AHMAD, Omar Khaled (US),АХМАД, Омар Кхалед (US),BROWN, Stephen Paul (US),БРАУН, Стефен Пол (US),DIRICO, Kenneth John (US),ДИРИКО, Кеннет Джон (US),DUSHIN, Russell (US),ДАШИН, Расселл (US),FILZEN, Gary
申请号：
RU2019123161
公开号：
RU0002732568C1
申请日:
2018.01.10
申请国别(地区):
RU
年份:
2020
代理人:
摘要：
FIELD: chemistry； medicine； pharmaceuticals.SUBSTANCE: present invention relates to novel calicheamicin derivatives (IIA), (IIIA) and (IVA), pharmaceutical derivatives containing them, pharmaceutical compositions and combinations applicable in medicine, methods of using them in treating leukaemia and inhibiting proliferation of leukaemia cells:or pharmaceutically acceptable salts thereof, where R3 is -CH2CH3； X is selected from -C2-C8 alkyl, optionally substituted with one R10； -(C0-C6 alkyl)-C3-C10 carbocyclyl； -(C0-C6 alkyl)-6-member heterocyclyl, wherein said 6-member heterocyclyl is optionally substituted with one R10 and said 6-member heterocyclyl contains one nitrogen heteroatom； -(C0-C6 alkyl)-phenyl, where said phenyl is optionally substituted with one R10； and -(C0-C6 alkyl)-6-member heteroaryl, wherein said 6-member heteroaryl is optionally substituted with one R10 and where said 6-member heteroaryl contains one nitrogen heteroatom； where X is optionally further substituted with 1 G； R10 is -R10a-R10b, wherein R10a is absent； R10b is selected from -CO2H； -CO2C1-C4 alkyl； -NH-R11； -CONH-R11； -CON(C1-C4 alkyl)-R11； -CONHNH-R11； R11 is -R11a-R11b-R11c, where R11a and R11b are absent； R11c is selected from a group consisting of -H and -C1-C4 alkyl； G is selected, independently for each case, from a group consisting of -NH2, -CO2H, -C1-C4 alkyl, = O and -CO2C1-C 4 alkyl； L and LR are linker fragments, AB is an antibody which binds immunospecifically to one or more antigens of the malignant cell, b equals 1–20.EFFECT: novel calicheamicin derivatives, a pharmaceutical composition and based combinations thereof, effective for treating leukaemia.28 cl, 50 ex, 14 tbl, 9 dwgНастоящее изобретение относится к применимым в медицине новым производным калихеамицина формул (IIA), (IIIA) и (IVA), содержащим их фармацевтическим композициям и комбинациям, способам их применения в лечении лейкоза и ингибировании пролиферации клеток лейкоза:или их фармацевтически приемлемым сол
