It is known that a sodium-dependent glucose transporter, hereinafter referred to as “SGLT”, which is a co-transporter of monosaccharide and sodium, has some subtypes. Namely, a sodium-dependent glucose transporter 1, hereinafter referred to as “SGLT1”, exists mainly in the small intestine and the S3 segment of the kidney's proximal tubule, and a sodium-dependent glucose transporter 2, hereinafter referred to as “SGLT2”, exists mainly in the S1 segment of the kidney's proximal tubule.
Among them, SGLT1 which exists in the small intestine participates in glucose and galactose absorption from the digestive tract (see Non-patent references 1 and 2). In diabetic patients, carbohydrate digestion and absorption increase. Actually, it is confirmed that SGLT1 and its mRNA highly increase in the small intestine (see Non-patent reference 3). Therefore, inhibiting SGLT1 can control increase of blood sugar level by suppression of glucose and galactose absorption in the small intestine (see Patent reference 1).
On the other hand, SGLT2 participates in reabsorption of glucose filtrated through the glomerulus (see Non-patent reference 4). Therefore, inhibiting SGLT2 can normalize blood sugar level by suppression of glucose reabsorption (see Patent reference 5).
As compounds inhibiting SGLT1, pyrazole derivatives (see Patent references 1 and 2), benzylphenol derivatives (see Patent reference 3) and the like are known. And as compounds inhibiting SGLT2, glucopyranosyloxypyrazole derivatives (see Patent reference 4), glucopyranosyloxybenzylbenzene derivatives (see Patent reference 5) and the like are known.
Recently, it was reported that fused heterocyclic compounds having a glycopyranosyloxy group show an excellent SGLT inhibitory activity (see Patent reference 6). However, in the report, nothing was described or suggested concerning a compound which has a substituent on a nitrogen atom of a fused heterocyclic compound wherein the hetero atom is a nitrogen atom.
[Non-patent reference 1] Yoshikatsu Kanai, Kidney and Dialysis, 1998.12, Vol. 45, extra edition, pp. 232-237;
[Non-patent reference 2] E. Turk and 4 persons, Nature, 1991.3, Vol. 350, pp. 354-356;
[Non-patent reference 3] J. Dyer and 4 persons, American Journal of Physiology, 2002.2, Vol. 282, No. 2, pp. G241-G248;
[Non-patent reference 4] Yoshikatsu Kanai and 4 persons, J. Clin. Invest., 1994.1, Vol. 93, pp. 397-404;
[Patent reference 1] International Publication No. WO2004/014932 pamphlet;
[Patent reference 2] International Publication No. WO2004/018491 pamphlet;
[Patent reference 3] Japanese patent publication No. JP2004-196788;
[Patent reference 4] International publication No. WO01/16147 pamphlet;
[Patent reference 5] International publication No. WO01/68660 pamphlet;
[Patent reference 6] International publication No. WO2004/087727 pamphlet.