申请人:Ohara Pharmaceutical Co., Ltd.
公开号:US20220347197A1
公开(公告)日:2022-11-03
[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 R
1
and R
2
are each independently a hydrogen atom or a silyl group represented by formula (II):
wherein R
3
, R
4
, and R
5
are 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 R
1
and R
2
are hydrogen atom is excluded.
[问题] 目的是提供一种化合物作为治疗或预防TKI耐药性CML的药物,以取代已在临床上用于高风险骨髓增生异常综合征和急性髓性白血病的注射剂“Dacogen®”。该化合物对胞嘧啶脱氨酶具有显著的稳定性,可以通过口服吸收,被纳入核酸的生物合成途径,并表现出抑制DNA甲基转移酶(DNMT)的作用。
[解决方案] 一种预防或治疗TKI耐药性CML的药物,包括公式(I)所表示的化合物或其盐,其中R1和R2分别是氢原子或由公式(II)表示的硅基团:其中R3、R4和R5各自独立地是可能具有取代基的烷基、可能具有取代基的芳基或可能具有取代基的芳基烷基,但排除R1和R2均为氢原子的情况。