Drug for cancer therapy characterized in that axl inhibitor and immune checkpoint inhibitor are administered in combination
AssigneeOno Pharmaceutical Co., Ltd.
InventorsKohei TANAKA, Tomoko YASUHIRO
Life of this patent
Estimating the term…
Abstract
A drug for cancer therapy characterized in that an Axl inhibitor and an immune checkpoint inhibitor (for example, an anti-PD-1 antibody) are administered in combination, wherein the Axl inhibitor is a compound represented by the general formula (I): (wherein in the formula, all of the symbols have the same meanings as defined in the specification), a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof, and the combination exhibits a strong anti-tumor effect and, therefore, is useful for cancer therapy.
Claims18
A drug for cancer therapy, comprising a combination of an Axl inhibitor and an immune checkpoint inhibitor, the Axl inhibitor being a compound represented by the general formula (I):
- wherein
- R1 represents (1) a C1-8 alkyl group optionally substituted with one to five R11, (2) a C3-7 carbon ring optionally substituted with one to five R12, or (3) a 4- to 7-membered heterocycle optionally substituted with one to five R13, and when the C1-8 alkyl group represented by R1 is a branched alkyl group, C1-3 alkyl groups branched from a same carbon atom may together form a saturated C3-7 carbon ring;
- R2 represents (1) a C1-4 alkyl group, (2) a halogen atom, (3) a C1-4 haloalkyl group, (4) an oxo group, or (5) an —OR21 group;
- R3 represents (1) a C1-4 alkyl group, (2) a halogen atom, or (3) a C1-4 haloalkyl group;
- R4 represents (1) a C1-4 alkoxy group, (2) a C1-4 haloalkyl group, or (3) an —OR41 group;
- R5 represents (1) a hydrogen atom, (2) a C1-4 alkyl group, (3) a halogen atom, (4) a C1-4 haloalkyl group, or (5) an —OR21 group;
- R11 represents (1) an —OR101 group, (2) an SO2R102 group, (3) an NR103R104 group, or (4) a C3-7 carbon ring optionally substituted with one to three halogen atoms;
- R12 represents (1) a C1-4 alkyl group, or (2) a halogen atom;
- R13 represents (1) a C1-4 alkyl group, or (2) a halogen atom;
- R21 represents (1) a hydrogen atom, or (2) a C1-4 alkyl group;
- R41 represents (1) a hydrogen atom, (2) a C1-8 alkylene group substituted with one to two substituents selected from the group consisting of (a) a 5- to 7-membered cyclic group, (b) NR401R402, and (c) a hydroxyl group, or (3) a C2-8 alkenylene group substituted with one to two substituents selected from the group consisting of (a) a 5- to 7-membered cyclic group, (b) NR401R402, and (c) a hydroxyl group;
- R101 represents (1) a hydrogen atom, or (2) a C1-4 alkyl group;
- R102 represents (1) a hydrogen atom, or (2) a C1-4 alkyl group;
- R103 and R104 each independently represent (1) a hydrogen atom, or (2) a C1-4 alkyl group;
- R401 and R402 each independently represent (1) a hydrogen atom, or (2) a C1-4 alkyl group;
- A represents (1) CH, or (2) a nitrogen atom;
- L represents (1) —O—, (2) —NH—, (3) —C(O)—, (4) —CR6R7—, (5) —S—, (6) —S(O)—, or (7) —S(O)2—;
- R6 and R7 each independently represent (1) a hydrogen atom, (2) a halogen atom, (3) a C1-4 alkyl, (4) a hydroxyl group, or (5) NH2;
- ring1 represents a 5- to 7-membered cyclic group;
- represents a single bond, or a double bond;
- m represents an integer of 0 to 5;
- n represents an integer of 0 to 5;
- p represents an integer of 0 to 2;
- q represents an integer of 0 to 4;
- when m is two or more, a plurality of R2s may be the same as or different from each other, and when two R2s represent a C1-3 alkyl group and are on the same carbon atom, the R2s together may form a C3-7 saturated carbon ring;
- when n is two or more, a plurality of R3s may be the same as or different from each other;
- and
- when q is two or more, a plurality of R4s may be the same as or different from each other,
- a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof.
Dependencies are inferred from the claim text.