Ohara Pharmaceutical Co., Ltd.

Saga University

Magoichi Sako

Shinpei Sugiyama

Xiong Luo

Kazuharu Kamachi

Hiroshi Ureshino

Yuki Kurahashi

Shinya Kimura

Tatsuro Watanabe

[Problems] The object is to provide a compound as a therapeutic or prophylactic agent for TKI-resistant CML to replace the injection “Dacogen®” which has been clinically used as a therapeutic agent for high-risk myelodysplastic syndrome and acute myeloid leukemia. The said compound has remarkable stability against cytidine deaminase, a hydrolytic enzyme, and is absorbed in vivo even by oral administration, incorporated into the biosynthesis route of nucleic acid, and exhibits the effect of inhibiting DNA methyltransferase (DNMT). [Solutions] A prophylactic or therapeutic agent for TKI-resistant CML, comprising a compound represented by formula (I) or a salt thereof, wherein Rand Rare each independently a hydrogen atom or a silyl group represented by formula (II): wherein R, R, and Rare each independently an alkyl group which may have a substituent, an aryl group which may have a substituent, or an arylalkyl group which may have a substituent, with the provision that the case where both Rand Rare hydrogen atom is excluded.

Use of DNMT inhibitor

The present invention relates to a prodrug of 5-azacytidine or 2'-deoxy-5-azacytidine having remarkable stability against cytidine deaminase, a metabolic hydrolyzing enzyme in replacement of current injections (5-azacytidine or 2&#x2032;-deoxy-5-azacytidine) which are clinically used as therapeutic agents for various myelomas including myelodysplastic syndrome. The present invention provides a compound represented by formula (1), or salt thereof, wherein, R is ORor a hydrogen atom, R, R, and Rare each independently hydrogen atom or silyl group represented by formula (2): wherein, R, R, and Rare each independently alkyl group which may have a substituent, aryl group which may have a substituent, or arylalkyl group which may have a substituent, with the provision that R, R, and Rare not hydrogen atom simultaneously.

Silyl etherified derivatives of 5-azacytidines in carbohydrate moiety

The present invention relates to a prodrug of 5-azacytidine or 2'-deoxy-5-azacytidine having remarkable stability against cytidine deaminase, a metabolic hydrolyzing enzyme in replacement of current injections (5-azacytidine or 2&#x2032;-deoxy-5-azacytidine) which are clinically used as therapeutic agents for various myelomas including myelodysplastic syndrome. The present invention provides a compound represented by formula (1), or salt thereof,  

The present invention relates to a novel compound represented by formula (1), or salt thereof, wherein R is hydroxy group or hydrogen atom; Rand Rare the same or different, and are each independently benzyl group which may have a substituent. The present invention provides therapeutically agents, which have remarkable stability against cytidine deaminase, a metabolic enzyme, can be absorbed in vivo by oral administration and inhibit protein synthesis by being incorporated easily into nucleic acid bio-synthesis in vivo for replacing injection agent (5-azacytidine or 2'-deoxy-5-azacytidine) used in clinic for treating myeloma.

Growing community of inventors

Shiga, Japan

Magoichi Sako