IP Library Granted Patent US 9,255,100
Granted Patent B2
US 9,255,100 · App. 13/822,175 · Granted Feb 9, 2016

Substituted imidazopyridazines

Inventors: Ulrich Klar (Berlin, DE); Marcus Koppitz (Berlin, DE); Rolf Jautelat (Haan, DE); Dirk Kosemund (Berlin, DE); Rolf Bohlmann (Berlin, DE); Philip Lienau (Berlin, DE); Gerhard Siemeister (Berlin, DE); Antje Margret Wengner (Berlin, DE)
Assignee: BAYER INTELLECTUAL PROPERTY GMBH
C07D487/04A61K31/506A61K31/5025A61K31/5377A61K45/06C07D471/04
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Quick Facts
Patent No.
US 9,255,100
App. No.
13/822,175
Granted
Feb 9, 2016
Kind
B2
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 3 , R 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.

Claims (494)

1. A compound of general formula I:

in which:

A represents a

-group;

wherein * indicates the point of attachment of said groups with the rest of the molecule;

Z represents a —C(═O)N(H)R 2 or —C(═S)N(H)R 2 group, or a group selected from

wherein * indicates the point of attachment of said groups with the rest of the molecule;

R 2 represents a hydrogen atom, or a C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, R 6a (R 6b )N—C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, —C 1 -C 6 -alkyl-CN, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 6 -alkynyl- or C 3 -C 6 -cycloalkyl- group;

wherein said C 3 -C 6 -cycloalkyl- group is optionally substituted, identically or differently, with 1, 2, 3 or 4 groups selected from: halogen, —OH, —CN, C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkyl-;

R 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 7 groups;

R 4a represents hydrogen;

R 4d represents hydrogen;

one of the groups R 4b and R 4c represents a hydrogen atom while the other one represents a group selected from: halo, CN, OH, C 1 -C 6 -alkyl- and C 1 -C 6 -alkoxy-;

R 5 represents a hydrogen atom, or a C 1 -C 6 -alkyl-, —(CH 2 ) n —C 2 -C 6 -alkenyl, —(CH 2 ) n —C 2 -C 6 -alkynyl, —(CH 2 ) m —C 3 -C 6 -cycloalkyl, —(CH 2 ) m -(3- to 7-membered heterocycloalkyl), aryl-C 1 -C 6 -alkyl-, heteroaryl-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, R 6a (R 6b )N—C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, —C 1 -C 6 -alkyl-CN, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C 2 -C 6 -alkenyl-, C 4 -C 8 -cycloalkenyl-, C 2 -C 6 -alkynyl-, aryl- or heteroaryl- group;

wherein said C 1 -C 6 -alkyl-, —(CH 2 ) n —C 2 -C 6 -alkenyl, —(CH 2 ) n —C 2 -C 6 -alkynyl, —(CH 2 ) m —C 3 -C 6 -cycloalkyl, —(CH 2 ) m -(3- to 7-membered heterocycloalkyl), aryl-C 1 -C 6 -alkyl-, heteroaryl-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, R 6a (R 6b )N—C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, —C 1 -C 6 -alkyl-CN, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 7-membered heterocycloalkyl-, C 4 -C 8 -cycloalkenyl-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3 or 4 R 8 groups;

R 6 , R 6a , R 6b , R 6c ,

represent, independently from each other, a hydrogen atom, or a C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, C 2 -C 6 -alkenyl-, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, aryl-C 1 -C 6 -alkyl- or heteroaryl-C 1 -C 6 -alkyl- group;

