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US 7,256,257 B2Granted
Pentapeptide compounds and uses related thereto
AssigneeSeattle Genetics, Inc.
InventorsSvetlana Doronina, Peter D. Senter, Brian E. Toki
Life of this patent
Estimating the term…
Abstract
Pentapeptide compounds are disclosed. The compounds have biological activity, e.g., cytotoxicity. Prodrugs having targeting groups and pentapeptide moieities, as well as precursors thereof are also disclosed. For example, precursors having a reactive linker that can serve as a reaction site for joining to a targeting agent, e.g., an antibody, as disclosed.
Claims52
A compound of the formula
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein, independently at each location:
- R1 is hydrogen or lower alkyl;
- R2 is hydrogen or lower alkyl;
- R3 is lower alkyl;
- R4 is lower alkyl, aryl, or —CH2—C5-7carbocycle when R5 is H or methyl, or R4 and R5 together form a carbocycle of the partial formula —(CRaRb)n— wherein Ra and Rb are independently hydrogen or lower alkyl and n is 2, 3, 4, 5 or 6;
- R6 is hydrogen or lower alkyl;
- R7 is sec-butyl or iso-butyl;
- R8 is-hydrogen or lower alkyl;
- and
- R9 is
- R11 is hydrogen or lower alkyl;
- R12 is lower alkyl, halogen, or methoxy, and m is 0-5 where R12 is independently selected at each occurrence;
- and
- wherein:
- R14 is a direct bond, lower alkylene, arylene, or arylene(lower alkylene);
- R15 is hydrogen, lower alkyl or aryl;
- R16 is arylene(lower alkylene), lower alkylene, arylene, aryl (lower alkylene), or —(CH2OCH2)pCH2— where p is 1-5;
- and
16 more elements
A compound of the formula
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein, independently at each location:
- R1 is hydrogen or lower alkyl;
- R2 is hydrogen or lower alkyl;
- R3 is lower alkyl;
- R4 is lower alkyl, aryl, or —CH2—C5-7carbocycle when R5 is H or methyl, or R4 and R5 together form a carbocycle of the partial formula —(CRaRb)n— wherein Ra and Rb are independently hydrogen or lower alkyl and n is 2, 3, 4, 5 or 6;
- R6 is hydrogen or lower alkyl;
- R7 is sec-butyl or iso-butyl;
- R8 is hydrogen or lower alkyl;
- R11 is hydrogen or lower alkyl;
- R12 is lower alkyl, halogen, or methoxy, and m is 0-5 where R12 is independently selected at each occurrence;
- and
- R20 is
- wherein:
- R14 is a direct bond, arylene(lower alkylene), lower alkylene or arylene;
- R15 is hydrogen, lower alkyl or aryl;
- R16 is lower alkylene, arylene(lower alkylene), arylene, or —(CH2OCH2)pCH2— where p is 1-5;
- and
- R17 is an activated ester, an anhydride, an acid chloride, an isocyanate, an isothiocyanate,
- wherein X is a leaving group.
17 more elements
A compound of the formula
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein, independently at each location:
- R1 is hydrogen or lower alkyl;
- R2 is hydrogen or lower alkyl;
- R3 is lower alkyl;
- R4 is lower alkyl, aryl, or —CH2—C5-7carbocycle when R5 is H or methyl, or R4 and R5 together form a carbocycle of the partial formula —(CRaRb)n— wherein Ra and Rb are independently hydrogen or lower alkyl and n is 2, 3, 4, 5 or 6;
- R6 is hydrogen or lower alkyl;
- R7 is sec-butyl or iso-butyl;
- R8 is hydrogen or lower alkyl;
- R11 is hydrogen or lower alkyl;
- R12 is lower alkyl, halogen, or methoxy, and m is 0-5 where R12 is independently selected at each occurrence;
- R16 is arylene(lower alkylene), lower alkylene, arylene, or —(CH2OCH2)pCH2— where p is 1-5;
- and
- R17 is an activated ester, an anhydride, an acid chloride, an isocyanate, an isothiocyanate,
- wherein X is a leaving group.
