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US 2016/0237064 A1Published application
Therapeutic methods and compositions involving allosteric kinase inhibition
AssigneeAmitech Therapeutic Solutions, Inc.
InventorsEric A. MURPHY, David A. CHERESH, Lee Daniel ARNOLD
Life of this patent
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Abstract
The present invention is directed to methods and compositions for suppressing lymphangiogenesis, angiogenesis and/or tumor growth. The methods comprise contacting the tumor with a compound that (i) stabilizes a protein kinase in the inactive state and (ii) is not an ATP competitive inhibitor of the protein kinase in the active state.
Claims30
A compound has the structure
- or an N-oxide, N,N′-dioxide, N,N′,N″-trioxide, or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are independently hydrogen, optional substituted alkyl, halogen, optional substituted amine, NH2, optional substituted alkyoxy, optional substituted thioalkyl, CF3S, optional substituted alkylsulfinyl or optional substituted alkylsulfonyl;
- Z′ is N or C;
- Rm is C1-6 alkyl, or halogen substituted C1-6 alkyl;
- and R3 is independently a hydrogen, C1-6 alkyl, halogen substituted C1-6 alkyl, halogen substituted C1-6 alkoxy, or C3-10cycloalkyl;
- or, optionally, Rm and R3 are joined to form a five to seven membered carbocycle;
- and n is 0-4.
3 more elements
A process for preparing a compound of formula I:
- comprising reacting a compound of formula II,
- with a compound of formula (III),
- in the presence of a base, wherein W is selected from the group consisting of pyridine, pyridazine, pyrimidine, pyrazine, triazine, 14uinolone, isoquinoline, cinnoline, quinazoline, quinoxaline, 1,2,4-benzotriazine and azaindole;
- X is O, S or NH;
- R1 and R2 are independently a hydrogen, optional substituted alkyl, halogen, optional substituted amine, —NH2, —OH, optional substituted alkoxy, optional substituted thioalkyl, —SCF3, optional substituted alkylsulfinyl or an optional substituted alkylsulfonyl;
- R3 is independently a hydrogen, C1-6 alkyl, halogen substituted C1-6 alkyl, halogen substituted C1-6 alkoxy, or C3-10cycloalkyl;
- or, optionally, two R3 are joined to form a 5 to 7 membered carbocycle;
- and m is 1-5.
5 more elements
A process for preparing a compound of formula Ia:
- comprising reacting a compound of formula Iia,
- with a compound of formula (IIIa),
- in the presence of a base, wherein R1 and R2 are independently a hydrogen, optional substituted alkyl, halogen, optional substituted amine, —NH2, —OH, optional substituted alkoxy, optional substituted thioalkyl, —SCF3, optional substituted alkylsulfinyl or an optional substituted alkylsulfonyl and R3 is a hydrogen, halogen substituted C1-6 alkyl, or halogen substituted C1-6 alkoxy.
A process for preparing a compound of formula IV:
- comprising reacting a compound of formula V,
- with a compound of formula (VI),
- in the presence of a base wherein L is a leaving group;
- Y is —SH, —OH, or —NH2;
- R1 and R2 are independently hydrogen, optional substituted alkyl, halogen, optional substituted protected amine, optional substituted alkoxy, optional substituted thioalkyl, CF3S, optional substituted alkylsulfinyl or optional substituted alkylsulfonyl and R4 is a C1-6 alkyl.
2 more elements
-63. (canceled)
-71. (canceled)
Dependencies are inferred from the claim text.