Inhibition of hypoxia inducible factor prolyl hydroxylase (PHD) represents a promising strategy for the discovery of a next generation treatment for renal anemia. We identified several 5,6-fused ring systems as novel scaffolds of the PHD inhibitor on the basis of pharmacophore analysis. In particular, triazolopyridine derivatives showed potent PHD2 inhibitory activities. Examination of the predominance of the triazolopyridines in potency by electrostatic calculations suggested favorable π-π stacking interactions with Tyr310. Lead optimization to improve the efficacy of erythropoietin release in cells and by improving cell permeability led to the discovery of JTZ-951 (compound), with a 5-phenethyl substituent on the triazolopyridine group, which increased hemoglobin levels with daily oral dosing in rats. Compound was rapidly absorbed after oral administration and disappeared shortly thereafter, which could be advantageous in terms of safety. Compound was selected as a clinical candidate.

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By a sensitive radioimmunoassay method, (2'-5')oligoadenylate synthetase was detected in serum from patients with viral, bacterial, or mycoplasmal infections at elevated levels compared with enzyme levels in serum from healthy individuals and patients suffering from noninfectious diseases.

The ratio of men to women was studied in 331 patients hospitalized into our department for the past three years for various liver diseases. Two factors seemed to affect the sex difference in the morbidity of liver disease. One was a history of drinking, the other a positive ratio of HBs antigen.So, heavy drinkers and HBs antigen positive cases were excluded from the patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma, and the male/female ratio was studied again .The ratio of men to women in the patients with liver cirrhosis was 1.3: 1, 4. 1: 1 in the patients with hepatocellular carcinoma and 2.0: 1 in the patients with chronic hepatitis. The male ratio was strikingly high in the case of hepatocellular carcinoma. It is thought that liver cirrhosis is a cause of hepatocellular carcinoma. And then differences in the results of liver function tests between men and women were studied in the patients with liver cirrhosis. However, no remarkable difference was found between men and women.

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