Claims for Patent: 9,751,887

Summary for Patent: 9,751,887

Title:	Imidazo[1,2-b]pyridazine derivatives as kinase inhibitors
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.
Inventor(s):	Yasuyuki Takeda, Kenji Yoshikawa, Yoshiko Kagoshima, Yuko Yamamoto, Ryoichi Tanaka, Yuichi Tominaga, Masaki Kiga, Yoshito Hamada
Assignee:	Daiichi Sankyo Co Ltd
Application Number:	US14/926,973
Patent Claims:	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 2. A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), Q represents an oxygen atom. 3. 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. 4. 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. 5. 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: 6. 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: 7. 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. 8. A compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein in the formula (I), Y4 is the following Ya or Yb: 9. A pharmaceutical composition comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof, as an active ingredient. 10. 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. 11. 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. 12. 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. 13. 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. 14. 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. 15. 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. 16. 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. 17. 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.