Selective FAK inhibitors
AssigneeCancer Therapeutics Crc Pty Limited
InventorsIan Peter Holmes, Yiva Bergman, Gillian Elizabeth Lunniss, Marcia Nikac, Neil Choi, Catherine Fae Hemley, Scott Raymond Walker, Richard Charles Foitzik, Danny Ganame, Romina Lessene
Life of this patent
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Abstract
A compound of the formula (I): where R1 or R2 is a cycle, amine group and R5 is an aromatic group with a carbonyl containing substituent for use as a FAK inhibitor.
Claims3
A method of inhibiting FAK in vitro or in vivo, comprising contacting a cell with an effective amount of a compound of the formula (I):
- wherein:
- R1 is selected from:
- H and
- wherein:
- RN1 is selected from H, C1-3 alkyl and C(═O)Me;
- RN2 is selected from H, C1-3 alkyl and C(═O)Me;
- RN3 is selected from H, C1-3 alkyl and C(═O)Me;
- RN4 is selected from H and CH3;
- R2 is selected from H and
- wherein:
- RN5 is selected from H, C1-3 alkyl and C(═O)Me;
- RN6 is selected from H, C1-3 alkyl and C(═O)Me;
- and wherein only one of R1 and R2 is H;
- R3 is selected from O—C1-2 alkyl, C1-2 alkyl, halo, cyano, where the C1-2 alkyl group may be substituted by one or more fluoro groups;
- R4 is selected from CF3, halo, CF2H and CN;
- and
- R5 is selected from groups of the following formulae:
- wherein:
- R6 is selected from H, (CHRC1)n1C(O)N(RN6)Z1 and (CH2)n2C(O)OZ2;
- wherein:
- n1 is 1;
- RC1 is H or Me;
- RN6 is H or CH3;
- Z1 is H, CH3 or OCH3;
- n2 is 1;
- and
- Z2 is CH3;
- and where only one of RN6 and Z1 can be CH3,
- R7 is selected from H, and (CH2)m1C(O)N(RM1)Y1, wherein:
- m1 is 0 or 1;
- RM1 is H;
- and
- Y1 is H, Me or OCH3;
- and only one of R6 and R7 is H;
- and
- R8 is H or, when R7 is C(═O)NH2, R8 is selected from H and C1-2 alkyl.
A method of treating a disease ameliorated by the inhibition of FAK comprising administering a compound of the formula
- wherein:
- R1 is selected from:
- H and
- wherein:
- RN1 is selected from H, C1-3 alkyl and C(═O)Me;
- RN2 is selected from H, C1-3 alkyl and C(═O)Me;
- RN3 is selected from H, C1-3 alkyl and C(═O)Me;
- RN4 is selected from H and CH3;
- R2 is selected from H and
- wherein:
- RN5 is selected from H, C1-3 alkyl and C(═O)Me;
- RN6 is selected from H, C1-3 alkyl and C(═O)Me;
- and wherein only one of R1 and R2 is H;
- R3 is selected from O—C1-2 alkyl, C1-2 alkyl, halo, cyano, where the C1-2 alkyl group may be substituted by one or more fluoro groups;
- R4 is selected from CF3, halo, CF2H and CN;
- and
- R5 is selected from groups of the following formulae:
- wherein:
- R6 is selected from H, (CHRC1)n1C(O)N(RN6)Z1 and (CH2)n2C(O)OZ2;
- wherein:
- n1 is 1;
- RC1 is H or Me;
- RN6 is H or CH3;
- Z1 is H, CH3 or OCH3;
- n2 is 1;
- and
- Z2 is CH3;
- and where only one of RN6 and Z1 can be CH3,
- R7 is selected from H, and (CH2)m1C(O)N(RM1)Y1, wherein:
- m1 is 0 or 1;
- RM1 is H;
- and
- Y1 is H, Me or OCH3;
- and only one of R6 and R7 is H;
- and
- R8 is H or, when R7 is C(═O)NH2, R8 is selected from H and C1-2 alkyl.
A method of treating a disease ameliorated by the inhibition of FAK comprising administering a composition comprising a pharmaceutically acceptable carrier or diluent;
- and a compound of the formula (I):
- wherein:
- R1 is selected from:
- H and
- wherein:
- RN1 is selected from H, C1-3 alkyl and C(═O)Me;
- RN2 is selected from H, C1-3 alkyl and C(═O)Me;
- RN3 is selected from H, C1-3 alkyl and C(═O)Me;
- RN4 is selected from H and CH3;
- R2 is selected from H and
- wherein:
- RN5 is selected from H, C1-3 alkyl and C(═O)Me;
- RN6 is selected from H, C1-3 alkyl and C(═O)Me;
- and wherein only one of R1 and R2 is H;
- R3 is selected from O—C1-2 alkyl, C1-2 alkyl, halo, cyano, where the C1-2 alkyl group may be substituted by one or more fluoro groups;
- R4 is selected from CF3, halo, CF2H and CN;
- and
- R5 is selected from groups of the following formulae:
- wherein:
- R6 is selected from H, (CHRC1)n1C(O)N(RN6)Z1 and (CH2)n2C(O)OZ2;
- wherein:
- n1 is 1;
- RC1 is H or Me;
- RN6 is H or CH3;
- Z1 is H, CH3 or OCH3;
- n2 is 1;
- and
- Z2 is CH3;
- and where only one of RN6 and Z1 can be CH3,
- R7 is selected from H, and (CH2)m1C(O)N(RM1)Y1, wherein:
- m1 is 0 or 1;
- RM1 is H;
- and
- Y1 is H, Me or OCH3;
- and only one of R6 and R7 is H;
- and
- R8 is H or, when R7 is C(═O)NH2, R8 is selected from H and C1-2 alkyl.
Dependencies are inferred from the claim text.