Heteroarylcarboxylic acid ester derivative
Compounds represented by the following formula (I); wherein each symbol is as defined in the specification, are useful as hyperglycemic inhibitors having a serine protease inhibitory action and as prophylactic or therapeutic drugs for diabetes.
1. A compound represented by formula (I):
wherein:
R 1 and R 2 are the same or different and each is independently a C 1-4 alkyl group or a C 2-4 alkenyl group, or R 1 and R 2 together with the carbon atom to which they are bonded form a C 3-8 cycloalkane ring;
X is a group represented by formula (II):
wherein:
R 6 is a hydrogen atom, a C 1-8 alkyl group, a carboxyl C 1-8 alkyl group, or a C 3-8 alkenyl group, wherein said C 1-8 alkyl group and said C 3-8 alkenyl group may be substituted with one or more substituents;
Ra and Rb are the same or different and each is independently a hydrogen atom, a C 1-8 alkyl group, a carboxyl C 1-8 alkyl group, a carboxyl group, an aryl group, a C 3-6 heterocyclic group containing 1 to 4 heteroatoms selected from the group consisting of O, N, and S, or a C 3-8 cycloalkyl group, or Ra and Rb together with the atom(s) to which they are bonded form a C 3-8 cycloalkane ring or a C 3-9 heterocycle containing 1-4 heteroatoms selected from the group consisting of O, N, and S, wherein said C 1-8 alkyl group, said aryl group, said C 3-8 cycloalkane ring and said C 3-9 heterocycle may be substituted with one or more substituents;
Ring A is an arene, a C 3-6 heterocycle containing 1-4 heteroatoms selected from the group consisting of O, N, and S, or a C 3-8 cycloalkane ring;
Ya is a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, a carbonyl group, a carboxyl C 1-3 alkyl group or a sulfo group;
Yb is a hydrogen atom, a halogen atom, a carboxyl group, a hydroxyl group, a carbonyl group, a carboxyl C 1-3 alkyl group, a nitro group, a cyano group or a C 1-3 alkoxyl group;
p is 0 or 1;
q is 1; and
R 7 is a hydrogen atom, a halogen atom or a nitro group, or a pharmaceutically acceptable salt thereof.
2. The compound or salt according to claim 1 , wherein R 6 is a hydrogen atom or a C 1-8 alkyl group.
3. The compound or salt according to claim 1 , wherein p =0.
4. The compound or salt according to claim 1 , wherein p =1, and Ra and Rb are the same or different and each is independently a hydrogen atom or a C 1-8 alkyl group, or Ra and Rb together with the atom(s) to which they are bonded form a C 3-8 cycloalkane ring, wherein said C 1-8 alkyl group and said C 3-8 cycloalkane ring may substituted with a group selected from the group consisting of a hydrogen atom, a carboxyl group, a carbamoyl group, a hydroxyl group, a phenyl group, and a C 3-8 cycloalkyl group.
5. The compound or salt according to claim 1 , wherein R 1 and R 2 are the same or different and each is independently a methyl group, an ethyl group or a propyl group, or R 1 and R 2 together with the carbon atom to which they are bonded form a cyclobutane ring or a cyclopentane ring.
6. The compound or salt according to claim 1 , wherein Ring A is a benzene ring, a pyridine ring, or a C 3-6 heterocycle containing 1-4 oxygen atoms.
7. The compound or salt according to claim 1 , wherein Ya is a halogen atom, a carboxyl group, a carboxyl C 1-3 alkyl group, a hydroxyl group, a sulfo group, or a carbonyl group, and Yb is a hydrogen atom, a halogen atom, a carboxyl group, or a hydroxyl group.
8. The compound or salt according to claim 1 , wherein, when Ra or Rb has substituent(s), said substituent is selected from the group consisting of a carboxyl group, a hydroxyl group, a phenyl group, an amino group, a methylthio group, a sulfanyl group, a carbamoyl group, a guanidino group, a C 3-8 cycloalkyl group, and a C 1-8 heterocyclic group containing 1-4 heteroatoms selected from the group consisting of O, N, and S.
9. A pharmaceutical composition, comprising a compound or salt according to claim 1 and at least one pharmaceutically acceptable carrier or excipient.
10. A compound represented by any of the following formulas:
or a pharmaceutically acceptable salt of said compound.
11. The compound or salt according to claim 1 , wherein p =1.
12. A pharmaceutical composition, comprising a compound or salt according to claim 10 and at least one pharmaceutically acceptable carrier or excipient.
13. A compound represented by the following formula:
or a pharmaceutically acceptable salt of said compound.
14. A pharmaceutical composition, comprising a compound or salt according to claim 13 and at least one pharmaceutically acceptable carrier or excipient.