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A transglycosylation reaction of 2'-amino-locked nucleic acid (LNA) from thymine (T) to other nucleobases adenine (A), guanine (G), and 5-methylcytosine (C) has been developed. This reaction proceeds in high yield and with high β-selectivity. The mild reaction conditions enable the coexistence of acid-labile protecting groups, including a 4,4'-dimethoxytrytyl (DMTr) group. 2'-Amino-LNAs bearing any nucleobase can now be easily synthesized.

We recently designed guanidine-bridged nucleic acids (GuNA), and GuNA bearing a thymine (T) nucleobase was synthesized and successfully incorporateed into oligonucleotides. The GuNA-T-modified oligonucleotides possessed high duplex-forming ability towards their...

Inhibition of hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) promotes erythropoietin (EPO) production by stabilizing the HIFα subunit. Thieno­[2,3-d]­pyrimidine 8 identified based on X-ray crystal structure analysis was optimized to lead to the discovery of pyrazolo­[4,3-d]­pyrimidine 13 as the lead compound of orally bioavailable HIF-PHD inhibitors. Conversion of the benzyl moiety in 13 gave pyrazolopyrimidine 19 with high solubility and bioavailability, which increased hemoglobin levels in anemic model rats after repeated oral administration. It was shown that pyrazolo­[4,3-d]­pyrimidine derivatives are promising therapeutic agents for renal anemia through the inhibition of HIF-PHD.