Claims for Patent: 9,255,100

Summary for Patent: 9,255,100

Title:	Substituted imidazopyridazines
Abstract:	The present invention relates to substituted imidazopyridazine compounds of general formula (I), which are Mps-1 (Monopolar Spindle 1) Kinase inhibitors (also known as Tyrosine Threonine Kinase, TTK) in which R.sup.3, R.sup.5, and A are as defined in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients. ##STR00001##
Inventor(s):	Klar; Ulrich (Berlin, DE), Koppitz; Marcus (Berlin, DE), Jautelat; Rolf (Haan, DE), Kosemund; Dirk (Berlin, DE), Bohlmann; Rolf (Berlin, DE), Lienau; Philip (Berlin, DE), Siemeister; Gerhard (Berlin, DE), Wengner; Antje Margret (Berlin, DE)
Assignee:	BAYER INTELLECTUAL PROPERTY GMBH (Monheim, DE)
Application Number:	13/822,175
Patent Claims:	1. A compound of general formula I: ##STR00883## in which: A represents a ##STR00884## -group; wherein * indicates the point of attachment of said groups with the rest of the molecule; Z represents a --C(.dbd.O)N(H)R.sup.2 or --C(.dbd.S)N(H)R.sup.2 group, or a group selected from ##STR00885## wherein * indicates the point of attachment of said groups with the rest of the molecule; R.sup.2 represents a hydrogen atom, or a C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, R.sup.6a(R.sup.6b)N--C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, --C.sub.1-C.sub.6-alkyl-CN, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, C.sub.2-C.sub.6-alkenyl-, C.sub.2-C.sub.6-alkynyl- or C.sub.3-C.sub.6-cycloalkyl- group; wherein said C.sub.3-C.sub.6-cycloalkyl- group is optionally substituted, identically or differently, with 1, 2, 3 or 4 groups selected from: halogen, --OH, --CN, C.sub.1-C.sub.6-alkyl-, C.sub.1-C.sub.6-alkoxy-, halo-C.sub.1-C.sub.6-alkyl-; R.sup.3 represents an aryl-X-- or heteroaryl-X-- group; wherein said aryl-X-- or heteroaryl-X-- group is optionally substituted, identically or differently, with 1, 2, 3, 4 or 5 R.sup.7 groups; R.sup.4a represents hydrogen; R.sup.4d represents hydrogen; one of the groups R.sup.4b and R.sup.4c represents a hydrogen atom while the other one represents a group selected from: halo, CN, OH, C.sub.1-C.sub.6-alkyl- and C.sub.1-C.sub.6-alkoxy-; R.sup.5 represents a hydrogen atom, or a C.sub.1-C.sub.6-alkyl-, --(CH.sub.2).sub.n--C.sub.2-C.sub.6-alkenyl, --(CH.sub.2).sub.n--C.sub.2-C.sub.6-alkynyl, --(CH.sub.2).sub.m--C.sub.3-C.sub.6-cycloalkyl, --(CH.sub.2).sub.m-(3- to 7-membered heterocycloalkyl), aryl-C.sub.1-C.sub.6-alkyl-, heteroaryl-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, R.sup.6a(R.sup.6b)N--C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, --C.sub.1-C.sub.6-alkyl-CN, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, C.sub.3-C.sub.6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C.sub.2-C.sub.6-alkenyl-, C.sub.4-C.sub.8-cycloalkenyl-, C.sub.2-C.sub.6-alkynyl-, aryl- or heteroaryl- group; wherein said C.sub.1-C.sub.6-alkyl-, --(CH.sub.2).sub.n--C.sub.2-C.sub.6-alkenyl, --(CH.sub.2).sub.n--C.sub.2-C.sub.6-alkynyl, --(CH.sub.2).sub.m--C.sub.3-C.sub.6-cycloalkyl, --(CH.sub.2).sub.m-(3- to 7-membered heterocycloalkyl), aryl-C.sub.1-C.sub.6-alkyl-, heteroaryl-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, R.sup.6a(R.sup.6b)N--C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, --C.sub.1-C.sub.6-alkyl-CN, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, C.sub.3-C.sub.6-cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C.sub.4-C.sub.8-cycloalkenyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3 or 4 R.sup.8 groups; R.sup.6, R.sup.6a, R.sup.6b, R.sup.6c, represent, independently from each other, a hydrogen atom, or a C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, C.sub.3-C.sub.6-cycloalkyl-, C.sub.2-C.sub.6-alkenyl-, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, aryl-C.sub.1-C.sub.6-alkyl- or heteroaryl-C.sub.1-C.sub.6-alkyl- group; R.sup.7 represents a hydrogen or halogen atom, or a HO--, --CN, C.sub.1-C.sub.6-alkoxy-, C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, R.sup.6a(R.sup.6b)N--C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, C.sub.2-C.sub.6-alkenyl, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, --C(.dbd.O)R.sup.6, --C(.dbd.O)N(H)R.sup.6a, --C(.dbd.O)N(R.sup.6a)R.sup.6b, --C(.dbd.O)O--R.sup.6, --N(R.sup.6a)R.sup.6b, NO.sub.2, --N(H)C(.dbd.O)R.sup.6, --N(R.sup.6c)C(.dbd.O)R.sup.6, --N(H)C(.dbd.O)N(R.sup.6a)R.sup.6b, --N(R.sup.6c)C(.dbd.O)N(R.sup.6a)R.sup.6b, --N(H)C(.dbd.O)OR.sup.6, --N(R.sup.6c)C(.dbd.O)OR.sup.6, --N(H)S(.dbd.O)R.sup.6, --N(R.sup.6c)S(.dbd.O)R.sup.6, --N(H)S(.dbd.O).sub.2R.sup.6, --N(R.sup.6c)S(.dbd.O).sub.2R.sup.6, --N.dbd.S(.dbd.O)(R.sup.6a)R.sup.6b, --OR.sup.6, --O(C.dbd.O)R.sup.6, --O(C.dbd.O)N(R.sup.6a)R.sup.6b, --O(C.dbd.O)OR.sup.6, --SR.sup.6, --S(.dbd.O)R.sup.6, --S(.dbd.O)N(H)R.sup.6, --S(.dbd.O)N(R.sup.6a)R.sup.6b, --S(.dbd.O).sub.2R.sup.6, --S(.dbd.O).sub.2N(H)R.sup.6, --S(.dbd.O).sub.2N(R.sup.6a)R.sup.6b or --S(.dbd.O)(.dbd.NR.sup.6c)R.sup.6 group; wherein said C.sub.1-C.sub.6-alkoxy-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2 or 3 C.sub.1-C.sub.6-alkyl-, C.sub.1-C.sub.6-alkoxy-, halo-C.sub.1-C.sub.6-alkoxy-, --C(.dbd.O)O--R.sup.6 or --OH groups; or when 2 R.sup.7 groups are present ortho to each other on an aryl- or heteroaryl-ring, said 2 R.sup.7 groups together form a bridge: *O(CH.sub.2).sub.2O*, *O(CH.sub.2)O*, *NH(C(.dbd.O))NH*, wherein * represent the point of attachment to said aryl- or heteroaryl- ring; R.sup.8 represents a hydrogen or halogen atom, or a --CN, C.sub.1-C.sub.6-alkoxy-, C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, R.sup.6a(R.sup.6b)N--C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, C.sub.2-C.sub.6-alkenyl-, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, --C(.dbd.O)R.sup.6, --C(.dbd.O)N(H)R.sup.6a, --C(.dbd.O)N(R.sup.6a)R.sup.6b, --C(.dbd.O)O--R.sup.6, --N(R.sup.6a)R.sup.6b, --NO.sub.2, --N(H)C(.dbd.O)R.sup.6, --N(R.sup.6c)C(.dbd.O)R.sup.6, --N(H)C(.dbd.O)N(R.sup.6a)R.sup.6b, --N(R.sup.6c)C(.dbd.O)N(R.sup.6a)R.sup.6b, --N(H)C(.dbd.O)OR.sup.6, --N(R.sup.6c)C(.dbd.O)OR.sup.6, --N(H)S(.dbd.O)R.sup.6, --N(R.sup.6c)S(.dbd.O)R.sup.6, --N(H)S(.dbd.O).sub.2R.sup.6, --N(R.sup.6c)S(.dbd.O).sub.2R.sup.6, --N.dbd.S(.dbd.O)(R.sup.6a)R.sup.6b, --OR.sup.6, --O(C.dbd.O)R.sup.6, --O(C.dbd.O)N(R.sup.6a)R.sup.6b, --O(C.dbd.O)OR.sup.6, --SR.sup.6, --S(.dbd.O)R.sup.6, --S(.dbd.O)N(H)R.sup.6, --S(.dbd.O)N(R.sup.6a)R.sup.6b, --S(.dbd.O).sub.2R.sup.6, --S(.dbd.O).sub.2N(H)R.sup.6, --S(.dbd.O).sub.2N(R.sup.6a)R.sup.6b, --S(.dbd.O)(.dbd.NR.sup.6c)R.sup.6 or --S(.dbd.O).sub.2-(3- to 