CA2620534A1 - Substituted imidazo[1,2b]pyridazines as kinase inhibitors, their preparation and use as medicaments - Google Patents

Abstract

The invention relates to novel inhibitors for kinases, methods for producing such inhibitors, intermediate products for producing the same, and uses thereof.

Description

Substituted imidazo[1,2b]pyridazines as kinase inhibitors, their preparation and use as medicaments The present invention relates to novel substituted imidazo[1,2b]pyridazines, their preparation and use as medicament for the treatment of various disorders.

The compounds described in this invention are suitable for inhibiting kinases, preferably kinases of the protein kinase (PK) family and, in this connection, io especially for inhibiting kinases of the PKC subfamily, very particularly for inhibiting the PKC theta kinase. The present compounds are suitable as kinase inhibitors for the treatment of a large number of disorders which are attributable to a dysfunction of a kinase, including immunological and general inflammatory processes, and oncological processes, but also disorders such as, for example, type II
diabetes is and asthma, and transplants; preferably inflammatory processes and immune responses which exhibit the clinical appearance of acute dermatitis, of contact dermatitis but also of psoriasis.

A single publication (Bioorg. Med. Chem. Lett. 2004, 14, 2249-2252.) discloses pyrimidine derivatives with an attached imidazo[1,2b]pyridazine residue as kinase 20 inhibitors. These compounds differ from the compounds of the invention through their structure, in particular on the imidazo[1,2b]pyridazine ring. The patent application WO 02/066481 (AstraZeneca) describes pyridazine-substituted pyrimidines as antiproliferative substances. Further prior art is mentioned hereinafter.

There is a continuing great need for effective medicaments for the treatment of immunological and also cell-proliferative disorders, in particular in dermatological indications.

It has now been found that substituted imidazo[1,2b]pyridazines of the general formula I in which N
R1~N N N

Q
B
Formula I
io where Q is aryl or heteroaryl - with the exception of pyrimidine;

A and B are identical or different and are selected from the group consisting of i) H, Hal, -OH, -NR3R4, -CN, or -NO2, ii) optionally mono- or poly-Hal-, -OH-, C3-C6-heterocycloalkyl-, -NR3R4-, is -SO2NR3R4- , -S02R3- or -(CO)-NR3-L-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or one or more double bonds, 20 and iii) -NR3(CO)-L, -NR3(CO)-NR3-L, -(CO)-R6, -O-(CH2)P-R6, -(CO)-(NR3)-L, -NR3(CS)-NR3R4, -NR3(S02)-L, -(SO2)-NR3R4, -NR3(CO)NR3R4, -(CO)NR3R4, -C02R7, -NR3(S02)R4 or -O-(CH2)P aryl, where the substituents in the case of polysubstitution may be identical or 25 different, A and B in addition to the aforementioned definition together form a Q-fused C5-C7-cycloalkyl or C5-C7-heterocycloalkyl ring, where the latter comprises at least one oxygen or one nitrogen atom in the ring, and may optionally comprise additionally in the ring one or more oxygen, nitrogen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, p isOto4, L is optionally mono- or poly-hydroxy-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-haloalkyl-, C1-C6-hydroxyalkoxy-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-alkoxyalkoxy-, C3-C6-heterocycloalkyl-, or -NR 3 R4-substituted C1-C6-alkyl, C1-C6-haloalkyl or C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, io where the C3-C6 heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or one or more double bonds;

R' and R2 are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6-heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L-, -NR3COOR'-, -COOR'-, -NR3CONR3R4-, -NR3SO2R4-, -SO2NR3R4- , -CONR3R4- or -SO2R3-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl or with -(CH2)r-R$ radical, where r is a number 0-3, and R 8 is a radical or H F

where aryl, heteroaryl, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl groups optionally present in R' or R2 may be substituted one or more times by -Hal, -CN, - OH, -C1-C6-alkyl, C1-C6-haloalkyl, -C1-C6-alkoxy, C1-C6-haloalkoxy, -C1-C6-hydroxyalkyl, -C3-C6-cycloalkyl, -NO2, -NH2, -C1-C6-haloalkyl, -NR3R4, -CONR3R4, -NR3COR4, NR3SO2R4, -COR6, C02R 7, -SO2NR3R4, -SR3, SOR3, -S02R3, -OR3, -O(CH2)pRs, where the substituents in the case of polysubstitution may be identical or different;

where two or more aryl or heteroaryl groups may not be substituents on the same carbon atom in R' or R2;

io R' and R2 in addition to the aforementioned definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally comprise additionally in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, is where the ring formed by R' and R2 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, C1-C6-haloalkoxy-, C1-C6-haloalkoxyalkyl, -NR3R4, -CONR6R', -(CO)-R6 or-COOR7 and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or 20 -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 are identical or different and are selected from the group consisting of j) -H, and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-2s cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R'-, -CONRsR'-, -(CO)-R6- or -COOR7-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-oycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may comprise in the ring 30 optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 in addition to the aforementioned definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally comprise additionally in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R3 and R4 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-haloalkoxy, C1-C6-haloalkoxyalkyl, C1-C6-alkoxyalkyl, or by -NR6R', -CONR6R', -(CO)-R6 or-COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R6 and R' are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN- substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)-or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different, and the isomers, diastereomers, enantiomers and salts thereof, represent effective compounds for inhibiting kinases (defined hereinafter) and therefore can be employed for a number of disorders (defined hereinafter).

Alkyl means in each case a straight-chain or branched alkyl radical such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl, nonyl and decyl.

Alkoxy means in each case a straight-chain or branched alkoxy radical such as, for example, methyloxy, ethyloxy, propyloxy, isoproplyloxy, butyloxy, isobutyloxy, sec butyloxy, pentyloxy, isopentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy or decyloxy.

The alkenyl substituents are in each case straight-chain or branched, with the following radicals being meant for example: vinyl, propen-1-yl, propen-2-yl, but-1-to en-l-yl, but-1 -en-2-yl, but-2-en-1-yl, but-2-en-2-yl, 2-methylprop-2-en-1-yl, 2-methylprop-1-en-1 -yl, but-1 -en-3-yi, but-3-en-1 -yl, allyi.

Alkynyl means in each case a straight-chain or branched alkynyl radical which comprises 2-6, preferably 2-4, C atoms. Examples of suitable radicals are the following: ethynyl, propyn-1 -yl, propyn-3-yl (propargyl), but-1 -yn-1-yi, but-1 -yn-4-yl, but-2-yn-1-yl, but-1-yn-3-yl, 3-methylbut-1-yn-3-yl.

C1-C6-Haloalkyl stands for a straight-chain or branched alkyl radical in which at least one hydrogen atom is replaced by a halogen atom (fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine), such as, for example fluoromethyl, trichloromethyl, 1,2-difluoroethyl, perfluoropropyl, 3,3,3-trifluoropropyl, 1-fluoroisopropyl, perfluorobutyl, etc. Perfluoromethyl and perfluoroethyl groups are very particularly preferred.

C1-C6-Haloalkoxy stands for a straight-chain or branched alkoxy radical in which at least one hydrogen atom is replaced by a halogen atom (fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine), such as, for example, fluoromethoxy, trichloromethoxy, 1,2-difluoroethoxy, perfluoropropoxy, 3,3,3-trifluoropropoxy, 1-fluoroisopropoxy, perFluorobutoxy, etc. Perfluoromethoxy and perfluoroethoxy groups are very particularly preferred.

C3-C6-Heterocycloalkyl stands for an alkyl ring including 3-6 carbon atoms, where the heterocycloalkyl comprises in the ring at least one atom, identical or different, from the following group oxygen, sulfur or nitrogen, and may optionally be interrupted by one or more -(CO)-, -(CS)- or -SO2- groups in the ring, and may optionally comprise one or more double bonds in the ring, and the ring itself may optionally be substituted one or more times, identically or differently.

Examples of heterocycloalkyl which may be mentioned are: oxiranyl, oxethanyl, dioxolanyl, dithianyl, dioxanyl, aziridinyl, azetidinyl, tetrahydrofuranyl, tetra hyd ro pyra nyl, dihydrooxazolyl, tetrahydrooxazolyl, tetrahydrothiazolyl, io tetrahydroisoquinolinyl, octahydroisoquinolinyl, tetrahydroquinolinyl, octahydroquinolinyl, tetrahydroimidazolonyl, pyrazolidinyl, pyrrolidinyl, pyrrolidonyl, piperidinyl, piperidonyl, piperazinyl, piperazinonyl, N-methylpyrolidinyl, 2-hydroxy-methylpyrolidinyl, 3-hydroxypyrolidinyl, N-methylpiperazinyl, N-benzylpiperazinyl, N-acetylpiperazinyl, N-methylsulfonylpiperazinyl, 4-hydroxypiperidinyl, 4-amino-carbonytpiperidinyl, 2-hydroxyethylpiperidinyl, 4-hydroxymethylpiperidinyl, imidazolidinyl, tetrahydroimidazolonyl, morpholinyl, thiomorpholinyl, 1,1-dioxothio-morpholinyl, trithianyl, tetrahydrotriazinthionyl, triazinthionyl, quinuclidinyl, nortropinyl, pydridonyl.

Preferred heterocycloalkyl groups which may be mentioned are:
tetrahydropyranyl, pyrrolidinyl, piperidinyl, N-methylpiperidinyl, piperazinonyl, N-methylpiperazinyl, morpholinyl, pyrridonyl.

Substituents on the heterocycloalkyl ring may be for example: cyano, halogen, hydroxy, C1-C6-alkyl, C1-C6-haloalkyi, C1-C6-alkoxy, C1-C6-haloalkoxy, Cl-C6-alkoxyalkyl, Cl-C6-hydroxyalkyl, C3-C6-cycloalkyl, aryl or optionally identically or differently mono- or poly-halogen-, hydroxyl- or Cl-C6-alkylthio-substituted alkyl, C1-C6-haloalkyl or a substituent from the group -(CO)-C1-C6-aIkyl, -(CO)-O-Cl-C6-alkyl, -(S02)-C1-C6-alkyl, -(S02)-phenyl, -NH2, -N(Cj-C6-alkyl)2, -NH(Cl-alkyl) etc.

Cycloalkyl means monocyclic alkyl rings such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl, but also bicyclic rings or tricyclic rings such as, for example, adamantanyl. The cycloalkyl may also optionally be benzo-fused, such as, for example, (tetralin)yl etc.

Preferred cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
Halogen means in each case fluorine, chlorine, bromine or iodine.

The aryl radical in Q and the aryl radical optionally present in R' and R2 includes in each case 3-12 carbon atoms and may in each case be benzo-fused. Examples which may be mentioned are: cyclopropenyl, cyclopentadienyl, phenyl, tropyl, io cyclooctadienyl, indenyl, naphthyl, azulenyl, biphenyl, fluorenyl, anthracenyl, tetralinyl etc.

The heteroaryl radical Q includes in each case 5-16 ring atoms and may comprise in place of the carbon one or more identical or different heteroatoms such as oxygen, nitrogen or sulfur in the ring, and may be mono-, bi- or tricyclic, and may additionally be in each case benzo-fused. Pyrimidine is not included as group Q in the definition of heteroaryl.

Examples which may be mentioned are: thienyl, furanyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyi, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, etc. and benzo derivatives thereof, such as, for example, 2o benzofuranyl, benzothienyl, benzoxazolyl, benzimidazolyl, indazolyl, indolyl, isoindolyl, etc.; or pyridyl, pyridazinyl, pyrazinyl, triazinyl, etc. and benzo derivatives thereof, such as, for example, quinolyl, isoquinolyl, etc.; or oxepinyl, azocinyl, indolizinyl, indolyl, indolinyl, isoindolyl, indazolyl, benzimidazolyl, purinyl, etc. and benzo derivatives thereof; or quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, tetralinyl, etc.

Preferred heteroaryl radicals are for example 5-membered heteroaromatic rings such as thienyl, furanyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl and benzo derivatives of the 5-membered heteroaromatic rings, and 6-membered heteroaromatic rings, such as pyridinyl, triazinyl, and benzo derivatives of the 5-membered heteroaromatic rings, such as quinolinyl, isoquinolinyl.

The heteroaryl radical optionally present in R' or R2 includes in each case 5-16 ring atoms and may comprise instead of the carbon one or more identical or different heteroatoms such as oxygen, nitrogen or sulfur in the ring, and may be mono-, bi-or tricyclic, and may additionally in each case be benzo-fused.

Examples of the heteroaryl radical in R' or R2 which may be mentioned are:
thienyl, furanyl, pyrroidinylyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, lo isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, etc. and benzo derivatives thereof, such as, for example, benzofuranyl, benzothienyl, benzoxazolyl, benzimidazolyl, indazolyl, indolyl, isoindolyl, etc.; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc. and benzo derivatives thereof, such as, for example, quinolyl, isoquinolyl, etc.; or oxepinyl, azocinyl, indolizinyl, indolyl, indolinyl, isoindolyl, ts indazolyl, benzimidazolyl, purinyl, etc. and benzo derivatives thereof; or quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, xanthenyl, tetralinyl, etc.

Examples of preferred heteroaryl radicals in R' or R2 are 5-membered 2o heteroaromatic rings such as thienyl, pyrazolyl, furanyl, oxazolyl, thiazolyl, triazolyl, imidazolyl and benzo derivatives thereof and 6-membered heteroaromatic rings such as pyridinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl and benzo derivatives thereof.

Particularly preferred heteroaryl radicals in R' or R2 are thienyl, pyrazolyl, furanyl, 25 oxazolyl, thiazolyl, triazolyl, imidazolyl, pyridinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl.

If a plurality of aryl or heteroaryl groups are present in R' or R2, two or more aryl or heteroaryl groups may not be substituents on the same carbon atom.

Thus, for example, a group C

-CH

is precluded as group R' or R2.

Should aryl, heteroaryl, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl groups be present in R' or R2, these may be substituted one or more times by -Hal, -CN, -OH, -C1-C6-alkyl, C1-C6-haloalkyl, -C1-C6-alkoxy, C1-C6-haloalkoxy, -C1-C6-hydroxyalkyl, -C3-C6-cycloalkyl, -NO2, -NH2, -Cl-C6-haloalkyl, -NR3R4, -CONR3R4, -NR3COR4, NR3SO2R4, -COR6, C02R 7, -SO2NR3R4, -SR3, SOR3, --S02R3, -OR3, to -O(CH2)PR6, where the substituents in the case of polysubstitution may be identical or different. In a preferred embodiment, the aryl, heteroaryl, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl groups present in R' or R2 have not more than 3 of the abovementioned substituents.

Isomers mean chemical compounds of the same molecular formula but different is chemical structure. A distinction is made in general between constitutional isomers and stereoisomers.

Constitutional isomers have the same molecular formula but differ through the manner of attachment of their atoms or atomic groups. These include functional isomers, positional isomers, tautomers or valence isomers.

20 Stereoisomers have in principle the same structure (constitution) - and thus also the same molecular formula - but differ through the spatial arrangement of the atoms.

A distinction is made in general between configurational isomers and conformational isomers. Configurational isomers are stereoisomers which can be 25 converted into one another only by breaking a bond. These include enantiomers, diastereomers and E/Z (cis/trans) isomers.

Enantiomers are stereoisomers which are related to one another as image and mirror image and have no plane of symmetry. All stereoisomers which are not enantiomers are referred to as diastereomers. E/Z (cis/trans) isomers at double bonds are a special case.

Conformational isomers are stereoisomers which can be converted into one another by rotation of single bonds.

See also the IUPAC rules section E (Pure Appl. Chem. 1976, 45, 11-30.) concerning the categorization of the type of isomerism.

The compounds of the invention of the general formula I also encompass the io possible tautomeric forms and include the E or Z isomers or, if a chiral center is present, also the racemates and enantiomers. Double-bond isomers are also to be understood thereby.

The compounds of the invention may also exist in the form of solvates, in particular of hydrates, in which case the compounds according to the invention accordingly is comprise polar solvents, in particular water, as structural element of the crystal lattice of the compounds according to the invention. The proportion of polar solvent, in particular water, may be in a stoichiometric or else non-stoichiometric ratio. Terms used in connection with stoichiometric solvates, hydrates are also hemi-, (semi-), mono-, sesqui-, di-, tri-, tetra-, penta-, etc. solvates or hydrates.

20 If an acidic function is present, suitable salts are the physiologically tolerated salts of organic and inorganic bases such as, for example, the readily soluble alkali metal and alkaline earth metal salts, and salts of N-methylglucamine, dimethylglucamine, ethylglucamine, lysine, 1,6-hexanediamine, ethanolamine, glucosamine, sarcosine, serinol, trishydroxymethylaminomethane, 25 aminopropanediol, Sovak base, 1-amino-2,3,4-butanetriol.

If a basic function is present, the physiologically tolerated salts of organic and inorganic acids are suitable, such as hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, fumaric acid, maleic acid, malic acid and others.

Preferred compounds of the general formula I are those compounds in which R' and R2 are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L-, or -NR3COOR'-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen io and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different. Q, A, B, R3, R4, R6, R7, p and L may in this case be varied as defined above.

Further preferred compounds of the general formula I are those in which R' and is are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryloxy-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L-, or -NR3COOR'-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, 20 C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, where the group aryl or heteroaryl defined in jj) may be substituted as long as alkyl is not 25 involved, and where the substituents in the case of polysubstitution may be identical or different. Q, A, B, R3, R4, R6, R7, p and L may in this case be varied as defined above.

Further preferred compounds of the general formula I are those in which Q is:
-OH-, -Hal-, -CN-, alkyl-, -OR6-, or -NR3R4-substituted phenyl, pyridyl, thiophenyl, 30 furyl, imidazolyl or pyrazolyl, where R' and R2 are identical or different and are SRG/US/53343 - 13 - AL.I/TDS
selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryloxy-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L- or -NR3COOR'-substituted C1-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, where the group aryl or heteroaryl defined in jj) may be io substituted as long as alkyl is not involved, and where the substituents in the case of polysubstitution may be identical or different. R3, R4, R6, R7, p and L may in this case be varied as defined above.

Further preferred compounds of the general formula I are those in which R' and R2 are identical or different and are selected from the group consisting of -H, NR3R4-substituted C1-C4 alkyl, optionally additionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3(CO)-L- or -NR3COOR'-substituted, optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3(CO)-L-, -NR3R4- or -NR3COOR'-substituted C5-C6-cycloalkyl, C5-heterocycloalkyl, where R3 and R4 may optionally be identically or differently C1-C6-alkyl, C1-C6-haloalkyl, where R3 and R4 may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, and where R6 and R7 is identically or differently -H, -OH, C1-C6-alkoxy, C1-C6-haloalkoxy, or C1-C3 alkyl.

Particularly preferred compounds of the general formula I are those in which R' is selected from the group consisting of -H and C1-C3-alkyl, where R2 is selected from the group consisting of NR3R4-substituted C3-C4 alkyl, optionally additionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3(CO)-L- or -NR3COOR'-substituted, where R3 and R4 are identically or differently optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, Cl-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, io C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R7-, -CONR6R'-, -(CO)-R6-or -COOR'-substituted Cl-C6-alkyl, C1-C6-haloalkyl, where R3 and R4 may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, and where R6 and R7 is identically or differently -H, -OH, C1-C6-alkoxy, C1-C6-haloalkoxy, or C1-C3 alkyl.

In a further preferred embodiment, R' or R 2 is a hydrogen atom.

The following compounds mentioned in the examples are particularly preferred:
. 2.0 - 2.21 = 3.0 - 3.80 = 4.0-4.11 = 5.0 - 5.389 = 6.0 - 6.2 = 7.0 - 7.1 = 8.0 - 8.1 A further aspect of the present invention is represented by a compound of the general formula Ila and the use thereof for preparing a compound according to formula I, in which rrN
R1, N N ,N ,/

General formula Ila Y is a halogen atom (preferably chlorine or bromine), R' and R2 are identical or different and selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L- or -NR3COOR'-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R' and R2 in addition to the preceding definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)-groups and/or optionally one or more double bonds, where the ring formed via R' and R2 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-haloalkoxyalkyl, C1-C6-haloatkoxy, C1-C6-alkoxyalkyl, -NR3R4, -CONRsR', -(CO)-R6 or -COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or SRG/US/53343 - 16 - AL.I/TDS
-(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;
where three or more nitrogen atoms in the ring may not be linked directly to one another;
where aryl, heteroaryl, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl groups optionally present in R' or R2 may be substituted one or more times by -Hal, -CN, - OH, -C1-C6-alkyl, C1-C6-haloalkyl, -C1-C6-alkoxy, C1-C6-haloalkoxy, -C1-C6-hydroxyalkyl, -C3-C6-cycloalkyl, -NO2, -NH2, -C1-C6-haloalkyl, -NR3R4, -CONR3R4, -NR3COR4, NR3SO2R4, -COR6, C02R7 , -SO2NR3R4, -SR3, SOR3, --SO2R3, -OR3, -O(CH2)pRs, where the substituents in the case of polysubstitution may be identical or different;
R3 and R4 are identical or different and selected from the group consisting of j) -H
and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R'-, -CONR6R'-, -(CO)-R6- or -COOR'-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 in addition to the preceding definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)-groups and/or optionally one or more double bonds, where the ring formed by R3 and R4 may optionally be substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl C1-C6-haloalkoxyalkyl, C1-C6-haloalkyl or -NR6R', -CONR6R', -(CO)-R6 or-COOR7 and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R6 and R7 are identical or different and selected from the group consisting of j) -H
and jj) optionally mono- or poly-Hal-, -OH-, -CN-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-/ ~N

X N, A
B

alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionallyt comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different, and the isomers, diastereomers, enantiomers and salts thereof.

is A further aspect of the present invention is represented by a compound of the general formula lib and the use thereof for preparing a compound according to formula I, in which general formula Ilb X is chlorine, bromine, O-S02-CF3 or O-SO2-C4F9;

Q is aryl or heteroaryl - with the exception of pyrimidine;

A and B are identical or different and selected from the group consisting of i) H, Hal, -OH, -NR3R4, -CN or -NO2, ii) optionally mono- or poly-Hal-, -OH-, C3-C6-heterocycloalkyl-, -NR3R4-, -SO2NR3R4-, -S02R3- or -(CO)-NR3-L-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or one or more double bonds, and iii) -NR3(CO)-L, -NR3(CO)-NR3-L, -(CO)-R6, -O-(CH2)p-R6, -(CO)-(NR3)-L, -NR3(CS)-NR3R4, -NR3(S02)-L, -(S02)-NR3R4, -NR3(CO)NR3R4, -(CO)NR3R4, -CO2R7, -NR3(SO2)NR4 or -O-(CH2)p-aryl, where the substituents in the case of polysubstitution may be identical or different, A and B in addition to the preceding definition together form a Q-fused C5-C7-cycloalkyl or C5-C7-heterocycloalkyl ring, where the latter comprises at ts least one oxygen or nitrogen atom in the ring and may optionally additionally comprise in the ring one or more oxygen, nitrogen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, p isOto4, 2o L is optionally mono- or poly-hydroxy-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-hydroxyalkoxy-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-alkoxyalkoxy-, C3-C6-heterocycloalkyl- or -NR3R4-substituted C1-C6-alkyl, C1-C6-haloalkyl or C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6 heterocycloalkyl may optionally comprise in the ring one or more 25 nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)-groups and/or one or more double bonds;

R3 and R4 are identical or different and selected from the group consisting of j) -H, and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-SRG/US/53343 - 19 - ALJlrDS
cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R'-, -CONR6R'-, -(CO)-R6- or -COOR'-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;
io R3 and R4 may in addition to the preceding definition together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)-groups and/or optionally one or more double bonds, where the ring is formed via R3 and R4 may optionally be substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, C1-C6-haloalkoxyalkyl, Cl-C6-haloalkoxy or by -NR6R', -CONR6R', -(CO)-R6 or-COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-2o haloalkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents may in the case of polysubstitution be identical or different;

R6 and R' are identical or different and selected from the group consisting of j) -H
and jj) optionally mono- or poly-Hal-, -OH-, -CN-substituted C1-C6-alkyl, 25 C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the 30 substituents in the case of polysubstitution may be identical or different and the isomers, diastereomers, enantiomers and salts thereof.

These compounds of the general formulae Ila and Ilb represent advantageous intermediates and can be employed in the synthesis of the abovementioned compounds of the general formula I.

The explanations made above for the compounds of the formula I, including the preferred embodiments of the radicals, apply in principle analogously to the compounds of the formulae Ila and llb. It is particularly preferred for 0 to be an optionally mono- or poly-OH-, -Hal-, -CN-, alkyl-, -OR6- or -NR3R4-substituted phenyl, pyridyl, thiophenyl, furyl, imidazolyl or pyrazolyl. It. is further preferred for X
lo to be -CI or-Br.

The following intermediates of the invention are particularly preferred: 3-bromo-6-chloroimidazo[1,2-b]pyridazines, imidazo[1,2-b]pyridazin-6-yl-(3-pyrrolidin-1-ylpropyl)amines, 6-chloro-3-phenylimidazo[1,2-b]pyridazines, 6-chloro-3-(3-chlorophenyl)imidazo[1,2-b]pyridazines, 6-chloro-3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazines, 6-chloro-3-thiophen-3-ylimidazo[1,2-b]pyridazines.
The intermediates 1.0-1.28 described in the examples are very particularly preferred.

Synthesis scheme:

X N"
N
Q A
v B
NH2 General formula IIb / -_N

jJ ~ N ~ -- ~ N ~ ~ ~ N ~
~
X N" X N" X N"

N A
I II

B VII
General formula I
R1. ( N-R1.N (W N N" R2 Y VI

General formula Ila The invention accordingly also relates to a method for preparing a compound of the invention with the following stages of the method:

Al) 3-amino-6-halopyrazine is converted into 6-haloimidazo[1,2-b]pyridazine II, A2) the product from stage Al is converted into a 3-halo-6-haloimidazo[1,2-b]pyridazine III, A3) the product from stage A2 is converted by reaction with a compound NHR'R2 io into the compound according to the general formula Ila, A4) the product from stage A3 is converted into the compound according to the general formula I, or 131) 3-amino-6-halopyrazine is converted into 6-haloimidazo[1,2-b]pyridazine II, is B2) the product from stage Bl is converted into a 3-halo-6-haloimidazo[1,2-b]pyridazine III, B3) the product from stage B2 is converted into the compound according to the general formula lib, B4) the product from stage B3 is converted into the compound according to the general formula I, or Cl) 3-amino-6-halopyrazine is converted into 6-haloimidazo[1,2-b]pyridazine II, C2) the product from stage Cl is converted by reaction with a compound NHR'R2 into an imidazo[1,2-b]pyridazin-6-yl)-(R')-(R2)-amine IV, C3) the product from stage C2 is converted into the compound according to the io general formula Ila, C4) the product from stage C3 is converted into the compound according to the general formula I.

Said reactions are preferably carried out as follows:

Al) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, A2) the product from stage Al is reacted with N-bromosuccinimide to give a 3-bromo-6-haloimidazo[1,2-b]pyridazine, A3) the product from stage A2 is converted by reaction with a compound NHR'R2 in a Buchwald-Hartwig cross-coupling reaction into a(3-bromoimidazo[1,2-b]pyridazin-6-yl)-(R' )-(R2)-amine, A4) the product from stage A3 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula I, or 131) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, B2) the product from stage B1 is reacted with N-bromosuccinimide to give a 3-bromo-6-haloimidazo[1,2-b]pyridazine, B3) the product from stage B2 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula II, B4) the product from stage B3 is converted by reacting with a compound NHR'R2 io in a Buchwald-Hartwig cross-coupling reaction into the compound according to the general formula I, or Cl) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, C2) the product from stage Cl is converted by reacting with a compound NHR'R2 in a Buchwald-Hartwig cross-coupling reaction into an imidazo[1,2-b]pyridazin-6-yi)-(R' )-(R2)-amine, C3) the product from stage C2 is reacted with N-bromosuccinimide to give a (3-bromoi mid azo[1,2-b]pyrid azin-6-yl)-(R')-(R 2)-amine, C4) the product from stage C3 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula I.

The compounds of the invention are particularly preferably prepared by synthesis route A1-A4.

To protect sensitive side groups, said synthesis routes can also be prepared with use of protective groups. Such protective group techniques are known to the skilled worker, e.g. from T.W. Greene, P.G.M. Wuts õProtective Groups in Organic Synthesis", 2"d edition, John Wiley and Sons, 1991.

Stages Al, Bl and Cl can be carried out for example by heating with, for example, chloracetaldehyde at 60 to 130 C, in particular 100 to 130 C, in n-butanol as solvent and for a period of from 1 hour to 10 days, in particular 3 to 6 days.

