HETEROCYCLIC COMPOUND

• US 20100256156A1
• Filed: 10/31/2008
• Published: 10/07/2010
• Est. Priority Date: 11/01/2007
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Tokunoh, Ryosuke, Hara, Ryoma, Banno, Yoshihiro
• Granted Patent: US 8,309,580 B2
• Time in Patent Office: Days
• US Class Current: 514/252.10
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07D 207/20 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 307/42 Singly bound oxygen atoms
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/16 by oxygen atoms
• CPC Class Codes: C07D 333/36 Nitrogen atoms
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 407/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond

Abstract

The present invention provides a heterocyclic compound represented by the following formula (I), which has a glucagon antagonistic action and is useful for the prophylaxis or treatment of diabetes and the like, a compound represented by

wherein ring A is an optionally substituted benzene ring and the like; Y is a nitrogen atom and the like; X is —O— and the like; R⁴ is a hydrogen atom and the like; R⁵ and R⁶ are each independently a hydrogen atom and the like; R¹ is an optionally substituted hydrocarbon group and the like; R² is a hydrogen atom and the like; and R³ is —(CH₂)₃—COOH and the like, or a salt thereof.

Claims

1. A compound represented by the formula (I):

2. The compound according to claim 1, wherein ring A is an optionally substituted benzene ring or an optionally substituted pyridine ring.

3. The compound according to claim 1, wherein X is —

CR⁴R⁵—

O—

or —

CR⁴R⁵—

NR⁶—

.

4. The compound according to claim 1, wherein R¹ is an optionally substituted C_1-6 alkyl group, an optionally substituted C_3-10 cycloalkyl group, an optionally substituted C_6-14 aryl group, an optionally substituted heterocyclic group, a C_1-6 alkyl-carbonyl group or a C_3-10 cycloalkyl-carbonyl group.

5. The compound according to claim 1, wherein R² is an optionally substituted C_1-6 alkyl group or an optionally substituted C_3-10 cycloalkyl group.

6. The compound according to claim 1, wherein R³ is —

NR⁷—

CR⁸R⁹—

CR¹⁰R¹¹—

COOH.

7. The compound according to claim 1, wherein ring A is an optionally substituted benzene ring or an optionally substituted pyridine ring;

Y is an oxygen atom, a sulfur atom or a nitrogen atom;

X is —

CR⁴R⁵—

O—

or —

CR⁴R⁵—

NR⁶—

;

R¹ is an optionally substituted C_1-6 alkyl group, an optionally substituted C_3-10 cycloalkyl group, an optionally substituted C_6-14 aryl group, an optionally substituted heterocyclic group, a C_1-6 alkyl-carbonyl group or a C_3-10 cycloalkyl-carbonyl group;

R² is an optionally substituted C_1-6 alkyl group or an optionally substituted C_3-10 cycloalkyl group; and

R³ is —

NR⁷—

CR⁸R⁹—

CR¹⁰R¹¹—

COOH.

13. A prodrug of the compound according to claim 1.

14. A medicament comprising the compound according to claim 1 or a prodrug thereof.

15. The medicament according to claim 14, which is a glucagon antagonist.

16. The medicament according to claim 14, which is an agent for the prophylaxis or treatment of diabetes.

17. A method of suppressing sugar production in a mammal, comprising administering the compound according to claim 1 or a prodrug thereof to the mammal.

18. A method for the prophylaxis or treatment of diabetes in a mammal, comprising administering the compound according to claim 1 or a prodrug thereof to the mammal.

8. 3-[{[4-({1-[5-(6-Methoxypyridin-3-yl)-2-methylfuran-3-yl]-3-methylbutyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid or a salt thereof.

9. 3-[{[4-({Cyclohexyl[5-(4-fluorophenyl)-2-(methoxymethyl)furan-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid or a salt thereof.

10. 3-[{[5-({Cyclohexyl[5-(4-fluorophenyl)-2-methylfuran-3-yl]methyl}amino)pyridin-2-yl]carbonyl}(methyl)amino]propanoic acid or a salt thereof.

11. 3-[{[4-({Cyclohexyl[5-(6-methoxypyridin-3-yl)-2-methylfuran-3-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoic acid or a salt thereof.

12. 3-{[(5-{[Cyclohexyl(2-methyl-5-phenylthiophen-3-yl)methyl]amino}pyridin-2-yl)carbonyl](methyl)amino}propanoic acid or a salt thereof.

19-20. -20. (canceled)