R 7 represents a hydrogen or halogen atom, or a HO—, —CN, C 1 -C 6 -alkoxy-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, R 6a (R 6b )N—C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, —C(═O)R 6 , —C(═O)N(H)R 6a , —C(═O)N(R 6a )R 6b , —C(═O)O—R 6 , —N(R 6a )R 6b , NO 2 , —N(H)C(═O)R 6 , —N(R 6c )C(═O)R 6 , —N(H)C(═O)N(R 6a )R 6b , —N(R 6c )C(═O)N(R 6a )R 6b , —N(H)C(═O)OR 6 , —N(R 6c )C(═O)OR 6 , —N(H)S(═O)R 6 , —N(R 6c )S(═O)R 6 , —N(H)S(═O) 2 R 6 , —N(R 6c )S(═O) 2 R 6 , —N═S(═O)(R 6a )R 6b , —OR 6 , —O(C═O)R 6 , —O(C═O)N(R 6a )R 6b , —O(C═O)OR 6 , —SR 6 , —S(═O)R 6 , —S(═O)N(H)R 6 , —S(═O)N(R 6a )R 6b , —S(═O) 2 R 6 , —S(═O) 2 N(H)R 6 , —S(═O) 2 N(R 6a )R 6b or —S(═O)(═NR 6c )R 6 group;

wherein said C 1 -C 6 -alkoxy-, aryl- or heteroaryl- group is optionally substituted, identically or differently, with 1, 2 or 3 C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, —C(═O)O—R 6 or —OH groups;

or

when 2 R 7 groups are present ortho to each other on an aryl- or heteroaryl-ring, said 2 R 7 groups together form a bridge:

*O(CH 2 ) 2 O*, *O(CH 2 )O*, *NH(C(═O))NH*, wherein * represent the point of attachment to said aryl- or heteroaryl- ring;

R 8 represents a hydrogen or halogen atom, or a —CN, C 1 -C 6 -alkoxy-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, R 6a (R 6b )N—C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, 3- to 7-membered heterocycloalkyl-, aryl-, heteroaryl-, —C(═O)R 6 , —C(═O)N(H)R 6a , —C(═O)N(R 6a )R 6b , —C(═O)O—R 6 , —N(R 6a )R 6b , —NO 2 , —N(H)C(═O)R 6 , —N(R 6c )C(═O)R 6 , —N(H)C(═O)N(R 6a )R 6b , —N(R 6c )C(═O)N(R 6a )R 6b , —N(H)C(═O)OR 6 , —N(R 6c )C(═O)OR 6 , —N(H)S(═O)R 6 , —N(R 6c )S(═O)R 6 , —N(H)S(═O) 2 R 6 , —N(R 6c )S(═O) 2 R 6 , —N═S(═O)(R 6a )R 6b , —OR 6 , —O(C═O)R 6 , —O(C═O)N(R 6a )R 6b , —O(C═O)OR 6 , —SR 6 , —S(═O)R 6 , —S(═O)N(H)R 6 , —S(═O)N(R 6a )R 6b , —S(═O) 2 R 6 , —S(═O) 2 N(H)R 6 , —S(═O) 2 N(R 6a )R 6b , —S(═O)(═NR 6c )R 6 or —S(═O) 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 1 -C 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(═O) p , O, NR 6 , CR 6a R 6b or C═CR 6a R 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 2 is selected from the groups consisting of:

C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, R 6a (R 6b )N—C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, —C 1 -C 6 -alkyl-CN, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl-, C 2 -C 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 5 represents a hydrogen atom, or a C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 7-membered heterocycloalkyl, or heteroaryl- group;

said C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, C 3 -C 6 -cycloalkyl-, 3- to 7-membered heterocycloalkyl, heteroaryl- group is optionally substituted, identically or differently, with 1, 2, 3, or 4 R 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 7 represents a halogen atom, or a HO—, —CN, C 1 -C 6 -alkoxy-, C 1 -C 6 -alkyl-, halo-C 1 -C 6 -alkyl-, HO—C 1 -C 6 -alkyl-, H 2 N—C 1 -C 6 -alkyl-, C 2 -C 6 -alkenyl, 3- to 7-membered heterocycloalkyl, —C(═O)N(H)R 6a , —N(R 6a )R 6b , —N(H)C(═O)R 6 , or —SR 6 group;

wherein said C 1 -C 6 -alkoxy-, or 3- to 7-membered heterocycloalkyl- group is optionally substituted, identically or differently, with 1, 2, or 3 C 1 -C 6 -alkyl-, C 1 -C 6 -alkoxy-, halo-C 1 -C 6 -alkoxy-, —C(═O)O—R 6 or —OH groups;

or

when 2 R 7 groups are present ortho to each other on an aryl or heteroaryl ring, said 2 R 7 groups together form a bridge:

*CH 2 (CH 2 ) 2 NH*, *CH 2 CH 2 N(R 6a )CH 2 *, *C(H)═C(H)—C(═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 6 , R 6a , R 6b , and R 6c represent, independently from each other, a hydrogen atom, or a C 1 -C 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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluoro-3-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluoro-4-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3,5-difluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluoro-2-methylphenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2-fluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluorophenyl)sulfanyl]-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-[(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]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}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-phenoxy-8-[(3,3,3-trifluoropropyl)amino]imidazo[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-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(2-fluoro-5-methylphenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(3-cyanophenoxy)-8-[(2-hydroxy-2-methylpropy)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

(RS)—N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfinyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfonyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-(phenylsulfanyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzenecarbothioamide,

4-{6-(3-chlorophenoxy)-8-[(2-hydroxy-2-methylpropy)amino]imidazo[1,2-b]pyridazin-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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(3-fluoro-5-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide

4-{6-(4-chlorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

4-{6-(3-chloro-4-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-{6-(2,3-difluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(2-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-(3-isopropylphenoxy)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(4-chloro-3-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-{6-(3,5-dimethylphenoxy)-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-(3-methylphenoxy)imidazo[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)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-(pyridin-3-yloxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-2-methyl-4-{8-[(2-methylpropyl)amino]-6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-2-methyl-4-{8-[(2-methylpropyl)amino]-6-(phenylsulfonyl)imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-2-methyl-4-{6-(phenylsulfanyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-(phenylsulfonyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoro-2-hydroxypropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2,6-difluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(2-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[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]imidazo[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-(trifluoromethyl)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]imidazo[1,2-b]pyridazin-3-yl}benzenecarbothioamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl}benzenecarbothioamide,

N-cyclopropyl-4-{6-[(3-fluorophenyl)sulfanyl]-8-[(2-hydroxy-2-methylpropyl)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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3,4-difluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3,5-difluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2,3-difluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(4-fluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(3,4-difluorophenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2,5-difluorophenyl)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-isopropoxyphenoxy)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)amino]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]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

4-{6-(4-chlorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2-fluorophenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-(6-{[2-(hydroxymethyl)phenyl]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-[(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-phenyl)sulfanyl]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-2-yloxy)imidazo[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]imidazo[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]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmethyl)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-ylmethyl)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-thiopyran-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-thiopyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(4-fluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide

4-{6-(4-chloro-3-fluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

4-{6-(4-chlorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-{6-(2,3-difluorophenoxy)-8-[(tetrahydro-2H-thiopyran-4-ylmethyl)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-methylbenzamide,

4-[6-(4-chlorophenoxy)-8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]amino}imidazo[1,2-b]pyridazin-3-yl]-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-[6-(4-fluorophenoxy)-8-({[(cis/trans)-1-oxidotetrahydro-2H-thiopyran-4-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

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-yl]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]amino}-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]amino}-6-(2-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-({[(cis/trans)-1-oxidotetrahydro-2H-thiopyran-4-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-(8-{[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)methyl]amino}-6-[(3-fluorophenyl)sulfanyl]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide,

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-yl]methyl}amino)-6-(phenylsulfanyl)imidazo[1,2-b]pyridazin-3-yl]benzamide,

N-cyclopropyl-4-(6-[(3-fluorophenyl)sulfanyl]-8-({[(cis)-1-oxidotetrahydro-2H-thiopyran-4-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide,

N-cyclopropyl-4-(6-[(3-fluorophenyl)sulfanyl]-8-({[(trans)-1-oxidotetrahydro-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)amino]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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(3-methylphenyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)amino]-8-[(2-hydroxy-2-methylpropyl)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]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[8-{[3-(dimethylamino)propyl]amino}-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(methylsulfonyl)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