The amination (stages A3, B4 and C2 respectively) can be carried out for io example by heating with the appropriate amine at 90-180 C, in particular 90 C, for a period of from 1 hour to 24 hours, in particular 1 hour to 16 hours. The heating can take place by means of conventional heating or else by means of microwave radiation through a suitable apparatus. The use of an auxiliary base such as, for example, K2CO3 or Et3N is not always necessary. The use of a solvent such as, for example, acetonitrile, EtOH, n-BuOH or NMP is not always necessary. It is possible to use for the amination for example the so-called Buchwald-Hartwig cross-coupling reaction. The Buchwald-Hartwig cross-coupling reaction can be carried out for example in accordance with one of the references D. Zim, S.L. Buchwald, Org. Lett., 5:2413-2415 (2003) or S. Urgaonkar, M.
2o Nagarajan, J.G. Verkade, J. Org. Chem., 68:452-459 (2003).

The reaction to give the 3-bromo intermediate (stages A2, B2 and C3) can take place by introducing the precursor compound into chloroform and adding the N-bromosuccinimide at -5 to 30 C, in particular at 0 to 10 C, followed by reaction for 1 hour to 2 days, in particular 5 to 15 hours, at 0 to 30 C, in particular at 15 to 25 C. However, alternative synthesis routes for preparing the 3-halo intermediates of the invention are also known to the skilled worker.
Stages A4, B3 and C4 can be carried out for example by introducing the precursor compound into dimethoxyethane and adding a boronic acid in the presence of a palladium(0) source, for example bis(dibenzylidene-acetone)palladium(O), of a ligand, for example tri-o-tolylphosphine and of a base, for example sodium bicarbonate, and by heating under reflux for 5 to 40 hours, in particular 10 to 20 hours.

Where the preparation of the starting compounds is not described, they are known or can be prepared in analogy to known compounds or methods described herein.
The isomer mixtures can be fractionated by conventional methods such as, for example, crystallization, chromatography or salt formation into the isomers such as, for example, into the enantiomers, diastereomers or E/Z isomers, as long as the isomers are not in equilibrium with one another.

io The salts are prepared in a conventional way by adding the equivalent amount or an excess of a base or acid, which is in solution where appropriate, to a solution of the compound of the formula I, and removing the precipitate or working up the solution in a conventional way.

Additional reference is made to the examples for merely exemplary details of the synthesis.

The invention further relates also to intermediates of the invention as defined in the claims.

Compounds of the invention are suitable as kinase inhibitors, in particular of tyrosine and serinelthreonine kinases. The compounds of the invention of the general formula I are inter alia inhibitors of the protein kinase C family, such as, for example, PKC theta, delta, iota, alpha and zeta.

An inhibitor of a kinase can therefore be employed on the one hand for investigating the mechanisms of functioning of the kinase, in particular research into a disorder which derives from a dysfunction of the kinase. However, it is also possible for a disorder derived from the dysfunction of the kinase to be treated or prevented using the kinase inhibitor.

The invention therefore further relates to the use of a compound of the invention of the general formula I for producing a pharmaceutical composition, in particular for inhibiting a cellular kinase, preferably kinases of the protein kinase (PK) family and in this connection in particular for inhibiting kinases of the PKC
subfamily, very especially for inhibiting the PKC theta kinase, and for the treatment or for the prophylaxis of a disorder which is associated with overexpression or mutation of a cellular kinase, in particular of such a cellular kinase.

It has additionally been found that, surprisingly, the compounds of the invention are also inhibitors of kinases of the ALK family. ALK means "activin receptor-like to kinase" or "activin-like kinase". In this connection, the compounds of the invention act on ALK1, ALK2, ALK4 and ALK5, in particular on ALK1 and ALK5. The compounds of the invention are therefore also suitable for the treatment or prophylaxis of disorders which are associated with overexpression or mutation of a kinase of the ALK family, in particular ALK1 and ALK5.

is In one embodiment of the invention, the disorder is a disorder from the group consisting of epidermal hyperproliferation such as psoriasis, Alzheimer's, autoinflammatory disorders, fibroses, impaired wound healing, diabetic retinopathy, nephropathy, age-related macular degeneration, Crohn's disease, exaggerated immune response, contact dermatitis, atopic dermatitis, multiple 20 sclerosis, ALS, diabetes, asthma.

In another embodiment of the invention, the disorder is a disorder from the group consisting of benign tumors, malignant tumors, leukemia such as myeloblastic leukemia, Iymphoma, sarcoma such as osteosarcoma or chondrosarcoma, neuroblastoma, Wilm's tumor, malignant neoplasms of the bladder, breast, lung, 25 pancreas, prostate, kidney, neoplasms of epithelial origin such as carcinoma of the breast or metastases thereof.

In a further embodiment of the invention, compounds of the invention are used for modulating, in particular reducing, an immune response, for example after a transplantation has taken place to prevent rejection of an organ.

A pharmaceutical composition of the invention can be produced by mixing a physiologically effective dose of a compound of the invention with at least one pharmaceutical excipient and manufacturing a desired dosage form.

A suitable physiologically effective dose is for example an amount of from 1 to s 1000 mg, in particular from 50 to 500 mg, per dose unit per day for a person weighing 75 kg, it being possible to give the dose as a single dose to be administered once or divided into 2 or more daily doses.

The pharmaceutical manufacture of a pharmaceutical composition of the invention can take place in a manner customary in the art. Examples of suitable counter ions io for ionic compounds are Na+, K+, Li+ or cyclohexylammonium, or CI-, Br, acetate, trifluoroacetate, propionate, lactate, oxalate, malonate, maleate, citrate, benzoate, salicylate etc. Examples of suitable solid or liquid pharmaceutical presentations are granules, powders, coated tablets, tablets, (micro)capsules, suppositories, syrups, solutions, ointments, suspensions, emulsions, drops or solutions for injection (i.v., 15 i.p., i.m., s.c.) or atomization (aerosols), transdermal systems, and products with protracted release of active ingredient which are produced by using conventional aids such as carriers, disintegrants, binders, coating agents, swelling agents, glidants or lubricants, and preservatives, stabilizers, wetting agents or emulsifiers;
salts to alter the osmotic pressure or buffers, flavorings, sweeteners and 20 solubilizers. Carrier systems which can also be used are surface-active excipients such as salts of bile acids or animal or vegetable phospholipids, but also mixtures thereof, and liposomes or constituents thereof. Excipients which may be mentioned are magnesium carbonate, magnesium stearate, gum Arabic, titanium dioxide, lactose, mannitol and other sugars, talc, milk protein, gelatin, starch, cellulose and 25 its derivatives, animal and vegetable oils such as fish liver oil, sunflower, peanut or sesame oil, polyethylene glycols and solvents such as, for example, sterile water and monohydric or polyhydric alcohols, for example glycerol. Preferred dosage forms are for topical application (ointments, transdermal systems, patches, dressings), for oral administration (tablets, coated tablets, solutions, powders) or 30 for parenteral use (suspension, injection).

A pharmaceutical composition of the invention can be produced by mixing at least one inhibitor used according to the invention in defined dose with a pharmaceutically suitable and physiologically tolerated carrier and, where appropriate, further suitable active ingredients, additives or excipients with a defined dose of inhibitor and manufacturing the desired dosage form. These pharmaceutical products are likewise an aspect of the present invention.

Finally, the invention also relates to a method for the treatment or prophylaxis of a disorder which is associated with overexpression of a cellulose kinase, where a pharmaceutical composition comprising a physiologically effective dose of a io compound as claimed in any of claims 1 to 8 is administered to a person suffering from or under threat of suffering from the disorder.

The invention is explained in more detail below by means of examples which represent merely exemplary embodiments.

ts Preparation of the starting materials:

6-Chloroimidazo [1, 2-b]pyridazine (Example 1.0 OP 3055) J~ZSYJN
cl N cl N

5.0 g (38.6 mmol) of 3-amino-6-chloropyridazine were heated together with 4.7 ml (40 mmol) of chloracetaidehyde (55% strength in water) in 15 ml of n-butanol at 20 120 C for a period of 5 days. After the reaction was complete, the reaction mixture was added to saturated sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate, and the solvent was removed in vacuo. In the final purification by chromatography on silica gel, 4.17 g (70%) of the 25 desired product were isolated in the form of an amorphous white solid.

'H-NMR (CDCI3, stored over molecular sieves): 8= 7.06 (d, 1 H); 7.79 (d, 1 H);
7.92, (d, 1 H); 7.96 (d, 1 H) ppm.

3-Bromo-6-chloroimidazo(1,2-b]pyridazine (Example 1.1 OP 3056) N
~ ,N_.%
CI N CI N
s Br 478 mg (3.11 mmol) of 6-chloroimidazo[1,2-b]pyridazine were introduced into 10 ml of chloroform under argon and, while cooling in ice, 664 mg (3.73 mmol) of N-bromo-succuinimide were added. After the addition was complete, the reaction mixture was stirred at room temperature overnight. The reaction mixture was then mixed with io water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat.
sodium chloride solution and dried over sodium sulfate. In the final removal of the solvent in vacuo, the desired product was isolated in quantitative yield in the form of ts an amorphous white solid which was employed without further chromatographic purification in subsequent reactions.

'H-NMR (CDCI3, stored over molecular sieves): 8= 7.12 (d, 1 H); 7.79 (s, 1 H);
7.90, (d, 1 H) ppm.

2o 6-Chloro-3-iodoimidazo[1,2-b]pyridazine (Example 1.2) i \ ~N
CI N CI N

14 g of 6-chloroimidazo[1,2-b]pyridazine (Example 1.0) were suspended in 364 ml of acetonitrile, and 20.51 g of N-iodosuccinimide were added. The mixture was stirred at RT for 19 hours. A further 4.31 g of N-iodosuccinimide were added, and the mixture was stirred for 24 hours. The reaction was cooled and the precipitated solid was filtered off with suction, washed with acetonitrile and dried. 17.67 g of the desired product are obtained.

'H-NMR (300 MHz, d6-DMSO): b= 7.40 (d, 1 H); 7.95 (s, 1 H); 8.19 (d, 1 H) ppm.
Preparation of the intermediates of the invention:

io lmidazo[1,2-b]pyridazin-6-yl-(3-pyrrolidin-1-ylpropyl)amine (Example 1.3) / -,N N
~ N
CI N N N
H
100 mg (0.65 mmol) of 6-chloroimidazo[1,2-b]pyridazine were introduced into 9 ml of tetrahydrofuran and 3 ml of dimethylformamide under argon. 83 mg (0.65 mmol, 1.0 eq.) of 1-(3-aminopropyl)pyrrolidine, 60 mg (0.065 mmol, 0.1 eq.) of (dibenzylideneacetone)palladium(0), 41 mg (0.065 mmol, 0.1 eq.) of rac. 2,2'-bis(diphenylphosphino)-1,1'binaphthyl and 125 mg (1.3 mmol, 2.0 eq) of sodium tert-butoxide were successively added, and the mixture was then heated at 80 C for 4 h.
The reaction mixture was then mixed with water and ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final purification by chromatography on silica gel, 53 mg (39%) of the desired product were isolated in the form of an amorphous white solid.

'H-NMR (CDCI3, stored over molecular sieves): S= 1.77-1.89 (m, 6H); 2.54 (m, 4H); 2.66 (m, 2H); 3.43 (m, 2H); 6.18 (s. br, 1 H); 6.31 (d, 1 H); 7.44 (d, 1 H); 7.57, (d, 1 H); 7.61 (d, 1 H) ppm.

LC-MS (ACN/H20 0.01% HCOOH; 33x4.6x1.5p ODSII, Gradient: 100% H20 4 90% ACN in 4.5 min): t = 0.41 min; m/z = 246 [M+H]+ 38%; 123 [M+H]++ 100%;
6-Chloro-3-phenylimidazoj1,2-bJpyridazine (Example 1.4) N -,N
\ ,N ~ N ~
cl N ~ cl N' Br 500 mg (2.15 mmol) of 3-bromo-6-chloroimidazo[1,2-b]pyridazine were introduced into 25 ml of dimethoxyethane under argon. 290 mg (2.4 mmol, 1.1 eq.) of phenyl to boronic acid, 250 mg (0.43 mmol, 0.2 eq.) of bis(dibenzylideneacetone)palladium(0) and 130 mg (0.43 mmol, 0.2 eq.) of tri-o-tolylphosphine, 2.2 ml of saturated sodium bicarbonate solution, were successively added, and the reaction mixture was heated under reflux for 15 hours.

The reaction mixture was then mixed with ethyl acetate and, after addition of saturated sodium bicarbonate solution, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat. sodium chloride solution and dried over sodium sulfate. In the final purification by chromatography on silica gel, 239 mg (48%) of the desired product were isolated.

' H-NMR (CDCI3, stored over molecular sieves): 8= 7.02 (d, 1 H); 7.35 (m, 1 H); 7.43 (m, 2H); 7.89 (d, 1 H); 7.95 - 8.0 (m, 3H) ppm.

MS (ES+): m/z = 230 (100%)([M+H]+; 232 (45%).

2-(3-Bromoimidazo[l, 2-b]p yridazin-6-ylamino)ethanol (Example 1.5) iN N
.N HO,~ N
cl N N N, ~
Br H Br 400 mg (1.72 mmol) of 3-bromo-6-chloroimidazo[1,2-b]pyridazine and 2.0 ml (33.4 mmol) of ethanolamine were stirred at 90 C for 16 h. After cooling, the mixture was concentrated. The resulting residue was purified by chromatography (DCM/EtOH 9:1). 282 mg of the product were obtained.

1H-NMR (300 MHz; d6-DMSO): 8= 3.28 - 3.34 (m, 2H, covered by solvent); 3.56 -3.61 (m, 2H); 4.74 (t, 1 H); 6.71 (d, 1 H); 7.13 (t, 1 H); 7.43 (s, 1 H); 7.64 (d, 1 H) ppm.
io MS (El+): m/z = 256; 258 (M+H)+. [mol. weight = 257.09].

2-(3-lodoimidazo(1, 2-b]pyridazin-6-ylamino)ethanol (Example 1.6) N N HO~~
CL
cl N N N ~
H

562 mg (2.0 mmol) of 6-chloro-3-iodoimidazo[1,2-b]pyridazine and 2.35 ml (39.2 mmol) of ethanolamine were stirred at 90 C for 16 h. After cooling, the mixture was concentrated. The resulting residue was purified by chromatography (DCM/EtOH 9:1). 224 mg of the product were obtained.

1H-NMR (300 MHz; d6-DMSO): S= 3.27 - 3.35 (m, 2H, covered by solvent); 3.58 -3.63 (m, 2H); 4.72 (t, 1 H); 6.67 (d, 1 H); 7.06 (t, 1 H); 7.42 (s, 1 H); 7.59 (d, 1 H) ppm.
MS (ESI+): m/z = 305 (M+H)+. [mol. weight = 304.09].

The following are prepared in an analogous manner:

Table 1:

Mol. weight ExNomple Structure and name of the main isomer 'H-NMR MS ES+
( ) 358 1.7 (CDCI3, stored over MW:
846 molecular sieves): 264.12 Cl N" S= 7.12 (d, 1 H); 7.38 (m, 1 H); 7.46 (m, 1 H); 7.94 (m, MS (ES+) 2H); 8.07 (m, 1H); 8.09 (s, [M+1] +:
1 H) ppm. 264 6-Chloro-3-(3-chloro-phenyl)-imidazo[1,2-b]pyridazine 358 1.8 (CDC13, stored over MW:
860 molecular sieves): 233.66 CI N"N S= 4.04 (s, 3H); 7.04 (d, 1 H);
7.92 (d, 2H); 7.96 (s, 1 H); MS (ES+) 8.03 (s, 1 H); 8.25 (s, 1 H) [M+1 ]+:
N-N ppm. 234 /

6-Chloro-3-(1-methyl-1 H-pyrazol-4-yI)-imidazo[1,2-b]pyridazine 358 1.9 /~N (CDCI3, stored over MW:
861 molecular sieves): 235.70 CI ~N"N S= 7.14 (d, 1 H); 7.48 (m, 1 H); 7.64 (m, 1 H); 8.02 (d, MS (ES+) 1 H); 8.07 (s, 1 H); 8.34 (m, [M+1 ]+:
1 H) ppm. 236 6-Chloro-3-thiophen-3-yl-imidazo [1,2-b] pyridazine 601 1.10 MW:
352 \ N / 244.69 6 CI N"
MS (Cl+) 3-(6-Chloro-imidazo[1,2-b]pyridazin -3-yl)-phenylamine 601 1.11 N MW:
373 286.72 Cl N
MS (CI+) N
/~--O
N-[3-(6-Chloro-imidazo[1,2-b]pyrida zin-3-yl)-phenyl]-acetamide 602 1.12 / ~N MW:
147 274.67 2 CI ~N,N
MS (CI+) N

6-Chloro-3-(3-nitro-phenyl)-imidazo [1,2-b]pyridazine 602 1.13 MW:
564 278.14 2 Cl ~N~N
MS (CI+) ci 6-Chloro-3-(3-chloro-4-methyl-pheny I)-imidazo[1,2-b]pyridazine 603 1.14 N (400 MHz, d6-DMSO): MW:
262 y 8= 3.87 (s, 3H); 7.49 (d, 1 H); 260.68 1 C' NN 7.62 (m, 1 H); 7.66 - 7.67 (m, 1 H); 8.24 - 8.26 (m, 1 H); MS (ES+) 8.32 (d, 1 H); 8.55 (s, 1 H) 261; 263 (CI
0 ppm, Isotopes) N \
6-Chloro-3-(2-methoxy-pyridin-4-yl )-imidazo 1,2-b ridazine 603 1.15 N (300 MHz, d6-DMSO): MW:
013 6 = 3.89 (s, 3H); 6.96 - 7.00 260.68 ~i NN 1 H); 7.38 (d, 1 H); 8.24 -8.28 (m, 2H); 8.28 - 8.32 (m, MS (ES+) 1 H); 8.82 - 8.83 (m, 1 H) 261; 263 (CI
N ppm. Isotopes) /
6-Chloro-3-(6-methoxy-pyrid in-3-yl )-imidazo 1,2-b ridazine 602 1.16 N (300 MHz, d6-DMSO): MW:
976 b= 3.84 (s, 6H); 6.58 (t, 1 H); 289.72 CI N~N 7.32 (d, 2H); 7.43 (d, 1 H);
8.30 (d, 1 H); 8.40 (s, 1 H) MS (ES+) ppm. 290; 292 (CI
\ Isotopes) --o 6-Chloro-3-(3,5-dimethoxy-phenyl)-imidazo[1,2-b ridazine 601 1.17 N (300 MHz, d6-DMSO):
957 S= 3.69 (s, 3H); 3.83 (s, 6H);
6 ci N~N ~ 7.38 (d, 1 H); 7.40 (s, 2H);
8.25 (d, 1 H); 8.33 (s, 1 H) PPm.

--O

/
6-Chloro-3-(3,4,5-trimethoxy-phenyl )-imidazo 1,2-b ridazine 601 1.18 (400 MHz, d6-DMSO):
~57 \ N/ S= 7.45 (d, 1 H); 7.73 - 7.78 ci N (m, 2H); 8.31 (d, 1 H); 8.36 -8.39 (m, 1 H); 8.46 (m, 2H) F pPm.
F F
6-Chloro-3-(3-trifluoromethyl-phenyl )-imidazo 1,2-b] ridazine 601 1.19 N (300 MHz, d6-DMSO):
957 6= 7.36 - 7.40 (m, 2H); 7.46 0 ci NN ~ (d, 1 H); 7.90 - 7.93 (m, 1 H);
8.02 - 8.05 (m, 1 H); 8.18 (s, s 1 H); 8.32 (d, 1 H); 8.43 (s, 1 H) ppm.
3-Benzo[b]thiophen-2-yl-6-chloro-imidazo[1,2-b ridazine 601 1.20 (300 MHz, d6-DMSO): MW:
370 S= 3.80 (s, 3H); 6.94 - 6.98 259.70 ~N 1 H); 7.37 - 7.45 (m, 2H);
ci N 7.63 - 7.66 (m, 2H); 8.26 (d, MS (ES+) 1 H); 8.32 (s, 1 H) ppm. 260; 262 (CI
0 Isotopes) ~
6-Chloro-3-(3-methoxy-phenyl)-imidazo[1,2-b ridazine 601 1.21 N (400 MHz, d6-DMSO):
8= 7.36 - 7.38 (m, 1 H); 7.43 ci N (d, 1 H); 7.62 - 7.66 (m, 1 H);
8.09 - 8.11 (m, 1 H); 8.13 (m, 1 H); 8.29 (d, 1 H); 8.41 (s, o F 1 H) ppm.
/V- F
F
6-Chloro-3-(3-trifluoromethoxy-phenyl )-imidazo 1,2-b ridazine 602 1.22 N (300 MHz, d6-DMSO): MW:
059 5 = 7.45 (d, 1 H); 7.77 (d, 1 H); 298.56 ~N ~ 8.09 (dd, 1 H); 8.29 (d, 1 H);
CI N 8.36 (d, 1 H); 8.43 (s, 1 H) MS (ES+) ppm, 298; 300;
302 (CI
CI Isotopes) ci 6-Chloro-3-(3,4-dichloro-phenyl)-imidazo[1,2-b ridazine 602 1.23 N (300 MHz, d6-DMSO):
059 8 = 7.42 (d, 1 H); 7.55 - 7.61 N~ (m, 7 1 H); 8.08 - 8.13 (m, 1 H);
ci N 8.27 - 8.31 (m, 2H); 8.36 (s, 1 H) ppm.
ci F
6-Chloro-3-(3-chloro-4-fl uoro-phenyl )-imidazo 1,2-b ridazine 602 1.24 :,-N (300 MHz, d6-DMSO):
059 8 = 7.45 (d, 1 H); 7.70 - 7.75 6 ~N (m, 1 H); 7.82 - 7.85 (m, 1 H);
CI N 8.31 (d, 1 H); 8.41 - 8.45 (m, 2H); 8.51 (m, 1 H) ppm.

~N
3-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-benzonitrile 603 1.25 N (400 MHz, d6-DMSO): MW:
336 6 = 7.05 - 7.10 (m, 1 H); 7.36 263.66 3 (d, 1 H); 7.72 - 7.74 (m, 1 H);
ci N 7.87 - 7.91 (m, 1 H); 8.22 - MS (ES+) 8.25 (m, 2H); 10.24 (br s, 1 H) 264; 266 (CI
F ppm. Isotopes) OH
4-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-2-fluoro- henol 1.26 N MW:
307.76 ~N ~
ci N MS (ES+) / \ 0 308; 310 (CI
\ o Isotopes) 6-Chloro-3-(3-methanesulfonyl-phenyl)-imidazo 1,2-b ridazine 600 1.27 :~),N ~N M W:
073 324.23 H N Br MS (EI+) (3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-(3-pyrrolidin-1-yl-propyl)-amine 6-Chloro-3-naphthalen-2-ylimidazo[1,2-b]pyridazine (Example 1.28) ~ / -ci ~ ~ -1.03 g of 6-chloro-3-naphthalen-2-ylimidazo[1,2-b]pyridazine were prepared from 3.5 g (12.52 mmol) of 6-chloro-3-iodoimidazo[1,2-b]pyridazine (Example 1.2) and 2.37 g(13.78 mmol) of 2-naphthylboronic acid (CAS No. 32316-92-0) in analogy to Example 1.4.

'H-NMR (400 MHz, d6-DMSO): 8= 7.43 (d, 1 H); 7.51 - 7.57 (m, 2H); 7.92 - 7.98 (m, 2H); 8.02 - 8.05 (m, 1 H); 8.13 - 8.16 (m, 1 H); 8.31 (d, 1 H); 8.43 (s, 1 H); 8.69 io (s, 1 H) ppm.

Preparation of the final products of the invention:

Method A: (3-phenylimidazo[1,2-b]pyridazin-6-yl)-(3-pyrrolidin-1-ylpropyl)-amine (Example 2.0) N
N
N N
CI N H

100 mg (0.435 mmol) of 6-chloro-3-phenylimidazo[1,2-b]pyridazine were dissolved in a mixture of 6 ml of tetrahydrofuran and 2 ml of dimethylformamide under argon.
56 mg (0.435 mmol, 1.0 eq.) of 1-(3-aminopropyl)pyrrolidine, 40 mg (0.07 mmol, 0.16 eq.) of bis(dibenzylideneacetone)palladium(0) (Pd2dba3), 27 mg (0.0435 mmol, 0.1 eq.) of rac. 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (rac-BINAP) and 84 mg lo (0.87 mmol, 2 eq.) of sodium tert-butoxide (NaOtBu) were successively added, and the reaction mixture was heated at 80 C for 4 hours.

The reaction mixture was then mixed with ethyl acetate and, after addition of water, the phases were separated. The aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were then washed with sat.
is sodium chloride solution and dried over sodium sulfate. After multiple purification on silica gel in the final chromatographic fractionation, 9 mg (6%) of the desired product were isolated in pure form.

'H-NMR (CDCI3, stored over molecular sieves): 6 = 1.8 (m, 4H); 1.88 (m, 2H);
2,55 (m, 4H); 2.68 (t, 2H); 3.51 (m, 2H); 6.19 (s, br. 1 H); 6.38 (d, 1 H); 7.33 (m, 1 H); 7.46 20 (m, 2H); 7.63 (d, 1 H); 7.79 (s, 1 H); 8.12 (d, 2H) ppm.

MS (ES+): m/z = 322 (100%)([M+H]+.

