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US 11,970,469 B2Granted
Compounds useful in the treatment of disorders associated with mutant RAS
AssigneeThe Institute of Cancer Research: Royal Cancer Hospital
InventorsTerrence Rabbitts, Camilo Quevedo, Carole Bataille
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Abstract
The present invention relates to compounds of Formula I as defined herein, and salts and solvates thereof. (I) The present invention also relates to pharmaceutical compositions comprising compounds of Formula (I), and to compounds of Formula (I) for use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which inhibition of a RAS-effector protein-protein interaction is implicated.
Claims10
A compound of Formula Ih, Ii, Ij or Ik, or a salt or solvate thereof:
- wherein,
- R1 is selected from C1-6 alkoxy and NRpRq, wherein Rp and Rq are independently selected from hydrogen, C1-6 alkyl and C(O)C1-3alkyl;
- R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, O—C1-6 alkyl and C1-6 alkyl;
- R4 is selected from hydrogen and C1-3 alkyl;
- R5 is selected from the group consisting of hydrogen, hydroxyl, ═O, halogen, CN, C1-6 haloalkyl, C1-6 haloalkoxy, O—C1-6 alkyl, C1-6 alkyl and NRpRq;
- R6 is selected from the group consisting of hydrogen, hydroxyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, O—C1-6 alkyl, C1-6 alkyl and NRpRq;
- R7a and R7b are independently selected from hydrogen, hydroxyl, halogen, C1-6 haloalkyl, C1-6 haloalkoxy, O—C1-6 alkyl and C1-6 alkyl;
- R8 is selected from selected from the group consisting of hydrogen and C1-6 alkyl;
- and
- R9 is selected from C1-6 alkyl, optionally substituted with one or more groups of HNMe or NMe2;
- or
- R9 is —(CH2)1-6-heterocycle, wherein said heterocycle is or morpholine optionally substituted with one or more C1-6 alkyl;
- or
- R9 if —C(O)NH(CH2)1-4-heterocycle, wherein said heterocycle is piperidine substituted by Rk;
- wherein Rk is selected from the group consisting of hydrogen, C1-6 alkyl optionally substituted with phenyl, —C(O)OH, and —C(O)OC1-6 alkyl.
12 more elements
A compound, or a salt or solvate thereof, selected from the group consisting of:
- N-(4-((dimethylamino)methyl)phenyl)-3′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((dimethylamino)methyl)phenyl)-3,3′-dimethoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((dimethylamino)methyl)phenyl)-2-fluoro-3,3′-dimethoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((dimethylamino)methyl)phenyl)-4′-fluoro-3′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((dimethylamino)methyl)phenyl)-3′,4′-difluoro-5′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((dimethylamino)methyl)phenyl)-3′-fluoro-5′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((dimethylamino)methyl)phenyl)-3′-methoxy-5′-methyl-[1,1′-biphenyl]-4-amine;
- N-(3,5-dimethylphenyl)-2-fluoro-3,3′-dimethoxy-[1,1′-biphenyl]-4-amine;
- N-(3,5-dimethylphenyl)-3′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(5-((dimethylamino)methyl)-2-methylphenyl)-3′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(3-((2,6-dimethylmorpholino)methyl)phenyl)-3′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((2,6-dimethylmorpholino)methyl)phenyl)-3′-methoxy-[1,1′-biphenyl]-4-amine;
- N-(4-((dimethylamino)methyl)phenyl)-2-methoxy-6-(3-methoxyphenyl)pyridin-3-amine;
- N-(3-((dimethylamino)methyl)phenyl)-2-methoxy-6-(3-methoxyphenyl)pyridin-3-amine;
- N-(4-((dimethylamino)methyl)phenyl)-6-(3-methoxyphenyl)pyridin-3-amine;
- 3-((3′-methoxy-[1,1′-biphenyl]-4-yl)amino)-N-(piperidin-4-ylmethyl)benzamide;
- N-(4-((dimethylamino)methyl)phenyl)-3′-methoxy-4′-methyl-[1,1′-biphenyl]-4-amine;
- 4-((3′-methoxy-[1,1′-biphenyl]-4-yl)amino)-N-(piperidin-4-ylmethyl)benzamide;
- N-((1-benzylpiperidin-4-yl)methyl)-4-((3′-methoxy-[1,1′-biphenyl]-4-yl)amino)benzamide;
- 4-((3′-methoxy-[1,1′-biphenyl]-4-yl)amino)-N-((1-methy 1piperidin-4-yl)methyl)benzamide;
- and
- 4-((3′,4′-difluoro-5′-methoxy-[1,1′-biphenyl]-4-yl)amino)-N-((1-methylpiperidin-4-yl)methyl)benzamide.
19 more elements
Dependencies are inferred from the claim text.