Antifungal agent containing heterocyclic compound

1. A compound represented by the formula (I-a), or a salt thereof:

wherein A 1 represents a 3-pyridyl group;

X 1 represents a group represented by the formula —C(═Y 1 )—NH—, wherein Y 1 represents an oxygen atom or a sulfur atom;

E represents a thienyl group;

with the proviso that A 1 optionally has 1 to 3 substituents selected from the following substituent groups a-1 and a-2, and that E has 1 or 2 substituents selected from the substituent groups a-1′ and a-2′;

<substituent group a-1>

substituent group a-1 represents the group consisting of: a halogen atom, a hydroxyl group, a mercapto group, a cyano group, a carboxyl group, an amino group, a carbamoyl group, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 3-8 cycloalkylidene C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 3-8 cycloalkoxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a C 6-10 aryl C 1-6 alkoxy group, a C 1-6 alkylthio group, a C 2-6 alkenylthio group, a C 2-6 alkynylthio group, a C 3-8 cycloalkylthio group, a C 6-10 arylthio group, a C 3-8 cycloalkyl C 1-6 alkylthio group, a C 6-10 aryl C 1-6 alkylthio group, a mono-C 1-6 alkylamino group, a mono-C 2-6 alkenylamino group, a mono-C 2-6 alkynylamino group, a mono-C 3-8 cycloalkylamino group, a mono-C 6-10 arylamino group, a mono-C 3-8 cycloalkyl C 1-6 alkylamino group, a mono-C 6-10 aryl C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a N—C 2-6 alkenyl-N—C 1-6 alkylamino group, a N—C 2-6 alkynyl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl C 1-6 alkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group, a C 1-6 alkylcarbonyl group, a C 1-6 alkoxycarbonyl group, a C 1-6 alkylsulfonyl group, a group represented by the formula —C(═N—R a1 )R a2 (wherein R a1 represents a hydroxyl group or a C 1-6 alkoxy group; R 2a represents a C 1-6 alkyl group), and a C 6-10 aryloxy C 1-6 group;

<substituent group a-2>

substituent group a-2 represents the group consisting of: a C 1-6 alkyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 3-8 cycloalkoxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a C 6-10 aryl C 1-6 alkoxy group, a C 1-6 alkylthio group, a C 2-6 alkenylthio group, a C 2-6 alkynylthio group, a C 3-8 cycloalkylthio group, a C 6-10 arylthio group, a C 3-8 cycloalkyl C 1-6 ,alkylthio group, a C 6-10 aryl C 1-6 alkylthio group, a mono-C 1-6 alkylamino group, a mono-C 2-6 alkenylamino group, a mono-C 2-6 alkynylamino group, a mono-C 3-8 cycloalkylamino group, a mono-C 6-10 arylamino group, a mono-C 3-8 cycloalkyl C 1-6 alkylamino group, a mono-C 6-10 aryl C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a N—C 2-6 alkenyl-N—C 1-6 alkylamino group, a N—C 2-6 alkynyl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl C 1-6 alkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group, and a C 6-10 aryloxy-C 1-6 alkyl group;

with the proviso that each group described in the substituent group a-2 has 1 to 3 substituents selected from the following substituent group b;

<substituent group b>

substituent group b represents the group consisting of: a halogen atom, a hydroxyl group, a mercapto group, a cyano group, a carboxyl group, an amino group, a carbamoyl group, a nitro group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 1-6 alkoxy group, a C 6-10 aryloxy group, a C 1-6 alkylcarbonyl group, a C 1-6 alkoxycarbonyl group, a C 1-6 alkylsulfonyl group, a trifluoromethyl group, a trifluoromethoxy group, a mono-C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a mono-C 6-10 arylamino group which optionally has one amino group or aminosulfonyl group and a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group which optionally has one amino group;

