Method of searching substrate having antidiabetic activity

A screening method of a substance having anti-diabetic activity, which comprises:

• [1] bringing a compound selected from compounds represented by the following formula I):
• (wherein R1A represents hydrogen, lower alkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group;
• R2A represents hydrogen, lower alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group;
• R3A represents hydrogen, lower alkyl, or substituted or unsubstituted aralkyl;
• X1 and X2 each independently represents hydrogen, lower alkyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted aryl;
• and n is an integer of 0 to 3) or compounds represented by the following formula (II):
• {wherein X—Y-Z represents R1N—C═O (wherein R1 represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl or a substituted or unsubstituted aromatic heterocyclic group) or N═C—W [wherein W represents halogen, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alicyclic heterocyclic group, —NR4R5 (wherein R4 and R5 are the same or different and each represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted aralkyl, or R4 and R5 together with adjacent nitrogen represent a heterocyclic group), —OR6 (wherein R6 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted aralkyl), —SR6a (wherein R6a has the same meaning as R6), substituted or unsubstituted lower alkyl, or cyano];
• R2 represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alicyclic heterocyclic group, halogen, lower alkylthio, —NR7R8 (wherein R7 and R8 have the same meanings as R4 and R5 as described above, respectively), —CO2H, lower alkoxycarbonyl, —COHal (wherein Hal represents halogen), —CONR9R10 (wherein R9 and R10 have the same meanings as R4 and R5 as described above, respectively), or —CHO;
• R3 represents hydrogen, lower alkyl, substituted or unsubstituted aralkyl, or lower alkoxyalkyl;
• n represents an integer of 0 to 3;
• V1 represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, or a substituted or unsubstituted aromatic heterocyclic group;
• and V2 represents substituted lower alkyl or a substituted or unsubstituted aromatic heterocyclic group, and when V1 represents hydrogen, lower alkyl, substituted or unsubstituted aralkyl or substituted or unsubstituted aryl and (a) X—Y-Z represents R1aN—C═O (wherein R1a represents the same groups defined for R1 except the substituted lower alkyl), and R2 represents substituted lower alkyl, substituted or unsubstituted aralkyl, a substituted or unsubstituted alicyclic heterocyclic group, halogen, lower alkylthio, —NR7R8 (wherein R7 and R8 have the same meanings as described above, respectively), —CO2H, lower alkoxycarbonyl, —COHal (wherein Hal has the same meaning as described above), —CONR9R10 (wherein R9 and R10 have the same meanings as described above, respectively), or —CHO, (b) X—Y-Z represents R1N—C═O (wherein R1 has the same meaning as described above) and R3 represents lower alkoxyalkyl, (c) X—Y-Z represents R1bN—C═O (wherein R1b represents substituted lower alkyl), (d) X—Y-Z represents N═C—W (wherein W has the same meaning as described above), and R2 represents substituted or unsubstituted lower alkyl, substituted or unsubstituted aralkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted alicyclic heterocyclic group, halogen, lower alkylthio, —NR7R8 (wherein R7 and R8 have the same meanings as described above, respectively), —CO2H, lower alkoxycarbonyl, —COHal (wherein Hal has the same meaning as described above), —CONR9R10 (wherein R9 and R10 have the same meanings as described above, respectively), or —CHO, or (e) X—Y-Z represents N═C—W (wherein W has the same meaning as described above), and R3 represents lower alkyl, substituted or unsubstituted aralkyl, or lower alkoxyalkyl, V2 may represent lower alkyl, substituted or unsubstituted aralkyl, or substituted or unsubstituted aryl] (hereinafter referred to as “condensed purine derivative”) into contact with a pancreatic β cell or a treated product of the cell in the presence of a tested substance to assay the binding amount of the condensed purine derivative to the pancreatic β cell or the treated product of the cell,
• [2] bringing the condensed purine derivative into contact with a pancreatic β cell or a treated product of the cell in the absence of the tested substance to assay the binding amount of the condensed purine derivative to the pancreatic β cell or the treated product of the cell,
• [3] comparing the assayed amount in the presence of the tested substance with that in the absence of the tested substance, and
• [4] selecting a substance which inhibits the binding of the condensed purine derivative to the pancreatic β cell or the treated product of the cell from the tested substances.