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FUNCTIONALIZED MORPHOLINYL ANTHRACYCLINE DERIVATIVES
专利权人:
发明人:
申请号:
HK17108830.8
公开号:
HK1235060A
申请日:
2017.09.01
申请国别(地区):
HK
年份:
2018
代理人:
摘要:
The present invention relates to new functionalized morpholinyl anthracycline derivatives which have cytotoxic activity and are useful in treating diseases such as cancer, cellular proliferation disorders and viral infections. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising them and methods of treating diseases utilizing such compounds, or the pharmaceutical compositions containing them. The invention also relates to the use of these derivatives in the preparation of conjugates. The morpholinyl anthracycline derivatives are of the formula Ant-L-W-Z-RM (I) wherein RM is null or a reactive moiety Z is null or a peptidic, non peptidic or hybrid - peptidic and non peptidic - linker W is null or a self-immolative system, comprising one or more self-immolative groups L is null or a conditionally-cleavable moiety Ant is an anthracycline moiety selected from the formulas (II), (III), (IV) and (V), wherein the wavy line indicates the attachment to the conditionally-cleavable moiety L, or to the self-immolative system W, or to the linker Z, or to the reactive moiety RM provided that at least one of L, W, Z and RM is not null R1 is halogen or NR4R5 R2 is OR6, NR7R8 or an optionally substituted group selected from straight or branched C1C4alkyl-, NR7R8-C1C4alkyl- and R60-C1C4alkyl- R4 and R5 are independently hydrogen, a monosubstituted-benzyl, a disubstituted-benzyl, or an optionally substituted group selected from straight or branched C1-C6alkyl, NR7R8-C1-C6alkyl-, R60-C1-C6alkyl-, R7R8N-C1-C6alkylcarbonyl-, R60-C1-C6alkylcarbonyl-, R7R8N-C1-C6alkoxycarbonyl- and R60-C1-C6alkoxycarbonyl- or R4 and R5, taken together with the nitrogen atom to which they are bound, form a heterocyclyl substituted with R4, wherein R4 is hydrogen or a group selected from straight or branched C1-C6alkyl and NR7R8-C1-C6alkyl- R15 is null or an optionally substituted bivalent group selected from -NR7-C1-C6alkyl*, -O-C1-C6alkyl*, -NR7-
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