54337-59-6Relevant academic research and scientific papers
Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents. 4. Synthesis and pharmacological properties of 4'- dehydroxyphlorizin derivatives substituted on the B ring
Tsujihara, Kenji,Hongu, Mitsuya,Saito, Kunio,Kawanishi, Hiroyuki,Kuriyama, Kayoko,Matsumoto, Mamoru,Akira, Oku,Ueta, Kiichiro,Tsuda, Minoru,Saito, Akira
, p. 5311 - 5324 (2007/10/03)
In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'- dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5- yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-β-D- glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by β-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3- (benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O- (6-O-methoxycarbonyl-β-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK- A(y) mice. Additionally, long-term treatment with 5 dose- dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.
Method of preparing 2-acylresorcinols
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, (2008/06/13)
A method of preparing a 2-acylresorcinol which comprises dehydrogenating a 2-acyl-1,3-cyclohexanedione of the general formula wherein R1 represents an alkyl, aralkyl or aryl group, and RZrepresents hydrogen, or an alkyl, alkoxy or acylamino group, in the presence of a dehydrogenation catalyst (such as a Group VIII metal) or a dehydrogenation agent (such as sulphur or selenium) at an elevated temperature, to provide a 2-acylresorcinol of the general formula wherein R1 and R2 are as defined.
