represents hydrogen, C 1-6 alkyl or C 3-8 cycloalkyl,

and a group represented by the formula:

wherein R 73 and R 74 each independently represents hydrogen, C 1-6 alkyl, C 2-7 acyl, C 1-6 alkylsulfonyl, —CO—NR 75 R 76 or —CS—NR 75 R 76 , and R 75 and R 76 each independently represents hydrogen or C 1-6 alkyl;

wherein Substituent Group B is the group consisting of halogen, C 1-6 alkoxy, cyano, hydroxyl, and C 3-8 cycloalkyl;

wherein A 1 represents a group represented by the formula:

wherein R 21 represents hydrogen or C 1-6 alkyl, and R 61a and R 62a each independently represents hydrogen, halogen, C 1-6 alkoxy, C 1-6 alkyl, or cyano; and

wherein R 51 , R 53 , R 54 , R 55 and R 57 each independently represents (1) hydrogen, (2) halogen, (3) cyano, (4) hydroxyl, (5) C 2-7 alkoxycarbonyl, (6) C 1-6 alkyl having between 0 and 4 substituents selected from the group consisting of hydroxyl, C 1-6 alkoxy, and halogen, (7) C 1-6 alkoxy having between 0 and 4 substituents selected from the group consisting of hydroxyl, C 1-6 alkoxy, and halogen, (8) 2-methylphenyloxymethyl or (9) 2-fluorophenyloxymethyl, a salt thereof or a hydrate of the foregoing.

24. A method for treating neuralgia, comprising administering to a patient a pharmacologically effective dose of a compound according to claim 23 , a salt thereof or a hydrate of the foregoing.

25. A method for treating diabetic neuralgia, HIV neuralgia, postherpetic neuralgia, trigemical neuralgia, stump pain, post spinal injury pain, thalamic pain or post-stroke pain, comprising administering to a patient a pharmacologically effective dose of a compound according to claim 23 , a salt thereof or a hydrate of the foregoing.

26. A method for treating low back pain, inflammatory pain, arthralgia, postoperative pain or cancer pain, comprising administering to a patient a pharmacologically effective dose of a compound according to claim 23 , a salt thereof or a hydrate of the foregoing.

27. A pharmaceutical composition, comprising a compound of claim 23 , and a pharmaceutically acceptable carrier.

28. The pharmaceutical composition of claim 27 , wherein the composition is formulated for parenteral administration.

29. The pharmaceutical composition of claim 27 , wherein the composition is formulated for oral administration.