Compound having 11β-HSD1 inhibitory activity
The present invention provides compounds having excellent 11β-HSD1 inhibitory activity. A compound represented by the following formula (I): [wherein X 1 represents an oxygen atom, or the formula —(CR 11 R 12 ) p —, etc., Y 1 represents a hydrogen atom, a hydroxyl group, etc., Z 1 represents an oxygen atom or the formula —(NR 14 )—, R 1 represents a hydrogen atom, a halogen atom, a cyano group, a C 1-4 alkyl group, a C 1-4 alkyl group substituted with 1 to 3 halogen atoms, a C 1-4 alkoxy group, a C 1-4 alkoxycarbonyl group, a carboxyl group, a carbamoyl group, or an amino group, and m represents an integer of 1 or 2, and R 2 represents a hydrogen atom or a C 1-4 alkyl group, and n represents an integer of 1 or 2].
1. A compound represented by the following formula (I):
[wherein
X 1 represents an oxygen atom, or the formula —(CR 11 R 12 ) p — (wherein R 11 and R 12 , which may be the same or different, each represent a hydrogen atom or a C 1-4 alkyl group, and p represents an integer of 0 to 2), a sulfur atom, the formula —S(O)—, the formula —S(O) 2 —, or the formula —N(R 13 )— (wherein R 13 represents a hydrogen atom, a C 1-4 alkyl group, a C 1-4 alkylcarbonyl group or a C 1-4 alkoxycarbonyl group),
Y 1 represents a hydrogen atom, a hydroxyl group, a halogen atom, a C 1-4 alkoxy group, a C 1-4 alkoxycarbonyl group, a carboxyl group, a carbamoyl group, a C 1-4 alkylsulfonyl group, a C 1-4 alkylsulfonyl-C 1-4 alkoxy group, or a carbamoylmethoxy group,
Z 1 represents an oxygen atom or the formula —(NR 14 )— (wherein R 14 represents a hydrogen atom or a C 1-4 alkyl group),
R 1 represents a hydrogen atom, a halogen atom, a cyano group, a C 1-4 alkyl group, a C 1-4 alkyl group substituted with 1 to 3 halogen atoms, a C 1-4 alkoxy group, a C 1-4 alkoxycarbonyl group, a carboxyl group, a carbamoyl group, or an amino group, and m represents an integer of 1 or 2, and
R 2 represents a hydrogen atom or a C 1-4 alkyl group, and n represents an integer of 1 or 2].
2. A compound represented by the following formula (II):
[wherein
X 1 represents an oxygen atom, or the formula —(CR 11 R 12 ) p — (wherein R 11 and R 12 , which may be the same or different, each represent a hydrogen atom or a C 1-4 alkyl group, and p represents an integer of 0 to 2), a sulfur atom, the formula —S(O)—, the formula —S(O) 2 —, or the formula —N(R 13 )— (wherein R 13 represents a hydrogen atom, a C 1-4 alkyl group, a C 1-4 alkylcarbonyl group or a C 1-4 alkoxycarbonyl group),
Y 1 represents a hydroxyl group, a halogen atom, a C 1-4 alkoxy group, a C 1-4 alkoxycarbonyl group, a carboxyl group, a carbamoyl group, a C 1-4 alkylsulfonyl group, a C 1-4 alkylsulfonyl-C 1-4 alkoxy group, or a carbamoylmethoxy group,
Z 1 represents an oxygen atom or the formula —(NR 14 )— (wherein R 14 represents a hydrogen atom or a C 1-4 alkyl group),
R 1 represents a hydrogen atom, a halogen atom, a cyano group, a C 1-4 alkyl group, a C 1-4 alkyl group substituted with 1 to 3 halogen atoms, a C 1-4 alkoxy group, a C 1-4 alkoxycarbonyl group, a carboxyl group, a carbamoyl group, or an amino group, and m represents an integer of 1 or 2, and
R 2 represents a hydrogen atom or a C 1-4 alkyl group, and n represents an integer of 1 or 2].
3. A compound represented by the following formula (III):
[wherein
X 2 represents an oxygen atom or the formula —(CR 21 R 22 ) r — (wherein R 21 and R 22 , which may be the same or different, each represent a hydrogen atom or a C 1-4 alkyl group, and r represents an integer of 0 to 2),
Y 2 represents a hydrogen atom, a hydroxyl group, a halogen atom, a C 1-4 alkoxy group, a C 1-4 alkoxycarbonyl group, a carboxyl group, or a carbamoyl group,
Z 2 represents an oxygen atom or the formula —(NR 23 )— (wherein R 23 represents a hydrogen atom or a C 1-4 alkyl group),
R 3 represents a hydrogen atom, a halogen atom, a cyano group, a C 1-4 alkyl group, or a C 1-4 alkoxy group, and m′ represents an integer of 1 or 2, and
R 4 represents a hydrogen atom or a C 1-4 alkyl group, and n′ represents an integer of 1 or 2].
4. A compound represented by the following formula (IV):
[wherein
X 2 represents an oxygen atom or the formula —(CR 21 R 22 ) r — (wherein R 21 and R 22 , which may be the same or different, each represent a hydrogen atom or a C 1-4 alkyl group, and r represents an integer of 0 to 2),
Y 2 represents a hydroxyl group, a halogen atom, a C 1-4 alkoxy group, a C 1-4 alkoxycarbonyl group, a carboxyl group, or a carbamoyl group,
Z 2 represents an oxygen atom or the formula —(NR 23 )— (wherein R 23 represents a hydrogen atom or a C 1-4 alkyl group),
R 3 represents a hydrogen atom, a halogen atom, a cyano group, a C 1-4 alkyl group, or a C 1-4 alkoxy group, and m′ represents an integer of 1 or 2, and
R 4 represents a hydrogen atom or a C 1-4 alkyl group, and n′ represents an integer of 1 or 2].
5. A compound represented by the following formula (V):
[wherein
X 3 represents —(CH 2 ) s — (wherein s represents an integer of 0 or 1),
Y 3 represents a hydrogen atom or a hydroxyl group,
R 5 represents a hydrogen atom, a halogen atom, a C 1-4 alkyl group or a C 1-4 alkoxy group, and
R 6 represents a hydrogen atom or a C 1-4 alkyl group].
6. The compound of formula (V) according to claim 5 , wherein Y 3 is a hydroxyl group.
7. A compound represented by the following formula (VI):
[wherein
X 3 represents —(CH 2 ) s — (wherein s represents an integer of 0 or 1),
R 5 represents a hydrogen atom, a halogen atom, a C 1-4 alkyl group or a C 1-4 alkoxy group, and
R 6 represents a hydrogen atom or a C 1-4 alkyl group].
8. A pharmaceutical composition which comprises the compound according to claim 1 and a pharmaceutical acceptable carrier.
9. A method for treating type II diabetes, which comprises administering to a subject in need thereof an effective amount of the compound according to claim 1 .