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US 7,888,361 B2Granted
Tyrosine kinase inhibitors containing a zinc binding moiety
AssigneeCuris, Inc.
InventorsXiong Cai, Changgeng Qian, Stephen Gould, Haixiao Zhai
Life of this patent
Estimating the term…
Abstract
The present invention relates to tyrosine kinase inhibitors that contain a zinc-binding moiety and their use in the treatment of tyrosine related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.
Claims9
A compound represented by formula (I) or (II):
- or a pharmaceutically acceptable salt thereof, wherein
- Cz is pyrimidine or substituted pyrimidine;
- Ar is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- X3 is NH, alkylamino, O or S;
- Z2 is O, S, NH or alkylamino;
- Y2 is N or CR20;
- where R20 is selected from hydrogen, halogen, aliphatic, substituted aliphatic, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
- R21 is hydrogen or aliphatic;
- B is a direct bond or straight- or branched-, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, cycloalkenyl, alkylarylalkyl, alkylarylalkenyl, alkylarylalkynyl, alkenylarylalkyl, alkenylarylalkenyl, alkenylarylalkynyl, alkynylarylalkyl, alkynylarylalkenyl, alkynylarylalkynyl, alkylheteroarylalkyl, alkylheteroarylalkenyl, alkylheteroarylalkynyl, alkenylheteroarylalkyl, alkenylheteroarylalkenyl, alkenylheteroarylalkynyl, alkynylheteroarylalkyl, alkynylheteroarylalkenyl, alkynylheteroarylalkynyl, alkylheterocyclylalkyl, alkylheterocyclylalkenyl, alkylheterocycloalkynyl, alkenylheterocyclylalkyl, alkenylheterocyclylalkenyl, alkenylheterocyclylalkynyl, alkynylheterocyclylalkyl, alkynylheterocyclylalkenyl, alkynylheterocyclylalkynyl, alkylaryl, alkenylaryl, alkynylaryl, alkylheteroaryl, alkenylheteroaryl, or alkynylhereroaryl, in which one or more methylenes can be interrupted or terminated by O, S, S(O), SO2, N(R8), C(O), substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic;
- where R8 is hydrogen, acyl, aliphatic or substituted aliphatic;
- C is selected from:
- where W is O or S;
- Y is absent, N, or CH;
- Z is N or CH;
- R7 and R9 are independently hydrogen, OR′, aliphatic or substituted aliphatic, wherein R′ is hydrogen, aliphatic, substituted aliphatic or acyl;
- provided that if R7 and R9 are both present, one of R7 or R9 must be OR′ and if Y is absent, R9 must be OR′;
- and R8 is as previously defined;
- where W is O or S;
- J is O, NH or NCH3;
- and R10 is hydrogen or lower alkyl;
- where W is O or S;
- Y1 and Z1 are independently N, C or CH;
- and
- where Z, Y, and W are as previously defined;
- R11 and R12 are independently selected from hydrogen or aliphatic;
- R1, R2 and R3 are independently selected from hydrogen, hydroxy, amino, halogen, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, CF3, CN, N3, NO2, sulfonyl, acyl, aliphatic, substituted aliphatic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic.
23 more elements
A compound represented by formula (VII):
- wherein M1 is absent, O, NH, alkylamino, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
- M2 is absent, C1-C6 alkyl, O, NH, alkylamine, S, SO, SO2, heterocyclic, heteroaryl, aryl, or C═O;
- M3 is absent, O, NH, alkylamino, C═O, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
- M4 is absent, O, NH, alkylamino, heterocyclic, heteroaryl or aryl;
- M5 is absent, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, heterocyclic, heteroaryl or aryl;
- R′ is hydrogen, aliphatic, substituted aliphatic or acyl;
- R1 is selected from hydrogen, hydroxy, amino, halogen, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, dialkylamino, substituted dialkylamino, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfonyl, CF3, CN, N3, NO2, sulfonyl, acyl, aliphatic, substituted aliphatic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic;
- Z2 is O, S, NH or alkylamino;
- Ar is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- and R21 is hydrogen or aliphatic.
7 more elements
A compound represented by formula (VIII):
- wherein M1 is absent, O, NH, alkylamino, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
- M2 is absent, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, O, NH, alkylamine, S, SO, SO2, heterocyclic, heteroaryl, aryl or C═O;
- M3 is absent, O, NH, alkylamino, S, SO, SO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, heterocyclic, heteroaryl, aryl or C═O;
- M4 is absent, O, NH, alkylamino, CO, S, SO, SO2, heterocyclic, heteroaryl or aryl;
- M5 is absent, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, heterocyclic, heteroaryl or aryl;
- R′ is hydrogen, aliphatic, substituted aliphatic or acyl;
- Z2 is O, S, NH or alkylamino;
- Ar is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- and R21 is hydrogen or aliphatic.
6 more elements
A compound selected from the compounds delineated in Table A or a pharmaceutically acceptable salt thereof:
- TABLE A
- Compound
- #
- Structure
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 16
- 17
- 18
- 19
- 20
- 21
- 22
- 23
- 24
- 25
- 26
- 27
- 28
- 29
- 30
- 31
- 32
- 33
- 34
- 35
- 36
- 37
- 38
- 39
- 40
- 41
- 42
- 43
44 more elements
Dependencies are inferred from the claim text.