<substituent group a-1′>

substituent group a-1′ represents the group consisting of: a halogen atom, a hydroxyl group, a mercapto group, a cyano group, a carboxyl group, an amino group, a carbamoyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 3-8 cycloalkylidene C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkenyloxy group, a C 3-8 cycloalkoxy group, a C 6-10 aryloxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a C 6-10 aryl C 1-6 alkoxy group, a C 1-6 alkylthio group, a C 2-6 alkenylthio group, a C 2-6 alkynylthio group, a C 3-8 cycloalkylthio group, a C 6-10 arylthio group, a C 3-8 cycloalkyl C 1-6 alkylthio group, a C 6-10 aryl C 1-6 alkylthio group, a mono-C 1-6 alkylamino group, a mono-C 2-6 alkenylamino group, a mono-C 2-6 alkenylamino group, a mono-C 3-8 cycloalkylamino group, a mono-C 6-10 arylamino group, a mono-C 3-8 cycloalkyl C 1-6 alkylamino group, a mono-C 6-10 aryl C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a N—C 2-6 alkenyl-N—C 1-6 alkylamino group, a N—C 2-6 alkynyl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl C 1-6 alkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group, a C 1-6 alkylcarbonyl group, a C 1-6 alkoxycarbonyl group, a C 1-6 alkylsulfonyl group, a group represented by the formula —C(═N—R a1 )R a2 (wherein R a1 represents a hydroxyl group or a C 1-6 alkoxy group; R a2 represents a C 1-6 alkyl group), and a C 6-10 aryloxy C 1-6 alkyl group;

<substituent group a-2′>

substituent group a-2′ represents the group consisting of: a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 3-8 cycloalkoxy group, a C 6-10 aryloxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a C 6-10 aryl C 1-6 alkoxy group, a C 1-6 alkylthio group, a C 2-6 alkenylthio group, a C 2-6 alkenylthio group, a C 3-8 cycloalkylthio group, a C 6-10 arylthio group, a C 3-8 cycloalkyl C 1-6 alkylthio group, a C 6-10 aryl C 1-6 alkylthio group, a mono-C 1-6 alkylamino group, a mono-C 2-6 alkenylamino group, a mono-C 2-6 alkynylamino group, a mono-C 3-8 cycloalkylamino group, a mono-C 6-10 arylamino group, a mono-C 3-8 cycloalkyl C 1-6 alkylamino group, a mono-C 6-10 aryl C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a N—C 2-6 alkenyl-N—C 1-6 alkylamino group, a N—C 2-6 alkynyl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl-N—C 1-6 alkylamino group, a N—C 3-8 cycloalkyl C 1-6 alkyl-N—C 1-6 alkylamino group, a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group, and a C 6-10 aryloxy-C 1-6 alkyl group;

with the proviso that each group described in the substituent group a-2′ has 1 to 3 substituents selected from the following substituent group b;

<substituent group b>

substituent group b represents the group consisting of: a halogen atom, a hydroxyl group, a mercapto group, a cyano group, a carboxyl group, an amino group, a carbamoyl group, a nitro group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 1-6 alkoxy group, a C 6-10 aryloxy group, a C 1-6 alkylcarbonyl group, a C 1-6 alkoxycarbonyl group, a C 1-6 alkylsulfonyl group, a trifluoromethyl group, a trifluoromethoxy group, a mono-C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a mono-C 6-10 arylamino group which optionally has one amino group or aminosulfonyl group and a N—C 6-10 aryl C 1-6 alkylamino group which optionally has one amino group;

with the proviso that the following is excluded:

a compound in which A 1 represents a group represented by the formula:

wherein R A5 represents a hydrogen atom, a C 1-6 alkyl group or a trifluoromethyl group; R A6 represents a hydrogen atom or a trifluoromethyl group; Ar 2 represents a phenyl group which optionally has a substituent; and X 1 represents a group represented by the formula —C(═O)—NH—.

2. The compound according to claim 1 , or the salt thereof, wherein A 1 represents a 3-pyridyl group, with the proviso that A 1 optionally has 1 to 3 substituents selected from the substituent group a-1 defined above.

3. The compound according to claim 1 , or the salt thereof, wherein A 1 represents a 3-pyridyl group, with the proviso that A 1 optionally has 1 to 3 substituents selected from the following substituent groups c-1 and c-2;

<substituent group c-1>

substituent group c-1 represents the group consisting of: a halogen atom, an amino group, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a C 6-10 aryl C 1-6 alkoxy group, a mono-C 1-6 alkylamino group, a mono-C 2-6 alkenylamino group, a mono-C 2-6 alkynylamino group, a mono-C 3-8 cycloalkylamino group, a mono-C 6-10 arylamino group, a mono-C 3-8 cycloalkyl C 1-6 alkylamino group, a mono-C 6-10 aryl C 1-6 alkylamino group, a C 1-6 alkylcarbonyl group and a group represented by the formula —C(═N—OH)R a2 , wherein R a2 has the same meaning as defined above;

