LI, Wei,MILLER, Michael,FISHKIN, Nathan,CHARI, Ravi V. J.
申请号：
ES12705600
公开号：
ES2567418T3
申请日:
2012.02.15
申请国别(地区):
ES
年份:
2016
代理人:
摘要：
A cytotoxic compound comprising a linking group with a reactive group attached thereto capable of covalently binding the cytotoxic compound to a cell binding agent (CBA), wherein said cytotoxic compound is represented by any one of the following formulas: ** Formula ** or a pharmaceutically acceptable salt thereof, wherein: the double line between N and C represents a single bond or a double bond, provided that when it is a double bond X is absent and Y is -H, or a linear alkyl or branched having 1 to 4 carbon atoms, and when it is a single bond, X is -H, the linking group with the reactive group attached to it, or an amine protecting portion； And it is -H or a leaving group selected from -OR, -OCOR ', -OCOOR', -OCONR'R '', -NR'R '', -NR'COR '', -NR'NR'R '' , an optionally substituted 5 or 6-membered nitrogen-containing heterocycle (e.g., piperidine, tetrahydropyrrole, pyrazole, morpholine, etc.), a guanidinium represented by -NR '(C>； = NH) NR'R' ', an amino acid , or a peptide represented by -NRCOP ', wherein P' is an amino acid or a polypeptide containing between 2 to 20 amino acid units, -SR, -SOR ', -SO2M, -SO3M, -OSO3M, halogen, cyano and an azido； or, Y is a sulphite (HSO3, HSO2 or a salt of HSO3-, SO32- or HSO2- formed with a cation), metabisulfite (H2S2O5 or a salt of S2O52- formed with a cation), mono-, di-, tri -, and tetrathiophosphate (PO3SH3, PO2S2H2, POS3H2, PS4H2 or a salt of PO3S3-, PO2S23-, POS33- or PS43- formed with a cation), thio phosphate ester (RiO) 2PS (ORi), RiS-, RiSO , RiSO2, RiSO3, thiosulfate (HS2O3 or a salt of S2O32- formed with a cation), dithionite (HS2O4 or a salt of S2O42- formed with a cation), phosphorodithioate (P (>； = S) (ORk ') (S) (OH) or a salt thereof formed with a cation), hydroxamic acid (Rk'C (>； = O) NOH or a salt formed with a cation), sulfoxylated formaldehyde (HOCH2SO2- or a HOCH2SO2- salt formed with a cation , such as HOCH2SO2-Na +) or a mixture thereof, wherein Ri is a linear or branched alkyl having 1 to