7-membered heterocycloalkyl) group; wherein said 3- to 7-membered heterocycloalkyl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3 or 4 C.sub.1-C.sub.6-alkyl- groups; m is an integer of 0, 1, 2, 3, 4, 5 or 6; n is an integer of 0, 1, 2, 3, 4 or 5; X represents S(.dbd.O).sub.p, O, NR.sup.6, CR.sup.6aR.sup.6b or C.dbd.CR.sup.6aR.sup.6b; p is an integer of 0, 1 or 2; or a stereoisomer, a tautomer, or a salt thereof, or a mixture of same. 2. A compound according to claim 1, wherein R.sup.2 is selected from the groups consisting of: C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, R.sup.6a(R.sup.6b)N--C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, --C.sub.1-C.sub.6-alkyl-CN, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl-, C.sub.2-C.sub.6-alkenyl-, C.sub.2-C.sub.6-alkynyl-; or a stereoisomer, a tautomer, or a salt thereof, or a mixture of same. 3. A compound according to claim 1, wherein R.sup.5 represents a hydrogen atom, or a C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, C.sub.3-C.sub.6-cycloalkyl-, 3- to 7-membered heterocycloalkyl, or heteroaryl- group; said C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, C.sub.3-C.sub.6-cycloalkyl-, 3- to 7-membered heterocycloalkyl, heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, or 4 R.sup.8 groups; or a stereoisomer, a tautomer, or a salt thereof, or a mixture of same. 4. A compound according to claim 1, wherein R.sup.7 represents a halogen atom, or a HO--, --CN, C.sub.1-C.sub.6-alkoxy-, C.sub.1-C.sub.6-alkyl-, halo-C.sub.1-C.sub.6-alkyl-, HO--C.sub.1-C.sub.6-alkyl-, H.sub.2N--C.sub.1-C.sub.6-alkyl-, C.sub.2-C.sub.6-alkenyl, 3- to 7-membered heterocycloalkyl, --C(.dbd.O)N(H)R.sup.6a, --N(R.sup.6a)R.sup.6b, --N(H)C(.dbd.O)R.sup.6, or --SR.sup.6 group; wherein said C.sub.1-C.sub.6-alkoxy-, or 3- to 7-membered heterocycloalkyl- group is optionally substituted, identically or differently, with 1, 2, or 3 C.sub.1-C.sub.6-alkyl-, C.sub.1-C.sub.6-alkoxy-, halo-C.sub.1-C.sub.6-alkoxy-, --C(.dbd.O)O--R.sup.6 or --OH groups; or when 2 R.sup.7 groups are present ortho to each other on an aryl or heteroaryl ring, said 2 R.sup.7 groups together form a bridge: *CH.sub.2(CH.sub.2).sub.2NH*, *CH.sub.2CH.sub.2N(R.sup.6a)CH.sub.2*, *C(H).dbd.C(H)--C(.dbd.O)--N(H)*, wherein * represent the point of attachment to said aryl or heteroaryl ring; or a stereoisomer, a tautomer, or a salt thereof, or a mixture of same. 5. A compound according to claim 1, wherein R.sup.6, R.sup.6a, R.sup.6b, and R.sup.6c represent, independently from each other, a hydrogen atom, or a C.sub.1-C.sub.6-alkyl- group; or a stereoisomer, a tautomer, or a salt thereof, or a mixture of same. 6. A compound which is selected from the group consisting of: N-cyclopropyl-4-{6-[(2-methoxyphenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, (RS)--N-cyclopropyl-2-methyl-4-[8-{[(4-methylmorpholin-2-yl)methyl]amino}- -6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl]benzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(4-hydroxyphenyl)- sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(4-methoxyphenyl)- sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-hydroxyphenyl)- sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-methoxyphenyl)- sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-hydroxy-3-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-m- ethylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-me- thylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-3-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-me- thylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-4-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-me- thylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-me- thylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,5-difluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylp- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-2-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-me- thylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(2-hydroxyphenyl)- sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(2-methoxyphenyl)- sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-phenoxyimidazo[1,2- -b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-phenoxy-8-[(3,3,3-trifluoropropyl)amino]imida- zo[1,2-b]pyridazin-3-yl}benzamide, 4-{8-[(2-amino-2-methylpropyl)amino]-6-[(3-fluorophenyl)sulfanyl]imidazo[- 1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)sulfanyl]-8-[(3,3,3-trifluor- opropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imid- azo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-fluoro-5-methylphenoxy)-8-[(2-hydroxy-2-methylpropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(3-cyanophenoxy)-8-[(2-hydroxy-2-methylpropy)amino]imidazo[1,2-b]pyr- idazin-3-yl}-N-cyclopropyl-2-methylbenzamide, (RS)--N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfinyl]-8-[(3,3,3-trifluoropr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfonyl]-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(phenylsulfanyl)-8-[(3,3,3-trifluoropropyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}benzenecarbothioamide, 4-{6-(3-chlorophenoxy)-8-[(2-hydroxy-2-methylpropy)amino]imidazo[1,2-b]py- ridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(4-methoxyphenoxy)- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluoro-5-methylphenoxy)-8-[(2-hydroxy-2-methylpropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluoro-5-methylphenoxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide 4-{6-(4-chlorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]p- yridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{6-(3-chloro-4-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidaz- o[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-(2,3-difluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)ami- no]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(3-isopropylphenox- y)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(4-chloro-3-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidaz- o[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-(3,5-dimethylphenoxy)-8-[(2-hydroxy-2-methylpropyl)ami- no]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(3-methylphenoxy)i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(quinolin-5-yloxy)- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(quinolin-6-yloxy)- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(quinolin-6-yloxy)-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-2-methyl-4-{6-(quinolin-5-yloxy)-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