# US 9,751,887 B2 · Imidazo[1,2-b]pyridazine derivatives as kinase inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,751,887 B2 - Document ID: US9751887B2 - Status: Granted - Kind: B2 - Application number: 14/926,973 - Filed: 2015-10-29 - Published: 2016-02-18 - Granted: 2017-09-05 - Earliest claimed: 2012-06-04 - Assignees: Daiichi Sankyo Company, Limited - Applicants: Daiichi Sankyo Company, Limited - Inventors: Yasuyuki Takeda; Kenji Yoshikawa; Yoshiko Kagoshima; Yuko Yamamoto; Ryoichi Tanaka; Yuichi Tominaga; Masaki Kiga; Yoshito Hamada - Web page: https://patentgrep.com/patent/US9751887B2 ## CPC - C07D 487/04: Ortho-condensed systems - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention is intended to provide a compound or a pharmacologically acceptable salt thereof which is useful in the treatment of a tumor through its ROS1 kinase enzyme activity inhibitory effect and NTRK kinase enzyme inhibitory effect. The present invention provides a compound having an imidazo[1,2-b]pyridazine structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, and a pharmaceutical composition comprising the compound. In the formula, R1, G, T, Y1, Y2, Y3, and Y4 are as defined herein. ## Claims ### Claim 1 A compound represented by the general formula (I) or a pharmacologically acceptable salt thereof: wherein R1 represents a hydrogen atom, a C1-C6 alkyl group, a fluoro-C1-C6 alkyl group, or a hydroxy-C1-C6 alkyl group; Q represents an oxygen atom or RaN, wherein Ra represents a hydrogen atom or a C1-C6 alkyl group; G is represented by the following formula (IV): wherein U represents a nitrogen atom or CH; R7 represents a hydrogen atom or a C1-C6 alkyl group; and R8 represents a hydrogen atom, a C1-C6 alkyl group, or a halogen atom, or is represented by Ga to Ge: T represents a nitrogen atom or CRb, wherein Rb represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, or a cyano group; Y1 and Y2 each independently represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, or a cyano group; Y3 represents a hydrogen atom; and Y4 is represented by —O-M2, formula (V), Ya, or Yb wherein M2 is any of the following M2a to M21: formula (V) is wherein n represents 1 or 2; and R21 and R31 each independently represents a hydrogen atom, an amino group, a C1-C6 alkyl group, an amino-C1-C6 alkyl group, or a C1-C6 alkylamino group; and Ya and Yb are ### Claim 2 (depends on 1) A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), Q represents an oxygen atom. ### Claim 3 (depends on 1) A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), Q represents RaN, wherein Ra represents a hydrogen atom or a C1-C6 alkyl group. ### Claim 4 (depends on 1) A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), G is represented by the following formula (IV): wherein U represents a nitrogen atom or CH; R7 represents a hydrogen atom or a C1-C6 alkyl group; and R8 represents a hydrogen atom, a C1-C6 alkyl group, or a halogen atom. ### Claim 5 (depends on 1) A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), G is any of the following Ga to Ge: ### Claim 6 (depends on 1) A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), Y4 represents —O-M2, wherein M2 is any of the following M2a to M21: ### Claim 7 (depends on 1) A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), Y4 is represented by the following formula (V): wherein n represents 1 or 2; and R21 and R31 each independently represents a hydrogen atom, an amino group, a C1-C6 alkyl group, an amino-C1-C6 alkyl group, or a C1-C6 alkylamino group. ### Claim 8 (depends on 1) A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), Y4 is the following Ya or Yb: ### Claim 9 (depends on 1) A pharmaceutical composition comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof, as an active ingredient. ### Claim 10 (depends on 1) A method for inhibiting proliferation of a cancer cell having a detectable increase in the expression level of ROS1 gene, comprising administering a compound according to claim 1 or a pharmacologically acceptable salt thereof. ### Claim 11 (depends on 1) A method for inhibiting proliferation of a cancer cell having a detectable increase in the expression level of NTRK gene, comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof. ### Claim 12 (depends on 1) A method for inhibiting proliferation of a cancer cell having a detectable expression of ROS1 fusion gene, comprising administering a compound according to claim 1 or a pharmacologically acceptable salt thereof. ### Claim 13 (depends on 1) A method for inhibiting proliferation of a cancer cell having a detectable expression of NTRK fusion gene, comprising administering a compound according to claim 1 or a pharmacologically acceptable salt thereof. ### Claim 14 (depends on 1) A method for inhibiting proliferation of a cancer cell by the inhibition of ROS1 kinase enzyme activity, comprising administering a compound according to claim 1 or a pharmacologically acceptable salt thereof. ### Claim 15 (depends on 1) A method for inhibiting proliferation of a cancer cell by the inhibition of NTRK kinase enzyme activity, comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof. ### Claim 16 (depends on 1) A method for inhibiting ROS1 kinase enzyme activity in a subject, comprising administering a compound according to claim 1 or a pharmacologically acceptable salt thereof. ### Claim 17 (depends on 1) A method for inhibiting NTRK kinase enzyme activity in a subject, comprising administering a compound according to claim 1 or a pharmacologically acceptable salt thereof.