The following are prepared in an analogous manner:

Table 2:

Mol. weight /
Example Structure and name of the main isomer 'H-NMR MS (ES+) No. [M+1 ]+

2.1 CIN N (CDCI3, stored over _ molecular sieves): b= 1.86 NH N (m, 2H); 2.50 (m, 4H); 2.54 0"') (m, 2H); 3.50 (m, 2H); 3.75 (m, 4H); 6.02 (s, br. 1 H); 6.41 (d, 1 H); 7.46 (m, 2H); 7.67 (3-Morpholin-4-yi-propyl)-(3-phenyl- (d, 1 H); 7.80 (s, 1 H); 8.12 (d, imidazo[1,2-b]pyridazin-6-yi)-amine 2H) ppm.
2.2 ~N (CDCI3, stored over MW:
/ molecular sieves): S= 1.81 355.87 GN H N (m, 4H); 1.89 (m, 2H); 2.56 /~ (m, 4H); 2.68 (m, 2H); 3.53 MS (ES+) - CI (m, 2H); 6.34 (s, br. 1 H); 6.39 [3-(3-Chloro-phenyl)-imidazo[1,2-b] (d, 1 H); 7.29 (m, 1 H); 7.38 [M+1 ]+:
pyridazin-6-yl]-(3-pyrrolidin-l-yl- (dd, 1 H); 7.64 (d, 1 H); 7.81 356 propyl)-amine (s, 1 H); 7.95 (m, 1 H); 8.30 (s, 1 H ppm.
2.3 5-N (CDCI3, stored over MW:
JI~~ IN / molecular sieves): 6 =1.88 371.87 rNI~\H N (m, 2H); 2.50 (m, 4H); 2.57 o~/ (m, 2H); 3.53 (m, 2H); 3.75 MS (ES+) CI (m, 4H); 6.08 (m, 1 H); 6.45 (d, 1 H); 7.29 (m, 1 H); 7.38 [M+1 ]+:
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-(3-morpholin-4-y1- (dd, 1 H); 7.67 (d, 1 H); 7.82 372 propyl)-amine (s, 1 H); 7.94 (dd, 1 H); 8.32 (d,.2H) ppm.
MW
:
2.4 fN
N ~ 385 .90 rN N N
OJ I / ~ MS (CI+) ~ CI

[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-methyl-(3-morpholin -4-yl-propyl)-amine 2.5 N (CDCI3, stored over N ~N molecular sieves): S= 1.45 y" N N (s, 9H); 2.04 (m, 1 H); 2.34 O H
(m, 1 H); 3.45-3.60 (m, 3H);
ci 3.77 (m, 1 H); 4.46 (m, 1 H);
4.65 (m, 1 H); 6.48 (d, 1 H);
3-[3-(3-Chloro-phenyl)-imidazo[1,2- 7.28 (m, 1 H); 7.37 (m, 1 H);
b]pyridazin-6-ylamino]-pyrrolidine- 7.70 (m, 1 H); 7.84 (m, 2H);
1-carboxylic acid tert-butyl ester 8.32 (m, 1H) ppm.
2.6 rl ~N MW:
N 394.48 N C JN H N' MS (ES+) ) ~
O

N-{3-[6-(3-Morpholin-4-yl-propylam i no)-imidazo[1,2-b]pyridazin-3-yl]-p henyl}-acetamide 2.7 \ , N MW:
I \ N CI 385.94 \iNN N' H MS (ES+) / ~ 386 ~
(S)-N*4*-[3-(3-Chloro-phenyl)-imida zo[1,2-b]pyridazin-6-yl]-N*1 *, N* 1 *-diethyl-pentane-1,4-diamine 2.8 \ / N MW:
1 1 385.94 NN ~N.N
H MS (ES+) CI

( R)-N *4*-[3-(3-C hloro-p henyl)-i mi da zo[1,2-b]pyridazin-6-yl]-N"1 *,N*1 *-diethyl-pentane-1,4-diamine 2.9 MW:
413.91 N N'N
~ MS (CI+) O 1f '/NJ \C I 414 4-[3-(3-Ch loro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-piperazine-l-carb oxylic acid tert-butyl ester 2.10 MW:
0,10 379.87 N=S N NN
H MS (CI+) / ~ 380 CI
2-[3-(3-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-ylamino]-ethanesulfon ic acid dimethylamide 2.11 N (CDCI3, stored over NN N_ / molecular sieves): 8= 1.09 (t, I H 6H); 1.85 (m, 2H); 2.43 (s, 3H); 2.53-2.69 (m, 6H); 3.49 CI (m, 2H); 6.40 (d, 1 H); 6.76 (m, 1 H); 7.39 (d, 1 H); 7.62 (d, 2H); 7.75 (s, 1 H); 7.93 (m, N'-[3-(3-Chloro-4-methyl-phenyl)-im 1 H); 8.01 (m, 1 H) ppm.
idazo[1,2-b]pyridazin-6-yl]-N,N-die thyl-propane-1,3-diamine 2.12 (300 MHz, d6-DMSO): 6=
3.03 - 3.08 (m, 2H); 3.63 -H 3.70 (m, 5H); 3.73 (s, 6H);
6.65 (d, 1 H); 7.15 - 7.26 (m, 3H); 7.54 (s, 2H); 7.64 - 7.71 q 0~ (m, 2H); 7.92 (s, 1 H); 8.46 -8.48 (m, 1 H) ppm.
(2-Pyridin-2-yl-ethyl )-[3-(3,4, 5-trimethoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-amine 2.13 / (400 MHz, d6-DMSO): 8 =
2.58 (s, 3H); 4.58 - 4.60 (m, H N 2H); 6.86 (d, 1 H); 7.39 - 7.40 N/ o (m, 2H); 7.47 - 7.50 (m, 1 H);
7.79 - 7.86 (m, 3H); 7.99 (s, 1 H); 8.09-8.12 (m, 1 H);
1-(3-{6-[(Pyridin-4-ylmethyl)-amino]- 8.49 - 8.50 (m, 2H); 8.67 -imidazo[1,2-b]pyridazin-3-yl}-phenyl)- 8.68 (m, 1 H) ppm.
ethanone 2.14 (400 MHz, d6-DMSO): 8=
0.93 (t, 3H); 1.58 - 1.67 (m, " 2H); (m, 2H, covered by solvent); 2.61 (s, 3H); 6.70 (d, 1 H); 7.09 - 7.11 (m, 1 H);
1-[3-(6-Propylamino-imidazo[1,2- 7.55 - 7.59 (m, 1 H); 7.73 (d, b]pyridazin-3-yI)-phenyl]-ethanone 1 H); 7.83 - 7.86 (m, 1 H);
7.97 (s, 1 H); 8.28 - 8.31 (m, 1H;8.96-8.97(m,1H) ppm.
2.15 0 (300 MHz, d6-DMSO): 8= MW:
1.40 - 1.52 (m, 2H); 1.98 - 354.41 " 2.03 (m, 2H); 3.34 - 3.42 (m, MS (ES+) 2H); 3.78 - 3.90 (m, 9H); 355 -o 6.43 (t, 1 H); 6.65 (d, 1 H);
[3-(3,5-Dimethoxy-phenyl)-imidazo[1,2- 7.02 - 7.05 (m, 1 H); 7.36 (d, b]pyridazin-6-yl]-(tetrahydro-pyran-4-yl)- 2H); 7.71 (d, 1 H); 7.90 (s, amine 1 H ppm.
2.16 0 (300 MHz, d6-DMSO): 8= MW:
~ 1.38 -1.52 (m, 2H); 1.98 - 310.36 " 2.03 (m, 2H); 3.38 - 3.46 (m, MS (ES+) 2H); 3.73 - 3.91 (m, 3H); 311 6.60 (d, 1 H); 6.79 - 6.82 (m, OH
4-[6-(Tetrahydro-pyran-4-ylamino) 2H); 6.95 - 6.97 (m, 1 H);
imidazo[1,2-b]pyridazin-3-yl]-phenol 7.66 - 7.69 (m, 2H); 7.91 -7.94 (m, 2H); 9.54 (s, 1 H) ppm.
2.17 0 r (400 MHz, d6-DMSO): 8=
N ~-N ~ 1.42-1.52(m,2H);1.96-" 2.01 (m, 2H); 3.34 - 3.40 (m, ~ F 2H); 3.78 - 3.90 (m, 3H);
F F 6.70 (d, 1 H); 7.13 - 7.15 (m, (Tetrahydro-pyran-4-yl)-[3-(3- 1 H); 7.60 - 7.67 (m, 2H);
trifluoromethyl-phenyl)-imidazo[1,2- 7.77 (d, 1 H); 8.02 (s, 1 H);
b]pyridazin-6-yl]-a m ine 8.24 - 8.27 (m, 1 H); 8.77 (br s, 1 H) ppm.
2=18 0 (300 MHz, d6-DMSO): 8 N -N 1.44 -1.57 (m, 2H); 2.10 -" 2.16 (m, 2H); 3.53 - 3.61 (m, 2H); 3.92 - 4.05 (m, 3H);
6.71 (d, 1 H); 7.23 - 7.25 (m, 1 H); 7.28 - 7.39 (m, 2H);
(3-Benzo[b]thiophen-2-yl-imidazo[1,2- 7.76 - 7.81 (m, 2H); 7.94 -b]pyridazin-6 yl) (tetrahydro pyran-4-yl) 7.97 (m, 1 H); 8.00 (s, 1 H);
8.05 (br s, 1 H) ppm.
amine 2.19 0 (400 MHz, d6-DMSO): 8 MW:
1.40 -1.50 (m, 2H); 1.96 - 325.37 " 2.00 (m, 2H); 3.39 - 3.45 (m, MS (ES+) rv 2H); 3.73 - 3.83 (m, 1 H); 326 3.85 - 3.89 (m, 5H); 6.66 (d, 0 1 H); 6.90 (d, 1 H); 7.06 - 7.07 [3-(6-Methoxy-pyridin-3-yl)-imidazo[1,2- (m, 1 H); 7.73 (d, 1 H); 7.81 (s, b]pyridazin-6-yl]-(tetrahydro-pyran-4-yl)- 1 H); 8.37 - 8.39 (dd, 1 H) amine 8.86 (N m, 1 H ppm.
2.20 0 (300 MHz, d6-DMSO): fi= MW:
1.41 - 1.53 (m, 2H); 2.02 - 325.37 " 2.06 (m, 2H); 3.41 - 3.49 (m, MS (ES+) 2H); 3.75 - 3.93 (m, 6H); 326 " 6.73 (d, 1 H); 7.20 - 7.22 (m, [3-(2-Methoxy-pyridin-4-yl)-imidazo[1,2- 1H); 7.61 - 7.63 (m, 1H);
b]pyridazin-6-yi]-(tetrahydro-pyran-4-yl)- 7.77 (d, 1 H); 7.82 (s, 1 H);
amine 8.12 - 8.15 m, 2H ppm.
2=21 0 / (400 MHz, d6-DMSO): S=
N-- I-N ~ 1.39 - 1.48 (m, 2H); 1.97 -" 0 1.99 (m, 2H); 3.23 (s, 3H);
/ s;o 3.48 - 3.53 (m, 2H); 3.82 -3.84 (m, 2H); 3.96 - 4.01 (m, [3-(3-Methanesulfonyl-phenyl)-imidazo[1,2- 1 H); 6.70 (d, 1 H); 7.10 - 7.11 b]pyridazin-6-yl]-(tetrahydro-pyran-4-yl)- (m, 1 H); 7.67 - 7.71 (m, 1 H);
amine 7.76(d, 1H); 7.81 -7.83(m, 1 H); 8.02 (s, 1 H); 8.29 - 8.31 (m, 1 H); 9.00 (m, 1 H) ppm.

Method B: [3-(1-methyl-1H-pyrazol-4-yl)imidazof9,2-b]pyridazin-6-ylJpyridin-3-ylmethylamine (Example 3.0) ~N
_ ,N N N N
CI N H
~I N ~I
/ ,N N,N
N

35 mg (0.15 mmol) of 6-chloro-3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazine were introduced into a mixture of 0.67 ml of tetrahydrofuran and 0.33 ml of dimethylformamide under argon. Then 0.5 ml of a 0.45 M solution of pyridin-3-ylmethylamine (0.225 mmol) in toluene was added. Addition of solutions of 1.72 mg of Pd2dba3 (18.8 pmol) and 3.5 mg of rac-BINAP (56.3 pmol) in 0.91 ml of THF
and io 31.7 mg of NaOtBu (0.3 mmol) in 0.91 ml of THF was followed by shaking of the reaction mixture at 80 C for 12 h.

The reaction mixture was then mixed with 1 ml of water and 3 ml of ethyl acetate.
The organic phase was separated off and freed of solvent. The crude product obtained in this way was purified by HPLC. 8.7 mg (19%) of the desired product were isolated.

HPLC-MS (analytical) of the purified product Detection: UV = 254 nm; column: Purospher STAR RP18e, 125x4mm, 5 pm (Merck KGaA, Darmstadt); eluent: A: H20/0.1 % TFA, B: CH3CN/0.1 % TFA, gradient: 5 to 95% B in 10 min; flow rate: 1 mI/min:

Retention time of the product = 3.85 min; MS of the product: m/z = 301 ([M+H]+) SRG/US/53343 - 45 - AL,I/TDS
The following are prepared in analogous manner:

Table 3:

HPLC-MS Mol. weight/
Example Structure and Name of the main isomer method Retention time MS (HPLC-No. No. No (see (HPLC, UV 254 MS
below) nm) [min] [M+1j+
KE1322- 3.1 A 4.59 301/
001-a N 302 ~ N
.N ~
N N
H
(3-Phenyi-imidazo[1,2-b]pyridazin-6 -yl)-pyridin-3-y1methyl-amine KE1322- 3.2 N A 4.85 319/
002-a \ N ~ 320 N'/--N--~~N N' ~--j H
(3-Imidazol-1-yl-propyl)-(3-phenyl-imidazo[1,2-b]pyridazin-6-yl)-amine KE1322- 3.3 'N A 7.37 318/
003-a / 319 N N' H
(4-Fluoro-benzyl)-(3-phenyl-imidazo [1,2-b]pyridazin-6-yl)-amine KE1322- 3.4 y N N A 8.36 306/
004-a 307 NN
H
01'~

Cyclohexylmethyl-(3-phenyl-imidazo [1,2-b]pyridazin-6-yl)-amine KE1322- 3.5 F Cz- ~A 7.49 336/
005-a 337 N ~
/ N N' F\ I H
(2,4-Difluoro-benzyl)-(3-phenyl-imidazo[1,2-b]pyridazin-6-yl)-amine KE1322- 3.6 / ~N A 5.42 332/
006-a \ ' N 333 N N
N,N~ H
H

[3-(5-Methyl-1 H-pyrazol-4-yl)-propyl]-(3-phenyl-imidazo[1,2-b]pyridazin-6-yi) -amine KE1322- 3.7 H 0 A 4.84 322/
007-a N-f 323 / ~o-N

N N.
H

1-[2-(3-Phenyl-imidazo[1,2-b]
pyridazin-6-ylamino)-ethyl]-imidazolidin-2-one KE1322- 3.8 A 4.71 323/
009-a 0~ 324 ~N

N
H.
(2-Morpholin-4-yl-ethyl)-(3-phenyl-imidazo[1,2-b]pyridazin-6-yl)-amine KE1322- 3.9 N A 5.51 351/
010-a 352 N N.N ~
H

N*1 *,N*1 *-Diethyl-N*4*-(3-phenyl-imidazo[1,2-b]pyridazin-6-yl)-pentane -1,4-diamine KE1322- 3.10 N A 5 323/
011-a 324 N
N N N ~
H
/

N,N-Diethyl-N'-(3-phenyl-imidazo [1,2-b]pyridazin-6-yl)-propane-1,3-diamine KE1322- 3.11 A 4.84 307/
012-a N 308 N N.
H
(3-Phenyl-imidazo[1,2-b]pyridazin-6-yl)-(2-pyrrolidin-l-yl-ethyl)-am ine KE1322- 3.12 A 5.09 336/
013-a N I 337 y N
,N
N N
H
CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-pyridin-3-ylmethyl-amine KE1322- 3.13 N A 5.36 353/
014-a 354 NNN N.N /
I H

CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-(3-imidazol-1-yl-propyl)-amine KE1322- 3.14 Z-N A 7.73 353/
015-a 354 \ N N'N

CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-y I] -(4-fluoro-benzyi )-amine KE1322- 3.15 A 8.87 341/
016-a 342 N N' i H o-cI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-cyclohexylmethyl-amine KE1322- 3.16 N A 7.93 371/
017-a F 'N 372 ~ N N
~ ~ H
F CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-(2,4-difl uoro-benzyl)-amine KE1322- 3.17 H 0 A 5.25 357/
019-a ~~ 358 zN

N N.
H
CI
1-{2-[3-(3-Chloro-phenyl)-imidazo [1,2-b]pyridazin-6-ylamino]-ethyl}-imidazolidin-2-one KE1322- 3.18 A 5.87 386/
022-a ~ 387 N N.

H
CI
N*4*-[343-Chloro-phenyl)-imidazo [1,2-b]pyridazin-6-yl]-N* 1 *,N*1 *-diethyl-pentane-1,4-diamine KE1322- 3.19 A 5.53 358/
023-a 359 N.N
~
Hi jci N'-[3-(3-Chloro-phenyl)-im idazo [1,2-b]pyridazin-6-yl]-N,N-diethyl-propane-1,3-diamine KE1322- 3.20 A 5.29 342/
024-a OtN Z-N 343 N N.
H
CI
[3-(3-Chloro-phenyl)-imidazo [1,2-b]pyridazin-6-yl]-(2-pyrrolidin-1-yl-ethyl)-amine KE1322- 3.21 N A 4.21 322/
026-a 323 N~N~N N
H N /
N,N
(3-Imidazol-l-yl-propyl)-[3-(1-methyl-1 H-pyrazol-4-yl)-imidazo [1,2-b]pyridazin-6-yl]-amine KE1322- 3.22 / N A 6.19 322/
027-a ~ 323 I )"~' N N H
F
N,N
/
(4-Fluoro-benzyt)-[3-(1-methyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]-pyridazin-6-yl]-amine KE1322- 3.23 N A 6.97 310/
028-a N 311 N N) H
N,N
Cyclohexylmethyl-[3-(1-methyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine KE1322- 3.24 N A 6.17 340/
029-a F / 341 / N N
F N
\ ~ H
N,N
(2,4-Difluoro-benzyl)-[3-(1-methyl-1 H-pyrazo[-4-yl)-imidazo[1,2-b]-pyridazin-6-yl]-amine _ KE1322- 3.25 N A 4.64 336/
030-a CN- // 337 r I N N, N.N,H
H N,N
[3-(1-Methyl-1 H-pyrazol-4-yl)-imidazo-[1,2-b]pyridazin-6-yl]-[3-(5-methyl-1 H-pyrazol-4-yl)-propyl]-amine KE1322- 3.26 H 0 A 4.09 326/
031-a N-f 327 N N"
H
N.N
1-{2-[3-(1-Methyl-1 H-pyrazol-4-yl)-im idazo[1,2-b]pyridazin-6-ylam ino]-ethyl}-imidazolidin-2-one KE1322- 3.27 A 3.91 327/
033-a 0 328 N
N
N N
H
N,N
[3-(1-Methyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-(2-morpholin-4-yl-ethyl)-amine KE1322- 3.28 \ / ~N A 4.6 355/
034-a 356 N N ~
N N' " ~ I
N-N
~
N"1 *,N*1 *-Diethyl-N*4*-[3-(1-methyl -1 H-pyrazol-4-yl)-imidazo[1,2-b]-pyridazin-6-yl]-pentane-1,4-diamine KE1322- 3.29 / YZIN A 4.29 327/
035-a 328 N, N /
"
N,N
N,N-Diethyl-N'-[3-(1-methyl-1 H-pyrazol-4-yi)-imidazo[1,2-b]pyridazin-6-yl]-propane-1,3-diamine KE1322-_ _ _ 3.30 A 4.11 311/
036-a N 312 YN
.N ~
N N
" 4 N,N
[3-(1-Methyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-12-nvrrolmdan-l-vi-athyll-am"ne KE1322- 3.31 A 4.55 307/
037-a N I 308 rN
N
N N
H
S
Pyridin-3-ylmethyl-(3-thiophen-3-yl-imidazo[1,2-b]pyridazin-6-yl)-amine .8 324/

KE1322- 3.32 C~~,N,N
038-a 325 N~N/~\N /
H
S
(3-Imidazol-1-yl-propyl)-(3-thiophen-3-yl-imidazo[1,2-b]pyridazin-6-yl)-amine KE1322- 3.33 N A 7.29 324/
039-a \ N ~ 325 I ~ N N

F ~ H
(4-Fluoro-benzyl)-(3-thiophen-3-yl-imidazo[1,2-b]pyridazin-6-yl)-amine KE1322- 3.34 IP, N A 8.26 312/
040-a 313 N 11-1 N~N

Hi Q
Cyclohexylmethyl-(3-thiophen-3-yi-imidazo[1,2-b]pyridazin-6-yl)-amine ___ KE1322- 3.35 N A 7.37 342/
041-a F 343 / I N J:LNN.N

F ~ H
(2,4-Difluoro-benzyl)-(3-thiophen-3-yl-imidazo[1,2-b]pyridazin-6-yl)-amine KE1322- 3.36 N A 5.31 338/
042-a \ N ~ 339 N N' N.N~ H
H S
[3-(5-Methyl-1 H-pyrazol-4-yl)-propyl]-(3-thiophen-3-yl-imidazo-[1,2-b]pyridazin-6-yl)-amine KE1322- 3.37 H 0 A 4.71 328/
043-a N~ 329 N / ~N

N N
H
S
1-[2-(3-Thiophen-3-yi-imidazo-[1,2-b]pyridazin-6-ylamino)-ethyl]-imidazolidin-2-one KE1322- 3.38 A 4.64 329/
045-a Dl~ 330 vN / N
N
N N
H
S
(2-Morpholin-4-yl-ethyl)-(3-thiophen-3-yl-imidazo[1,2-b]
pyridazin-6-yi)-amine KE1322- 3.39 \ / ~N A 5.42 358/
046-a 1 1 359 NN,N
N ~ ~
H

N*1 *,N*1 *-Diethyl-N''4*-(3-thiophen-3-yi-imidazo[1,2-b]pyridazin-6-yl)-pentane-1,4-diamine KE1322- 3.40 A 4.92 329/
047-a 330 NN NN /
H' J

N,N-Diethyl-N'-(3-thiophen-3-yl-imidazo[1,2-b]pyridazin-6-yl)-propane-1,3-diamine ___ KE1322- 3.41 A 4.74 313/
048-a OtN 314 ~N

N N.
H
S
(2-Pyrrolidin-l-yl-ethyl)-(3-thiophen-3-yl-imidazo[1,2-b]-pyridazin-6-yi)-amine HU6083- 3.42 CJJ"~ , B 7.99 359.43 /
002 ,N 360.06 /
N N

O
[3-(3-Methoxy-phenyl)-im idazo[1,2-b ]pyridazin-6-yl]-methyl-(2-pyrid i n-2-yl-ethyl)-amine HU6083- 3.43 B 9.42 413.40 /
003 , N I 413.99 N N N
/ ' ~ O
F F
F
Methyl-(2-pyridi n-2-yl-ethyl )-[3-(3 -trifl uoromethoxy-phenyl)-im idazo[1 ,2-b]pyridazin-6-yl]-amine HU6083- 3.44 C3~N B 10.03 398.30 /
004 397.94 N, CI
CI

[3-(3,4-Dichloro-phenyl)-imidazo[1, 2-b]pyridazin-6-yl]-methyl-(2-pyrid in-2-yl-ethyl)-am ine HU.6083- 3.45 CIIN B 9.16 381.84 006 ,381.95 N N N

CI
F

[3-(3-Chloro-4-fluoro-phenyl)-im ida zo[1, 2-b]pyridazi n-6-yi]-m ethyl-( 2-pyridin-2-yi-ethyl)-amine HU6083- 3.46 N B 9.32 379.46/
007 380.02 N N N

Methyl-(3-naphthalen-2-yl-imidazo[1 , 2-b] p y ri d az i n-6-y I)-( 2-py ri d i n-2 -y 1-ethyl)-amine HU6083- 3.47 , Y-N B 7.47 345.40 / 346.

N N N~
H
~

[3{3-Methoxy-phenyl)-imidazo[1,2-b ]pyridazi n-6-yl]-(2-pyridin-2-yi-et hyl)-amine HU6083- 3.48 N B 9.21 384.27 /
012 N 383.94 N H N

Qci CI
[3-(3,4-Dichloro-phenyl)-imidazo[1, 2-b]pyridazin-6-y1]-(2-pyridi n-2-yI
-ethyl )-am ine HU6083- 3.49 N B 7.30 340.39/
013 N~ N 341.06 N N"
H

N
3-[6-(2-Pyridin-2-yl-ethylamino)-im idazo[1,2-b]pyridazin-3-yi]-benzoni trile HU6083- 3.50 ~N B 8.84 363.85 /
017 N 363.97 N H N

CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazi n-6-yl]-[2-(6-m ethyl -py ri d i n-2-yl)-ethyl]-am ine SRG/US/53343 - 56 - ALJlTDS
.24 413.40 /

HU6083- 3.51 J:~N-019 413.99 N N N
H

O
F~F
F
[2-(6-Methyl-pyridi n-2-yl)-ethyl]-[
3-(3-trifluoromethoxy-phenyl)-imida zo[1,2-b]pyridazin-6-yi]-amine HU6083- 3.52 ,~N B 9.15 379.46/
023 N 380.02 N H N

[2-(6-Methyl-pyridin-2-yl)-ethyl]-( 3-naphthalen-2-yl-imidazo[1,2-b]pyr idazin-6-yl)-amine HU6083- 3.53 B 9.76 398.30 /
036 6-N",~ ~N 397.94 N \N N
H

Qci CI
[3-(3,4-Dichloro-phenyl)-imidazo[1, 2-b] pyridazi n-6-yl]-[2-(4-methyl -py ri d i n-2-yl )-ethyl] -a m i ne HU6083- 3.54. B 9.15 379.46/
039 6-NI~ ~ 380.02 N N N
H
[2-(4-Methyl-pyridin-2-yl)-ethyl]-( 3-naphthalen-2-yl-imidazo[1,2-b]pyr idazin-6-yl)-amine HU6083- 3.55 , J~~N- B 9.36 413.401 067 413.93 N N
N

O
F F
F
[2-(3-Methyl-pyrid i n-2-yl )-ethyl]-[
3-(3-trifluoromethoxy-phenyl)-imida zo[1,2-b]pyridazin-6-y1]-am ine HU6108- 3.56 5;1 , N B 8.13 359.43 /
058 N 359.17 N
N N

O

[3-(3-Methoxy-phenyl)-imidazo[1,2-b ] pyridazin-6-y1]-[2-(5-m ethyl-pyri d i n-2-yl )-ethyl]-a m i n e HU6108- 3.57 n-J N B 9.49 413.40 /
059 ,N /
H 413.15 N

O
F F
F
[2-(5-Methyl-pyrid i n-2-yl )-ethyl]-[
3-(3-trifluoromethoxy-phenyl)-imida zo[1,2-b]pyridazin-6-yl]-am ine HU6108- 3.58 N B 10.11 398.30/
060 N 397.94 N N N
H
Qci CI
[3-(3,4-Dichloro-phenyl)-imidazo[1, 2-b]pyridazi n-6-yl]-[2-(5-m ethyl-py ridin-2-yt)-eethyl]-amine HU6108- 3.59 B 9.24 381.84/
062 381.12 HU6108- 3.60 B 10.16 398.30 /
068 ~ 397.09 N H N, CI
CI

[3-(3,4-Dichloro-phenyl)-imidazo[1, 2-b] pyridazin-6-yl]-[2-(3-m ethyl -py ridin-2-yl)-ethyl]-amine HU6083- 3.61 N B 9.79 398.30 /
020 397.94 N N N"
H

Q-ci CI
[3-(3,4-Dichloro-phenyl )-im idazo[1, 2-b]pyridazin-6-yl]-[2-(6-methyl-py ri d i n-2-y I)-ethy I]-a m i n e :_. _. .._...
HU6083- 3.62 N / N B 7.62 350.81 /
025 C 351.01 N N N"
H

CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyri dazi n-6-y l]-( 2-pyrazi n-2-yl-eth yl)-amine HU6083- 3.63 N , ~N B 6.88 346.39 /
026 (-N)"'N N'N 347.03 H
~

[3-(3-Methoxy-phenyl)-imidazo[1,2-b ]pyridazin-6-yl]-(2-pyrazi n-2-yi-et hyl)-amine HU6083- 3.64 N N B 7.79 368.80 /
N, N 368.92 030 CN ~ H
J Y
Qci F

[3-(3-Chloro-4-fluoro-phenyl)-imida zo[1,2-b]pyridazin-6-yl]-(2-pyrazin -2-yl-ethyl)-am ine HU6083- 3.65 N B 8.01 366.43/
031 CN1J v 'N N"N 366.99 H
(3-Naphthalen-2-yl-imidazo[1,2-b]py ridazin-6-yl )-(2-pyrazin-2-yl-ethyl )-amine HU6083- 3.66 B 8.78 363.85 /

6NI~ N 363.97 N ~N N
H
CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-[2-(4-methyl-pyridi n-2-yl)-ethyl]-amine HU6083- 3.67 B 9.19 413.40/
035 ~N 413.99 N N N
6N"~
H

O
F F
F
[2-(4-Methyl -pyri d i n-2-y I )-ethyl]-[
3-(3-trifl uoromethoxy-phenyl)-im ida zo[1,2-b]pyridazin-6-yl]-amine HU6083- 3.68 B 8.92 381.84 /

038 6'N",~ N 381.95 N ~N N
H

Qci F
[3-(3-Chloro-4-fluoro-phenyl)-im ida zo[1,2-b]pyridazin-6-y1]-[2-(4-meth yI-pyridin-2-yl)-ethyl]-amine HU6083- 3.69 ~N B 7.90 338.80 /
049 ~N N3N 339.00 H

CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-(2-pyrazol-1-yl-eth yI)-amine _--HU6083- 3.70 N B 7.15 334.38/
050 N N / 335.02 N~ ~~N N
H

O
[3-(3-Methoxy-phenyl)-imidazo[1,2-b ]pyridazin-6-yl]-(2-pyrazol-1-yl-et hyl)-amine HU6083- 3.71 flYN N B 8.37 388.35 /
051 ,338.95 N~ N N
H

O
~-F
F
(2-Pyrazol-l-yl-ethyl)-[3-(3-triflu oromethoxy-phenyl)-imidazo[1,2-b]py ridazin-6-yl]-amine HU6083- 3.72 1 , N B 8.66 373.25 /
052 N , N ~- H - N, N 372.90 Qci CI
[3-(3,4-Dichloro-phenyl)-imidazo[1, 2-b]pyridazin-6-yi]-(2-pyrazol-l-yl -ethyl)-amine HU6083- 3.73 N B 6.86 329.37/
053 N, N~~N IN,N 330.02 H
~
/ ~N
3-[6-(2-Pyrazol-l-yl-ethylamino)-im idazo[1,2-b]pyridazin-3-yl]-benzoni trile HU6083- 3.74 B 8.04 356.79 /
054 ,N,~ N 356.98 H N

Qci F
[3-(3-Chloro-4-fluoro-phenyl)-imida zo[1,2-b]pyridazin-6-yl]-(2-pyrazol -1-yl-ethyl)-am ine HU6083- 3.75 Cz N B 8.22 354.42 /
055 ,N 335.05 N' N N
H
(3-Naphthalen-2-yi-imidazo[1,2-b]py ridazin-6-yl)-(2-pyrazol-l-yl-ethyl )-amine HU6108- 3.76 B 7.98 402.38/
402.14 075 (,N
N N N
H
~
O
F~F
F

[2-(1-Methyl-1 H-imidazol-4-yl)-ethy I]-[3-(3-trifl uorom ethoxy-phe nyl )-i m idazo[1,2-b]pyridazin-6-yl]-amine HU6108- 3.77 B 6.65 343.39/
~ N 343.15 ~~

N N N' N
H
~
~ ~N
3-{6-[2-(1-Methyl-1 H-imidazol-4-yl) -ethylamino]-imidazo[1,2-b]pyridazi n-3-yl }-be nz on i tri l e -----HU6108- 3.78 B 7.75 368.44 /
~ ~ N 368.18 079 N -N.N
N
H
[2-(1-Methyl-1 H-imidazol-4-yl)-ethy I]-(3-naphthalen-2-yl-imidazo[1,2-b ]pyridazin-6-yl)-amine SG26724- 3.79 N N B 6.89 339.79 /
51-A N\-N'~"N NN 339.10 H
~
- CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazi n-6-yl]-(2-[1,2,4]triazol-1 -yl-ethyl)-amine SG26724- 3.80 -N B 9.38 363.85/
53-A . ~ . N 363.13 N N N' CI
[3-(3-Chloro-phenyl)-im idazo[1,2-b]
pyridazin-6-yi]-methyl-(2-pyridi n-2 -yl-ethyl)-amine Description of the HPLC-MS analysis conditions for the examples listed in Table 3:
HPLC-MS method A: detection: UV = 254 nm; column: Purospher STAR RP1 8e, 125x4mm, 5 pm (Merck KGaA, Darmstadt); eluent: A: H20/0.1 % TFA, B:
CH3CN/0.1 % TFA, gradient: 5 to 95% B in 10 min; flow rate: 1 mI/min:
HPLC-MS method B: detection: UV = 254 nm; column XBridge C18, RP18e, 150x4.8 mm, 5pm (Waters); gradient 5-95% acetonitrile (0.1 % NH4OH) in water (0.1 % NH4OH/NH4HCO3) (10 min.); flow rate 1.0 mI/min.