-3-yloxy)i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(pyridin-3-yloxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-2-methyl-4-{8-[(2-methylpropyl)amino]-6-(phenylsulfanyl)imi- dazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-2-methyl-4-{8-[(2-methylpropyl)amino]-6-(phenylsulfonyl)imi- dazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-2-methyl-4-{6-(phenylsulfanyl)-8-[(3,3,3-trifluoropropyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(phenylsulfonyl)-8-[(3,3,3-trifluoropropyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(phenylsulfanyl)im- idazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoro-2-hydro- xypropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2,6-difluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylp- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-hydroxyphenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-methoxyphenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-hydroxyphenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-(8-[(2-hydroxy-2-methylpropyl)amino]-6-{[4-(trifluorometh- yl)phenyl]sulfanyl}imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-phenoxyimidazo[1,2- -b]pyridazin-3-yl}benzenecarbothioamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]i- midazo[1,2-b]pyridazin-3-yl}benzenecarbothioamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(phenylsulfanyl)im- idazo[1,2-b]pyridazin-3-yl}benzenecarbothioamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}benzenecarbothioamide, N-cyclopropyl-2-methyl-4-(6-{[4-(trifluoromethyl)phenyl]sulfanyl}-8-[(3,3- ,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl)benzamide, N-cyclopropyl-4-{6-[(2,5-difluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylp- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,4-difluorophenyl)sulfanyl]-8-[(3,3,3-trifluoroprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,5-difluorophenyl)sulfanyl]-8-[(3,3,3-trifluoroprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2,3-difluorophenyl)sulfanyl]-8-[(3,3,3-trifluoroprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(4-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3,4-difluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)ami- no]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2,5-difluorophenyl)sulfanyl]-8-[(3,3,3-trifluoroprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(4-isopropoxypheno- xy)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(4-isopropoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2,3-difluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-fluoro-5-methylphenoxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3,4-difluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(2-thienylsulfanyl- )imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3,5-di fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin- -3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(6-methylpyridin-- 3-yl)oxy]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyrimidin-5-yloxy- )imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(3-chlorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{6-(4-chlorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)sulfanyl]-8-[(3,3,3-trifluor- opropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-(6-{[2-(hydroxymethyl)phenyl]sulfanyl}-8-[(3,3,3-trifluor- opropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-methoxy-phenyl- )sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-isopropyl-phen- yl)sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-2-yloxy)i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[3-(2-hydroxy-2-methylpropoxy)phenoxy]-8-[(2-hydroxy-2- -methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(2-hydroxy-ethyl)amino]i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(2-hydroxyethyl)amino]imidazo[1,2- -b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-hydroxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmeth- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluoro-5-methylphenoxy)-8-[(tetrahydro-2H-thiopyran- -4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-fluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmeth- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(phenylsulfanyl)-8-[(tetrahydro-2H-thiopyran-- 4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(tetrahydro-2H-thiopyran- -4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)sulfanyl]-8-[(tetrahydro-2H-- thiopyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide- , N-cyclopropyl-4-{6-[(3-hydroxyphenyl)sulfanyl]-8-[(tetrahydro-2H-thiopyr- an-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(pyridin-3-yloxy)-8-[(tetrahydro-2H-thiopyran- -4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(2-hydroxyphenyl)sulfanyl]-8-[(tetrahydro-2H-thiopyra- n-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(4-fluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmeth- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide 4-{6-(4-chloro-3-fluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmethyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{6-(4-chlorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmethyl)amino]imida- zo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-(2,3-difluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-yl- methyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-[6-(4-chlorophenoxy)-8-({[(cis/trans)-1-oxidotetrahydro-2H-thiopyran-4-- yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl]-N-cyclopropyl-2-methylbenzam- ide, 4-[6-(4-chlorophenoxy)-8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)m- ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-[6-(4-fluorophenoxy)-8-({[(cis/trans)-1-oxidotetrahydro-2- H-thiopyran-4-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzam- ide, N-cyclopropyl-4-[8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]- amino}-6-(4-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-2-methyl-4-[8-({[(cis)-1-oxidotetrahydro-2H-thiopyran-4-yl]- methyl}amino)-6-(pyridin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzamide, N-cyclopropyl-2-methyl-4-[8-({[(trans)-1-oxidotetrahydro-2H-thiopyran-4-y- l]methyl}amino)-6-(pyridin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzamide, N-cyclopropyl-4-[8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]amin- o}-6-(pyridin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]amin- o}-6-(2-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-({[(cis/trans)-1-oxidotetrahydro-2- H-thiopyran-4-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzam- ide, N-cyclopropyl-4-[8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]- amino}-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,4-difluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylp- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-(8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]amin- o}-6-[(3-fluorophenyl)sulfanyl]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenza- mide, N-cyclopropyl-4-[8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl- ]amino}-6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-2-methyl-4-[8-({[(cis)-1-oxidotetrahydro-2H-thiopyran-4-yl]- methyl}amino)-6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl]benzamide, N-cyclopropyl-2-methyl-4-[8-({[(trans)-1-oxidotetrahydro-2H-thiopyran-4-y- l]methyl}amino)-6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl]benzamide, N-cyclopropyl-4-(6-[(3-fluorophenyl)sulfanyl]-8-({[(cis)-1-oxidotetrahydr- o-2H-thiopyran-4-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl)-2-methylben- zamide, N-cyclopropyl-4-(6-[(3-fluorophenyl)sulfanyl]-8-({[(trans)-1-oxido- tetrahydro-2H-thiopyran-4-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl)-2-- methylbenzamide, N-cyclopropyl-4-{6-[(4-fluorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-anilino-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3- -yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,4-difluorophenyl)amino]-8-[(2-hydroxy-2-methylprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-methylphenyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)amino]-8-[(2-hydroxy-2-methy- lpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(4-chlorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1- ,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[(1-methylpiperidin-4-yl)methyl]a- mino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[8-{[3-(dimethylamino)propyl]amino}-6-(3-fluorophenoxy)im- idazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(methylsulfonyl)ethyl]amino}im- idazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, 4-{8-[(2-amino-2-methylpropyl)amino]-6-(3-fluorophenoxy)imidazo[1,2-b]pyr- idazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{8-[(azetidin-3-ylmethyl)amino]-6-phenoxyimidazo[1,2-b]pyridazin-3-yl}-- N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(4H-1,2,4-triazol-- 3-ylsulfanyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(4-methyl-1H-imid- azol-2-yl)sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(1H-imidazol-2-yls- ulfanyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(1-methyl-1H-pyra- zol-5-yl)oxy]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[4-(piperazin-1-yl- )phenoxy]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(1-methyl-1H-pyra- zol-4-yl)oxy]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, tert-butyl 4-[4-({3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-8-[(2-hydroxy-2-methyl- propyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]piperazine-1-carboxyl- ate, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(tetrahydro-2H-pyran-4-ylmeth- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amin- o]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(3-hydroxy-3-methylbutyl)amino]im- idazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[8-{[(1,1-dioxidotetrahydrothiophen-3-yl)methyl]amino}-6-- (3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(tetrahydrofuran-3-ylmethyl)amino- ]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[(1-methyl-5-oxopyrrolidin-3-yl)m- ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[8-{[(3,3-difluorocyclobutyl)methyl]amino}-6-(3-fluorophe- noxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-4-yloxy)i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-4-ylsulfa- nyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-2-ylsulfa- nyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{8-[(2-cyanoethyl)amino]-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-y- l}-N-cyclopropyl-2-methylbenzamide, 4-{6-[(4-chloro-2-fluorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(5-methoxy-2-meth- ylphenyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,5-difluorophenyl)amino]-8-[(2-hydroxy-2-methylprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2,3-difluorophenyl)amino]-8-[(2-hydroxy-2-methylprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-4-methoxyphenyl)amino]-8-[(2-hydroxy-2-meth- ylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(4-methoxyphenyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(3-chlorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1- ,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(2,4-difluorophenyl)amino]-8-[(2-hydroxy-2-methylprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-2-ylamino- )imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amin- o]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-3-ylamino- )imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluoro-4-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-me- thylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(3-isopropoxypheno- xy)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluoro-4-methylphenyl)sulfanyl]-8-[(3,3,3-trifluor- opropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-4-ylamino- )imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(6-methoxypyridin- -3-yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluoro-5-methylphenyl)amino]-8-[(3,3,3-trifluoropr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-anilino-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl- }-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amin- o]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-(6-{[2-(hydroxymethyl)phenyl]amino}-8-[(3,3,3-trifluoropr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)amino]-8-[(3,3,3-trifluoropr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(4-chloro-3-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,4-difluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(4-chlorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-- b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)amino]-8-[(3,3,3-trifluoropr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(4-chloro-2-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{6-[(5-chloro-2-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,5-difluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(3-chlorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-- b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(2,3-difluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-[3-(propan-2-yloxy)phenoxy]-8-[(3,3,3-trifluo- ropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(4-fluoro-3-methylphenyl)amino]-8-[(2-hydroxy-2-methy- lpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluoro-5-methylphenyl)amino]-8-[(2-hydroxy-2-methy- lpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-isopropylpheny- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-(6-{[4-(2-hydroxyethyl)phenyl]amino}-8-[(2-hydroxy-2-meth- ylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-2-methylphenyl)sulfanyl]-8-[(3,3,3-trifluor- opropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-methoxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)ami- no]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-[2-(methylamino)phenoxy]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(2-hydroxy-2-methylpropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-(6-{[4-chloro-2-(hydroxymethyl)phenyl]sulfanyl}-8-[(3,3,3-trifluoroprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide, 4-(6-{[4-chloro-2-(hydroxymethyl)phenyl]sulfanyl}-8-[(2-hydroxy-2-methylp- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)amino]-8-[(2-hydroxy-2-methy- lpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(2-aminophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyrid- azin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{6-(2-amino-4-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,- 2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-2-hydroxyphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(2-chloro-3-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidaz- o[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-methoxy-2-meth- ylphenyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-hydroxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)ami- no]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-3-methoxyphenyl)amino]-8-[(2-hydroxy-2-meth- ylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(4-chloro-3-fluorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(2-methoxyphenyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-methoxyphenyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(5-chloro-2-methylphenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{6-[(2-chloro-4-fluorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(6-fluoropyridin-3-yl)amino]-8-[(2-hydroxy-2-methylpr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-ethenylphenyl)amino]-8-[(2-hydroxy-2-methylpropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(6-fluoropyridin-3-yl)oxy]-8-[(2-hydroxy-2-methylprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 5-({3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-8-[(2-hydroxy-2-methylpro- pyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)nicotinamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyrazin-2-ylsulfa- nyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(4-methyl-4H-1,2,- 4-triazol-3-yl)sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(1H-pyrazol-5-ylox- y)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(5-methyl-1H-pyra- zol-3-yl)oxy]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(2-amino-4-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]i- midazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[2-methoxy-3-(propan-2-yl)phenoxy]-8-[(3,3,3-trifluoro- propyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]-8-- [(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-2-methyl-4-{6-(pyrazin-2-ylsulfanyl)-8-[(3,3,3-trifluoropro- pyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(4-fluoro-3-methoxyphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-[(3-methylphenyl)amino]-8-[(3,3,3-trifluoropr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(3-fluoro-4-methoxyphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-methoxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)ami- no]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-methoxy-2-methylphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-(6-{[4-(2-hydroxyethyl)phenyl]amino}-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-3-methylphenyl)amino]-8-[(3,3,3-trifluoropr- opyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(6-methoxypyridin-3-yl)amino]-8-[(3,3,3-trifluoroprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-methoxy-2-methylphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(2-hydroxyphenyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-2-methoxyphenyl)amino]-8-[(2-hydroxy-2-meth- ylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-(6-{[2-(hydroxymethyl)phenyl]amino}-8-[(2-hydroxy-2-methy- lpropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, 4-(6-{[4-(2-aminoethyl)phenyl]amino}-8-[(2-hydroxy-2-methylpropyl)amino]i- midazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(6-fluoropyridin-3-yl)oxy]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(6-fluoropyridin-3-yl)amino]-8-[(3,3,3-trifluoropropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[2-hydroxy-3-(propan-2-yl)phenoxy]-8-[(3,3,3-trifluoro- propyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-3-hydroxyphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-hydroxy-2-methylphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-- ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-hydroxyphenyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3,4-difluorophenyl)amino]-8-[(4,4,4-trifluorobutyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)amino]-8-[(4,4,4-trifluorobu- tyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)sulfanyl]-8-[(4,4,4-trifluor- obutyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(2,3-difluorophenyl)amino]-8-[(4,4,4-trifluorobutyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-[(5-chloro-2-methylphenyl)amino]-8-[(4,4,4-trifluorobutyl)amino]imid- azo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluoro-5-methylphenoxy)-8-[(4,4,4-trifluorobutyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(cyclopentylamino)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyr- idazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-hydroxy-2-methylphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(cyclopentyloxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyrid- azin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-hydroxy-2-methylphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(4-fluoro-2-methoxyphenyl)amino]-8-[(4,4,4-trifluorob- utyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[2-fluoro-3-(methylsulfanyl)phenoxy]-8-[(2-hydroxy-2-m- ethylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-2-methyl-N-(1-methylcyclopropyl)benzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N-(1-methoxycyclopropyl)-2-methylbenzamide, N-(1-cyanocyclopropyl)-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-fluoropyridin-3-yl)oxy]-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(2-amino-5-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,- 