4-{8-[(2-amino-2-methylpropyl)amino]-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-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-imidazol-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-ylsulfanyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(1-methyl-1H-pyrazol-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-pyrazol-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-methylpropyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]piperazine-1-carboxylate,

N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(3-hydroxy-3-methylbutyl)amino]imidazo[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)methyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[8-{[(3,3-difluorocyclobutyl)methyl]amino}-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-4-yloxy)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-4-ylsulfanyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyridin-2-ylsulfanyl)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{8-[(2-cyanoethyl)amino]-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl}-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-methylphenyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3,5-difluorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2,3-difluorophenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluoro-4-methoxyphenyl)amino]-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-[(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-methylpropyl)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)amino]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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(3-isopropoxyphenoxy)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2-fluoro-4-methylphenyl)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-(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-trifluoropropyl)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)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-(6-{[2-(hydroxymethyl)phenyl]amino}-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-[(4-chloro-3-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[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-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-[(4-chloro-2-fluorophenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

4-{6-[(5-chloro-2-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[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-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-[(4-fluoro-3-methylphenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2-fluoro-5-methylphenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2-fluorophenyl)amino]-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-[(3-isopropylphenyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-(6-{[4-(2-hydroxyethyl)phenyl]amino}-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluoro-2-methylphenyl)sulfanyl]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2-methoxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-[2-(methylamino)phenoxy]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-(6-{[4-chloro-2-(hydroxymethyl)phenyl]sulfanyl}-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-2-methylbenzamide,

4-(6-{[4-chloro-2-(hydroxymethyl)phenyl]sulfanyl}-8-[(2-hydroxy-2-methylpropyl)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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(2-aminophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-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-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(2-chloro-3-fluorophenoxy)-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-[(3-methoxy-2-methylphenyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2-hydroxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluoro-3-methoxyphenyl)amino]-8-[(2-hydroxy-2-methylpropyl)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-methylpropyl)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-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

5-({3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)nicotinamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-(pyrazin-2-ylsulfanyl)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-yloxy)imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2-hydroxy-2-methylpropyl)amino]-6-[(5-methyl-1H-pyrazol-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]imidazo[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-trifluoropropyl)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-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-[(4-fluoro-3-methoxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-[(3-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-[(3-fluoro-4-methoxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-methoxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-methoxy-2-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-(6-{[4-(2-hydroxyethyl)phenyl]amino}-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluoro-3-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(6-methoxypyridin-3-yl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(5-methoxy-2-methylphenyl)amino]-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-hydroxyphenyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluoro-2-methoxyphenyl)amino]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-(6-{[2-(hydroxymethyl)phenyl]amino}-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide,

4-(6-{[4-(2-aminoethyl)phenyl]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)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-trifluoropropyl)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-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluoro-3-hydroxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(5-hydroxy-2-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)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)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(5-fluoro-2-methylphenyl)amino]-8-[(4,4,4-trifluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-fluoro-5-methylphenyl)sulfanyl]-8-[(4,4,4-trifluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(2,3-difluorophenyl)amino]-8-[(4,4,4-trifluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-[(5-chloro-2-methylphenyl)amino]-8-[(4,4,4-trifluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-{6-(3-fluoro-5-methylphenoxy)-8-[(4,4,4-trifluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(cyclopentylamino)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-hydroxy-2-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(cyclopentyloxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-{6-[(5-hydroxy-2-methylphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(4-fluoro-2-methoxyphenyl)amino]-8-[(4,4,4-trifluorobutyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[2-fluoro-3-(methylsulfanyl)phenoxy]-8-[(2-hydroxy-2-methylpropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methyl-N-(1-methylcyclopropyl)benzamide,

4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-(1-methoxycyclopropyl)-2-methylbenzamide,

N-(1-cyanocyclopropyl)-4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]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}benzamide,