Method C: (4 [6-(2-hydroxyethylamino)imidazo[1,2-b]pyridazin-3-ylJphenol io (Example 4.0) / N
HO""-\N N
N N H
H Br OH

85 mg (0.33 mmol) of 2-(3-bromoimidazo[1,2-b]pyridazin-6-ylamino)ethanol (Example 1.5), 69 mg (0.5 mmol) of 4-hydroxybenzene boronic acid and 76 mg (0.066 mmol) of tetrakis(triphenylphosphine)palladium(0) were mixed under argon with 3.4 ml of dimethyl glycol and 2 ml of an aqueous NaOH solution (a stock solution of 190 mg of NaOH in 10 ml of water). The mixture was stirred at 90 C
for 19 hours. After cooling, the mixture was diluted with sat. NaCI solution and extracted 2x with ethyl acetate. The combined organic phases were washed with sat. NaCI
solution, filtered through a silicone filter (from Whatman) and concentrated.
The resulting crude product was recrystallized from methanol. 40 mg of the desired to product are obtained.

'H-NMR (400 MHz; d6-DMSO): fi= 3.30 - 3.31 (m, 2H, covered by solvent); 3.61 -3.62 (m, 2H); 4.74 (m, 1 H); 6.66 (d, 1 H); 6.81 (d, 2H); 6.94 - 6.96 (m, 1 H); 7.64 -7.67 (m, 2H); 7.93 (d, 2H); 9.57 (br s, 1 H) ppm.

MS (ESI+): m/z = 271 ([M+H]+). [mol. weight = 270.29].

The following are prepared in an analogous manner:

Table 4 Mol. weight Example Structure and Name of the main isomers 'H-NMR ~
No. MS (ES+) 4.1 / N MW 284.32 HN N MS (ES+):
[M+1 ]+ 285 OH
OH
4-[6-((R)-2-Hydroxy-l-methyl-ethylam ino)-imidazo[1,2-b p ridazin-3 I]-phenol 4.2 MW 314.35 MS (ES+):
HN N
[M+1 ]+ 315 OH
OH
4-[6-((R)-2-Hydroxy-l-methyl-ethylam ino)-imidazo[1,2-b]pyridazin-3-yl]-2-methoxy-heno!
4.3 , N MW:
N 332.38 H N
MS (ES+) ~o 333 ~:
O
2-[3-(4-Methanesulfonyl-phenyl )-imidazo[1,2-b]pyridazin-6-ylamino]-ethanol 4.4 N MW:
HO~/~N 389.48 H
MS (ES+) s 0 o 390 HN

N-tert-Butyl-4-[6-(2-hydroxy-e/th1yl am ino)-imidazo 1,2-b]pyridazin-3 I]-benzenesulfonamide 4.5 MW:
HO~~ ~ ~N
H N 347.40 MS (ES+) O, NH 348 ~~

N-{4-[6-( 2-H yd roxy-eth yl a m i n o)-imidazo[1,2-b]pyridazin-3-yl]-phenyl}-methanesulfonamide 4.6 -,N MW:
HO~"N NN ~
389.48 H
O
~ g_N MS (ES+) N-tert-B utyl-3-[6-(2-h ydroxy-eth yl a m i no )-imidazo[1,2-b]pyridazin-3-yi]-benzenesulfonamide 4.7 Cl~,r ~N MW:
HONN N332.38 H
/ MS (ESI+) ~ Ir-o 2-[3-( 3-Methanesulfonyl-phenyl )-im idazo[1,2-b]pyridazin-6-ylamino]-ethanol 4.8 N MW:
HO \ N
N N 300.38 H
MS (ESI+) s 2-[3-(3-Methylsulfanyl-phenyl)-imidazo[1,2-b p ridazin-6- lamino -ethanol 4.9 / N (300 MHz; d6-DMSO): 6 MW:
N~ 2.93 - 2.98 (m, 2H); 3.49 -H N 3.56 (m, 2H); 6.39 - 6.40 (m, 354.42 1 H); 6.61 (d, 1 H); 7.15 - 7.19 (m, 1 H); 7.24 - 7.28 (m, 1 H);
7.34 - 7.36 (m, 1 H); 7.43 (d, N 1 H); 7.64 - 7.68 (m, 1 H);
H
[3-(1 H-Indol-5 YI)-imidazo[i,2-b]PY ridazin- 7.70 (d, 1 H); 7.74 (s, 1 H);
6-yI]-(2-pyridin-3-yl-ethyl)-amine 7.76 - 7.79 (m, 1 H); 8.39 -8.41 (m, 2H); 8.50 - 8.51 (m, 1 H); 11.16 (s, 1 H) ppm.

4.10 / ~ (400 MHz; d6-DMSO): S= MW:
2.94 - 2.98 (m, 2H); 3.55 -N N N,N 3.60 (m, 2H); 6.65 (d, 1 H); 321.41 H 7.19-7.22 (m, 1H); 7.28-7.31 (m, 1 H); 7.63 - 7.65 (m, s 1 H); 7.67 - 7.68 (m, 1 H);
(2-Pyridin-3-yl-ethyl)-(3-thiophen-3-yl- 7.70 - 7.74 (m, 2H); 7.85 (s, imidazo[1,2-b]pyridazin-6-yl)-amine 1 H); 8.32 - 8.33 (m, 1 H);
8.39 - 8.40 (m, 1 H); 8.48 -8.49 (m, 1 H) ppm.
4.11 N (400 MHz; d6-DMSO): fi= MW:
~ 2.92 - 2.96 (m, 2H); 3.50 -N N N,N / 3.55 (m, 2H); 6.69 (d, 1 H); 333.37 H 7.09 - 7.13 (m, 1 H); 7.27 -7.30 (m, 2H); 7.42 - 7.48 (m, F 1 H); 7.65 - 7.68 (m, 1 H);
[3-(3-Fluoro-phenyl)-imidazo[1,2- 7.75 (d, 1 H); 7.96 (s, 1 H);
b]pyridazin-6-yl]-(2-pyridin-3-yl-ethyl)- 7=97 - 7.99 (m, 1 H); 8.09 -8.13 (m, 1 H); 8.38 - 8.40 (m, amine 1 H); 8.47 - 8.48 (m, 1 H) ppm.

The following are prepared in an analogous manner:
Table 5:

Retention time Mol. weight/
Char Example (HPLC, UV MS(HPLC-No. No. Structure and Name of the main isomer 254 nm) [min]. MS) ._--229_0 5.0 (\ ~ ~

- N N N~

365.44 (3-Naphthalen-2-yl-imidazo[1,2-b]pyridazin-6-yl)-(2-p ridin-2- I-eth I -amine 229 0 5.1 (N~ 1150 N N N-349.82 CI

[3-(4-Ch loro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-(2-pyridin-2-yl-eth yl)-amine 2290 5.2 -~N

343.43 [3-(3,4-Dimethyl-phenyl)-imidazo[1, 2-b]pyridazin-6-yl]-(2-pyridin-2-yI
-ethyl)-amine 229_0 5.3 1150 ~ _N

Fx F 399.37 F

(2-Pyridin-2-yi-ethyl)-[3-(3-trifluoromethoxy-phenyl)-imidazo[1,2-b] ridazin-6 I]-amine 2290 5.4 164 N ~ H N~

367.81 C
F
[3-(3-Chloro-4-fluoro-phenyl)-imidazo[1,2-b]pyridazin-6- I- 2-p ridin-3- I-ethyl -amine 2290 5.5 1150 "IN

349.82 CI

[3-(3-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(2-pyridin-2- I-eth I -amine 2290 5.6 349.82 i [3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyrid azi n-6-yI]-(2-pyrid i n-3-yl -eth yl)-amine 229_0 5.7 383.38 F
F
(2-Pyridin-2-yl-ethyl )-[3-(3-trifluoromethyl-phenyl)-imidazo 1,2-b ridazin-6- I -amine 2290 5.8 333.37 F

[3-(3-Fluoro-phenyl )-im idazo[1,2-b]pyridazin-6-yl]-(2-pyridin-2-yl-eth I -amine 2290 5.9 /
1150 \ ~

333.37 [3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(2-ridin-2- I-eth -amine ---! 2290 5.10 335.43 [3-(4-Methyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-I] 2-p ridin-2- I-eth I-amine SRG/US/53343 - 70 - ALJ/T"DS
2290 5.11 HO,,,t~ /

360.82 c F
4-[3-(3-Chloro-4-fluoro-phenyl)-imidazo[1,2-b p ridazin-6- lamino]-cyclohexanol 2290 5.12 /
1154 ~ ~

0 357.42 1 -{3-[6-(2-Pyridin-2-yi-ethylamino)-im idazo[1, 2-b ridazin-3 I] hen -ethanone 229_0 5.13 , N
115_6 z~, N
N N N
488 H 10,=S/ 408.48 \
H
N-{3-[6-(2-Pyrid in-2-yl -ethyl am ino)-im idazo[1,2-b]pyridazin-3-yl]-phenyl}-methanesulfonamide 2290 5.14 ol N
150 i 340.39 N
4-[6-(2-Pyrid in-2-yi-ethylam ino)-im idazo[1, 2-b idazin-3- I -benzonitrile 2290 5.15 1154 \ I \ ~

329.41 (2-Pyrid in-2-yl-ethyl)-(3-p-tolyl-im idazo[1, 2-b ridazin-6 I -amine 2290 5.16 H
315.38 (3-Phenyl-imidazo[1,2-b]pyridazin-6-yl)-(2-pyridin-2-I-eth I -amine 2290 5.17 365.44 k\

(3-Naphthalen-1-yl-imidazo[1,2-b]pyridazin-6-yl)-(2-ridin-2- I-ethyl -amine 2290 5.18 355.40 i (3-Benzofuran-2-yl-imidazo[1,2-b]pyridazin-6-yl)-(2-yridin-2 I-ethyl -amine 2290 5.19 367.81 F
[3-(3-Chloro-4-fluoro-phenyl)-imidazo[1,2-b]pyridazin-6- I- 2- ridin-2- I-eth I-amine 2290 5.20 371.47 i (3-Benzo[b]thiophen-2-yl-imidazo[1,2-b]pyridazin-6-I- 2- ridin-2- I-eth I-amine 2290 5.21 115_0 \ \ -N

359.39 Qiii-_ (3-Benzo[1,3]dioxol-5-yl-imidazo[1,2-b]pyridazin-6-yl)-2- ridin-2 I-eth I -amine __ 2290 5.22 o c 1150 l'-~Irl ,280 H

345.40 [3-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-2- ridin-2- I-eth I -amine ;
" 2290 5.23 ~
2310 N\ N

405.46 o o \ %
(2-Pyridin-3-yl-ethyl)-[3-(3, 4,5-trimethoxy-phenyl )-imidazo 1,2-b]p ridazin-6- I -amine ,______--2290 5.24 ~2310 Nv ~N

333.37 F
[3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(2-ridin-3 I-eth I -amine _____ 2290 5.25 / / N
2310 N\ I \ N
068 H N~
359.39 o o 3-Benzo 1,3]dioxol-5- I-imidazo[1,2-b pyridazin-6- I-(2-pyrid i n-3-yl -eth yl )-a m i ne 2290 5.26 / / ~
2310 N \ I \ ,N

345.40 O
~
[3-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-2-p ridin-3-yl-eth I)-amine 229_0 5.27 / ( / ~Ni ,345 N \ N N
H
335.43 [3-(4-Methyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-I 2-p ridin-3-yl-ethyl)-amine EZ 5.28 N
H
O
355.40 ~

(3-Benzofuran-2-yl-i m idazo[1, 2-b] pyridazi n-6-yl )-(2-ridin-3- I-eth I -amine 2290 5.29 / N
2310 N\ I \ ~rv 365.44 (3-Naphthalen-2-yl-imidazo[1,2-b]pyridazin-6-yl)-(2-p ridin-3-yi-eth I -amine 2290 5.30 / 01?

NS 371.47 i (3-Benzo[b]thiophen-2-yl-imidazo[1,2-b]pyridazin-6-I - 2-p idin-3-yl-eth I -amine 2290 5.31 / Xy 2310 N\ ~
61 H N, / 315.38 ~

(3-Phenyl-imidazo[1,2-b]pyridazin-6-yl)-(2-pyridin-3--eth I -amine 2290 5.32 i 2310 N~ I ~ N
160 H N~
/ \ 349.82 CI
[3-(4-Chloro-phenyl )-im idazo[1,2-b]pyridazin-6-yl]-(2-p ridin-3- I-eth I -amine 2290 5.33 / / N
231_0 N~ I ~ N ~

340.39 N
4-[6-(2-Pyridin-3-yl-ethylamino)-imidazo[1,2-b p idazin-3- I]-benzonitrile 2290 5.34 N

N N~

F 383.38 F F
(2-Pyridin-3-yl-ethyl)-[3-(3-trifluoromethyl-phenyl)-imidazo[1,2-b]p ridazin-6- I]-amine 2290 5.35 N

2317 N\ \ N

N 319.37 N~

[3-(1-Methyl-1 H-pyrazol-3-yl)-imidazo[1,2-b]pyridazin-6- I- 2- ridin-3- I-eth I-amine , 229_0 5.36 2314 147 N N NN 321.41/320 H 0.67 (negative ~ S
mode) (2-Pyridin-3-yl-ethyl)-(3-thiophen-2-yl-imidazo[1,2-b]pyridazin-6- I -amine 229-0 5.37 N
231 6 N~ N
N N

H 408.48 N
O~I I
O
N-{3-[6-(2-Pyrid in-3-yl-eth yl am ino)-im idazo[1, 2-b]pyridazin-3- I]-phen I -methanesulfonamide 229_0 5.38 ~ i 339 N N~N
H
308.32 F
[3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-furan-2- Imeth -amine 229_0 5.39 / N

061 cur"~ N N
H 290.33 Furan-2-ylmethyl-(3-phenyl-imidazo[1,2-b]pyridazin-6-yl -amine 2290 5.40 280 ~ N N~N
\ H
O / \
320.35 ~
Furan-2-ylmethyl-[3-(4-methoxy-phenyl )-im idazo[1,2-b]p idazin-6 I -amine 229_0 5.41 / N

329.36 N
H
Furan-2-ylmethyl-[3-(1 H-indol-5-yl)-imidazo[1,2-b]pyridazin-6- I]-amine 229_0 5.42 YN, 135 Cyo H N333.39 ~ N

[3-(3-Dim ethyl amino-phenyl)-i m idazo[1, 2-b]pyridazin-6 I -furan-2- Imethyl-amine 229_0 5.43 i { 1444 ~N
i140 - H N
\\ o ~ \ 320.35 Furan-2-ylmethyl-[3-(3-methoxy-phenyl)-imidazo[1,2-b p idazin-6 I -amine 2290 5.44 YN, 081 Cor H N 347.38 H

N

N 3-{6-[(Furan-2- meth I -amino]-imidazo[1,2-b]pyridazin-3-yl}-phenyl)-acetam ide 2290 5.45 CZ~, 1440 N

291 Co H N320.35 OH
( 3-{6-[( Furan-2-ylmethyl )-am no]-im id azo[ 1, 2-b pyridazin-3- I -phen I -methanol 229_0 5.46 N
080 N N~
\ O H

306.32 OH
4-{6-[(Furan-2-ylmethyl)-amino]-imidazo[1,2-b]pyridazin-3- I -phenol 2290 5.47 Cyo N N/N

/ \ 306.32 ~ OH

3-{6-[(Furan-2-ylmethyl)-amino]-imidazo[1,2-b]pyridazin-3- I -phenol ,_.
2290 5.48 :w-N
1440 'IN
;347 H N
p 333.35 3-{6-[(Furan-2-ylmethyl)-amino]-imidazo[1,2-b]pyridazin-3 I}-benzamide __ 229_0 5.49 ~
144_6 N
488 O'H /
~ H 383.43 \

N-( 3-{6-[( F u ran-2-yl m ethyl )-a m i n o]-i m id azo[ 1, 2-b]pyridazin-3-yl}-phen I -methanesulfonamide 2290 5.50 / ~

314 Cyo ~N N
H 336.35 OH
4-{6-[(Furan-2-ylmethyl)-amino]-imidazo[1,2-b]p ridazin-3-yl}-2-methox -phenol _..
229_0 5.51 N
144_4 H N
145 COT", p 332.36 1-(3-{6-[(Furan-2-ylmethyl)-amino]-imidazo[1,2-b]p ridazin-3- I -phenyl)-ethanone 229_0 5.52 / i 144_0 H
/
~N 321.34 ~
Furan-2-ylmethyl-[3-(6-methoxy-pyridin-3-yi)-imidazo[1,2-b pyridazin-6 I]-amine _.
2290 5.53 - / i ~1440 H / 291.31 N
D
Furan-2-ylmethyl-(3-pyridin-3-yi-imidazo[1,2-b]pyridazin-6-yl -amine 229_0 5.54 144_0 i 196 N N~N
H 321.34 O / \
N
O

Furan-2-ylmethyl-[3-(5-methoxy-pyrid in-3-yl )-imidazo 1,2-b]pyridazin-6-yl]-amine 2290 5.55 1440 ~i 069 cur"~~ N N
,N 291.31 N
Furan-2-ylmethyl-(3-pyridin-4-yl-imidazo[1,2-b] ridazin-6 I -amine 2290 5.56 / i H
366.44 -~o /O
[3-(3,4-Dimethoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-thiophen-2-ylmethyl-amine N
229_0 5.57 CII~N, 60 Csr~ N
087 H 396.47 --o /
Thiophen-2-ylmethyl-[3-(3,4,5-trimethoxy-phenyl)-imidazo 1,2-b ridazin-6- I]-amine 229_0 5.58 / ~
; 1464 ~ ~N

S ~ \ O 348.43 1-(3-{6-[(Thiophen-2-ylmethyl)-amino]-imidazo[1,2-b]p ridazin-3-yl}-phenyl)-ethanone 2290 5.59 ~

1460 Os N NN 284 H 322.39 OH

3-{6-[(Thiophen-2-ylmethyl)-amino]-imidazo[1,2-b ridazin-3 I henol 2290 5.60 ~

N N

H
S \ 337.41 N~ O

[3-(5-Methoxy-pyridin-3-yl )-im idazo[1, 2-b]pyridazin-6-I]-thiophen-2 Imeth I-amine 229_0 5.61 X-,NI,N i 285 \ N
\ H
S
~ 336.42 ~

HO
(4-{6-[(Thiophen-2-ylmethyl)-amino]-imidazo[1,2-b]p ridazin-3-yl henyl)-methanol 2290 5.62 , ~
1460 N N~N
i192 H
o 393.47 H
_OH
N-(2-Hydroxy-ethyl )-3-{6-[(thiophen-2-ylm ethyl)-amino]-imidazo[1,2-b]p ridazin-3-yl}-benzamide 229_0 5.63 345 cur N NN
H
S 326.45 [3-(4-Meth I-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-yi]-thiophen-2-ylmethyl-amine 2290 5.64 H 1.02 312.42/314 U
(3-Thiophen-2-yl-imidazo[1,2-b]pyridazin-6-yl)-thiophen-2- Imethyl-amine 2290 5.65 1460 /i N N
074 cur , N H 312.42 S
(3-Thiophen-3-yl-imidazo[1,2-b]pyridazin-6-yl)-thiophen-2 Imeth 1-amine 229_0 5.66 / i 146_0 N H
311 cur,~ N N

~N 337.41 ~
/
/O
[3-(6-Methoxy-pyrid in-3-yl )-i m idazo[1, 2-b]pyrid azin-6-I -thio hen-2 Imeth I-amine , 2290 5.67 :10 N N
H
\ S /
345.43 N
H
[3-(1 H-Indol-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-thiophen-2- Imeth I-amine 2290 5.68 YN, 349.46 N

[3-(3-Dim ethylam ino-phenyl)-im idazo[1, 2-b]pyridazin-6 I]-thiophen-2- Imeth I-amine 229_0 5.69 N

339 N N~N

324.38 F
[3-(4-Fluoro-phenyl)-im idazo[1,2-b]pyridazin-6-yl]-thio hen-2- Imeth I-amine 229_0 5.70 ~

H 310.38 N--NN"
[3-(1-Methyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6 I]-thio hen-2 Imeth I-amine 2290 5.71 CZ~,-~ 1 460 H 307.38 N

(3-Pyridi n-3-yl-i m idazo[1, 2-b]pyridazin-6-yl )-th iophen-2-ylmeth I-amine 229_0 5.72 / ~
146_0 ~
N /
081 O'H
~ H 363.44 N

~
O
N-(3-(6-[(Thiophen-2-ylmethyl)-amino]-imidazo[1,2-b]p ridazin-3 I hen I)-acetamide 229_0 5.73 / ~
146_4 N N~N
140 Or H
1.01 336.42/338 \

[3-( 3-Methoxy-phenyl )-im idazo[1, 2-b] pyrid azin-6-yl]-thiophen-2- Imeth I-amine 229_0 5.74 146_0 ~N

S / \
322.39 OH
4-{6-[(Thiophen-2-ylmethyl)-amino]-imidazo[1,2-b] ridazin-3- I phenol 229_0 5.75 1460 - \ ~N N

~ S H /J 307.38 N
(3-Pyridin-4-yl-imidazo[1,2-b]pyridazin-6-yl)-thiophen-2-ylmeth I-amine 229_0 5.76 / i Os N N~N H
352.42 ~
OH
2-Methoxy-4-{6-[(th iophe n-2-ylmethyl )-am ino]-imidazo[1,2-b]pyridazin-3-yl -phenol 229_0 5.77 XZ i 1460 ~N
347 Cys H N
0 349.42 3-{6-[(Thiophen-2-ylmethyl)-amino]-im idazo[1,2-b]pyridazin-3 I -benzamide 229_0 5.78 N
146_6 ~N
N N
488 O'H H 399.50 N
O 7~

N-(3-{6-[(Thiophen-2-ylmethyl)-am ino]-im idazo[1,2-b p ridazin-3- I} hen I-methanesulfonamide 2290 5.79 / i ~ 350.40 OH

4-{6-[(Thiophen-2-ylmethyl)-amino]-im idazo[1, 2-b]pyridazin-3- I -benzoic acid 2290 5.80 ~
N NN

N 0.62 331.38/332 ~ \

[3-(3-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-ridin-4 Imeth I-amine 2290 5.81 J~ll ~
237_0 ,,,N
H N

385.35 F
F ~
Pyridin-4-ylmethyl-[3-(3-trifluoromethoxy-phenyl)-imidazo[1,2-b]pyridazin-6 I -amine 2290 5.82 N

279 I ~ H N
N / 335.80 Ci [3-(3-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-p ridin-4-ylmeth I-amine 2290 5.83 Xz ~
2370 ,N

N F 369.35 F F
Pyridin-4-ylmethyl-[3-(3-trifluoromethyl-phenyl)-imidazo 1,2-b ridazin-6 I -amine 2290 5.84 N

:10 \ H N
N /
353.79 CI

F
[3-(3-Chloro-4-fluoro-phenyl)-imidazo[1,2-b]pyridazin-6- I]-p ridin-4- Imeth I-amine 229_0 5.85 XZ'~ i ~N
073 \ H N
N
/ / ~ 341.37 (3-Benzofuran-2-yl-imidazo[1,2-b]pyridazin-6-yi)-p ridin-4-ylmeth I-amine 229_0 5.86 N

167 \ H N
N /
329.41 [3-(3,4-Di m ethyl-phenyl )-im idazo[1, 2-b]pyridazi n-6-yl]-yridin-4-ylmethyl-amine 229_0 5.87 N
/
237_4 ,139 N N~N
H
N / / \ 0.66 315.38/316 Pyridin-4 Imethyl-(3-p-tol I-imidazo[1,2-b]p ridazin-6-yI )-am ine 229_0 5.88 X i 147 I ,N /
I H N
N / S 0.61 307.38/308 i Pyrid i n-4-yl m ethyl-(3-th iophen-2-yl-im idazo[1, 2-b pyridazin-6- I)-amine 229_0 5.89 N

H
N 301.35 (3-Phenyl-im idazo[1,2-b]pyridazin-6-yl)-pyridin-4-Imeth I-amine 229_0 5.90 N
2370 \ N N/N ~

N /
/ \ 345.36 ~ 0 0~
~
(3-Benzo[1,3]dioxol-5-yi-imidazo[1,2-b]pyridazin-6-yl)-ridin-4-ylmeth I-amine _ 2290 5.91 :w-N

N 351.41 (3-Naphthalen-2-yl-imidazo[1,2-b]pyridazin-6-yl)-p ridin-4-ylmeth I-amine 229_0 5.92 N

~ \ ~N

N / S 357.44 (3-Benzo[b]thiophen-2-yl-imidazo[1,2-b]pyridazin-6-yl )-pyrid in-4-ylmethyl-am ine 2290 5.93 -2370 / i 160 rH N N N N 335.80 CI
[3-(4-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-p ridin-4- Imeth -amine 229_0 5.94 N

277 ~ H N
N / 380.25 Br [3-(3-Bromo-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-ridin-4- Imeth I-amine 2290 5.95 N

H 394.46 N
O.;~i--N-(3-{6-[(Pyridin-4-ylmethyl)-amino]-imidazo[1,2-b]p ridazin-3- I -phenyl -methanesulfonamide 2290 5.96 _ / N

:038 ~ N N~N /
F
H
N / 319.34 [3-(2-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yi]-p ridin-4- Imeth -amine ___ 2294 5.97 N
0070 \ N

391.43 --o Pyridi n-2-yl m ethyl-[3-(3,4,5-trim ethoxy-phenyl )-imidazo[1,2-b]pyridazin-6- I]-amine 229_4 5.98 X~~ i 339 ~ H N N~

/ 319.34 F
[3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-p ridin-2- Imethyl-amine 2294 5.99 0070 \
073 rlH N J NO

341.37 (3-Benzofuran-2-yi-im idazo[1,2-b]pyridazin-6-yl )-p ridin-2- Imeth I-amine 2294 5.100 YN, H
351.41 (3-Naphthalen-2-yl-imidazo[1,2-b]pyridazin-6-yl)-p ridin-2- Imeth I-amine 2294 5.101 007_0 H N
N 332.37 O

