Oseltamivir phosphate-Lifting the restriction on its use to treat teenagers with influenza in Japan.

Purpose: In 2007, Ministry of Health, Labour and Welfare (MHLW) warned to refrain from prescribing oseltamivir for teenagers when two Japanese teenagers with influenza fell from a high-rise building after taking oseltamivir. Revisions of the warning texts of anti-influenza drugs were discussed by the Subcommittee of Pharmaceutical Affairs and Food Sanitation Council, MHLW, based on the studies and trends of anti-influenza medication over the last 10 years.

Method: The research group led by Dr Nobuhiko Okabe conducted nationwide survey since the 2007/2008 influenza season.

Discovery of non-competitive thrombin inhibitor derived from competitive tryptase inhibitor skeleton: Shift in molecular recognition resulted from skeletal conversion of carboxylate into phosphonate.

A novel series of terminal and internal phosphonate esters based on our previously developed aryl carboxylate-type tryptase selective inhibitor 1 was synthesized. The potency of these synthesized compounds was assessed in vitro with an enzyme inhibition assay using three available serine proteases, that is, tryptase, trypsin, and thrombin. The internal phosphonate derivative 6 showed potent thrombin inhibitory activity with an IC50 value of 1.

Development of tryptase inhibitors derived from thalidomide.

A novel series of tryptase inhibitors with a N-phenylphthalimide skeleton structurally derived from thalidomide (1) has been developed. Structure-activity relationship studies led to a potent and selective tryptase inhibitor, 2-(4-cyanophenyl)isoindole-1,3-dione-5-yl 3-(2-aminopyridin-5-yl)propanoate (7), with the IC50 value of 78 nM.

beta-Naphthoflavone analogs as potent and soluble aryl hydrocarbon receptor agonists: improvement of solubility by disruption of molecular planarity.

The physiological role of aryl hydrocarbon receptor (AhR) is not yet fully understood, and investigation is hampered by the limited solubility of reported AhR ligands in aqueous media. To achieve improved solubility, we focused on our previous finding that planarity-disruption of molecules leads to less efficient crystal packing and greater aqueous solubility. Here, we describe chemical modification of an AhR agonist, beta-naphthoflavone, focusing on planarity-disruption.

Enhancement of chemically-induced HL-60 cell differentiation by 3,3'-diindolylmethane derivatives.

3,3'-Diindolylmethane (DIM, 1) and its derivatives have been prepared, and their enhancing effects on chemically-induced HL-60 cell differentiation were analyzed. Among the prepared compounds, IndDIM (12) showed the most potent enhancing effect on HL-60 cell differentiation induced by chemicals, including retinoids, 1,25-dihydroxyvitamin D(3), 12-O-tetradecanoyl phorbol-13-acetate and dimethyl sulfoxide.

Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin.

A series of hybrid compounds of bestatin (1) and actinonin (3), which promote degradation of cellular inhibitor of apoptosis protein 1 (cIAP1), were designed and synthesized. Structure-activity relationship studies indicated that absolute configuration, hydrophobicity at the alpha-position of the internal amide carbonyl group, and the presence of a small substituent at the alpha-position of the ester group are important factors for the expression of potent cIAP1 degradation-promoting activity. HAB-5A (30b) showed the most potent activity (IC(50)=0.