N-cyclopropyl-2-methyl-4-{6-(3-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-(4-methoxyphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(4-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(2-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-(2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]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]imidazo[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-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-(4-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-[(4-fluoro-2-hydroxyphenyl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-[(3-hydroxypyridin-4-yl)amino]-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-{6-(1-phenylethenyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-(3-fluoro-4-methoxybenzyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-{6-(3-fluoro-4-methylbenzyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(3-bromobenzyl)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-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)imidazo[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]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-({[3-(hydroxymethyl)oxetan-3-yl]methyl}amino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-{8-[(2,3-dihydroxypropyl)amino]-6-(3-fluorophenoxy)imidazo[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-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[8-{[(4,4-difluorocyclohexyl)methyl]amino}-6-(3-fluorophenoxy)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]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-[8-{[2-(dimethylamino)-2-methylpropyl]amino}-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-methyl-2-(morpholin-4-yl)propyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(piperidin-1-yl)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo[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}imidazo[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]pyridazin-3-yl]-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[3-(piperidin-1-yl)propyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[3-(morpholin-4-yl)propyl]amino}imidazo[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}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

4-[8-{[3-(acetylamino)propyl]amino}-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl]-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-(methylamino)imidazo[1,2-b]pyridazin-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)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-{6-(3-fluorophenoxy)-8-[(2,2,2-trifluoroethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[2-(1H-pyrazol-1-yl)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-{[2-(methylsulfonyl)ethyl]amino}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)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(2-fluoro-4-methoxyphenoxy)-8-{[2-(methylsulfonyl)ethyl]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]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide

4-{8-[(2-amino-2-methylpropyl)amino]-6-(pyridin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

4-[6-(4-chlorophenoxy)-8-{[2-(dimethylamino)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-[8-{[2-(dimethylamino)ethyl]amino}-6-(pyridin-3-yloxy)imidazo[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)methyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-2-methyl-4-[8-{[(1-methylpiperidin-4-yl)methyl]amino}-6-(pyridin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzamide,

N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-(methylamino)imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-[6-(3,4-difluorophenoxy)-8-(methylamino)imidazo[1,2-b]pyridazin-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]imidazo[1,2-b]pyridazin-3-yl}benzamide,

N-cyclopropyl-4-{6-[(2-hydroxyphenyl)(methyl)amino]-8-(methylamino)imidazo[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]amino}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-yl)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]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

N-cyclopropyl-4-(6-[(5-fluoropyridin-3-yl)oxy]-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl)-2-methylbenzamide,

N-cyclopropyl-4-[6-(3-fluorophenoxy)-8-{[(1-methylazetidin-3-yl)methyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

4-{8-[(azetidin-3-ylmethyl)amino]-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-3-yl}-N-cyclopropyl-2-methylbenzamide,

N-cyclopropyl-4-[6-(2,3-difluorophenoxy)-8-{[(1-methylazetidin-3-yl)methyl]amino}imidazo[1,2-b]pyridazin-3-yl]-2-methylbenzamide,

4-{8-[(azetidin-3-ylmethyl)amino]-6-(2,3-difluorophenoxy)imidazo[1,2-b]pyridazin-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)imidazo[1,2-b]pyridazin-8-yl}amino)propane-1-sulfonic acid,

2-({3-[4-(cyclopropylcarbamoyl)-3-methylphenyl]-6-(3-fluorophenoxy)imidazo[1,2-b]pyridazin-8-yl}amino)ethanesulfonic acid,

N-(1-cyanocyclopropyl)-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]pyridazin-3-yl}-2-methylbenzamide,

4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-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]pyridazin-3-yl}-N-isopropyl-2-methylbenzamide,

4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methyl-N-(3,3,3-trifluoropropyl)benzamide,

4-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-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)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

-{6-(3-fluorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N-isobutyl-2-methylbenzamide,

4-{6-(4-chlorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide,

4-{6-(4-chlorophenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[1,2-b]pyridazin-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}imidazo[1,2-b]pyridazin-3-yl]benzamide,

4-[6-(4-methoxyphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo[1,2-b]pyridazin-3-yl]-N, 2-dimethylbenzamide,