2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(1,2,3,4-tetrahydroquinolin-8-yloxy)-8-[(3,3,- 3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-(8-hydroxy-3,4-dihydroquinolin-1 (2H)-yl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-- methylbenzamide, N-cyclopropyl-2-methyl-4-{6-[(2-oxo-1,2-dihydroquinolin-8-yl)oxy]-8-[(3,3- ,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-2-methyl-4-{6-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl- )oxy]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzami- de, N-cyclopropyl-2-methyl-4-{6-(3-methylphenoxy)-8-[(3,3,3-trifluoropropy- l)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-(4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(4-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imid- azo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(2-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imid- azo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-(6-{[4-(acetylamino)pyridin-3-yl]oxy}-8-[(3,3,3-trifluoropropyl)amino]i- midazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide, 4-{6-(2-amino-3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,- 2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-[(2-fluoro-6-hydroxyphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(4-methylphenoxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(4-fluoro-2-hydroxyphenyl)amino]-8-[(3,3,3-trifluorop- ropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(3-hydroxypyridin-4-yl)amino]-8-[(3,3,3-trifluoroprop- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{6-(1-phenylethenyl)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-(3-fluoro-4-methoxybenzyl)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluoro-4-methylbenzyl)-8-[(3,3,3-trifluoropropyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(3-bromobenzyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyrida- zin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoro-2-hydroxypropyl)- amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[8-{[2-(dimethylamino)ethyl]amino}-6-(3-fluorophenoxy)imi- dazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[(1-methyl-1H-pyrazol-3-yl)methyl- ]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(1H-pyrazol-3-ylmethyl)amino]imid- azo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-({[3-(hydroxymethyl)oxetan-3-yl]me- thyl}amino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{8-[(2,3-dihydroxypropyl)amino]-6-(3-fluorophenoxy)imidaz- o[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2- -b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[8-{[3-(dimethylamino)-3-oxopropyl]amino}-6-(3-fluorophen- oxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[8-{[(4,4-difluorocyclohexyl)methyl]amino}-6-(3-fluorophe- noxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(oxetan-3-ylmethyl)amino]imidazo[- 1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(1H-tetrazol-5-ylmethyl)amino]imi- dazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[8-{[2-(dimethylamino)-2-methylpropyl]amino}-6-(3-fluorop- henoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-methyl-2-(morpholin-4-yl)propy- l]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(piperidin-1-yl)ethyl]amino}im- idazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}im- idazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(4-methylpiperazin-1-yl)ethyl]- amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(pyrrolidin-1-yl)ethyl]amino}i- midazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-({3-[methyl(methylcarbamoyl)amino]- propy}amino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, 4-[8-{[2-(acetylamino)ethyl]amino}-6-(3-fluorophenoxy)imidazo[1,2-b]pyrid- azin-3-yl]-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[3-(piperidin-1-yl)propyl]amino}i- midazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[3-(morpholin-4-yl)propyl]amino}i- midazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[3-(pyrrolidin-1-yl)propyl]amino}- imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[3-(methylsulfonyl)propyl]amino}i- midazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, 4-[8-{[3-(acetylamino)propyl]amino}-6-(3-fluorophenoxy)imidazo[1,2-b]pyri- dazin-3-yl]-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-(methylamino)imidazo[1,2-b]pyridaz- in-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(1H-tetrazol-5-yl)ethyl]amino}- imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{8-[(2,2-difluoroethyl)amino]-6-(3-fluorophenoxy)imidazo[- 1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[8-{[4-(dimethylamino)butyl]amino}-6-(3-fluorophenoxy)imi- dazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(2,2,2-trifluoroethyl)amino]imida- zo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(1H-pyrazol-1-yl)ethyl]amino}i- midazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-{[2-(methylsulfonyl)ethyl]amin- o}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(5-fluoro-2-methylphenoxy)-8-{[2-(methylsulfonyl)ethyl- ]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluoro-4-methoxyphenoxy)-8-{[2-(methylsulfonyl)ethy- l]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(2-fluoro-4-methoxyphenoxy)-8-{[2-(methylsulfonyl)ethy- l]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, 4-{8-[(2-amino-2-methylpropyl)amino]-6-(3,4-difluorophenoxy)imidazo[1,2-b- ]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{8-[(2-amino-2-methylpropyl)amino]-6-(4-chlorophenoxy)imidazo[1,2-b]pyr- idazin-3-yl}-N-cyclopropyl-2-methylbenzamide 