12 more elements
A compound of the formula
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein, independently at each location:
- R1 is hydrogen or lower alkyl;
- R2 is hydrogen or lower alkyl;
- R3 is lower alkyl;
- R4 is lower alkyl, aryl, or —CH2—C5-7carbocycle when R5 is H or methyl, or R4 and R5 together form a carbocycle of the partial formula —(CRaRb)n— wherein Ra and Rb are independently hydrogen or lower alkyl and n is 2, 3, 4, 5 or 6;
- R6 is hydrogen or lower alkyl;
- R7 is sec-butyl or iso-butyl;
- R8 is hydrogen or lower alkyl;
- R11 is hydrogen or lower alkyl;
- R12 is lower alkyl, halogen, or methoxy, and m is 0-5 where R12 is independently selected at each occurrence;
- and
- where R20 is
- wherein:
- R14 is a direct bond, arylene(lower alkylene), lower alkylene or arylene;
- R15 is hydrogen, lower alkyl or aryl;
- R16 is arylene(lower alkylene), lower alkylene, arylene, or —(CH2OCH2)pCH2— where p is 1-5;
- and
- R17 is an activated ester, an anhydride, an acid chloride, an isocyanate, an isothiocyanate,
- wherein X is a leaving group.
17 more elements
A compound of the formula
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein, independently at each location:
- R1 is hydrogen or lower alkyl;
- R2 is hydrogen or lower alkyl;
- R3 is lower alkyl;
- R4 is lower alkyl, aryl, or —CH2—C5-7carbocycle when R5 is H or methyl, or R4 and R5 together form a carbocycle of the partial formula —(CRaRb)n— wherein Ra and Rb are independently hydrogen or lower alkyl and n is 2, 3, 4, 5 or 6;
- R6 is hydrogen or lower alkyl;
- R7 is sec-butyl or iso-butyl;
- R8 is hydrogen or lower alkyl;
- R11 is hydrogen or lower alkyl;
- R12 is lower alkyl, halogen, or methoxy, and m is 0-5 where R12 is independently selected at each occurrence;
- R16 is arylene(lower alkylene), lower alkylene, arylene, or —(CH2OCH2)pCH2— where p is 1-5;
- and
- R17 is an activated ester, an anhydride, an acid chloride, an isocyanate, an isothiocyanate,
- wherein X is a leaving group.
12 more elements
A compound of the formula
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein, independently at each location:
- R1 is hydrogen or lower alkyl;
- R2 is hydrogen or lower alkyl;
- R3 is lower alkyl;
- R4 is lower alkyl, aryl, or —CH2—C5-7carbocycle when R5 is H or methyl, or R4 and R5 together form a carbocycle of the partial formula —(CRaRb)n— wherein Ra and Rb are independently hydrogen or lower alkyl and n is 2, 3, 4, 5 or 6;
- R6 is hydrogen or lower alkyl;
- R7 is sec-butyl or iso-butyl;
- R8 is hydrogen or lower alkyl;
- and
- R20 is
- wherein:
- R14 is a direct bond, arylene(lower alkylene), lower alkylene or arylene;
- R15 is hydrogen, lower alkyl or aryl;
- R16 is arylene(lower alkylene), lower alkylene, arylene, or —(CH2OCH2)pCH2— where p is 1-5;
- and
- R17 is an activated ester, an anhydride, an acid chloride, an isocyanate, an isothiocyanate,
- wherein X is a leaving group.
15 more elements
A compound of the formula
- or a pharmaceutically acceptable salt or solvate thereof,
- wherein, independently at each location:
- R1 is hydrogen or lower alkyl;
- R2 is hydrogen or lower alkyl;
- R3 is lower alkyl;
- R4 is lower alkyl, aryl, or —CH2—C5-7carbocycle when R5 is H or methyl, or R4 and R5 together form a carbocycle of the partial formula —(CRaRb)n— wherein Ra and Rb are independently hydrogen or lower alkyl and n is 2, 3, 4, 5 or 6;
- R6 is hydrogen or lower alkyl;
- R7 is sec-butyl or iso-butyl;
- R8 is hydrogen or lower alkyl;
- and R20 is
- wherein, R15 is hydrogen or lower alkyl, R16 is arylene(lower alkylene), lower alkylene, arylene, or —(CH2OCH2)pCH2— where p is 1-5;
- and
- R17 is an activated ester, an anhydride, an acid chloride, an isocyanate, an isothiocyanate,
- wherein X is a leaving group.
11 more elements
Dependencies are inferred from the claim text.