4-[6-(2-fluoro-4-methoxyphenoxy)-8-{[2-(morpholin-4-yl)ethyl]amino}imidazo[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]imidazo[1,2-b]pyridazin-3-yl}-N, 2-dimethylbenzamide,

N,2-dimethyl-4-{6-(2-methylphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]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]pyridazin-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]pyridazin-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]pyridazin-3-yl}-N,

2-dimethylbenzamide,

4-{6-(3,4-difluorophenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridazin-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]pyridazin-3-yl}-N,2-dimethylbenzamide,

4-{6-(5-fluoro-2-methylphenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N, 2-dimethylbenzamide,

4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(2-methoxyethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-N, 2-dimethylbenzamide,

4-{8-[(2-methoxyethyl)amino]-6-phenoxyimidazo[1,2-b]pyridazin-3-yl}-N,2-dimethylbenzamide,

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]amino}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]imidazo[1,2-b]pyridazin-3-yl}-N-ethyl-2-methylbenzamide,

N-ethyl-2-methyl-4-{6-(2-methylphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)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-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-ethyl-4-{6-(5-fluoro-2-methylphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-ethyl-4-{6-(3-fluoro-4-methoxyphenoxy)-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]imidazo[1,2-b]pyridazin-3-yl}-2-methylbenzamide,

N-ethyl-2-methyl-4-{6-(2-methylphenoxy)-8-[(3,3,3-trifluoropropyl)amino]imidazo[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]imidazo[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]pyridazin-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:

in which R 3 and R 5 are as defined in claim 1 , and A′ is

wherein * indicates the point of attachment of said group with the rest of the molecule; R 4a , R 4b , R 4c and R 4d are as defined in claim 1 , and Z′ represents a group selected from:

—C(═O)OH, —C(═S)OH, —C(═O)O—(C 1 -C 6 -alkyl) or —C(═S)O—(C 1 -C 6 -alkyl).

8. A compound of general formula IV:

in which A, and R 5 are as defined in claim 1 , and R 3′ is a leaving group.

9. A compound of general formula VII:

in which A, and R 3 are as defined in claim 1 , and Q 1 represents an optionally protected NH 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:

in which A, and R 5 are as defined in claim 1 , and R 3′ is a leaving group;

to react with a compound of general formula IVa:

R 3 —Y  IVa

in which R 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:

in which A, R 3 , and R 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:

in which R 3 and R 5 are as defined in claim 1 ;

and A′ is

wherein * indicates the point of attachment of said group with the rest of the molecule; R 4a , R 4b , R 4c and R 4d are as defined in claim 1 , and Z′ represents a group selected from:

—C(═O)OH, —C(═S)OH, —C(═O)O—(C 1 -C 6 -alkyl) or —C(═S)O—(C 1 -C 6 -alkyl);

to react with a compound of general formula Ib:

H 2 NR 2   Ib

in which R 2 is as defined in claim 1 , thereby giving, upon optional deprotection, a compound of general formula I:

in which R 3 , R 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:

in which R 3 and A are as defined in claim 1 , and Q 1 is a leaving group,

to react with a compound of general formula VIIa:

R 5 —CH 2 —NH 2   VIIa

in which R 5 is as defined in claim 1 ,

thereby giving, upon optional deprotection, a compound of general formula I:

in which R 3 , R 5 and A are as defined in claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 28, 2014
From: KLAR, ULRICH, DR.; KOPPITZ, MARCUS, DR.; JAUTELAT, ROLF, DR.; KOSEMUND, DIRK, DR.; BOHLMANN, ROLF, DR.; LIENAU, PHILIP, DR; SIEMEISTER, GERHARD, DR.; WENGNER, ANTJE MARGRET, DR.
To: BAYER INTELLECTUAL PROPERTY GMBH
Reel/Frame 032552/0802 →
Priority Claims (4)
EP 10176134 · Sep 10, 2010 · regional
EP 11075022 · Feb 4, 2011 · regional
EP 11170771 · Jun 21, 2011 · regional
EP 11170775 · Jun 21, 2011 · regional
Continuity (1)
Related Publication 20130338133A1 · Dec 19, 2013