ЛИ Вей (US),МИЛЛЕР Майкл (GB),ФИШКИН Нейтан (US),ЧАРИ Рави В. Дж. (US)
申请号：
RU2013141829/04
公开号：
RU2013141829A
申请日:
2012.02.15
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
1. A cytotoxic compound comprising a linking group with a reactive group attached thereto capable of covalently attaching said cytotoxic compound to a cell binding agent (CBA), said cytotoxic compound being any of the following formulas: or a pharmaceutically acceptable salt thereof, wherein: double the line between N and C is a single bond or a double bond, provided that when it is a double bond, X is absent, and Y is —H either linear or branched alkyl group containing from 1 to 4 carbon atoms, and when it is a single bond, X is —H, a linking group with an attached reactive group or an amine blocking group； Y is —H or a leaving group selected from —OR, —OCOR ', -OCOOR', -OCONR'R ", -NR'R", -NR'COR ", -NR'NR'R", optionally substituted with a 5- or 6-membered nitrogen-containing heterocycle (e.g. piperidine, tetrahydropyrrole, pyrazole , morpholine, etc.), guanidinium represented by -NR '(C = NH) NR'R ", an amino acid or peptide represented by -NRCOP', wherein P 'is an amino acid a lot or polypeptide containing from 2 to 20 amino acid residues, -SR, -SOR ', -SOM, -SOM, -OSOM, halogen, cyano group and azide group； or Y is sulfite (HSO, HSO or a cationic salt of HSO, SO or HSO), metabisulfite (HSO or a cationic salt of SO), mono-, di-, tri- and tetratiophosphate (POSH, POSH, POSH, PSH or POS, POS , POS or PS formed by a cation), thiophosphate ester (RO) PS (OR), RS-, RSO, RSO, RSO, thiosulfate (HSO or SO salt formed by a cation), dithionite (HSO or SO salt formed by a cation), phosphorodithioate (P (= S) (OR) (S) (OH) or its s1. Цитотоксическое соединение, включающее связывающую группу с присоединенной к ней реакционноспособной группой, способной ковалентно присоединять указанное цитотоксическое соединение к агенту, связывающемуся с клетками (СВА), причем указанное цитотоксическое соединение представлено любой из следующих формул:или его фармацевтически приемлемой солью, где:двойная линиямежду N и С представляет собой одинарную связь или двойную связь, при условии, что
