Remedy for diabetes
A method of screening a compound having a hypoglycemic effect (hereinafter referred to as “hypoglycemic compound”), a remedy for diabetes which contains a compound having a novel function mechanism, etc. More specifically speaking, a method of screening a hypoglycemic compound capable of binding to the β subunit of a trimeric GTP-binding protein, a remedy for diabetes comprising a hypoglycemic compound, which is characterized by being capable of binding to the β subunit of a trimeric GTP-binding protein, as the active ingredient, etc.
1. A compound represented by general formula (I) or a pharmaceutically acceptable salt thereof:
wherein
in the general formula (I), A and B may be the same or different and independently represent an optionally substituted aromatic ring, an optionally substituted heterocyclic ring, or an optionally substituted aliphatic ring;
R 1 represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, or a lower alkoxy group, the groups being optionally substituted by 1 to 3 substituents;
—X— and —Y— may be the same or different and independently represent a hydrogen atom, —O—, —NR 2 —, —S—, —SO—, —SO 2 —, —CH 2 —, —CR 3 R 4 —, —COO—, —CONR 2 —, or —CO—, in which R 2 represents a hydrogen atom, an optionally substituted lower alkyl group, an optionally substituted acyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted carbamoyl group, or an optionally substituted sulfonyl group, and R 3 and R 4 may be the same or different and independently represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, a mercapto group, an alkoxy group, an alkylthio group, an alkylsulfonyl group, an acyl group, an acyloxy group, an amino group, an alkylamino group, a carboxyl group, an alkoxycarbonyl group, a carbamoyl group, a nitro group, a cyano group, or a trifluoromethyl group;
—W— represents an optionally substituted alkyl chain having 1 to 20 carbon atoms, and 1 to 10 carbon atoms in the alkyl chain may be replaced by —O—, —NR 5 —, —S—, —SO—, —SO 2 —, or —CO—, in which R 5 represents a hydrogen atom, an optionally substituted lower alkyl group, an optionally substituted acyl group, an optionally substituted alkoxycarbonyl group, an optionally substituted carbamoyl group, or an optionally substituted sulfonyl group;
Q represents a hydrogen atom, biotin, a fluorophore, a chromophore, a chemiluminescent functional group, an enzyme, a solid phase, a diazo group, or an azido group;
one or more atoms in the formula may be (a) radioisotope(s);
with the proviso that:
i) in the optionally substituted groups, each substituent is selected from the group consisting of halogen atoms, a hydroxyl group, alkyl groups, mercapto groups, alkoxy groups, alkylthio groups, alkylsulfonyl groups, acyl groups, acyloxy groups, amino groups, alkylamino groups, a carboxyl group, alkoxycarbonyl groups, carbamoyl groups, a nitro group, a cyano group, a trifluoromethyl group, aryl groups, heteroaryl groups, diazo groups, and azido groups, and the substituent may be labeled with biotin, a fluorophore, a chromophore, a chemiluminescent moiety, or an enzyme;
ii) when —X— is a hydrogen atom, —W—, —Y—, and Q do not exist;
iii) when —Y— is a hydrogen atom, Q does not exist; and
iv) the compound of the general formula (I) satisfies at least one of the following conditions a) to f):
a) —X— and —Y— are other than a hydrogen atom, and Q is biotin, a fluorophore, a chromophore, a chemiluminescent functional group, or an enzyme;
b) —X— and —Y— are other than a hydrogen atom, and Q is a diazo group or an azido group;
c) —X— and —Y— are other than a hydrogen atom, and Q is a solid phase;
d) labeled with at least one radioisotope atom;
e) substituted with at least one substituent which is labeled with biotin, a fluorophore, a chromophore, a chemiluminescent moiety, or an enzyme; or
f) substituted with at least one diazo group or azido group as a substituent.
2. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein —X— and —Y— are other than a hydrogen atom, and Q is biotin, a fluorophore, a chromophore, a chemiluminescent functional group, or an enzyme.
3. A compound or a pharmaceutically acceptable salt thereof according to claim 2 , wherein each substituent in the optionally substituted groups is not labeled with biotin, a fluorophore, a chromophore, a chemiluminescent moiety, or an enzyme.
4. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein —X— and —Y— are other than a hydrogen atom, and Q is a diazo group or an azido group.
5. A compound or a pharmaceutically acceptable salt thereof according to claim 4 , wherein each substituent in the optionally substituted groups is not labeled with biotin, a fluorophore, a chromophore, a chemiluminescent moiety, or an enzyme.
6. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein —X— and —Y— are other than a hydrogen atom, and Q is a solid phase.
7. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein at least one atom in the general formula (I) is a radioisotope.
8. A compound or a pharmaceutically acceptable salt thereof according to claim 7 , wherein X is a hydrogen atom.
9. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound has at least one substituent which is labeled with biotin, a fluorophore, a chromophore, a chemiluminescent moiety, or an enzyme.
10. A compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound has at least one diazo group or azido group as a substituent.