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US 12,637,441 B2Granted
Prodrugs of the tyrosine kinase inhibitor for treating cancer
AssigneeRisen (Suzhou) Pharma Tech Co., Ltd.
InventorsJiasheng Lu, Jiamin Gu, Gang Chen, Qiguo Zhang, Chengyong Sun, Xianqi Kong
Life of this patent
Estimating the term…
Abstract
There are provided compounds of Formula I, and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, useful for inhibition or modulation of the activity of tyrosine kinases and treatment of disease states or conditions mediated by tyrosine kinases, including cancers.
Claims20
A compound of Formula I, or a pharmaceutically acceptable salt or ester thereof:
- where,
- R1 and R2 are independently a hydrogen or a protecting group,
- wherein the protecting group is R4W(R5R6C)m—, where m is an integer selected from 0 to 6;
- W is absent;
- R5 and R6 are independently a hydrogen or a lower alkyl group;
- and
- (a) R4 is
- where X is oxygen (—O—), sulfur (—S—), nitrogen (—NH—), or a methylene (—CH2—) group;
- R7 and R8 are independently a hydrogen, a substituted or unsubstituted alkyl or cycloalkyl, an aryl or heteroaryl group without or with substitution, a PEG moiety, or an ester-forming group;
- or, the combination of R7 and X is an aryl group with or without further substitution;
- or
- (b) R4 is
- where R7 is a PEG moiety and X is O, S, NH or —CH2—;
- and
- R3 is absent or a protecting group selected from acyl group, carbonyl group, thiocarbonyl group, carbamoyl group, substituted or unsubstituted acetyl, substituted or unsubstituted aminoalkanoyl, substituted or unsubstituted α-aminoalkanoyl, an acyl group derived from a natural or an unnatural amino acid with or without substitution, an acyl group of a peptide residue, cycloalkane-carbonyl, heterocycloalkane-carbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroalkoxycarbonyl, and heteroaryloxycarbonyl;
- provided that the compound of Formula I is not axitinib.
13 more elements
A compound of Formula II, or a pharmaceutically acceptable salt or ester thereof:
- where,
- R1 and R2 are independently a hydrogen or a protecting group,
- wherein:
- the protecting group is R4W(R5R6C)m—, where m is an integer selected from 0 to 6;
- W is oxygen (—O—), sulfur (—S—), nitrogen (—NH—), or absent;
- R5 and R6 are independently a hydrogen or a lower alkyl group;
- and
- (a) R4 is
- where X is oxygen (—O—), sulfur (—S—), nitrogen (—NH—), or a methylene (—CH2—) group;
- R7 and R8 are independently a hydrogen, a substituted or unsubstituted alkyl or cycloalkyl, an aryl or heteroaryl group without or with substitution, a PEG moiety, or an ester-forming group;
- or, the combination of R7 and X is an aryl group with or without further substitution;
- provided that when R4 is
- and X is O, then R7 and R8 are not both hydrogen;
- or
- (b) R4 is
- where R7 is a PEG moiety and X is O, S, NH or —CH2—;
- provided that the compound of Formula II is not axitinib.
14 more elements
A compound of Formula III, or a pharmaceutically acceptable salt or ester thereof:
- where,
- R3 is absent or a protecting group, wherein:
- (a) the protecting group is selected from acyl group, carbonyl group, thiocarbonyl group, carbamoyl group, substituted or unsubstituted acetyl, substituted or unsubstituted aminoalkanoyl, substituted or unsubstituted a-aminoalkanoyl, an acyl group derived from a natural or an unnatural amino acid with or without substitution, an acyl group of a peptide residue, cycloalkane-carbonyl, heterocycloalkane-carbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroalkoxycarbonyl, and heteroaryloxycarbonyl;
- or
- (b) the protecting group is R4W(R5R6C)m—, where m is an integer selected from 0 to 6;
- W is oxygen (—O—), sulfur (—S—), nitrogen (—NH—), or absent;
- R5 and R6 are independently a hydrogen or a lower alkyl group;
- and R4 is
- where X is oxygen (—O—), sulfur (—S—), nitrogen (—NH—), or a methylene (—CH2—) group;
- R7 and R8 are independently a hydrogen, a substituted or unsubstituted alkyl or cycloalkyl, an aryl or heteroaryl group without or with substitution, a PEG moiety, or an ester-forming group;
- or, the combination of R7 and X is an alkyl or aryl group with or without further substitution;
- Y⊖ is a counterion;
- provided that the compound of Formula III is not axitinib.
10 more elements
A compound which is:
- or a pharmaceutically-acceptable salt or ester thereof.
Dependencies are inferred from the claim text.