[3-(6-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-6-yl]-pyridin-2- Imeth I-amine 229_4 5.102 / i 357.44 (3-Benzo[b]thiophen-2-yl-imidazo[1,2-b]pyridazin-6-I -pyridin-2- Imeth -amine 2294 5.103 / ~
0070 N \ ,N
N N
168 H F 385.35 /~- F

Pyridin-2-ylmethyi-[3-(3-trifluoromethoxy-phenyl)-imidazo 1,2-b ridazin-6 I]-amine _ 2294 5.104 X~-~ N

N
H /
307.38 S

Pyridin-2-ylmethyl-(3-thiophen-3-yl-imidazo[1,2-b pyridazin-6- I -amine 2294 5.105 N
:i0 H N
F 369.35 F F
Pyridi n-2-ylmethyl-[3-(3-trifluoromethyl-phenyl )-imidazo 1,2-b ridazin-6-yl]-amine 229_4 5.106 N

344.42 N

[3-( 3-Dimethylam ino-phenyl)-im idazo[ 1, 2-b] pyridazin-6-yl] ridin-2- meth 1-amine 2294 5.107 164 H N~

353.79 CI

F
[3-(3-Chloro-4-fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-pyridin-2- Imeth I-amine 229_4 5.108 N
007_0 N Z!., N
280 ~ H N
/
331.38 [3-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-p ridin-2 Imeth I-amine 2294 5.109 N

361.40 [3-(3,4-Dim ethoxy-phenyl )-i m idazo[1, 2-b]pyridazi n-6-I - ridin-2- Imeth I-amine 2290 5.110 N
2230 cl 314 H N 380.83/380 0.93 (negative o ~ mode) OH
4-[6-( 3-Chloro-benzylam ino)-im idazo[1, 2-b]pyridazin-3- I]-2-methox -phenol SRG/US/53343 - 91 - AL.I/TDS
2290 5.111 / N
2230 C~
\ N
~ ~

364.83 HO
{4-[6-(3-Chloro-benzylamino)-imidazo[1,2-b]pyridazin-3- I - hen I -methanol 229_0 5.112 N
2230 ci N
H

365.82 N_ 0 ( 3-Ch loro-be nzyl )-[3-( 5-m ethoxy-pyrid i n-3-yl )-imidazo[1,2-b]p ridazin-6- I -amine 2290 5.113 / ~
2230 ci ~ ~N

350.81 OH

3-[6-(3-Chloro-benzylamino)-imidazo[1,2-b]pyridazin-3-yI]-phenol 229 0 5.114 (~Nl 2230 ~N
;071 H
/ \ 335.80 N

(3-Chloro-benzyl)-(3-pyridin-3-yl-imidazo[1,2-b]p ridazin-6 I -amine 229_0 5.115 2230 ci NNI ~N 349.82/349 H N
005 0.92 (negative NH2 mode) [3-(3-Amino-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(3-chloro-benz I -amine 2290 5.116 ~
2230 ~I N

N 365.82 O

( 3-Chloro-benzyl )-[3-(6-methoxy-pyrid i n-3-yl )-imidazo 1,2-b yridazin-6 I]-amine 2290 5.117 XZ~~ YN
2230 Cl 080 H N 350.81 /350 0.89 (negative mode) OH
4-[6-(3-Chloro-benzylamino)-imidazo[1,2-b]pyridazin-3-yl]-phenol 2290 5.118 XZz~, YN

335.80 N
(3-Chloro-benzyl)-(3-pyridin-4-yl-imidazo[1,2-b]p ridazin-6 I -amine 229_0 5.119 2230 ci '347 H N~
O 377.83 3-[6-(3-Chloro-benzylamino)-imidazo[1,2-b]pyridazin-3- I]-benzamide 2290 5.120 ~
2230 ci 378.82 OH
O
4-[6-(3-Chloro-benzylamino)-imidazo[1,2-b]pyridazin-3- I -benzoic acid SRG/US/53343 - 93 - ALJII"DS
229_0 5.121 CZ~, y X\ 0.77 319.34/320 ~
N
(4-Fluoro-benzyl )-( 3-pyridin-4-yl-i m idazo[1, 2-b ridazin-6- I -amine 2290 5.122 N
224_0 \ N

F 0.86 334.35/335 OH
4-[6-(4-Fluoro-benzylamino)-im idazo[1, 2-b]pyridazin-3 I]-phenol 2290 5.123 ~

\

F / 0.92 349.37/350 N' O

(4-Fluoro-benzyl)-[3-(5-methoxy-pyrid in-3-yl)-imidazo[1,2-b]pyridazin-6- I]-amine 229_0 5.124 / ~
2240 ~

F 334.35 OH

3-[6-(4-Fluoro-benzylamino)-imidazo[1,2-b]pyridazin-3- I - henol 2290 5.125 NI

1.14 338.41/340 F

(4-Fluoro-benzyl )-[3-(4-m ethyl-th iophen-2-yl )-imidazo 1,2-b]pyridazin-6- I -amine 2290 5.126 1.02 362.36/363 o OJ
(3-Benzo[1,3]dioxol-5-yl-imidazo[1,2-b]pyridazin-6-yl)-4-fluoro-benz I -amine 2290 5.127 ~
! 2240 ~N

0.96 357.39/358 N
H
(4-Fluoro-benzyl)-[3-(1 H-indol-5-yl)-imidazo[1,2-b ridazin-6- I]-amine ~.
229_0 5.128 / N

'280 H N

F 1.04 348.38/349 o (4-Fluoro-benzyl)-[3-(4-methoxy-phenyl)-imidazo[1,2-b]p ridazin-6 I]-amine 229_0 5.129 / i F 1.00 349.37/350 N

/
(4-Fl uoro-benzyl)-[3-(6-m ethoxy-pyrid i n-3-yl )-imidazo[1,2-b]pyridazin-6-yl]-amine _.._._..
229_0 5.130 / ~
224_0 N /

~H N
0.89 375.41/376 F ~ H

N 3-[6-(4-Fluoro-benzylamino)-imidazo[1,2-b]p ridazin-3- I]-phenyl}-acetamide 229_0 5.131 0.83 319.34/320 N
/~
(4-Fluoro-benzyl)-(3-pyridin-3-yl-imidazo[1,2-b]pyridazin-6- I)-amine 229_0 5.132 / YN

24 0 ,285 H N

0.85 348.38/349 HO
{4-[6-(4-Fluoro-benzylam ino)-im idazo[1, 2-b]pyridazin-3- I hen I -methanol 2290 5.133 , N
2240 , ~N
~ H N
347 ~
F ~ O 361.38 NHz 3-[6-(4-Fluoro-benzylamino)-imidazo[1,2-b]pyridazin-3 I -benzamide __.
2290 5.134 N
224_0 \ N ~
y F ~ \
362.36 ~

O
HO
4-[6-(4-Fluoro-benzylamino)-imidazo[1,2-b]pyridazin-3-yl]-benzoic acid 2290 5.135 YN
2444 \ 139 H N
1.06 344.42/345 (4-Methox -benzyl)-(3-p-tolyl-imidazo[1,2-b]pyridazin-6-yl)-amine 2290 5.136 XII-I ~
2440 ,N
160 H N 364.83/364 1.13 (negative mode) ci [3-(4-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(4-methoxy-benzyl)-amine 2290 5.137 N

345 H N 350.44/349 o S 1.09 (negative mode) (4-Methoxy-benzyl)-[3-(4-methyl-thiophen-2-yl)-imidazo[1,2-b]p ridazin-6- I]-amine 2290 5.138 / ~
2440 ~ ~N
H N

0.93 369.43/370 N
H
[3-(1 H-Indol-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-(4-methox -benz I -amine N
2290 5.139 J~IIN

;280 H N

360.42 (4-Methoxy-benzyl)-[3-(4-methoxy-phenyl )-im idazo[1, 2-b]pyridazin-6-yl]-am ine 2290 5.140 N

339 ~ H N

o / 1.04 348.38/349 F
[3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(4-methoxy-benzyl)-am ine 2290 5.141 N
244_0 N

0.85 346.39/347 OH
4-[6-(4-Methoxy-benzylam ino)-im idazo[1,2-b p ridazin-3 I]-phenol 229_0 5.142 / N
244_7 N
467 H 0.72 320.35/321 \o / ~
_,NH
N
(4-Methoxy-benzyl )-[3-(1 H-pyrazol-4-yl )-im id azo[1, 2-b]p ridazin-6- I -amine 229 0 5.143 N
2447 ~N
Jj\ N N
468 ~ H 0.82 334.38/335 o 1\ N
N
(4-Methoxy-benzyl )-[3-(1-m ethyl-1 H-pyrazol-4-yl )-imidazo[1,2-b]p ridazin-6-yl]-amine 2290 5.144 N

\ H N
140 ~

374.40 O
HO
4-[6-(4-Methoxy-benzylamino)-imidazo[1,2-b] idazin-3- I -benzoic acid 229_6 5.145 3070 o 087 HzN H
o Xo 469.52 /C
4-{[3-(3,4, 5-Trim ethoxy-phenyl )-i m idazo[1, 2-b p ridazin-6-ylamino]-methyl}-benzenesulfonamide 229_6 5.146 3070 rH

314 H2N ~~~ 425.47 -OH
4-{[3-(4-Hyd roxy-3-m ethoxy-phenyl )-i m idazo[1, 2-b]p idazin-6 lamino]-meth I -benzenesulfonamide 229_6 5.147 ~N
3070 rH
284 H2 395.44 ~%0 H
4-{[3-(3-Hydroxy-phenyl)-imidazo[1,2-b]pyridazin-6-lamino]-methyl}-benzenesulfonamide 2296 5.148 057 H2N , H
429.50 o 4-[(3-Naphthalen-2-yl-im idazo[1,2-b]pyridazin-6-ylamino)-meth I]-benzenesulfonamide 229_6 5.149 \
139 "
z /
393.47 o \o 4-[(3-p-Tolyl-imidazo[1,2-b]pyridazin-6-ylamino)-meth ]-benzenesulfonamide !
229_6 5.150 , i307_0 N ~N
167 Hz~ "
o~ ~ 407.50 o 4-{[3-(3,4-Dimethyl-phenyl)-imidazo[1,2-b]pyridazin-6-ylamino]-meth I -benzenesulfonamide 229_6 5.151 /
307_0 N~N

HZ N
0 404.45 ' 4-{[3-(4-Cyano-phenyl)-imidazo[1,2-b]pyridazin-6-lamino -meth I benzenesulfonamide 229_6 5.152 H
312 HzN~ 447.44 o %0 F
4-{[3-(3-Trifluoromethyl-phenyl)-imidazo[1,2-b]p ridazin-6-ylamino]-meth l}-benzenesulfonamide 2296 5.153 /
307_0 ~ /
204 HzN~ H
418.48 O\O
N
H
4-{[3-(1 H-Indol-5-yl)-imidazo[1,2-b]pyridazin-6-ylamino]-methyl}-benzenesulfonamide 229_6 5.154 307_0 ~

~ 423.45 0 'o 4-[(3-Benzo[1,3]dioxol-5-yl-imidazo[1,2-b]pyridazin-6-lamino -meth -benzenesulfonamide 2296 5.155 307_0 'IN /
164 HzN~ H
431.88 o ~o ci 4-{[3-( 3-Chloro-4-fl uoro-phenyl )-im idazo[1, 2-b] yridazin-6- lamino]-meth I}-benzenesulfonamide SRG/US/53343 - 100 - ALJIfDS
229_6 5.156 307_0 H
168 "_"
o 463.44 F

4-{[3-(3-Trifluoromethoxy-phenyl )-im idazo[1,2-b]pyridazin-6-ylamino]-meth I}-benzenesulfonamide 229_6 5.157 307_0 H

o 409.47 4-{[3-(4-Methoxy-phenyl)-imidazo[1, 2-b]pyridazin-6-ylamino]-meth I -benzenesulfonamide 229_6 5.158 H

~o 395.44 OH
4-{[3-(4-Hydroxy-phenyl)-imidazo[1, 2-b]pyridazin-6-ylamino]-methyl}-be nzenesulfonamide 229_6 5.159 H

OAo 409.47 OH
4-{[3-(3-Hydroxym ethyl-phenyl )-im id azo[1,2-b]pyridazin-6-ylamino]-meth I -benzenesulfonamide 229_6 5.160 307_4 H
145 "_" 0 421.48 ~,\O

4-{[3-(3-Acetyl-phenyl )-im idazo [1, 2-b] pyridazi n-6-ylamino]-methyl -benzenesulfonamide 229_6 5.161 3077 \ -N
H
468 H=N 383.43 0 >~10 4-{[3-(1-Methyl-1 H-pyrazoI-4-yI)-im idazo[1, 2-b]p ridazin-6-ylamino]-methyl}-benzenesulfonamide 2290 5.162 2270 c' H

1.14 459.33 / 461 ~o \
/o (3,4-Dichloro-benzyl)-[3-(3,4,5-trimethoxy-phenyl)-imidazo 1,2-b ridazin-6 I -amine 229_0 5.163 ~ N
2270 ci Cjf"~N N"N H
080 ci 385.25 OH
4-[6-(3,4-Dichloro-benzylamino)-imidazo[1,2-b]pyridazin-3-yl]-phenol 2290 5.164 c' X rH ~"
280 c 399.28 (3,4-Dichloro-benzyl )-[3-(4-methoxy-phenyl)-imidazo[1,2-b]p ridazin-6- I -amine 229_0 5.165 i 227_0 c r\
H
311 c I ~
400.27 -/O
(3,4-Dichloro-benzyl )-[3-(6-methoxy-pyridin-3-yl )-imidazo[1,2-b]pyridazin-6- I]-amine 229_0 5.166 2270 :I'D, 20 4 408.29 H
(3, 4-Dich loro-benzyl )-[3-(1 H-indol-5-yl )-i m idazo[1, 2-b]p ridazin-6 I]-amine 229_0 5.167 2270 c )~H

413.26 HO
4-[6-(3,4-Dichloro-benzylamino)-imidazo[1,2-b]p ridazin-3- I]-benzoic acid 229_0 5.168 236_0 C H
069 ' 0.74 345.36/346 N
Benzo[1,3]dioxol-5-ylmethyl-(3-pyridin-4-yl-imidazo 1,2-b ridazin-6- I -amine 229_0 5.169 314 390.40 OH
4-{6-[(Benzo[1, 3]dioxol-5-ylmethyl)-am ino]-i m id azo[ 1, 2-b] pyridazi n-3-yl}-2-m ethoxy-phenol 229_0 5.170 280 < H
0.97 374.40/375 /o Benzo[1,3]dioxol-5-ylmethyl-[3-(4-methoxy-phenyl)-imidazo 1,2-b ridazin-6- I -amine 2290 5.171 '236_0 0.95 375.39/376 Benzo[1,3]dioxol-5-ylmethyl-[3-(6-methoxy-pyridin-3-I -imidazo[1,2-b p ridazin-6 I -amine 229_0 5.172 2360 < D~H

0.83 360.37/361 H
4-{6-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-imidazo[1,2-b]pyridazin-3- I -phenol 2290 5.173 236_0 284 O 0.87 360.37/361 3-{6-[(Benzo[1,3]dioxol-5-yfinethyl)-amino]-imidazo 1,2-b]p ridazin-3 I -phenol :2290 5.174 ~

2367 )~H ~
468 0.79 348.36/349 Benzo[1,3]dioxol-5-ylmethyl-[3-(1-methyl-1 H-pyrazol-4- f-imidazo 1,2-b p idazin-6 I]-amine __._ 229_0 5.175 ;2360 < ~
140 o /
388.38 HO
4-{6-[(Benzo[1, 3]dioxol-5-yf inethyl )-am ino]-imidazo 1,2-b] yridazin-3 I-benzoic acid 229_0 5.176 488 O I \ H
437.48 o=S-o I
I
N-(3-{6-[(Benzo[1, 3]dioxol-5-ylm ethyl )-am i no]-imidazo[1,2-b]pyridazin-3-yl)-phenyl)-methanesulfonamide 1229 0 5.177 !2360 387.40 NHZ
3-{6-[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-imidazo[1,2-b ridazin-3- I -benzamide 229_0 5.178 033_0 ~
H

0.84 358.40/359 -o /
(2-Methoxy-ethyl )-[3-(3,4,5-trimethoxy-phenyl )-imidazo 1,2-b ridazin-6- I -amine SRG/US/53343 - 104 - AL.J/TDS
229_0 5.179 033_0 -" ~
H
284 / \ 284.32 (2-Methoxy-ethyl)-[3-(3-methoxy-phenyl)-imidazo[1,2-b] ridazin-6- I -amine 229_0 5.180 033_0 i "/-, N ~
H
314 / \ 314.34 OH
2-Methoxy-4-[6-(2-methoxy-ethylamino)-imidazo[1,2-b p idazin-3- I henol 229_0 5.181 033_0 i "/'~, 4 " ~
H
196 / \ 299.33 (2-Methoxy-ethyl )-[3-(5-methoxy-pyrid i n-3-yl )-imidazo 1,2-b]p ridazin-6- I -amine 229_0 5.182 033_0 057 1.00 318.38/319 (2-Methoxy-ethyl)-(3-naphthalen-2-yl-im idazo[1,2-b p ridazin-6- I -amine 229_0 5.183 ; 033_0 H

\N 299.33 %
(2-Methoxy-ethyl)-[3-(6-methoxy-pyrid in-3-yl)-imidazo 1,2-b ridazin-6- I]-amine 229_0 5.184 033_0 H 324.41/323 1.07 (negative mode) (3-Benzo[b]thiophen-2-yi-im idazo[1,2-b]pyridazin-6-I - 2-methox -eth I -amine 229_0 5.185 033_0 -N ~
H
160 / \ 302.76 C
[3-(4-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yi]-(2-methox -eth I -amine 2290 5.186 033_0 ~/~,, H

0.84 298.34/299 /
(2-Methoxy-ethyl)-[3-(4-methoxy-phenyl)-imidazo[1,2-b ridazin-6- I -amine 229_0 5.187 033_0 io H
068 / \ 312.33 J

(3-Benzo[1,3]dioxol-5-yl-imidazo[1,2-b]pyridazin-6-yl)-(2-methox -eth I -amine 229_0 5.188 033_0 i ~~ ~

312 H /\ F 1.02 336.32/337 F F
(2-Methoxy-ethyl )-[3-(3-trifluorom ethyl-phenyl)-imidazo[1,2-b ridazin-6- I -amine 229_0 5.189 033 0 io ~ ~
- H
'081 / \
N 0.71 325.37/326 o N-{3-[6-(2-Methoxy-ethylamino)-imidazo[1,2-b pyridazin-3 I hen I-acetamide 229_0 5.190 033_0 H
! 168 0 F 1.05 352.32/353 / -F
V
F
( 2-M eth oxy-eth yl )-[3-( 3-trifl uo ro m ethoxy-p h e n yl )-imidazo 1,2-b ridazin-6- I -amine 229_0 5.191 033_0 H
204 0.78 307.36/308 NH
[3-(1 H-Indol-5-yl)-im idazo[1,2-b]pyridazin-6-yi]-(2-methox -eth I -amine __ 229_0 5.192 033 0 i - H
279 302.76 [3-(3-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(2-methox -eth I -amine .2290 5.193 033_0 i 345 H - 0.92 288.37/289 s ~

(2-Methoxy-ethyl )-[3-(4-methyl-thiophen-2-yl )-imidazo 1,2-b]p ridazin-6- I -amine 229_0 5.194 033_0 'N /
H
080 / \ 0.68 284.32/285 OH
4-[6-(2-Methoxy-ethylam ino)-im idazo[1, 2-b]pyridazin-3 I henol 2290 5.195 - H
1285 / \
0.67 298.34/299 HO
{4-[6-(2-Methoxy-ethylamino)-imidazo[1,2-b]pyridazin-3- I hen -methanol 229_0 5.196 033_4 io"N
H
140 / \ 0.86 298.34/299 (2-Methoxy-ethyl )-[3-(3-m ethoxy-phenyl )-i m idazo[1, 2-b ridazin-6- I -amine SRG/US/53343 - 107 - AL.I/TDS
229_0 5.197 033_0 "N
H
277 347.22 Br [3-(3-Brom o-phenyl )-im idazo[1, 2-b]pyridazin-6-yi]-(2-methox -eth I)-amine 229_0 5.198 H

312.33 HO
4-[6-(2-Methoxy-ethylamino)-imidazo[1,2-b]pyridazin-3-yl -benzoic acid 229_0 5.199 033_0 H
347 0 311.34 NHz 3-[6-(2-Methoxy-ethylamino)-imidazo[1,2-b]pyridazin-3-yI]-benzamide 229_0 5.200 033 6 i _ H

H 361.42 o ~~

N-{3-[6-(2-Methoxy-ethylamino)-imidazo[1,2-b idazin-3- I -phen I -methanesulfonamide l---_____.
229_0 5.201 1033 7 i -N 348.4 1 [3-(1-Benzyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-i 6 I]- 2-methox -eth I-amine 229_0 5.202 033_0 1, "" /

0 328.37 %
[3-(3,4-Dimethoxy-phenyl)-imidazo[1,2-b]pyridazin-6-- 2-methox -eth I -amine 229_0 5.203 033_4 'N /
H
1145 \ 310.36 1-t3-[6-(2-Methoxy-ethylam ino)-im idazo[1, 2-b ridazin-3- I- hen I-ethanone 229_0 5.204 0.76 358.40/359 ~o \
%
3-[3-(3,4,5-Trimethoxy-phenyl)-imidazo[1,2-b] ridazin-6-ylamino -propan-1-ol 229_0 5.205 248_0 Ho~~
H
314 / \ 314.34 OH
4-[6-(3-Hydroxy-propylamino)-imidazo[1,2-j b ridazin-3- I-2-methox - henol 229_0 5.206 2480 Ho~~~rv H
1277 / 347.22 Br 3-[3-(3-Bromo-phenyl)-imidazo[1,2-b]pyridazin-6-lamino] ro an-l-ol 1 229_0 5.207 248_0 HO H
!079 / \
0.73 328.37/329 /
3-[3-(3,4-DimethoxY-PhenYf)= imidazo[1,2-b]PYridazin-6- lamino -propan-1-ol 229_0 5.208 248_0 Ho~/~rr /
H
312 F 336.32 F F
3-[3-(3-Trifluoromethyl-phenyl )-im idazo[1,2-b]p ridazin-6- amino]-pro an-1-ol 229_0 5.209 248_7 HO H
468 272.31 N-N\
3-[3-(1-Methyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]p ridazin-6 lamino ropan-1-ol 229_0 5.210 _ Ho~/~rr H
168 o 352.32 /V- F
F
3-[ 3-( 3-Trif l u o ro m e t hoxy-p h e n yl )-i m i d a zo [ 1, 2-b ridazin-6- lamino ro an-1-ol 2290 5.211 248_0 HO H
345 / S 288.37 3-[3-(4-Methyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6- lamino ropan-l-ol __ 229_0 5.212 248_0 HO
~ /
H
1057 / 0.90 318.38/319 3-(3-Naphthalen-2-yl-imidazo[1,2-b]pyridazin-6-lamino - ropan-l-ol _ 229_0 5.213 248_4 HO 139 / \ 0.79 282.35/283 3-(3-p-Tolyl-im idazo[1,2-b]pyridazin-6-ylam ino)-propan-l-ol 229_0 5.214 ~

074 0.72 274.35/275 s 3-(3-Thiophen-3-yl-imidazo[1,2-b]pyridazin-6-lamino - ropan-1-ol 229_0 5.215 248_0 Ho~~~N
H

0.94 324.41/325 3-(3-Benzo[b]thiophen-2-yl-imidazo[1,2-b]pyridazin-6-lamino - ro an-1-ol 229_0 5.216 248_0 Ho-N
H

~N 0.69 299.33/300 /
3-[3-(6-Methoxy-pyridin-3-yl)-im idazo[1, 2-b]pyridazin-6 lamino]-propan-1-ol 229_0 5.217 J\, 248_0 Ho204 H 0 .71 307.36/308 3-[3-(1 H-Indol-5-yl)-imidazo[1,2-b]pyridazin-6-lamino - ro an-1-ol .___ 229_0 5.218 , 248_0 H
!280 0.75 298.34/299 3-[3-(4-Methoxy-phenyl)-im idazo[1, 2-b]pyridazin-6-lamino - ro an-1-ol 229_0 5.219 _ HO H
164 320.75 ci F
3-[3-(3-Chioro-4-fluoro-phenyl)-imidazo[1,2-' b p idazin-6- lamino]-pro an-1-ol 229_0 5.220 248_0 Ho~/~
H
279 / \ 302.76 ci 3-[3-(3-Chloro-phenyl )-im idazo[1,2-b]pyridazin-6-lamino]-propan-1-ol 229_0 5.221 , 248_6 H
488 N 361.42 o N-{3-[6-(3-Hydroxy-propylam i no)-im idazo[1, 2-b]p ridazin-3- I -phen I -methanesulfonamide 229_0 5.222 ,,........ N-N 348.41 L....,. ~ ~

3-[3-(1-Benzyl-1 H-pyrazol-4-yl )-im idazo[1, 2-b p ridazin-6 lamino]-propan-1-ol .229_0 5.223 248_0 HO H
135 311.39 3-[3-(3-Dimethylamino-phenyl)-imidazo[1,2-b ridazin-6- lamino - ro an-1-ol 229_0 5.224 J248_0 HO H
062 / 318.38 3-(3-Naphthalen-1-yl-imidazo[1,2-b]pyridazin-6-lamino - ro an-1-ol _ 229_0 5.225 226_0 H
087 / \
0 0.94 342.40/343 ~o Propyl-[3-(3,4,5-trimethoxy-phenyl)-imidazo[1,2-b]p ridazin-6- -amine 229_0 5.226 226_0 H
314 0.81 298.34/299 OH
2-Methoxy-4-(6-propylamino-imidazo[1,2-b]pyridazin-3-yl)-phenol 229_0 5.227 H
079 0 0.91 312.37/313 o-[3-(3,4-Dimethoxy-phenyl)-imidazo[1,2-b]pyridazin-6-I - ropyl-amine .229_0 5.228 226_0 ,204 / \
291.36 ~ NH
[3-(1 H-Indol-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-propyl-amine __ 229_0 5.229 226_4 H
140 282.35 [3-(3-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-ro I-amine -229_0 5.230 1 226_0 . ~
H
1081 N 0.80 309.37/310 ~

N-[3-(6-Propylamino-imidazo[1,2-b]pyridazin-3-yi)-phen I]-acetamide 1229_0 5.231 226_0 H

0 1.18 336.32/337 F ' F\TF
Propyl-[3-(3-trifluoromethoxy-phenyl)-imidazo[1,2-i b]p ridazin-6- I]-amine 229_0 5.232 226_0 N
/

0.96 282.35/283 /
[3-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-rop I-amine 229_0 5.233 226_0 U~, N /
074 H - 0.95 258.35/259 s Propyl-(3-thiophen-3-yl-imidazo[1,2-b]pyridazin-6-yl)-amine 2290 5.234 226_0 345 / 1.06 272.37/273 [3-(4-Methyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-i]-prop I-amine 229_0 5.235 /
226_0 ~,, N
H
071 0.73 253.31/254 N