<substituent group c-2>

substituent group c-2 represents the group consisting of: a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, C 6-10 aryl C 1-6 alkoxy group, a mono-C 1-6 alkylamino group, a mono-C 2-6 alkenylamino group, a mono-C 2-6 alkynylamino group, a mono-C 3-8 cycloalkylamino group, a mono-C 6-10 arylamino group, a mono-C 3-8 cycloalkyl C 1-6 alkylamino group, and a mono-C 6-10 aryl C 1-6 alkylamino group;

with the proviso that each group described in substituent group c-2 has 1 to 3 substituents selected from the following substituent group d;

<substituent group d>

substituent group d represents the group consisting of: a halogen atom, a hydroxyl group, a carboxyl group, an amino group, a carbamoyl group, a C 1-6 alkoxy group, a mono-C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a mono-C 6-10 arylamino group that optionally having one amino group or aminosulfonyl group, a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group optionally having one amino group, a cyano group, a C 6-10 aryl group, and a C 1-6 alkoxycarbonyl group.

4. The compound according to claim 3 , or the salt thereof, wherein A 1 represents a group represented by the formula:

wherein R 1 , R 2 and R 3 are the same as or different from each other and represent a substituent selected from the substituent groups c-1 and c-2 defined above.

5. The compound according to claim 3 , or the salt thereof, wherein A 1 represents a group represented by the formula:

wherein R 1 and R 2 are the same as or different from each other and represent a substituent selected from the substituent groups c-1 and c-2 defined above; and

R 6 and R 7 are the same or different from each other and represent a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group or a group represented by the formula —CHR 8 —(CH 2 ) n1 —R 9 , wherein R 8 represents a hydrogen atom, a carboxyl group or a C 1-6 alkoxycarbonyl group; R 9 represents a hydroxyl group, a carboxyl group, a carbamoyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 1-6 alkoxycarbonyl group, a mono-C 1-6 alkylamino group, a di-C 1-6 alkylamino group, a phenyl group optionally having 1 to 3 substituents selected from the substituent group d defined above, a mono-C 6-10 arylamino group optionally having one amino group or an N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group optionally having one amino group; and n1 represents an integer from 0 to 3.

6. The compound according to claim 1 , or the salt thereof, wherein A 1 represents a group represented by the formula:

wherein R 11 represents a hydrogen atom or a group represented by the formula —CHR 12 —(CH 2 ) n2 —R 13 , wherein R 12 represents a hydrogen atom or a carboxyl group; R 13 represents a carboxyl group or a phenyl group optionally having 1 to 3 substituents selected from the substituent group d defined above; and n2 represents an integer from 0 to 3.

7. The compound according to claim 1 , or the salt thereof, wherein A 1 represents a group represented by the formula:

wherein R 14 represents a C 1-6 alkyl group having one C 1-6 alkoxy group.

8. A compound represented by the formula (I-a), or a salt thereof:

wherein A 1 represents a 3-pyridyl group, wherein optionally has 1 to 3 substituents selected from the following substituent groups c′-1 and c′-2;

<substituent group c′-1>

substituent group c′-1 represents the group consisting of: an amino group, a C 1-6 alkyl group and a mono-C 1-6 alkylamino group; and

<substituent group c′-2>

substituent group c′-2 represents the group consisting of a C 1-6 alkyl group and a mono-C 1-6 alkylamino group;

with the proviso that each group described in substituent group c′-2 has 1 to 3 substituents selected from the following substituent group d′;

<substituent group d′>

substituent group d′ represents the group consisting of: a halogen atom, a hydroxyl group, a cyano group, a carboxyl group and a C 1-6 alkoxy group;

X 1 represents a group represented by the formula —C(═Y 1 )—NH—;

Y 1 represents an oxygen atom or a sulfur atom;

wherein E represents a thienyl group, wherein E has 1 or 2 substituents selected from the following substituent groups e-1 and e-2;

<substituent group e-1>

substituent group e-1 represents the group consisting of: a halogen atom, a hydroxyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 3-8 cycloalkylidene C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 6-10 aryloxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a C 6-10 aryl C 1-6 alkoxy group, a C 6-10 arylthio group, a C 6-10 aryl C 1-6 alkylthio group, a mono-C 6-10 arylamino group, a mono-C 6-10 aryl C 1-6 alkylamino group, a N—C 6-10 aryl-N—C 1-6 alkylamino group, a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group, and a C 6-10 aryloxy C 1-6 alkyl group;