4-{8-[(2-amino-2-methylpropyl)amino]-6-(pyridin-3-yloxy)imidazo[1,2-b]pyr- idazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-[6-(4-chlorophenoxy)-8-{[2-(dimethylamino)ethyl]amino}imidazo[1,2-b]pyr- idazin-3-yl]-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-[8-{[2-(dimethylamino)ethyl]amino}-6-(pyridin-3-yloxy)imi- dazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3,4-difluorophenoxy)-8-{[2-(dimethylamino)ethyl]amino- }imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-{[(1-methylpiperidin-4-yl)meth- yl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-2-methyl-4-[8-{[(1-methylpiperidin-4-yl)methyl]amino}-6-(py- ridin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzamide, N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-(methylamino)imidazo[1,2-b]pyr- idazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3,4-difluorophenoxy)-8-(methylamino)imidazo[1,2-b]pyr- idazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(5-fluoro-2-methylphenoxy)-8-(methylamino)imidazo[1,2-- b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-2-methyl-4-{8-(methylamino)-6-[2-(methylamino)phenoxy]imida- zo[1,2-b]pyridazin-3-yl}benzamide, N-cyclopropyl-4-{6-[(2-hydroxyphenyl)(methyl)amino]-8-(methylamino)imidaz- o[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-{6-[(5-fluoropyridin-3-yl)oxy]-8-(methylamino)imidazo[1,2- -b]pyridazin-3-yl}-2-methylbenzamide, N-cyclopropyl-4-[6-(2-fluoro-4-methoxyphenoxy)-8-(methylamino)imidazo[1,2- -b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluoro-4-methoxyphenoxy)-8-(methylamino)imidazo[1,2- -b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-{[2-(morpholin-4-yl)ethyl]amin- o}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-[6-(5-fluoro-2-methylphenoxy)-8-{[2-(morpholin-4-yl)ethyl- ]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-2-methyl-4-(6-[2-(methylamino)phenoxy]-8-{[2-(morpholin-4-y- l)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl)benzamide, N-cyclopropyl-4-(6-[(2-hydroxyphenyl)(methyl)amino]-8-{[2-(morpholin-4-yl- )ethyl]amino}imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, N-cyclopropyl-4-[6-(3,4-difluorophenoxy)-8-{[2-(morpholin-4-yl)ethyl]amin- o}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-cyclopropyl-4-(6-[(5-fluoropyridin-3-yl)oxy]-8-{[2-(morpholin-4-yl)ethy- l]amino}imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide, N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[(1-methylazetidin-3-yl)methyl]am- ino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, 4-{8-[(azetidin-3-ylmethyl)amino]-6-(3-fluorophenoxy)imidazo[1,2-b]pyrida- zin-3-yl}-N-cyclopropyl-2-methylbenzamide, N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-{[(1-methylazetidin-3-yl)methy- l]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, 4-{8-[(azetidin-3-ylmethyl)amino]-6-(2,3-difluorophenoxy)imidazo[1,2-b]py- ridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{8-[(azetidin-3-ylmethyl)amino]-6-[(5-fluoropyridin-3-yl)oxy]imidazo[1,- 2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{8-[(azetidin-3-ylmethyl)amino]-6-(5-fluoro-2-methylphenoxy)imidazo[1,2- -b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide, 4-{8-[(3-aminopropyl)amino]-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-- yl}-N-cyclopropyl-2-methylbenzamide, 3-({3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-6-(3-fluorophenoxy)imidaz- o[1,2-b]pyridazin-8-yl}amino)propane-1-sulfonic acid, 2-({3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-6-(3-fluorophenoxy)imidaz- o[1,2-b]pyridazin-8-yl}amino)ethanesulfonic acid, N-(1-cyanocyclopropyl)-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)a- mino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-2-methylbenzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N,2-dimethylbenzamide, N-ethyl-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,- 2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N-isopropyl-2-methylbenzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-2-methyl-N-(3,3,3-trifluoropropyl)benzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-2-methyl-N-(2,2,3,3,3-pentafluoropropyl)benzamide, N-(2,2-difluoroethyl)-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, -{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyrid- azin-3-yl}-N-isobutyl-2-methylbenzamide, 4-{6-(4-chlorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(4-chlorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N-ethyl-2-methylbenzamide, 4-{6-(2-fluoro-4-hydroxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[- 1,2-b]pyridazin-3-yl}-N, 2-dimethylbenzamide, N-ethyl-4-{6-(2-fluoro-4-hydroxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-[6-(3,4-difluorophenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo[1,2-- b]pyridazin-3-yl]-N,2-dimethylbenzamide, N,2-dimethyl-4-[6-(2-methylphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imi- dazo[1,2-b]pyridazin-3-yl]benzamide, 4-[6-(4-methoxyphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo[1,2-b]p- yridazin-3-yl]-N, 2-dimethylbenzamide, 4-[6-(2-fluoro-4-methoxyphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidaz- o[1,2-b]pyridazin-3-yl]-N,2-dimethylbenzamide, 4-[6-(5-fluoro-2-methylphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo- [1,2-b]pyridazin-3-yl]-N,2-dimethylbenzamide, 4-{6-(3,4-difluorophenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]imida- zo[1,2-b]pyridazin-3-yl}-N, 2-dimethylbenzamide, N,2-dimethyl-4-{6-(2-methylphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)am- ino]imidazo[1,2-b]pyridazin-3-yl}benzamide, 4-{6-(3-fluorophenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]imidazo[1- ,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]imidazo[- 1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino- ]imidazo[1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(5-fluoro-2-methylphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino- ]imidazo[1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(3,4-difluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]- pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyri- dazin-3-yl}-N, 2-dimethylbenzamide, 4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[- 1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(5-fluoro-2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1- ,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[- 1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{8-[(2,2-difluoroethyl)amino]-6-(3,4-difluorophenoxy)imidazo[1,2-b]pyri- dazin-3-yl}-N, 2-dimethylbenzamide, 4-{8-[(2,2-difluoroethyl)amino]-6-(2-fluoro-4-methoxyphenoxy)imidazo[1,2-- b]pyridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(2,3-difluorophenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridaz- in-3-yl}-N, 2-dimethylbenzamide, 4-{6-(3,4-difluorophenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridaz- in-3-yl}-N, 2-dimethylbenzamide, 4-{8-[(2-methoxyethyl)amino]-6-(2-methylphenoxy)imidazo[1,2-b]pyridazin-3- -yl}-N,2-dimethylbenzamide, 4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]p- yridazin-3-yl}-N,2-dimethylbenzamide, 4-{6-(5-fluoro-2-methylphenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]py- ridazin-3-yl}-N, 