Propyl-(3-pyridin-3-yi-im idazo[1,2-b]pyridazin-6-yl )-amine 229_0 5.236 226_0 H
311 ~ ~N 0.91 283.33/284 /
[3-(6-Methoxy-pyrid in-3-yl )-i m idazo [1,2-b]pyridazin-6-yl]-pro yl-amine 229 0 5.237 226_0 080 H / ~ 0.78 268.32/269 OH
4 6-Prop lamino-imidazo[1,2-b p ridazin-3- I-phenol 2290 5.238 2260 '' H
068 0.94 296.33/297 oJ
(3-Benzo[1,3]dioxol-5-yl-imidazo[1, 2-b]pyridazin-6-yl )-pro I-amine 229_0 5.239 226_0 -N ~
H
291 0.81 282.35/283 OH
[3-(6-Propylam ino-im idazo[1,2-b]pyridazin-3-yl)-hen I -methanol 229_0 5.240 226_0 296.33 HO
4-(6-Propylamino-imidazo[1,2-b]pyridazin-3-yl)-benzoic acid 229_0 5.241 226_0 H
347 0 295.34 NHZ
3-(6-Propylamino-imidazo[1,2-b]pyridazin-3-yl)-benzamide 229_0 5.242 1226_0 H
135 295.39 [3-(3-Dimethylamino-phenyl)-imidazo[1,2-b]pyridazin-6 I]-prop I-amine 229_0 5.243 284 H 268.32 OH
3- 6-Prop lamino-imidazo[1,2-b]pyridazin-3- I)-phenol SRG/US/53343 - 115 - AL.,I/TDS
229_0 5.244 226_0 H
005 / \ 267.33 [3-(3-Am ino-phenyl)-im idazo[1,2-b]pyridazin-6-yl]-prop I-amine 2290 5.245 226_0 /
H
333 / 267.33 [3-(4-Am ino-phenyl)-im idazo[1,2-b]pyridazin-6-yl]-rop I-amine 229 0 5.246 226_0 H
004 / \ 295.39 N-~
[3-(4-Dimethylamino-phenyl)-im idazo[1,2-b]pyridazin-6-yI]-pro I-amine 229_0 5.247 226_0 H
285 / \
282.35 HO
[4-(6-Propylamino-imidazo[1,2-b]pyridazin-3-yl)-phen I -methanol 229_0 5.248 226_0 H
1196 / \ 283.33 [3-(5-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-6-yI]-prop -amine 229_4 5.249 016_4 139 / \ 295.39 N, N-Dim ethyl-N'-(3-p-tolyl-im idazo[1, 2-b]pyridazin-6--ethane-1,2-diamine 229_4 5.250 016_0 H
073 / o 0.78 321.38/322 N'-(3-Benzofuran-2-yl-imidazo[1,2-b]pyridazin-6-yl)-N,N-dimeth I-ethane-1,2-diamine , 229_4 5.251 - H
074 287.39 \ s N,N-Dimethyl-N'-(3-thiophen-3-yi-imidazo[1,2-b ridazin-6- -ethane-1,2-diamine 12294 5.252 I
016_0 -r, /
H
057 ~ \ 331.42 N,N-Dimethyl-N'-(3-naphthalen-2-yl-imidazo[1,2-b] ridazin-6 )-ethane-1,2-diamine 229_4 5.253 I
016_0 " -" /
H
076 s 337.45 N'-(3-Benzo[b]thiophen-2-yl-imidazo[1,2-b]pyridazin-6- I -N,N-dimeth I-ethane-1,2-diamine 2294 5.254 ~
1016_0 i I ~
H
,079 341.41 %
N'-[3-(3,4-Dimethoxy-phenyl)-im idazo[1, 2-b]pyridazin-6- I -N,N-dimeth I-ethane-1,2-diamine 229_4 5.255 I
016_0 H
339 299.35 F
N'-[3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-N,N-dimeth -ethane-1,2-diamine 2294 5.256 H
279 315.81 ~ CI
N'-[3-(3-Chloro-phenyl )-im idazo[1, 2-b]pyridazin-6-yl]-N,N-dimeth -ethane-1,2-diamine __ 229_0 5.257 HN

1 / 0 386.45 pH \

O~
(S)-3-Methyl-2-[3-(3,4,5-trimethoxy-phenyl)-imidazo 1,2-b ridazin-6- amino]-butan-1-ol 2290 5.258 - HN

Y l \ / 0 342.40 OH
OH
4-[6-((S)-1-Hydroxymethyl-2-methyl-propylam ino)-imidazo[1,2-b]p ridazin-3-yl]-2-methoxy-phenol 2290 5.259 - HN

.
\
/ 0 356.42 oH
O-(S)-2-[3-(3,4-Dimethoxy-phenyl)-imidazo[1,2-b]p ridazin-6- lamino -3-meth I-butan-1-ol 2290 5.260 ,1254 0 - HN
1284 - 312.37 OH OH
3-[6-((S)-1-Hydroxymethyl-2-methyl-propylamino)-imidazo[1,2-b]pyridazin-3 I]-phenol 229 0 5.261 254 0 ~ /
- HN
,080 ~
312.37 OH
4-[6-((S)-1-Hydroxymethyl-2-methyl-propylamino)-imidazo[1,2-b]pyridazin-3- I - henol SRG/US/53343 . - 118- ALJ/TDS
2290 5.262 - HN

~ \ / 326.40 HO
(S )-2-[3-(4-Hyd roxymethyl-phenyl )-i m idazo[1, 2-b ridazin-6- lamino 3-meth I-butan-1-ol 229 0 5.263 HN
135 339.44 YI""] N
OH

(S)-2-[3-(3-Dimethylamino-phenyl )-im idazo[1,2-b]p ridazin-6- lamino 3-meth I-butan-1-ol 2290 5.264 - HN

346.43 H

(S)-3-Methyl-2-(3-naphthaien-2-yl-imidazo[1,2-b]pyridazin-6-ylamino -butan-1-ol 229_0 5.265 - HN
312 F 364.37 ~H \ /
F F
(S )-3-Methyl-2-[3-(3-triFluorom ethyl-phenyl )-imidazo 1,2-b]p ridazin-6 lamino]-butan-1-ol _ 229_0 5.266 ,254 0 - HN
,068 -H 340.38 o (S)-2-(3-Benzo[1,3]dioxol-5-yl-iJQ
midazo[1,2-b ridazin-6- lamino 3-meth I-butan-1-ol 229_0 5.267 - HN
345 / 316.43 OH

(S )-3-Methyl-2-[3-(4-methyl-th iophen-2-yl )-imidazo 1,2-b p ridazin-6- lamino]-butan-1-ol 229_0 5.268 , 254_0 HN \ /
074 302.40 S
OH
(S)-3-Methyl-2-(3-thiophen-3-yl-imidazo[1,2-b p idazin-6- lamino -butan-1-ol __ 229_0 5.269 254_0 HN ," ~

YI""] o 380.37 OH ' /
/1C_ F
F
( S )-3-Methyl-2-[3-( 3-trifl uorom ethoxy-phenyl )-imidazo 1,2-b]p ridazin-6- lamino -butan-l-ol 229_0 5.270 254_0 HN I" ~

279 Y-",] 330.82 OH \ / CI
(S)-2-[3-(3-Chloro-phenyl )-i m idazo[1, 2-b]pyridazi n-6-amino]-3-methyl-butan-l-ol 229_0 5.271 254_0 HN

/ 314.36 Y""IH \

F
(S)-2-[3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-lamino -3-meth I-butan-l-ol 229_0 5.272 254_0 HN
..,,204 335.41 OH ' N
H
(S)-2-[3-(1 H-Indol-5-yl)-im idazo[1,2-b]pyridazin-6-ylamino -3-meth I-butan-1-ol 229_0 5.273 254_0 HN
347 0 339.40 =''~ H \

3-[6-((S)-1-Hydroxymethyl-2-methyl-propylam ino)-imidazo[1,2-b ridazin-3- I -benzamide 229_0 5.274 5~"
254_4 HN
145 o 338.41 H

1 -{3-[6-((S)-1-Hydroxymethyl-2-methyl-propylam ino)-imidazo 1,2-b p ridazin-3- I]- hen I-ethanone _ 229_0 5.275 254_0 HN

196 327.39 OH N

(S )-2-[3-(5-Methoxy-pyrid in-3-yl )-i m idazo[1, 2-b ridazin-6- amino -3-methyl-butan-l-ol ;__ 12290 5.276 \ / \ 372.42 CH

%
2-[3-(3,4,5-Trimethoxy-phenyl )-im idazo[1,2-b ridazin-6- Iamino ino]-butan-229_0 5.277 153_0 HN

\ / ci 334.78 oH
F
2-[3-(3-Chloro-4 fluoro-phenyl)-imidazo[1,2-b] ridazin-6- amino -butan-1-ol 229_0 5.278 153_0 HN
i057 \ 0.99 332.41 /333 "

2-(3-Naphthalen-2-yi-imidazo[1,2-b]pyridazin-6-amino -butan-1-ol 229_0 5.279 _ HN

1.02 366.34/367 " l~~_ F
F
2-[3-(3-Trifluoromethoxy-phenyl)-imidazo[1,2-b ridazin-& lamino -butan-l-ol SRG/US/53343 - 121 - AL.I/TDS
229_0 5.280 153_0 HN
O.H.
074 0.82 288.37/289 s 2-(3-Thiophen-3-yl-imidazo[1,2-b]pyridazin-6-lamino -butan-1-ol __ 229_0 5.281 153_0 H

0.86 312.37/313 OH
O

2-[3-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-lamino]-butan-1-ol ',...
229_0 5.282 - H
345 s 0.90 302.40/303 OH

2-[3-(4-Methyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6 lamino]-butan-1-ol 229_0 5.283 153_0 HN _,-N /
279 316.79 oti \ / ci 2-[3-(3-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-lamino -butan-1-ol ! 229_0 5.284 153_0 H

N 0.79 313.36/314 OH

2-[3-(6-Methoxy-pyridin-3-yl)-im idazo[1, 2-b]pyridazin-6- lamino]-butan-1-ol 229_0 5.285 153_7 HN
468 ~ 0.67 286.34/287 OH N-N\
2-[3-(1-Methyl-1 H-pyrazol-4-yl)-im idazo[1, 2-b p ridazin-'r lamino -butan-1-ol 2290 5.286 277 ~ - 361.24 OH Br 2-[3-(3-Bromo-phenyl )-im idazo[1,2-b]pyridazin-6-ino]-butan-l-ol 229 0 5.287 _ HM
! 312 F 1.00 350.34/351 OH
F F
2-[3-(3-Trifluoromethyl-phenyl)-imidazo[1,2-b ridazin-6- lamino -butan-l-ol 2290 5.288 \
140 0.86 312.37/313 OH

2-[3-( 3-Methoxy-phenyl )-i m idazo[1, 2-b]pyrid azin-6-amino]-butan-1-ol 229_0 5.289 153_0 347 0 325.37 OH
NHz 3-[6-(1-Hydroxymethyl-propylamino)-imidazo[1,2-b]pyridazin-3- I]-benzamide 229_0 5.290 153_0 HN
i140 oH 326.35 OH

4-[6-(1-Hydroxymethyl-propylamino)-imidazo[1,2-b ridazin-3 I -benzoic acid ~ 229_0 5.291 1537 _ HN

469 OH N'" 362.44 2-[3-(1-Benzyl-lH-pyrazol-4-yl)-imidazo[1,2-b p ridaan-6-ylamino -butan-1-ol 229_0 5.292 ~
1536 HN'~ /
488 ~
H
N 375.45 oH
o I~

N-{3-[6-(1-Hydroxymethyl-propylamino)-imidazo[1,2-b]p ridazin-3- I - henyl -methanesulfonamide 2290 5.293 - HN

145 10H / ~ o 324.38 -1-{3-[6-(1-Hydroxymethyl-propylamino)-imidazo[1,2-b]p idazin-3- -phen I -ethanone 2290 5.294 F
153_0 HN / 079 oH 342.40 2-[3-(3, 4-Dim ethoxy-phenyl )-im idazo[1, 2-b]pyridazi n-6 lamino]-butan-1-ol 229_0 5.295 153_0 HN
196 313.36 OH N--~

2-[3-(5-Methoxy-pyridin-3-yl)-imidazo[1,2-b]pyridazin-6- lamino -butan-1-ol _ i2290 5.296 12420 aN
H
:087 \1 ; 384.43 -o (Tetrahydro-pyran-4-yl )-[3-(3, 4, 5-tri methoxy-phenyl )-imidazo[1,2-b ridazin-6- I -amine 2290 5.297 2424 aN
H
140 / ~ 324.38 [3-(3-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro- ran-4- I -amine 229 0 5.298 242 0 a /
N
312 H / F 362.35 F F
(Tetrahydro-pyran-4-yl)-[3-(3-trifluoromethyl-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-amine 2290 5.299 242_0 aN -N
/
'285 /
324.38 ~

HO
{4-[6-(Tetrahydro-pyran-4-ylamino)-imidazo[1,2-b ridazin-3-yi -phen I -methanol 229_0 5.300 242_0 aN
H
345 / S 314.41 [3-(4-Methyl-thiophen-2-yl)-imidazo[1,2-b]pyridazin-6-I]- tetrah dro-pyran-4-yl)-amine 2290 5.301 /
H
164 / 346.79 ci F
[3-(3-Chloro-4-fluoro-phenyl)-imidazo[1,2-b]pyridazin-6- I- tetrah dro- ran-4- I-amine ,.
2290 5.302 i2420 aN
H

/ 373.25 er [3-(3-Bromo-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro-p an-4 I -amine 229_0 5.303 242_7 aN
H
468 ~ 298.35 N

[3-(1-Methyl-1 H-pyrazol-4-yl)-im idazo[1, 2-b]pyridazin-6- I- tetrah ydro-pyran-4-0)-a mine 2290 5.304 0 N
2420 ~-' H
291 324.38 OH
{3-[6-(Tetrahydro-pyran-4-ylamino)-imidazo[1,2-b]p ridazin-3- I]-phen I -methanol .2290 5.305 2420 aN
H
196 / ~ 325.37 N \

[3-(5-Methoxy-pyrid in-3-yl )-im idazo[1, 2-b]pyridazin-6-I- tetrah dro-p ran-4- I-amine _ 229_0 5.306 - N
H

324.38 /
[3-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro-pyran-4-yl)-amine 229_0 5.307 N
H
339 312.35 F
[3-(4-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro-p ran-4- I -amine 2290 5.308 ;2420 aN

333.39 N
H
[3-(1 H-Indol-5-yl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro-p ran-4- I -amine 1229 5.309 aN
,242 0 H
135 337.43 N
[3-(3-Dimethylamino-phenyl)-imidazo[1,2-b]pyridazin-6 - tetrah dro-pyran-4 I)-amine 2290 5.310 o 2420 N -r' 057 / \ 1.01 344.42/345 (3-Naphthalen-2-yl-imidazo[1,2-b]pyridazin-6-yl)-tetrah dro-p ran-4-yi)-amine 2290 5.311 aN

, H
167 0.95 322.41 /323 [3-(3,4-Dimethyl-phenyl)-imidazo[1,2-b]pyridazin-6-yi]-tetrah dro- ran-4- I -amine 229_0 5.312 0 2420 N -r' /
142 H ~ 0.81 284.32/285 (3-Furan-2-yl-imidazo[1, 2-b]pyridazin-6-yl )-tetrahydro-pyran-4-yi )-am ine i 2290 5.313 a N
242 0 " -'' 192 o 0.67 381.43/382 N
H
OH
N-(2-Hyd roxy-ethyl)-3-[6-(tetrahydro-pyran-4-lamino -imidazo[1,2-b ridazin-3- -benzamide , 229_0 5.314 aN

0.90 352.39/353 O
\

4-[6-(Tetrahydro-pyran-4-ylamino)-imidazo[1,2-b ridazin-3- I-benzoic acid meth I ester 229_0 5.315 0 i - N
H
139 / \ 0.90 308.38/309 (Tetrahydro-pyran-4-yl)-(3-p-tolyl-imidazo[1,2-b]pyridazin-6 I -amine SRG/US/53343 - 127 - ALJlTDS
2290 5.316 a - N
333 0.68 309.37/310 NHZ
[3-(4-Amino-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro-p ran-4 I)-amine 229_0 5.317 aN

004 337.43 /N-[3-(4-Dimethylam ino-phenyl)-im idazo[1,2-b]pyridazin-6-yl - tetrah dro-p ran-4- I-amine 229_0 5.318 aN

:081 H 0.73 351.41/352 N
~
O
N-{3-[6-(Tetrahydro-pyran-4-ylam ino)-i m id azo[1,2-b]p ridazin-3- I]-phen I -acetamide 2290 5.319 aN 242 0 005 H / \ 309.37 [3-(3-Amino-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro- ran-4- I -amine .229 0 5.320 , - ~
i242_4 N F
038 H / \ 0.85 312.35/313 [3-(2-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-(tetrah dro- ran-4- I -amine 2290 5.321 aN

242 0 062 H / ~ \ 344.42 (3-Naphthalen-1-yl-im idazo[1,2-b]pyridazin-6-yl )-tetrah dro- ran-4-yl -amine 229_0 5.322 0 242_0 N -'' ~
H 0.65 295.34/296 ~ ~N

( 3-Pyri d i n-3-yl-i m i d azo[1, 2-b] pyrid azi n-6-yl )-tetrah dro-p ran-4 I -amine 2290 5.323 aN

160 328.80 ci [3-(4-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro ran-4- I -amine 2290 5.324 aN
2420 -' H
068 338.37 o oJ
(3-Benzo[1, 3]dioxol-5-yl-im idazo[1, 2-b]pyridazi n-6-yl )-(tetrah dro ran-4-yl -amine 2290 5.325 0 - N
284 H / ~ 0.74 310.36/311 - OH
3-[6-(Tetrahydro-pyran-4-ylamino)-imidazo[1,2-b] ridazin-3- I]- henol 229_0 5.326 ~N <', ,2420 ~

1074 H 0.84 300.38/301 s (Tetrahydro-pyran-4-yl)-(3-thiophen-3-yl-imidazo[1,2-b p idazin-6- I -amine 2290 5.327 aN

079 o 0.81 354.41/355 /
[3-(3,4-Dimethoxy-phenyl)-imidazo[1,2-b]pyridazin-6-I- tetrah dro-p ran-4- I-amine 229_0 5.328 aN

168 / \ 1.06 378.35/379 F
(Tetrahyd ro-pyran-4-yl )-[3-(3-trifluorom ethoxy-phen I -imidazo[1,2-b]pyridazin-6 I -amine _._ ' 2290 5.329 aN 2420 313 H 312.35 [3-(3-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro- ran-4- I -amine , I2290 5.330 aN

314 340.38 \
OH
2-Methoxy-4-[6-(tetrahydro-pyran-4-yl am i no)-imidazo[1,2-b]pyridazin-3- I]-phenol 229_0 5.331 a - N
147 H ~ 0.83 300.38/301 (Tetrahydro-pyran-4-yl)-(3-thiophen-2-yl-imidazo[1,2-b]p ridazin-6 I -amine 229_0 5.332 aN

242 7 1467 H 0.59 284.32/285 NiNH
[3-(1 H-Pyrazol-4-yi)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro- ran-4- I-amine 2290 5.333 aN

347 0 337.38 NHz 3-[6-(Tetrahydro-pyran-4-ylam ino)-im idazo[1, 2-b p ridazin-3- I -benzamide 229_0 5.334 aN 2427 H

N- 374.45 [3-(1-Benzyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6 I]- tetrah dro-p ran-4- I)-amine 2290 5.335 0 2420 N < -r' /
H
140 ~
338.37 HO
4-[6-(Tetrahydro-pyran-4-ylamino)-imidazo[1,2-b] ridazin-3- I]-benzoic acid 2290 5.336 aN

2426 488 5 \ H 387.46 N
ol:oll_ O
N-{3-[6-(Tetrahydro-pyran-4-ylam ino)-im idazo[1,2-b]pyridazin-3- I]-phenyl}-methanesulfonamide 2290 5.337 2420 aN -'' /
H
.80 279 o_-cI 328 [3-(3-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-yl]-tetrah dro- ran-4 I -amine -----__---1229 _0 5.338 HO~
~' /

H 354.41/353 \ 0.70 (negative o mode) OH
4-[6-( 4-H yd ro xy-cycl o h exyl a m i n o)-i m i d a zo [ 1, 2-b ridazin-3- I -2-methox -phenol SRG/US/53343 - 131 - ALJlTDS
2290 5.339 "o,,a N
168 392.38 f r F
4-[3-(3-Trifl uoromethoxy-phenyl )-im idazo[1, 2-b p ridazin-6- lamino]-c clohexanol 2290 5.340 HO"a<"&

0.79 338.41 /339 4-[3-(3-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-Iamino]-c clohexanol 229_0 5.341 HO*,,a ~
2400 N ~
-074 H 314.41 \ s 4-(3-Thiophen-3-yl-imidazo[1,2-b]pyridazin-6-ylamino)-cyclohexanol 2290 5.342 "o ~ ~N /

076 r / s 364.47 \ /
4-(3-Benzo[b]thiophen-2-yl-imidazo[1,2-b]pyridazin-6-lamino -c clohexanol 2290 5.343 HO
{2400 -aN
1135 " 351.45 4-[3-(3-Dimethylamino-phenyl)-imidazo[1,2-b]pyridazin-6-ylamino]-cyclohexanol 2290 5.344 H0,,a /

,313 H / 326.37 F
4-[3-(3-Fluoro-phenyl)-imidazo[1,2-b]pyridazin-6-ylamino]-cyclohexanol 2290 5.345 "o~

N
062 H / 0.83 358.44/359 4-(3-Naphthalen-1-yl-imidazo[1,2-b]pyridazin-6-lamino -c clohexanol 2290 5.346 HO-aN <':

081 H 365.44 N
O~-N-{3-[6-(4-Hydroxy-cyclohexylamino)-imidazo[1,2-b ridazin-3- I]-phen I -acetamide _ 229_0 5.347 HO~
2400 N "'' H
080 324.38 OH
4-[6-(4-Hydroxy-cyclohexylam i no)-im id azo[1, 2-b]p ridazin-3-yl]-phenol 2290 5.348 H0"aN

057 358.44 4-(3-Naphthalen-2-yl-imidazo[1,2-b]pyridazin-6-amino -c clohexanol 1229_0 5.349 HO
240_0 N
~
061 H / 308.38 4-(3-Phenyl-imidazo[1,2-b]pyridazin-6-ylamino)-cyclohexanol 229_0 5.350 "o 240 0 ~ ~-N
N
H
204 347.42 ~ NH
4-[3-(1 H-Indol-5-yl)-imidazo[1,2-b]pyridazin-6-amino]-c clohexanol SRG/US/53343 - 133 - AlJ/TDS
229_0 5.351 "o 240_0 ~N
004 "
351.45 /N-4-[3-(4-Dimethylamino-phenyl)-imidazo[1,2-b ridazin-6- lamino]-c clohexanol 229 0 5.352 "o 240_0 N

280 338.41 4-[3-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-6-lamino]-cyclohexanol 229 0 5.353 "o " N
078 z 359.43 4-(3-Quinolin-8-yi-imidazo[1,2-b]pyridazin-6-ylamino)-cyclohexanol 2290 5.354 "o 2400 N ~ ~
H
142 298.34 , /
~
4-(3-Furan-2-yl-imidazo[1,2-b]pyridazin-6-ylamino)-c clohexanol 229_0 5.355 HO
2402 ~N
366.42/365 0.82 (negative o mode) 0 \
4-[6-(4-Hydroxy-cyclohexylamino)-imidazo[1,2-b]p ridazin-3- I-benzoic acid meth I ester 229_0 5.356 HO
240_0 ~N
085 "
392.38 F--f-F
F
4-[3-(4-Trifluoromethoxy-phenyl )-im idazo[1, 2-b]p ridazin-6-ylamino]-c clohexanol 2290 5.357 HO-_a i N
167 H 336.44 4-[3-(3,4-Dimethyl-phenyl}imidazo[1,2-b]pyridazin-6-lamino] clohexanol 229_0 5.358 HO
240_0 __a N
H
285 / ~
338.41 HO
4-[3-(4-Hydroxymethyl-phenyl)-imidazo[1,2-b ridazin-6- Iamino -c clohexanol 229_0 5.359 HO
2400 ~
H
160 342.83 ci 4-[3-(4-Chloro-phenyl)-imidazo[1,2-b]pyridazin-6-lamino -c clohexanol 229_0 5.360 HO
240_0 H
311 N 339.40 O-4-[3-(6-Methoxy-pyrid i n-3-yl)-im idazo[1, 2-b]pyridazin-6- lamino clohexanol 1229_0 5.361 HO
I2400 ~
H
196 J 339.40 N
-O
4-[3-(5-Methoxy-pyridin-3-yi)-im idazo[1, 2-b]pyridazin-6-ylaminoj-c lohexanol 229 0 5.362 HO

H
284 / ~ 324.38 OH
3-[6-(4-Hydroxy-cyclohexylam ino )-im idazo[1, 2-b pyridazin-3- I]-phenol 2290 5.363 "o 2400 N ,-N
H

~ 352.39 ~

OH
O
4-[6-(4-Hydroxy-cyclohexyl am ino)-im idazo[1, 2-b yridazin-3- I]-benzoic acid 229_4 5.364 0510 V, /

/
0 354.41 -o Cyclopropylmethyl-[3-(3,4,5-trimethoxy-phenyl)-imidazo 1,2-b]p ridazin-6 I -amine 229_4 5.365 314 \/ H
/ 310.36 OH
4-[6-(Cyclopropylmethyl-amino)-imidazo[1,2-b]pyridazin-3- ]-2-methoxy-phenol 229_4 5.366 324.38 o-Cyclopropylmethyl-[3-(3,4-dimethoxy-phenyl)-imidazo 1,2-b p idazin-6- I-amine 229_4 5.367 051_0 VII~N
135 H / 307.40 \
Cyclopropylmethyl-[3-(3-dimethylam ino-phenyl )-imidazo[1,2-b]pyridazin-6-yl]-amine 229_4 5.368 ~
, 051 _0 N ~ /
069 / ~ 265.32 N
Cyclopropylmethyl-(3-pyridin-4-yl-imidazo[1,2-b pyridazin-6 I -amine 229_4 5.369 051_0 N _-r' ~
291 \ 294.36 OH
{3-[6-(Cyclopropylmethyl-am ino)-im idazo[1,2-b]pyridazin-3-yl]-phen I}-methanol 2294 5.370 <', ~

140 H / \ 294.36 Cyclopropylmethyl-[3-(3-methoxy-phenyl)-imidazo 1,2-b]p ridazin-6 I -amine 229_4 5.371 0517 -'' 468 268.32 N-N
Cyclopropyl m ethyl-[3-(1-m ethyl-1 H-pyrazol-4-yl )-im idazo[1,2-b]pyridazin-6-yl]-amine 229_4 5.372 0517 -'' 467 254.30 N-NH
Cyclopropylmethyl-[3-(1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine 2294 5.373 051 _0 N -r' ~
068 \/ H
308.34 J

(3-Benzo[1, 3]dioxol-5-yl-im idazo[1, 2-b]pyridazi n-6-yl )-c clo ro Imeth I-amine 229 4 5.374 051 0 ~_/N 1 ~' 280 ~/ H
294.36 /
Cyclopropyl methyl-[3-(4-m ethoxy-phenyl )-imidazo[1,2-b]pyridazin-6 I]-amine 229_4 5.375 5~"
0510 '"~N -N
074 H 270.36 s Cyclopropylmethyl-(3-thiophen-3-yl-imidazo[1,2-b p ridazin-6- I -amine 229_4 5.376 051_0 '311 ~N 295.34 /
Cyclopropylmethyl-[3-(6-methoxy-pyridin-3-yl)-imidazo[1,2-b]p idazin-6- I]-amine 229_4 5.377 051 _0 N
345 284.39 Cyclopropylmethyl-[3-(4-methyl-thiophen-2-yl )-imidazo[1,2-b]pyridazin-6- I]-amine 229_4 5.378 0510 ~
N
081 N 321.38 N-{3-[6-(Cyclopropylmethyl-amino)-imidazo[1,2-b]pyridazin-3- I - hen I -acetamide __ 2294 5.379 H
~192 o 351.41 H
OH
3-[6-(Cyclopropylmethy!-amino)-im idazo[1,2-b] ridazin-3-yl]-N- 2-hydrox -eth I -benzamide 229_4 5.380 294.36 HO
{4-[6-(Cyclopropylmethyl-amino)-imidazo[1,2-b]pyridazin-3-yl -phenyl}-methanol 229_4 5.381 051_0 080 280.33 OH
4-[6-(Cyclopropylmethyl-amino)-imidazo[1,2-b]p idazin-3- I]-phenol 2294 5.382 0510 IV ~
284 / - 280.33 OH
3-[6-(Cyclopropylmethyl-amino)-im idazo[1,2-b idazin-3- I - henol 2294 5.383 N

H 357.44 o N-{3-[6-(Cyclopropylmethyl-a m i no)-im id azo[1, 2-b ridazin-3 ]-phen I -methanesulfonamide 229_4 5.384 N
139 0 308.34 OH
3-[6-(Cyclopropylmethyl-amino)-im idazo[1, 2-b idazin-3 -benzoic acid 229_4 5.385 i ; 051 7 N
''.....469 N~" 344.42 / ~
~
[3-(1-Benzyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6- I]-cyclopro Imeth I-amine 229 4 5.386 N

308.34 HO
4-[6-(Cyclopropylmethyl-amino)-imidazo[1,2-b p ridazin-3-yl]-benzoic acid 2294 5.387 051_0 N
347 0 307.36 3-[6-(Cyclopropylmethyl-amino)-imidazo[1,2-b pyridazin-3 I -benzamide 229_4 5.388 051 _4 N
145 0 306.37 1-{3-[6-(Cyclopropylmethyl-amino)-imidazo[1,2-b ridazin-3- I- hen I-ethanone , 229_4 5.389 ~-7 ~ 47 v H 270.36 Cyclopropylmethyl-(3-thiophen-2-yl-imidazo[1,2-b]p ridazin-6 I -amine Description of the HPLC-MS analysis conditions for the examples listed in Table 5:
Detection: UV = 200 - 350 nm (Waters Acquity HPLC)/ MS 100-800 Daltons; 20 V
(Micromass / Waters ZQ 4000); column: X Bridge (Waters), 2.1 x 50 mm, BEH
1.7 pm; eluent: A: H20/0.05% HCOOH, B: CH3CN/0.05% HCOOH.
Gradient: 10-90% B in 1.7 min, 90% B for 0.2 min, 98-2% B in 0.6 min; flow rate:
1.3 mI/min.

