Patent ID: 11884656
Assignee: SENTINEL ONCOLOGY LIMITED
Field: Organic fine chemistry (Chemistry)
Classification: CPC C  A | IPC A  C

Claim 16:
17. A method for the treatment of a disease state or condition characterised by the presence of a mutated form of KRAS, which method comprises administering a therapeutically effective amount of a compound to a patient who has been screened and has been determined as suffering from a disease or condition which would be susceptible to treatment with a compound having activity against KRAS, wherein the compound is a compound of formula (3):, or a pharmaceutically acceptable salt or tautomer thereof, wherein:
Z is selected from a pyrrole, pyrazole or isoxazole ring;
ring X is a benzene or pyridine ring;
ring Y is a benzene, pyridine, thiophene or furan ring;
Ar1 is a benzene, pyridine, thiophene or furan ring optionally substituted with one or more substituent R5;
m is 0, 1 or 2;
n is 0, 1 or 2;
R1 is CF3;
Hyd1 and Hyd2 are the same or different and are C1-4 hydrocarbon groups;
R2 is selected from hydrogen and a C1-4 hydrocarbon group;
R3 is selected from hydrogen and a C1-4 hydrocarbon group;
R4 is selected from:
fluorine;
chlorine;
bromine;
hydroxyl;
cyano;
carboxyl;
C(O)O(Hyd1);
amino;
-(Hyd2)NH;
(Hyd2)2N; and
a C1-5 hydrocarbon group where 0, 1 or 2 of the carbons in the hydrocarbon group are replaced with a heteroatom selected from N, O and S, the hydrocarbon group being optionally substituted with one or more fluorine atoms;

R5 is selected from halogen; O—Ar2; cyano, hydroxy; amino; Hyd1-SO2— and a non-aromatic C1-8 hydrocarbon group where 0, 1 or 2 but not all of the carbons in the hydrocarbon group are optionally replaced with a heteroatom selected from N, O and S and where the hydrocarbon group is optionally substituted with one or more fluorine atoms:
Ar2 is a phenyl, pyridyl or pyridone group optionally substituted with 1 or 2 substituents selected from halogen; cyano and a C1-4 hydrocarbon group optionally substituted with one or more fluorine atoms;
R6 is a group Q1-Ra—Rb;
Q1 is absent or is a C1-3 saturated hydrocarbon linker;
Ra is selected from O; C(O); C(O)O; CONRc; N(Rc)CONRc, NRc; and SO2NRc;
Rb is selected from:
hydrogen;
a C1-8 non-aromatic hydrocarbon group where 0, 1 or 2 of the carbon atoms in the hydrocarbon group are replaced with a heteroatom selected from N and O, the C1-8 non-aromatic hydrocarbon group being optionally substituted with one or more substituents selected from fluorine and a group Cyc1; and
a group Cyc1;

Cyc1 is a non-aromatic 4-7 membered carbocyclic or heterocyclic ring group containing 0, 1 or 2 heteroatom ring members selected from N, O and S and being optionally substituted with one or more substituents selected from hydroxyl; amino; (Hyd2)NH; (Hyd2)2N; and a C1-5 hydrocarbon group where 0, 1 or 2 of the carbons in the hydrocarbon group are replaced with a heteroatom selected from N, O and S, the hydrocarbon group being optionally substituted with one or more fluorine atoms or by a 5- or 6-membered heteroaryl group containing 1 or 2 heteroatom ring members selected from N and O;
Rc is selected from hydrogen and a C1-4 non-aromatic hydrocarbon group;
R7 is selected from R4;
with the proviso that when n is 2 and both occurrences of R7 are —OCH3, R6 is not —NH2 or —NHCH3; and
provided that the compound is other than:
(i) a compound wherein R6 is hydroxy, methoxymethyl or unsubstituted or fluoro-substituted C1-8 alkoxy;
(ii) a compound wherein the ring Z is an isoxazole ring and Ar1 is an unsubstituted 4-pyridyl group attached to the isoxazole 3-position; and R2 and R3 are both absent or
(iii) a compound wherein Z is an isoxazole ring and R4 is an azetidin-4-yloxy group, with the proviso that said treatment excludes prophylaxis and prevention of recurrence.