2-dimethylbenzamide, 4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]p- yridazin-3-yl}-N, 2-dimethylbenzamide, 4-{8-[(2-methoxyethyl)amino]-6-phenoxyimidazo[1,2-b]pyridazin-3-yl}-N,2-d- imethylbenzamide, 4-[6-(3,4-difluorophenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo[1,2-- b]pyridazin-3-yl]-N-ethyl-2-methylbenzamide, N-ethyl-2-methyl-4-[6-(2-methylphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino- }imidazo[1,2-b]pyridazin-3-yl]benzamide, N-ethyl-4-[6-(4-methoxyphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo- [1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-ethyl-4-[6-(2-fluoro-4-methoxyphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amin- o}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-ethyl-4-[6-(5-fluoro-2-methylphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino- }imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide, N-ethyl-2-methyl-4-(8-{[2-(morpholin-4-yl)ethyl]amino}-6-phenoxyimidazo[1- ,2-b]pyridazin-3-yl)benzamide, 4-{6-(3,4-difluorophenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]imida- zo[1,2-b]pyridazin-3-yl}-N-ethyl-2-methylbenzamide, N-ethyl-2-methyl-4-{6-(2-methylphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethy- l)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide, N-ethyl-4-{6-(4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmeth- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethy- l)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmeth- yl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-2-methyl-4-{6-(2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]i- midazo[1,2-b]pyridazin-3-yl}benzamide, N-ethyl-4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]i- midazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]- imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide, 4-{8-[(2,2-difluoroethyl)amino]-6-(2-fluoro-4-methoxyphenoxy)imidazo[1,2-- b]pyridazin-3-yl}-N-ethyl-2-methylbenzamide, 4-{8-[(2,2-difluoroethyl)amino]-6-(5-fluoro-2-methylphenoxy)imidazo[1,2-b- ]pyridazin-3-yl}-N-ethyl-2-methylbenzamide, 4-{6-(3,4-difluorophenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridaz- in-3-yl}-N-ethyl-2-methylbenzamide, N-ethyl-4-{6-(2-fluoro-4-methoxyphenoxy)-8-[(2-methoxyethyl)amino]imidazo- [1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(2-methoxyethyl)amino]imidazo[- 1,2-b]pyridazin-3-yl}-2-methylbenzamide, N-ethyl-4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(2-methoxyethyl)amino]imidazo- [1,2-b]pyridazin-3-yl}-2-methylbenzamide, or a stereoisomer, a tautomer, or a salt thereof, or a mixture of same. 7. A compound of general formula Ia: ##STR00886## in which R.sup.3 and R.sup.5 are as defined in claim 1, and A' is ##STR00887## wherein * indicates the point of attachment of said group with the rest of the molecule; R.sup.4a, R.sup.4b, R.sup.4c and R.sup.4d are as defined in claim 1, and Z' represents a group selected from: --C(.dbd.O)OH, --C(.dbd.S)OH, --C(.dbd.O)O--(C.sub.1-C.sub.6-alkyl) or --C(.dbd.S)O--(C.sub.1-C.sub.6-alkyl). 8. A compound of general formula IV: ##STR00888## in which A, and R.sup.5 are as defined in claim 1, and R.sup.3' is a leaving group. 9. A compound of general formula VII: ##STR00889## in which A, and R.sup.3 are as defined in claim 1, and Q.sup.1 represents an optionally protected NH.sub.2-group or a leaving group. 10. A pharmaceutical composition comprising a compound according to claim 1, or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, or a mixture of same, and a pharmaceutically acceptable diluent or carrier. 11. A pharmaceutical combination comprising: one or more compounds according to claim 1, or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, or a mixture of same; and one or more agents selected from: a taxane, such as Docetaxel, Paclitaxel, or Taxol; an epothilone, such as Ixabepilone, Patupilone, or Sagopilone; Mitoxantrone; Predinisolone; Dexamethasone; Estramustin; Vinblastin; Vincristin; Doxorubicin; Adriamycin; Idarubicin; Daunorubicin; Bleomycin; Etoposide; Cyclophosphamide; Ifosfamide; Procarbazine; Melphalan; 5-Fluorouracil; Capecitabine; Fludarabine; Cytarabine; Ara-C; 2-Chloro-2'-deoxyadenosine; Thioguanine; an anti-androgen, such as Flutamide, Cyproterone acetate, or Bicalutamide; Bortezomib; a platinum derivative, such as Cisplatin, or Carboplatin; Chlorambucil; Methotrexate; and Rituximab. 12. A method of preparing a compound according to claim 1, said method comprising the step of allowing an intermediate compound of general formula IV: ##STR00890## in which A, and R.sup.5 are as defined in claim 1, and R.sup.3' is a leaving group; to react with a compound of general formula IVa: R.sup.3--Y IVa in which R.sup.3 is as defined in claim 1, and Y is a substituent which is displaced in a coupling reaction, such as a hydrogen atom, or a boronic acid group, or a boronic ester group, for example, thereby giving a compound of general formula I: ##STR00891## in which A, R.sup.3, and R.sup.5 are as defined in claim 1. 13. A method of preparing a compound according to claim 1, said method comprising the step of allowing an intermediate compound of general formula Ia: ##STR00892## in which R.sup.3 and R.sup.5 are as defined in claim 1; and A' is ##STR00893## wherein * indicates the point of attachment of said group with the rest of the molecule; R.sup.4a, R.sup.4b, R.sup.4c and R.sup.4d are as defined in claim 1, and Z' represents a group selected from: --C(.dbd.O)OH, --C(.dbd.S)OH, --C(.dbd.O)O--(C.sub.1-C.sub.6-alkyl) or --C(.dbd.S)O--(C.sub.1-C.sub.6-alkyl); to react with a compound of general formula Ib: H.sub.2NR.sup.2 Ib in which R.sup.2 is as defined in claim 1, thereby giving, upon optional deprotection, a compound of general formula I: ##STR00894## in which R.sup.3, R.sup.5 and A are as defined in claim 1. 14. A method of preparing a compound according to claim 1, said method comprising the step of allowing an intermediate compound of general formula VII: ##STR00895## in which R.sup.3 and A are as defined in claim 1, and Q.sup.1 is a leaving group, to react with a compound of general formula VIIa: R.sup.5--CH.sub.2--NH.sub.2 VIIa in which R.sup.5 is as defined in claim 1, thereby giving, upon optional deprotection, a compound of general formula I: ##STR00896## in which R.sup.3, R.sup.5 and A are as defined in claim 1.

Details for Patent 9,255,100

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2030-09-10
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2030-09-10
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2030-09-10