[3-(2-Methoxyp yridin-4-yl)imidazo[1, 2-b]p yridazin-6-yl]piperidin-4-ylamine (Example 6.0) HaN N
H
_0 Stage A: 4-[3-(2-methoxypyridin-4-yl)imidazo[1,2-b]pyridazin-6-ylamino]piperidine-1-carboxylic acid tert-butyl ester (Example 6.1) O'~'N
CI H

N _O N
--O-292 mg of 4-[3-(2-methoxypyridin-4-yl)imidazo[1,2-b]pyridazin-6-ylamino]piperidine-s 1-carboxylic acid tert-butyl ester were prepared from 300 mg (1.15 mmol) of chloro-3-(2-methoxypyridin-4-yl)imidazo[1,2-b]pyridazine (Example 1.14) and 230 mg (1.15 mmol) of 4-aminopiperidine-l-carboxylic acid tert-butyl ester (CAS
No. 87120-72-7) by method A.

1 H-NMR (300 MHz, d6-DMSO): 8= 1.32 - 1.38 (m, 11 H); 2.02 - 2.08 (m, 2H);
to 2.92-3.00(m, 2H); 3.72-3.92(m, 6H); 6.73 (d, 1H); 7.17-7.19(m, 1H); 7.64-7.66 (m, 1 H); 7.76 - 7.79 (m, 2H); 8.11 - 8.16 (m, 2H) ppm.

MS (ES+): m/z = 425 (M+H)+ [mol. weight = 424.51].

Stage B: [3-(2-methoxypyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl]piperidin-4-i5 ylamine (Example 6.0) O~N HN
l N
v ' H N
H
N
~O _O N

280 mg (0.66 mmol) of 4-[3-(2-methoxypyridin-4-yl)imidazo[1,2-b]pyridazin-6-ylamino]piperidine-1-carboxylic acid tert-butyl ester were introduced into 3 mi of THF

and, after addition of 0.8 ml of HCI in dioxane (4M), stirred at RT overnight.
HCI
(conc.) was added, and the mixture was heated at 70 C for 4 hours. The reaction was diluted with water, adjusted to pH 11 with Et3N and extracted three times with ethyl acetate. The combined organic phases were filtered through a silicone filter s (from Whatman) and concentrated. In the final fractionation by chromatography on silica gel, 92 mg of the desired product were isolated.

1 H-NMR (300 MHz, d6-DMSO): b= 1.30 - 1.43 (m, 2H); 2.03 - 2.08 (m, 2H); 2.59 -2.67 (m, 2H); 2.99 - 3.06 (m, 2H); 3.66 - 3.75 (m, 1 H), 3.89 (s, 3H); 6.77 (d, 1 H);
7.15 - 7.18 (m, 1 H); 7.66 - 7.69 (m, 1 H); 7.80 (d, 1 H); 8.87 (s, 1 H); 8.15 - 8.19 (m, io 2H) ppm.

MS (ES+): m/z = 325 (M+H)+ [mol. weight = 324.39].
The following example was prepared analogously:

Example Structure and name of the main isomer 'H-NMR Mol. weight/
No. MS (ES+) [M+1 ]+

6.2 HN (300 MHz, d6-DMSO): 324.39/325 = 1.22 - 1.35 (m, H 2H); 1.92 - 1.97 (m, / \ 2H); 2.49 - 2.57 (m, N 2H, partly covered by o solvent); 2.90 - 2.97 ~ (m, 2H); 3.55 - 3.67 I3 (6-MethoxY-pY ridin-3-YI)-imidazo[1,2- (m, 1H); 3.86 (s, 3H);
-b]pyridazin-6-yl]-piperidin-4-yl-am ine 6.64 (d, 1 H); 6.96 6.98 (m, 1 H); 7.70 (d, 1 H); 7.80 (s, 1 H); 8.38 (dd, 1 H) ppm.

3-(6-(2-Hydroxyeth ylamino)imidazo[1, 2-b]pyridazin-3-yl]benzenesulfonamide (Example 7.0) N N

HO~~ HO~"~ ~N
N~ N N
H --- H

S~NHz S' ~11 -/ I H O O

82 mg (0.21 mmol) of N-tert-butyl-3-[6-(2-hydroxyethylamino)imidazo[1,2-b]pyridazin-3-yl]benzenesulfonamide were mixed under argon with 1.7 ml of trifluoroacetic acid and stirred at 50 C for 5 hours. After cooling, the mixture was concentrated in vacuo, and the residue was taken up in ethyl acetate. The organic phase was washed with saturated NaHCO3 solution and saturated NaCI solution, filtered through a Whatman filter and concentrated. The resulting residue was lo purified by chromatography (DCM/EtOH 6:4). 47 mg of the product were obtained.

1 H-NMR (400 MHz, d6-DMSO): 8= 3.36 - 3.40 (m, 2H); 3.61 - 3.65 (m, 2H); 4.77 (t, 1 H); 6.78 (d, 1 H); 7.17 (t, 1 H); 7.35 (s, 2H); 7.59 - 7.63 (m, 1 H); 7.70 -7.76 (m, 2H);
7.95 (s, 1 H); 8.25 (d, 1 H); 8.87 (m, 1 H) ppm.

The following example was prepared analogously:

Example Structure and name of the main isomer 1H-NMR Mol. weight /
No. MS (ESI) [M+1 l+

MW:
,N 333.37 HN N
MS (ESI+):

7.1 S

4-[6-( 2-H yd rox y-et h yl a m i n o)-i m i d a zo [1,2-b]pyridazin-3-yl]-benzenesulfon amide The following examples were prepared from 4-(6-chloroimidazo[1,2-b]pyridazin-3-yI)phenol and the appropriate amine in analogy to Example 1.5:

Example Structure and name of the main isomer H-NMR Mol. weight /
No. MS (ES+) [M+1 ]+

MW 311.39 HN NN MS (ES+):
[M+1 ]+ 312 8.0 1-11N
~ OH
4-[6-(3-Dimethylamino-propylamino)-imidazo[1,2-b]pyridazin-3-yl]-phenol / N (DMSO-d6, stored ~ N over molecular HN N~ sieves): 8= 2.40 (m, 4H); 2.54 (m, 2H);
8.1 N 3.37 (m, 2H); 3.56 (m, c) OH 4H); 6.63 (d, 1 H); 6.80 O (d, 1 H); 6.92 (m, 1 H);
4-[6-(2-Morpholin-4-yl-ethylamino)- 7.66 (m, 2H); 7.94 (d, 1 H) ppm.
imidazo[1,2-b]pyridazin-3-yl]-phenoi Biological effects The following examples describe the biological effect of the compounds of the invention:

It is clear to the skilled worker that there is a number of disorders in which the cause of the disorder derives from a dysfunction of one or more kinases.
Dysfunctions of kinases can be induced by a large number of mechanisms, e.g. a kinase may be overexpressed, leading to a faulty cellular activity, or a mutated to kinase may be overexpressed, likewise leading to a faulty cellular activity. The faulty cellular activity may be for example a faulty cellular proliferation, especially an increased cellular proliferation (cellular hyperproliferation). The result of such dysfunctions may be for example a disorder which is characterized by overexpression or mutation of the kinase.
Appropriate assays for testing the efficacy of the compounds of the invention for the ability to modulate kinase activity are known. Also known are assays in order to investigate the efficacy of the compounds of the invention in modulating cellular proliferation.

The following biological examples therefore serve merely to describe by way of example the uses according to the invention of the claimed compounds and are therefore not to be understood as limiting in any way.

Significance of IL-2 in the T cell immune response The extent to which test substance influence antibody-induced interleukin 2 (IL-2) secretion was investigated in the following test system. IL-2 represents a central cytokine which is produced and released by activated T cells. IL-2 synthesis in the T cells is regulated by a plurality of kinases. An inhibitory effect of substances on kinases leads inter alia to inhibition of IL-2 synthesis and inhibition of the T cell io immune response. The cytokine determinations were carried out using an ELISA
kit.

Description of the test system Peripheral blood mononuclear cells (PBMC) were isolated from heparinized human is whole blood by gradient centrifugation using Histopaque 1077 (Sigma) at room temperature, and the erythrocytes were lyzed hypotonically and, after washing twice in PBS, taken up in cell culture medium (10% fetal inactivated calf serum in RPMI-1640 + Glutamax-I [Gibco]).

The 96 well culture plates (Costar) were previously incubated with 100 pl of 2o antibody solution in PBS 0.1 pg/mi in PBS [Gibco]) per well at 4 C for 18 hours.
The antibodies used were anti-CD3 and anti-CD28 monoclonal antibodies (PharMingen). After washing with PBS three times, the plates were charged with 200 Ni of the cell suspension (40 000 cells/well). In addition, the test substances were added in concentrations such that they were present in concentrations of 25 1 x 10-6 - 1 x10-12 M.

The cultures were incubated in an incubator at 37 C for 20 hours. After this incubation, the plates were briefly shaken and centrifuged, and 250 pl of supernatant were removed, and the supernatants were then frozen at -20 C.

Interleukin-2 was determined using an ELISA kit (Bioscience), and the absorption of the color change was analyzed in a SpectraMax 340 PC (wavelength 450 nm).
Active substances brought about a reduction in the absorption.

Table 1: Assay data Example Structure Inhibition IC50 [mol/1] (concentration No. of PKC for 50% inhibition of IL-2) theta inhibition at 10 pM

[mol/1]
OP 3070 ,N 6.1 X 10-6 1.4x10 ,>95 a inhibition N N'N at 10 pM
H

(3-Phenyl-imidazo[1,2-b]pyridazin-6 -yI)-(3-pyrrolidin-1-yl-propyI)-amine OP 3071 N 1.7 x 10 2.5x10 , >95% inhibition N N N'N at 10 pM
~
oJ H
(3-Morpholin-4-yl-propyl)-(3-phenyl-imidazo[1,2-b]pyridazin-6-yl)-amine OP 3073 N 2.5 x 10 2.1 x10 , >95% inhibition at 10 pM
N~~N C~N N&C1 G H

[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazin-6-yl]-(3-pyrrolidin-1-yi-propyl)-amine OP 3074 N 4.1 x 10" 9.2x10 , >95% inhibition ~NN N' at 10 pM
o'J H
Ci [3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazi n-6-yl]-(3-morpholi n-4-y I-propyl)-amine KE1322- ~~N 1.29 x 10- 1.7 x 10-002-a NNN N~~
j H
(3-Imidazol-l-yl-propyl)-(3-phenyl-imidazo[1,2-b] pyridazin-6-yl)-amine KE1322- N 1.13 x 10 2.0 x 10 006-a ~
~N
N,N H
H

[3-(5-Methyl-1 H-pyrazol-4-yl)-propyl]
(3-phenyl-imidazo[1,2-b]pyridazin-6--amine KE1322- , N 5.4 x 10" 1.1 x 10 010-a ,N
N N
H

N*1 *,N*1 *-Diethyl-N*4*-(3-phenyl-imidazo[1,2-b]pyridazin-6-yl)-pentane -1,4-diamine KE1322- ;;_N 5.5 x 10 2.6 x 10 011-a ,N
N N N
J H

N,N-Diethyl-N'-(3-phenyl-imidazo [1,2-b]pyridazin-6-yi)-propane-1,3-diamine KE1322- 7.2 x 10 1.1 x 10 014-a ,N
N N N
N ' H

CI
[3-(3-Chloro-phenyl)-imidazo[1,2-b]
pyridazi n-6-yl]-(3-im idazol-l-yl-propyl)-amine KE1322- ~~N 2.2 x 10 2.9 x 10 022-a ~ ,N
N N
H
/ CI
N*4*-[3-(3-Chloro-phenyl)-im idazo [1,2-b]pyridazin-6-yl]-N*1 *,N*1 *-diethyl-pentane-1,4-diam ine KE1322- ~N 2.5 x 10 2.1 x 10 023-a ~~ ,N
N N N
J H
c I
N'-[3-(3-Chloro-phenyl)-imidazo [1,2-b]pyridazin-6-yl]-N,N-diethyl-propane-1,3-diamine KE1322- 1.7 X 10 1.0 X 10 024-a CLLfYN
.N
N N
H
CI
[3-(3-Chloro-phenyl)-imidazo [1,2-b]pyridazin-6-yl]-(2-pyrrolidin-1-yl-ethyl)-amine KE1322- 7.0 x 10 028-a N
N N
H
N,N
Cyclohexylmethyl-[3-(1-methyl-1 H-pyrazol-4-yl)-imidazo[1,2-b]pyridazi 6-yl]-amine KE1322- CINX N 7.2 x 10 0.7 x 10 030-a /
N N
N'N I H
H N-N
[3-(1-Methyl-1 H-pyrazol-4-yl)-imidaz [1,2-b]pyridazin-6-yl]-[3-(5-methyl-1 H-pyrazol-4-yl)-propyl]-amine KE1322- 1.3 x 10 0.4 x 10 042-a ,N
N N
N.N I H
H
[3-(5-Methyl-1 H-pyrazol-4-yl)-propyl]-(3-thiophen-3-yl-imidazo-[1,2-b]pyridazin-6-yl)-amine ALK1 Kinase flashplate assay In order to examine the activity of compounds, an ALK1 kinase flashplate assay was established and used.
ALK1 phosphorylates serine/threonine residues of the biotinylated substrate bovine a-casein in the presence of [y-33P]ATP. The radiolabeled product is detected through binding to streptavidin-coated flashplates. The biotin residues of the biotinylated casein bind with high affinity to the streptavidin. Radiolabeled biotinylated casein resulting from the ALK1 kinase reaction causes a chemiluminescence signal after the streptavidin-mediated binding to the scintillator-containing surface of the flashplate has taken place. This signal derives from the closeness of the radioactive label to the scintillator in the surface of the well of the flashplate. Unphosphorylated substrate causes no signal because it contains no radiolabeled phosphate groups. Free [y-33P]ATP remaining unbound in the solution (supernatant) is washed out of the wells of the flashplates and therefore makes no significant contribution to a background signal. The measured signals are therefore a measure of the ALK1 kinase activity. Measurement takes place in a Perkin-Elmer io top count apparatus or a Perkin-Elmer ViewLux instrument.

Material:
Enzyme: purified human recombinant ALK1 kinase (GST fused to the intracellular domain of ALK1 [His142-GIn503]); self-prepared; aliquots are stored at -80 C;
diluted enzyme working solution: 2.5 ng/pi ALK1 (in assay buffer) is freshly prepared and stored on ice until used.
Substrate: biotinylated bovine a-casein. Unbiotinylated casein from Sigma is biotinylated by standard methods using a biotin-N-hydroxysuccinimide (NHS) ester.
Substrate working solution: 0.83 pM ATP, 1.67 pM biotinylated a-casein, 7.4 nCi of [Y_33P]ATP/pI in assay buffer Assay plates: 384-well plates, small volume, white, Greiner (# 784075) Flashplates: streptavidin-coated flashplates, Perkin Elmer (384-Well #
SPM410A) Assay buffer: 50 mM Tris/HCI pH 8.0, 1 mM MnCl2, 1 mM DTT, 0.01 % NP40, 0.5x complete EDTA-free Stop solution: 33.3 pM ATP, 33.3 mM EDTA, 0.07% Triton X-100 in PBS
Saturation solution for flashplates: 100 pM ATP, 0.2% Triton X-100 in PBS
Adhesive film for plates: Greiner (# 676080) Description of assay Protocol for a 5 pi assay (all steps are carried out at 20 C; a CyBi-well pipettor and a multidrop microdispensor is used for pipetting):
1. 50 ni or 250 ni of substance in 100% DMSO
2. addition of 3 pl of substrate working solution using a CyBi-Well pipettor 3. addition of 2 pi of enzyme working solution using a multidrop microdispensor Incubation at room temperature (20 C) for 60 min 4. addition of 15 pi of stop solution using a CyBi-Well pipettor 5. transfer of 18 NI of assay mixture into flashplates** using a CyBi-Well pipettor Incubation at room temperature for at least 3 h or at 4 C overnight in order to allow io binding to the streptavidin-coated flashplates.

6. washing of the flashplates three times with 50 pl of PBS without Ca++ and Mg++
each time 7. sealing of the plates with adhesive film 8. measurement in the top count (60 sec/well) is **Saturation of the flashplates: the flashplates are preincubated with 50 pi of saturation solution for at least 1 h. 18 lal of this solution are discarded before 18 pl of assay mixture are transferred into the flashplates Final concentrations calculated for a reaction volume of 5 ul: 5 ng of ALK1/well;
20 1 pM biotinylated a-casein; 0.5 pM ATP; 22 nCi/well [y-33P]ATP; 1 mM MnC12;
1 mM DTT; 50 mM Tris-HCI, pH 8.0; 0.01 % NP40; 0.5x complete EDTA-free; 1 %
or 5% DMSO.

The data are normalized (enzyme reaction without inhibitor = 0% inhibition, 25 enzyme reaction in the presence of 10 mM EDTA = 100% inhibition) and IC50 values are calculated using a 4-parameter fit with the aid of an in-house software.
ALK4 kinase flashplate assay In order to examine the activity of compounds, an ALK4 kinase flashplate assay 30 was established and used.

ALK4 phosphorylates serine/threonine residues of the biotinylated substrate bovine a-casein in the presence of [y-33P]ATP. The radiolabeled product is detected through binding to streptavidin-coated flashplates. The biotin residues of the s biotinylated casein bind with high affinity to the streptavidin.
Radiolabeled biotinylated casein resulting from the ALK4 kinase reaction causes a chemiluminescence signal after the streptavidin-mediated binding to the scintillator-containing surface of the flashplate has taken place. This signal derives from the closeness of the radioactive label to the scintillator in the surface of the well of the io flashplate. Unphosphorylated substrate causes no signal because it contains no radiolabeled phosphate groups. Free [y-33P]ATP remaining unbound in the solution (supernatant) is washed out of the wells of the flashplates and therefore makes no significant contribution to a background signal. The measured signals are therefore a measure of the ALK1 kinase activity. Measurement takes place in a Perkin-Elmer 15 top count apparatus or a Perkin-Elmer ViewLux instrument.

Material:
Enzyme: commercially available recombinant human ALK4 kinase (amino acids, 150-505), fused to GST at the N terminus, expressed by recombinant 2o baculoviruses in Sf21 insect cells (Upstate Biotechnology, Dundee, Scotland;
Cat#14-614MG), Lot#28232U; aliquots are stored at -80 C; diluted enzyme working solution, 2.5 ng/pl ALK1 (in assay buffer) is freshly prepared and stored on ice until used.
Substrate: biotinylated bovine a-casein. Unbiotinylated casein from Sigma is 25 biotinylated by standard methods using a biotin-N-hydroxysuccinimide (NHS) ester.
Substrate working solution: 0.83 pM ATP, 1.67 pM biotinylated a-casein, 7.4 nCi of [y-33P]ATP/taI in assay buffer Assay plates: 384-well plates, small volume, white, Greiner (# 784075) Flashplates: streptavidin-coated flashplates, Perkin Elmer (384-Well #
SPM410A) Assay buffer: 50 mM Tris/HCI pH 8.0, 1 mM MnCI2, 1 mM DTT, 0.01 % NP40, 0.5x complete EDTA-free Stop solution: 33.3 pM ATP, 33.3 mM EDTA, 0.07% Triton X-100 in PBS
Saturation solution for flashplates: 100 pM ATP, 0.2% Triton X-1 00 in PBS
Adhesive film for plates: Greiner (# 676080) Description of assay Protocol for a 5 NI assay (all steps are carried out at 20 C; a CyBi-well pipettor and a multidrop microdispensor is used for pipetting):
lo 1. 50 nI or 250 ni of substance in 100% DMSO
2. addition of 3 pl of substrate working solution using a CyBi-Well pipettor 3. addition of 2 pl of enzyme working solution using a multidrop microdispensor Incubation at room temperature (20 C) for 45 min 4. addition of 15 pl of stop solution using a CyBi-Well pipettor 5. transfer of 18 pl of assay mixture into flashplates** using a CyBi-Well pipettor Incubation at room temperature for at least 3 h or at 4 C overnight in order to allow binding to the streptavidin-coated flashplates.
6. washing of the flashplates three times with 50 pl of PBS without Ca++ and Mg++
each time 2o 7. sealing of the plates with adhesive film 8. measurement in the top count (60 sec/well) **Saturation of the flashplates: the flashplates are preincubated with 50 pl of saturation solution for at least 1 h. 18 pl of this solution are discarded before 18 pl of assay mixture are transferred into the flashplates Finai concentrations calculated for a reaction volume of 5 pl: 1 ng of ALK1/well;
1 pM biotinylated a-casein; 0.5 pM ATP; 22 nCi/well [y-33P]ATP; 1 mM MnC12;
1 mM DTT; 50 mM Tris-HCI, pH 8.0; 0.01 /a NP40; 0.5x complete EDTA-free; 1 %
or 5% DMSO.

The data are normalized (enzyme reaction without inhibitor = 0% inhibition, enzyme reaction in the presence of 10 mM EDTA = 100% inhibition) and IC50 values are calculated using a 4-parameter fit with the aid of an in-house software.

ALK1 transactivation assay In this case, HepG2 cell cultures are transiently transfected with an ALK1 plasmid (expression vector for the human ALK1 receptor) by known techniques. At the same time, an ID1 reporter plasmid which 1.3 kB (-1370 to +86) of the ID1 io promoter upstream of the luciferase gene is cotransfected. ID1 is a known target gene of ALK1 and is therefore transactivated by cotransfection with the ALK1 receptor. The specific transactivation is quantified by ("relative light units", RLU) which are detected depending on the luciferase. A commercially available kit for detecting luciferase, comprising the substrate luciferin, is used for this.

Material:
HepG2 cells (hepatocellular carcinoma), ATCC HB-8065 96 well culture plates 96 white (Packard # 6005680) 96 well plate polypropylene for compound dilution in DMSO
PBS-; PBS++, DMSO
DMEM Ham's F12 (Biochrom #F4815) with 10% FCS after dialysis, 1% PenStrep and 200 mM Glutamine OPTI MEM (Gibco #51985-026) Fugene (Roche #1814443 1 mL) steadyliteHTS (Perkin Elmer# 6016981) Experimental procedure:

Day 1: Seeding of the cells on 96-well plates HepG2 cells are seeded on 96-well plates at a density of 7000 cell/well in DMEM/HamsF12 + 5%FCS (+ 1% P/S, +1% GIn).

Day 2: Transfection of the cells Per well:
200 ng DNA: 100 ng lDl-luc (in pGL3basic, Promega)+ 5 ng ALKlwt (in pcDNA3.1) + 95 ng pcDNA3.1 (empty vector, Invitogen) 0.4 pl of fugene 6 pl of OptiMEM
Fugene and OptiMEM are incubated at RT for 5 min. This mixture is incubated with the DNA at RT for 15 minutes.
The plate is then incubated under shaking conditions at RT for 1 hour. After 4 hours at 37 C, the supernatant is aspirated off, and medium (100 ial/well) which contains a little serum (0.2% FCS) and test substance is added to the wells.
The plates are incubated at 37 C for a further 18 hours.

Day 3: RLU measurement 100 pI of luciferase substrate (steadyliteHTS, Packard) is added per well, and the plates are measured after 10 minutes in a luminometer (e.g. Viktor luminometer, Perkin Elmer). The luciferase activity is quantified by relative light units (RLU).
Calculation of the IC50:

ALK1 wt - DMSO control (without ALK1) = 100%
Substance (+ALK1 wt) -DMSO control (without ALK1) = x %
IC50 = 50% inhibition of ALK1 transactivation DU-145 proliferation assay Firstly, DU-145 cells were seeded in a concentration of 200 cells per well in a 96-well microtiter plate (CulturPlate-96, flat bottom transparent) (volume of the culture medium: 100 pl; negative control in starvation medium) and grown under culturing conditions for 18 h. Then 100 NI of the culture medium were removed, and 100 NI
of substance solution (dilution in culture medium) were added. The cells are incubated under culturing conditions for 72 h. After the end of the substance treatment, 5 pl of an Alamar Blue labeling solution (Biosource cat # DAL 1100, Lot # 143152SA; dissolved in culture medium) were added (in order to produce a to 1:20 dilution) and the cells were grown under culturing conditions for a further 3 h.
The proliferation rate was then analyzed by measurement in an FLx800 (fluorescence measuring instrument from BIO-TEK) at 528 nm and 590 nm in each case.

Cell lines and cell culture Human cell culture lines were used: DU-1 45 (prostate cell line ATCC No. HTB-81).
All cell lines were grown in 175 cm2 culture bottles at 37 C, 5% CO2 and 95%
humidity and split 1:5 to 1:65 at 80% confluence in accordance with the respective rates of division. For this purpose, the cells were initially washed with 10 ml of PBS
2o and wetted with 2 ml of trypsin (Gibco). Excess trypsin was removed, and the cells were incubated at room temperature for 10 min. Complete detachment of the treated cells was checked under the microscope. The cells were then taken up in culture medium and transferred in the appropriate volumetric ratio into new cell culture bottles.

DU-145 culture medium:
DMEM HAM's F-12 (from Biochrom AG, cat# F4815) + 1% P/S + 1% glutamine +
10% FCS (from Biochrom AG, Lot'0218G) DU-145 starvation medium:
3o DMEM HAM's F-12 (from Biochrom AG, cat# F4815) + 1 /o P/S + 1% glutamine Further proliferation assays DNA-replicating cells can be labeled using bromodeoxy uiridine (BrdU) and used as measure of the proliferation of eukaryotic cells. In this method, cells which are in the synthesis phase (S phase) incorporate the thymidine analog BrdU instead of thymidine into the growing DNA chain. The replicated DNA is thus labeled with the modified nucleotide BrdU and can subsequently be detected with the aid of a fluorophore-labeled anti-BrdU antibody. The method was used in order to investigate the effect of substances on cellular proliferation.
Firstly, HeLa cells were seeded in a 96-well microtiter plate in a concentration of io 7500 cells per well (volume: 200 pl) and grown under culturing conditions for 18 h.
Then 100 pl of the culture medium were removed, and 100 NI of substance solution (dilution in culture medium) were added. The cells were incubated under culturing conditions for 6 h, 18 h or 48 h. After the end of the substance treatment, the BrdU-labeling solution (dissolved in culture medium) was added (final concentration of is BrdU 10 pM), and the cells were grown under culturing conditions for a further 3 h.
The BrdU-containing supernatant was then removed, and the cells were washed with PBS. The cells were subsequently fixed with 4% strength formalin solution (dissolved in PBS, 0.1% Triton-X-100) at 4 C for 18 h and washed three times with 200 NI of PBS. In order to make the incorporated BrdU accessible for antibody 20 labeling, the DNA of the cells was digested with nuclease (GE/Amersham).
BrdU
was subsequently detected with the aid of a monoclonal anti-BrdU antibody (GE/Amersham). For this purpose, the fixed cells were incubated with an antibody/nuclease solution (50 pl/well) at 37 C for 45 min and then washed three times with 200 pl of PBS. The fluorescence labeling took place with a fluorophore-25 labeled second antibody which binds to the anti-BrdU antibody. The chromatin of the cell nuclei was stained with Hoechst 33342.
In each case 9 image sections per well were recorded in the various fluorescence channels using an automated microscope (Discovery-1, Molecular Devices), and the BrdU incorporation and the proliferation rate were analyzed by means of a 3o high-content analysis (HCA) method.

Cell lines and cell culture Human cell culture lines were used: HeLa (from cervical carcinoma), PC3 (from prostatic carcinoma) and MCF-7 (from carcinoma of the breast). In addition, CHO
cells (from Chinese hamster ovaries) were cultured.
All cell lines were grown in 175 cm2 culture bottles at 37 C, 5% CO2 and 95%
humidity and split 1:5 to 1:65 at 80% confluence in accordance with the respective rates of division. For this purpose, the cells were initially washed with 10 ml of PBS
and wetted with 2 ml of trypsin (Gibco). Excess trypsin was removed, and the cells were incubated at room temperature for 10 min. Complete detachment of the io treated cells was checked under the microscope. The cells were then taken up in culture medium and transferred in the appropriate volumetric ratio into new cell culture bottles.