<substituent group e-2>

substituent group e-2 represents the group consisting of: a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 6-10 aryl group, a C 3-8 cycloalkyl C 1-6 alkyl group, a C 6-10 aryl C 1-6 alkyl group, a C 1-6 alkoxy group, a C 2-6 alkenyloxy group, a C 2-6 alkynyloxy group, a C 6-10 aryloxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a C 6-10 aryl C 1-6 alkoxy group, a C 6-10 arylthio group, a C 6-10 aryl C 1-6 alkylthio group, a mono-C 6-10 arylamino group, a mono-C 6-10 aryl C 1-6 alkylamino group, a N—C 6-10 aryl-N—C 1-6 alkylamino group, a N—C 6-10 aryl C 1-6 alkyl-N—C 1-6 alkylamino group, and a C 6-10 aryloxy C 1-6 alkyl group;

with the proviso that each group described in substituent group e-2 has 1 to 3 substituents selected from the following substituent group f;

<substituent group f>

substituent group f represents the group consisting of: a halogen atom, a hydroxyl group, a cyano group, an amino group, a nitro group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group, a C 6-10 aryloxy group, a C 1-6 alkylcarbonyl group, a C 1-6 alkoxycarbonyl group, a C 1-6 alkylsulfonyl group, a mono-C 6-10 arylamino group, a trifluoromethyl group, a trifluoromethoxy group and a C 1-6 alkyl group.

9. The compound according to claim 8 , or the salt thereof, wherein X 1 represents a group represented by the formula —C(═O)—NH—.

10. The compound according to claim 8 , or the salt thereof, wherein E represents a thienyl group, wherein E has one substituent selected from the following substituent groups g-1 and g-2;

<substituent group g-1>

substituent group g-1 represents the group consisting of a C 3-8 cycloalkyl C 1-6 alkyl group, a phenyl C 1-6 alkyl group, a C 1-6 alkoxy group, a phenoxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a phenyl C 1-6 alkoxy group, and a phenoxy C 1-6 alkyl group;

<substituent group g-2>

substituent group g-2 represents the group consisting of: a C 3-8 cycloalkyl C 1-6 alkyl group, a phenyl C 1-6 alkyl group, a C 1-6 alkoxy group, a phenoxy group, a C 3-8 cycloalkyl C 1-6 alkoxy group, a phenyl C 1-6 alkoxy group, and a phenoxy C 1-6 alkyl group;

with the proviso that each group described in substituent group g-2 has 1 to 3 substituents selected from the following substituent group h;

<substituent group h>

substituent group h represents the group consisting of: a halogen atom, a hydroxyl group, a cyano group and a C 1-6 alkyl group.

11. The compound according to claim 10 , or the salt thereof, wherein E represents a 2-thienyl group, wherein E has one substituent selected from the substituent groups g-1 and g-2 defined above.

12. The compound according to claim 10 , or the salt thereof, wherein X 1 represents a group represented by the formula —C(═O)—NH—, and A 1 represents a group represented by the formula:

wherein R 1 , R 2 and R 3 are the same as or different from each other and represent a substituent selected from the substituent c′ 1 and c′-2;

with the proviso that each group described in substituent group c′-2 has 1 to 3 substituents selected from the substituent group d′; and

E represents a 2-thienyl group, wherein E has one substituent selected from the substituent group g-1 or g-2 defined above.

13. The compound according to claim 12 , or the salt thereof, wherein A 1 represents a group represented by the formula:

wherein R 1 and R 2 have the same meanings as defined above; and

R 6 and R 7 are the same or different from each other and represent a hydrogen atom, or a C 1-6 alkyl group which optionally has 1 to 3 substituents selected from the following substituent group d′ below;

<substituent group d′>

substituent group d′ represents the group consisting of: a halogen atom, a hydroxyl group, a cyano group, a carboxyl group and a C 1-6 alkoxy group.

14. The compound according to claim 12 , or the salt thereof, wherein A 1 represents a group represented by the formula:

R 14 represents a C 1-6 alkyl group having one C 1-6 alkoxy group.

15. A pharmaceutical composition comprising the compound according to claim 1 , or the salt thereof; and

a pharmaceutically acceptable carrier.

16. A method for prevention or treatment of fungal infection comprising administering a pharmacologically effective amount of the compound according to claim 1 , or the salt thereof.

17. A pharmaceutical composition comprising the compound according to claim 8 , or the salt thereof; and

a pharmaceutically acceptable carrier.