HeLa culture medium:
Dulbecco's medium (Gibco), 2 mM glutamine (Gibco), 100 U/ml penicillin (Gibco), 100 pg/mI streptomycin (Gibco) and 10% (v/v) fetal calf serum (PAA) PC3 culture medium:
RPMI 1640 medium (Gibco), 2 mM glutamine (Gibco), 100 U/ml penicillin (Gibco), 100 Ng/mI streptomycin (Gibco) and 10% (v/v) fetal calf serum (PAA) MCF-7 culture medium:
RPMI 1640 medium (Gibco), 2 mM glutamine (Gibco), 100 U/mI penicillin (Gibco), 100 pg/mi streptomycin (Gibco) and 10% (v/v) fetal calf serum (PAA), 0.1 nM
estradiol (Sigma) and 0.2 U/mI insulin (Sigma) CHO culture medium:
Ham's F12 medium (PAA), 2 mM glutamine (Gibco), 100 U/mI penicillin (Gibco), 100 pg/mi streptomycin (Gibco) and 3% (v/v) fetal calf serum (PAA) SRG/US/53343 - 159 - AL.I/TDS
Further prior art Further prior art is formed by the following publications and the literature cited in these publications:

Gorup et al., Tetrahedron 30 (1974), Byth et al. Bioorganic & Medicinal 2251-2256 Chemistry Letters 14 (2004) 2249-2252 Polanc et al., J. Heterocyclic Chemistry Watanabe et al, Synthesis 11 (1977.), (1973), 565-567 761-763 Bioorganic & Medicinal Chemistry Bioorganic & Medicinal Chemistry Letters 2006,1353 Letters 2005,1943 Bioorganic & Medicinal Chemistry Journal of Medicinal Chemistry 2005, Letters 2004 ,6095 7604 Priorities of the present application:

The present patent application claims the priority of German patent application DE 10 2005 042 742.1 (date of filing: Sept. 2, 2005), and it also claims all the advantages of filing of the US patent application 60/713 333 (date of filing:
Sept. 2, 2005, provisional application).

The independent claims of the priority application read as follows:
1. A compound of the formula I

N rN Formel I
CN-R1, N
R2 yA
Q
B
where Q is aryl or heteroaryl;

A and B are identical or different and are selected from the group consisting of i) H, Hal, -OH, -NR3R4, -CN, or -NO2, ii) optionally mono- or poly-Hal-, -OH-, C3-C6-heterocycloalkyl-, -NR3R4-, or -(CO)-NR3-L-substituted C1-C6-alkyl, C1-C6-alkoxy, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SOz)- groups and/or one or more double bonds, and iii) -NR3(CO)-L, -NR3(CO)-NR3-L, -(CO)-R6, -O-(CH2)P R6, -(CO)-(NR3)-L, -NR3(CS)-NR3R4 or -O-(CH2)p-aryl, where the substituents in the case of polysubstitution may be identical or different, A and B in addition or alternatively to the aforementioned definition together form a Q-fused C5-C7-cycloalkyl or C5-C7-heterocycloalkyl ring, where the latter comprises at least one oxygen or one nitrogen atom in the ring, and may optionally comprise additionally in the ring one or more oxygen, nitrogen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, p isOto4, L is optionally mono- or poly-C1-C6-alkyl-, C1-C6-hydroxyalkoxy-, C1-C6-alkoxyalkoxy, C3-C6-heterocycloalkyl-, or -NR3R4-substituted C1-C6-alkyl, or C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6 heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or one or more double bonds;

R' and R2 are identical or different and are selected from the group consisting of j) -H
and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L-or-NR3COOR7-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-.
heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R' and R2 in addition or alternatively to the aforementioned definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally comprise additionally in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R' and R2 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, -NR3R4, -CONR6R7, -(CO)-R6 or-COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 are identical or different and are selected from the group consisting of j) -H, and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NRsR'-, -CONR6R'-, -(CO)-R6- or -COOR'-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)-or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 in addition to the aforementioned definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally comprise additionally in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R3 and R4 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, or by -NR6R', -CONR6R', -(CO)-R6 or -COOR' and/or by optionally mono- or poiy-Hal-, C1-C6-alkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R6 and R' are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different, and the isomers, diastereomers, enantiomers and salts thereof.

2. The compound as claimed in claim 1, where R' and R2 are identical or different and selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl, -(CO)-R6-, -NR3R4-, -NR3(CO)-L- or -NR3COOR7-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may is optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, where the substituents may in the case of polysubstitution be identical or different, and where R' and R2 in addition or alternatively to the preceding definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R' and R2 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, -NR3R4, -CONR6R', -(CO)-R6 or -COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy- or -(CO)-Rs-substituted aryl or heteroaryl, where the substituents may in the case of polysubstitution be identical or different.

3. The compound as claimed in claim 1 or 2, wherein R' and R2 are identical or different and selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryloxy-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L- or-NR3COOR'-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the (ng one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, where the group aryl or heteroaryl defined in jj) may be substituted as long as alkyl is not involved, where the substituents may in the case of polysubstitution be identical or different, and where R' and R2 in addition or alternatively to the preceding definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)-is groups and/or optionally one or more double bonds, where the ring formed by R' and R2 is optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, -NR3R4, -CONR6R', -(CO)-R6 or -COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents may in the case of polysubstitution be identical or different.
4. The compound as claimed in claim 3, where Q is -OH-, -Hal-, -CN-, alkyl-, -OR6- or -NR3R4-substituted phenyl, pyridyl, pyrimidinyl, thiophenyl, furyl, imidazolyi, or pyrazolyl.

5. The compound as claimed in claim 4, where R' and R2 are identical or different and selected from the group consisting of -H, NR3R4-substituted C1-C4-alkyl, optionally additionally substituted one or more times by -Hal, -OH, -CN, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-hydroxyalkyl, C3-C6-cycloalkyl, C3-C6 heterocycloalkyl, C2-C6-alkynyl, aryl, aryloxy, heteroaryl, -S-C1-C6-alkyl, -(CO)-R6, -NR3(CO)-L, or -NR3COOR', where R3 and R4 may optionally, identically or differently, be C1-C6-alkyl, where R3 and R4 may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, and where R6 and R7 is identically or differently -H, -OH, C1-C6-alkoxy, or C1-C3-alkyl.

6. The compound as claimed in any of claims 4, where R' is selected from the group consisting of -H and C1-C3-alkyl, where R2 is selected from the group consisting of NR3R4-substituted C3-C4 alkyl, optionally additionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3(CO)-L- or -NR3COOR'-substituted, where R3 and R4 are identically or differently optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R7-, -CONR6R'-, -(CO)-R6- or-COOR'-substituted Cl-C6-alkyl, where R3 and R4 may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, and where R6 and R7 is identically or differently -H, -OH, C 1 -C6-alkoxy, or C1-C3 alkyl.
7. The compound as claimed in claim 1, namely:
(3-phenylimidazo[1,2-b]pyridazin-6-yl)-(3-pyrrolidin-l-ylpropyl)amine (3-morpholin-4-ylpropyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine (3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl)-(3-pyrrolidin-1-ylpropyl)amine (3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl)-(3-morpholin-4-ylpropyl)amine [3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]pyridin-3-ylmethylamine (3-phenylimidazo[1,2-b]pyridazin-6-yl)pyridin-3-ylmethylamine (3-imidazol-1-ylpropyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine (4-fluorobenzyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine cyclohexylmethyl(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine (2,4-difluorobenzyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine [3-(5-methyl-1 H-pyrazol-4-yl)propyl]-(3-phenylimidazo[1,2-b]pyridazin-6-yI)amine 1-[2-(3-phenylimidazo[1,2-b]pyridazin-6-ylamino)ethyl]imidazolid in-2-one (2-morpholin-4-ylethyl))-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine N*1,N*1 *-diethyl-N*4-(3-phenylimidazo[1,2-b]pyridazin-6-yl)pentane-1,4-diamine N,N-diethyl-N "-(3-phenylimidazo[1,2-b]pyridazin-6-yl)propane-1,3-diamine (3-phenylimidazo[1,2-b]pyridazin-6-yl)-(2-pyrrolidin-1-ylethyl)amine [3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl]pyridin-3-ylmethylamine is [3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl]-(3-imidazol-1-ylpropyl)amine 3-(3-chlorophenyl )imidazo[1, 2-b]pyridazin-6-yl)-(4-fluorobenzyl)amine 3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl)cyclohexylmethylamine 3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl)-(2,4-d ifluorobenzyl)amine 1-{2-[3-(3-phenyl)imidazo[1,2-b]pyridazin-6-ylamino]ethyl}imidazolidin-2-one N*4*-[3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl]-N*1 *,N*1 diethylpentane-1,4-diamine N "-[3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yi]-N,N-diethylpropane-2s 1,3-diamine [3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl]-(2-pyrrolidin-l-ylethyl)amine (3-imidazol-1-ylpropyl)-[3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]amine (4-fluorobenzyl)-[3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]amine cyclohexylmethyl-[3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]amine (2,4-difluorobenzyl)-[3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]amine [3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]-[5-methyl-1 H-pyrazol-4-yl)propyl]amine 1-{2-[3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-ylamino]ethyl}imidazolidin-2-one (3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)-(2-morpholin-4-ylethyl)amine Is N*1,N*1 *-diethyl-N*4-[3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]pentane-l,4-diamine N,N-diethyl-N "-[3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]propane-1,3-diamine [3-(1-methyl-1 H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]-(2-pyrrolidin-1 -ylethyl)amine pyridin-3-ylmethyl-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine (4-fluorobenzyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine cyclohexylmethyl-(3-thiophen-3-ylim idazo[1,2-b]pyridazin-6-yl)amine (2,4-d ifluorobenzyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl )amine [3-(5-methyl-1 H-pyrazol-4-yl)propyl]-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine 1-[2-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-ylamino)ethyl]imidazolidin-2-one (2-morpholin-4-ylethyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine N*1,N*1 *-diethyl-N*4-[3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl]pentane-1,4-diamine N, N-diethyl-N "-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl]propane-1,3-diamine (2-pyrrolidin-1 -ylethyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine 8. A method for preparing a compound as claimed in any of claims 1 to 7, with the following stages of the method:

Al) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, to A2) the product from stage Al is reacted with N-bromosuccinimide to give a bromo-6-haloimidazo[1,2-b]pyridazine, A3) the product from stage A2 is converted by reaction with a compound NHR'R2 in a Buchwald-Hartwig cross-coupling reaction into a (3-bromoimidazo[1,2-b]pyridazin-6-yl)-(R')-(R 2)-amine, A4) the product from stage A3 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula I, or 131) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, B2) the product from stage B1 is reacted with N-bromosuccinimide to give a 3-bromo-6-haloimidazo[1,2-b]pyridazine, B3) the product from stage B2 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula II, SRG/US/53343 - 169 - AL,1/TDS
B4) the product from stage B3 is converted by reacting with a compound NHR'R2 in a Buchwaid-Hartwig cross-coupling reaction into the compound according to the general formula I, or C1) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, C2) the product from stage Cl is converted by reacting with a compound NHR'R2 in a Buchwald-Hartwig cross-coupling reaction into an imidazo[1,2-b]pyridazin-6-yl)-(R' )-(R2)-amine, io C3) the product from stage C2 is reacted with N-bromosuccinimide to give a(3-bromoimidazo[1,2-b]pyridazin-6-yl)-(R' )-(R2)-amine, C4) the product from stage C3 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula I.

9. The use of a compound as claimed in any of ciaims 1 to 7 for producing a pharmaceutical composition.

10. The use of a compound as claimed in any of claims 1 to 7 for inhibiting a cellular kinase, in particular a kinase from the group of the protein kinase C
family such as, for example, PKC theta, delta, iota, alpha and zeta.

11. The use of a compound as claimed in any of claims 1 to 7 for producing a pharmaceutical composition for the treatment or for the prophylaxis of a disorder which is associated with overexpression or mutation of a cellular kinase, in particular a cellular kinase according to claim 10.

12. The use as claimed in claim 9, where the disorder is a disorder from the group consisting of "epidermal hyperproliferation such as psoriasis, Alzheimer's, autoinflammatory disorders, Crohn's disease, exaggerated immune response, contact dermatitis, atopic dermatitis, multiple sclerosis, ALS, diabetes, asthma".

13. The use as claimed in claim 9 for modulating, in particular reducing, an immune response, for example after a transplantation has taken place to avoid rejection of an organ.

14. A method for producing a pharmaceutical composition, where a physiologically effective dose of a compound as claimed in any of claims 1 to 7 is mixed with at least one pharmaceutical excipient, and a dosage form is manufactured.

io 15. A method for the treatment or prophylaxis of a disorder which is associated with overexpression or mutation of a cellular kinase, in particular a disorder according to claim 12, where a pharmaceutical composition comprising a physiologically effective dose of a compound as claimed in any of claims 1 to 7 is administered to a person suffering from or under threat of suffering from the disorder.

16. An intermediate according to formula Ila / ~N

R1, C N ~
N N ~

General formula Ila where Y is replaced by -H or -Hal, R' and R2 are identical or different and selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L- or -NR3COOR'-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R' and R2 in addition or alternatively to the preceding definition may together to form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed via R' and R2 may be optionally substituted one or more times by -CN, -Hal, -OH, Cl-C6-alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, -NR3R4, -CONR6R7, -(CO)-R6 or-COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 are identical or different and selected fi-om the group consisting of j) -H
and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R'-, -CONR6R'-, -(CO)-R6- or-COOR'-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)-or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 in addition or alternatively to the preceding definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R3 and R4 may optionally be substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl or by -NR6R7, -CONR6R', -(CO)-R6 or -COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R6 and R' are identical or different and selected from the group consisting of j) -H
and jj) optionally mono- or poly-Hal-, -OH-, -CN-substituted C1-C6-alkyl, C1-ts C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionallyt comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different, and the isomers, diastereomers, enantiomers and salts thereof.
17. An intermediate according to general formula Ilb X N, A
Q

B
General formula Iib Q is aryl or heteroaryl;

A and B are identical or different and selected from the group consisting of i) H, Hal, -OH, -NR3R4, -CN or -NO2, ii) optionally mono- or poly-Hal-, -OH-, C3-C6-heterocycloalkyl-, -NR3R4-, or -(CO)-NR3-L-substituted C1-C6-alkyl, C1-C6-alkoxy, C3-C6-cycloalkyl io or C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or one or more double bonds, and iii) -NR3(CO)-L, -NR3(CO)-NR3-L, -(CO)-R6, -O-(CH2)P-R6, -(CO)-(NR3)-L, -NR3(CS)-NR3R4, or -O-(CH2)P-aryl, where the substituents in the case of polysubstitution may be identical or different, A and B in addition or alternatively to the preceding definition together form a Q-fused C5-C7-cycloalkyl or C5-C7-heterocycloalkyl ring, where the latter comprises at least one oxygen or nitrogen atom in the ring and may optionally additionally comprise in the ring one or more oxygen, nitrogen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, p isOto4, L is optionally mono- or poly-C1-C6-alkyl-, C1-C6-hydroxyalkoxy-, C1-C6-alkoxyalkoxy-, C3-C6-heterocycloalkyl- or -NR3R4-substituted C1-C6-alkyl or C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6 heterocycloalkyl may optionally comp(se in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or one or more double bonds;

X is chlorine, bromine, O-S02-CF3 or O-SO2-C4F9;

R3 and R4 are identical or different and selected from the group consisting of j) -H, and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-alkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R'-, -CONR6R'-, -(CO)-Rs-or-COOR7-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;
is R3 and R4 may in addition or alternatively to the preceding definition together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed via R3 and R4 may optionally be substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, or by -NR6R7, -CONR6R', -(CO)-R6 or-COOR' and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents may in the case of polysubstitution be identical or different;

R6 and R' are identical or different and selected from the group consisting of j) -H
and jj) optionally mono- or poly-Hal-, -OH-, -CN-substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution s may be identical or different and the isomers, diastereomers, enantiomers and salts thereof.

Claims (24)

1. A compound of the formula I

where Q is aryl or heteroaryl - with the exception of pyrimidine;

A and B are identical or different and are selected from the group consisting of i) H, Hal, -OH, -NR3R4, -CN, or -NO2, ii) optionally mono- or poly-Hal-, -OH-, C3-C6-heterocycloalkyl-, -NR3R4-, -SO2NR3R4-, -SO2R3-or-(CO)-NR3-L-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or one or more double bonds, and iii) -NR3(CO)-L, -NR3(CO)-NR3-L, -(CO)-R6, -O-(CH2)p-R6, -(CO)-(NR3)-L, -NR3(CS)-NR3R4, -NR3(SO2)-L, -(SO2)-NR3R4, -NR3(CO)NR3R4, -(CO)NR3R4, -C02R7, -NR3(SO2)R4 or -O-(CH2)p-aryl, where the substituents in the case of polysubstitution may be identical or different, A and B in addition to the aforementioned definition together form a Q-fused C5-C7-cycloalkyl or C5-C7-heterocycloalkyl ring, where the latter comprises at least one oxygen or one nitrogen atom in the ring, and may optionally comprise additionally in the ring one or more oxygen, nitrogen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, p is 0 to 4, L is optionally mono- or poly-hydroxy-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-haloalkyl-, C1-C6-hydroxyalkoxy-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-alkoxyalkoxy-, C3-C6-heterocycloalkyl-, or -NR3R4-substituted C1-C6-alkyl, C1-C6-haloalkyl or C3-C6-cycloalkyl or C3-C6-heterocycloalkyl, where the C3-C6 heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -(SO2)-groups and/or one or more double bonds;

R1 and R2 are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6-heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L-, -NR3COOR7-, -COOR7-, -NR3CONR3R4-, -NR3SO2R4-, -SO2NR3R4- , -CONR3R4- or -SO2R3-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl or with -(CH2)r-R8 radical, where r is a number 0-3, and R8 is a radical where aryl, heteroaryl, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl groups optionally present in R1 or R2 may be substituted one or more times by -Hal, -CN, - OH, -C1-C6-alkyl, C1-C6-haloalkyl, -C1-C6-alkoxy, C1-C6-haloalkoxy, -C1-C6-hydroxyalkyl, -C3-C6-cycloalkyl, -NO2, -NH2, -NR3R4, -CONR3R4, -NR3COR4, NR3SO2R4, -COR6, C02R 7, -SO2NR3R4, -SR3, SOR3, -SO2R3, -OR3, -O(CH2)PR6, where the substituents in the case of polysubstitution may be identical or different;

where two or more aryl or heteroaryl groups may not be substituents on the same carbon atom in R1 or R2;

R1 and R2 in addition to the aforementioned definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally comprise additionally in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R1 and R2 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, C1-C6-haloalkoxyalkyl, C1-C6-haloalkoxy-, -NR3R4, -CONR6R7, -(CO)-R6 or -COOR7 and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 are identical or different and are selected from the group consisting of j) -H, and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R7-, -CONR6R7-, -(CO)-R6-or-COOR7-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different;

R3 and R4 in addition to the aforementioned definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally comprise additionally in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R3 and R4 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, C1-C6-haloalkoxyalkyl, C1-C6-haloalkoxy-, or by -NR6R7, -CONR6R7, -(CO)-R6 or-COOR7 and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents in the case of polysubstitution may be identical or different;

R6 and R7 are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN- substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may comprise in the ring optionally one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)-or -SO2- groups and/or one or more double bonds, and where the substituents in the case of polysubstitution may be identical or different, and the isomers, diastereomers, enantiomers and salts thereof.

2. The compound as claimed in claim 1, where R1 and R2 are identical or different and selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L- or -NR3COOR7-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, where the substituents may in the case of polysubstitution be identical or different, and where R1 and R2 in addition the preceding definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R1 and R2 may be optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, C1-C6-haloalkoxyalkyl, C1-C6-haloalkoxy, -NR3R4, -CONR6R7, -(CO)-R6 or -COOR7 and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents may in the case of polysubstitution be identical or different.

3. The compound as claimed in claim 1, where R1 and R2 are identical or different and selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C2-haloalkyl-, C1-C6-alkoxy-, C1-C2-haloalkoxy-, C3-C6-cycloalkyl-, C3-C6-heterocycloalkyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L-, -NR3COOR7-, -COOR7-, -NR3SO2R4-, -SO2NR3R4-, -CONR3R4- or -SO2R3-substituted C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl or by -(CH2)R8 radical where R8 is a radical where aryl, heteroaryl, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl groups optionally present in R1 or R2 may be substituted one or more times by -Hal, -CN, - OH, -C1-C6-alkyl, -C1-C2-haloalkyl, -C1-C6-alkoxy, -C1-C2-haloalkoxy, -C1-C6-hydroxyalkyl, -C3-C6-cycloalkyl, -NO2, -NH2, -C1-C6-haloalkyl, -NR3R4, -CONR3R4, -NR3COR4, NR3SO2R4, -COR6, CO2R7, -SO2NR3R4, -SR3, SOR3, --SO2R3, -OR3, -O(CH2)PR6, where the substituents may in the case of polysubstitution be identical or different;

where two or more aryl or heteroaryl groups in R1 or R2 may not be substituents of the same carbon atom;

4. The compound as claimed in claim 1 or 2, wherein R1 and R2 are identical or different and selected from the group consisting of j) -H and jj) optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryloxy-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3R4-, -NR3(CO)-L- or -NR3COOR7-substituted C1-C6-alkyl, C1-C6-haloalkyl-, C1-C6-alkoxy, C1-C6-haloalkoxy-, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-heterocycloalkyl, aryl or heteroaryl, where the C3-C6-heterocycloalkyl may optionally comprise in the ring one or more nitrogen, oxygen and/or sulfur atoms and/or one or more -(CO)- or -SO2- groups and/or one or more double bonds, where the group aryl or heteroaryl defined in jj) may be substituted as long as alkyl is not involved, where the substituents may in the case of polysubstitution be identical or different, and where R' and R2 in addition the preceding definition may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, where the ring formed by R1 and R2 is optionally substituted one or more times by -CN, -Hal, -OH, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl, C1-C6-haloalkoxyalkyl, C1-C6-haloalkoxy, -NR3R4, -CONR6R7, -(CO)-R6 or -COOR7 and/or by optionally mono- or poly-Hal-, C1-C6-alkoxy-, C1-C6-haloalkoxy- or -(CO)-R6-substituted aryl or heteroaryl, where the substituents may in the case of polysubstitution be identical or different.

5. The compound as claimed in claim 3 or 4, where Q is an optionally mono- or poly-OH-, -Hal-, -CN-, alkyl-, -OR6- or -NR3R4-substituted phenyl, pyridyl, thiophenyl, furyl, imidazolyl, or pyrazolyl.

6. The compound as claimed in claim 5, where R1 and R2 are identical or different and selected from the group consisting of -H, NR3R4-substituted C1-C4-alkyl, optionally additionally substituted one or more times by -Hal, -OH, -CN, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-hydroxyalkyl, C3-C6-cycloalkyl, C3-C6 heterocycloalkyl, C2-C6-alkynyl, aryl, aryloxy, heteroaryl, -S-C1-C6-alkyl, -(CO)-R6, -NR3(CO)-L, or -NR3COOR7, where R3 and R4 may optionally, identically or differently, be C1-C6-alkyl, C1-C6-haloalkyl where R3 and R4 may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, and where R6 and R7 is identically or differently -H, -OH, C1-C6-alkoxy, C1-C6-haloalkoxy or C1-C3-alkyl.

7. The compound as claimed in any of claims 1-4, where R1 is selected from the group consisting of -H and C1-C3-alkyl, where R2 is selected from the group consisting of NR3R4-substituted C3-C4 alkyl, optionally additionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -S-C1-C6-alkyl-, -(CO)-R6-, -NR3(CO)-L- or -NR3COOR7-substituted, where R3 and R4 are identically or differently optionally mono- or poly-Hal-, -OH-, -CN-, C1-C6-alkyl-, C1-C6-haloalkyl-, C1-C6-alkoxy-, C1-C6-haloalkoxy-, C1-C6-hydroxyalkyl-, C3-C6-cycloalkyl-, C3-C6 heterocycloalkyl-, C2-C6-alkynyl-, aryl-, aryloxy-, heteroaryl-, -NR6R7-, -CONR6R7-, -(CO)-R6-or-COOR7-substituted C1-C6-alkyl, C1-C6-haloalkyl, where R3 and R4 may together form a C3-C6-heterocycloalkyl ring which comprises at least one nitrogen atom in the ring and may optionally additionally comprise in the ring one or more nitrogen, oxygen or sulfur atoms and/or one or more -(CO)- or -(SO2)- groups and/or optionally one or more double bonds, and where R6 and R7 is identically or differently -H, -OH, C1-C6-alkoxy, C1-C6-haloalkoxy, or C1-C3 alkyl.

8. The compound as claimed in any of claims 1-7, where R1 or R2 is equal to -H.

9. The compound as claimed in claim 1, namely:
(3-phenylimidazo[1,2-b]pyridazin-6-yl)-(3-pyrrolidin-1-ylpropyl)amine (3-morpholin-4-ylpropyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine (3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl)-(3-pyrrolidin-1-ylpropyl)amine (3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yl)-(3-morpholin-4-ylpropyl)amine [3-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]pyridin-3-ylmethylamine (3-phenylimidazo[1,2-b]pyridazin-6-yl)pyridin-3-ylmethylamine (3-imidazol-1-ylpropyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine (4-fluorobenzyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine cyclohexylmethyl-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine (2,4-difluorobenzyl)-(3-phenylimidazo[1,2-b]pyridazin-6-yI)amine [3-(5-methyl-1H-pyrazol-4-yl)propyl]-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine 1-[2-(3-phenylimidazo[1,2-b]pyridazin-6-ylamino)ethyl]imidazolidin-2-one (2-morpholin-4-ylethyl))-(3-phenylimidazo[1,2-b]pyridazin-6-yl)amine N*1,N*1 *-diethyl-N*4-(3-phenylimidazo[1,2-b]pyridazin-6-yl)pentane-1,4-diamine (3-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl)-(2-morpholin-4-ylethyl)amine N*1,N*1 *-diethyl-N*4-[3-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]pentane-1,4-diamine N, N-diethyl-N'-[3-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]propane-1,3-diamine [3-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-6-yl]-(2-pyrrolidin-1 -ylethyl)amine pyridin-3-ylmethyl-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine (4-fluorobenzyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine cyclohexylmethyl-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine (2,4-difluorobenzyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine [3-(5-methyl-1H-pyrazol-4-yl)propyl]-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine 1-[2-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-ylamino)ethyl]imidazolidin-2-one (2-morpholin-4-ylethyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine N*1,N*1 *-diethyl-N*4-[3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl]pentane-1,4-diamine N, N-diethyl-N'-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl]propane-1, 3-diamine (2-pyrrolidin-1-ylethyl)-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yl)amine.

10. The compound as claimed in claim 1, namely compound according to any of the examples:

.cndot. 2.0 - 2.21, .cndot. 3.0 - 3.80, .cndot. 4.0 - 4.11, .cndot. 5.0 - 5.389, .cndot. 6.0 - 6.2, .cndot. 7.0 - 7.1 or .cndot. 8.0 - 8.1.

11. A method for preparing a compound as claimed in any of claims 1 to 10, with the following stages of the method:

A1) 3-amino-6-halopyrazine is converted into 6-haloimidazo[1,2-b]pyridazine II, A2) the product from stage A1 is converted into a 3-halo-6-haloimidazo[1,2-b]pyridazine III, A3) the product from stage A2 is converted by reaction with a compound NHR1R2 into the compound according to the general formula Ila, A4) the product from stage A3 is converted into the compound according to the general formula I, or 131) 3-amino-6-halopyrazine is converted into 6-haloimidazo[1,2-b]pyridazine II, B2) the product from stage B1 is converted into a 3-halo-6-haloimidazo[1,2-b]pyridazine III, B3) the product from stage B2 is converted into the compound according to the general formula IIb, B4) the product from stage B3 is converted into the compound according to the general formula I, or C1) 3-amino-6-halopyrazine is converted into 6-haloimidazo[1,2-b]pyridazine II, C2) the product from stage C1 is converted by reaction with a compound NHR1R2 into an imidazo[1,2-b]pyridazin-6-yl)-(R1)-(R2)-amine IV, C3) the product from stage C2 is converted into the compound according to the general formula Ila, C4) the product from stage C3 is converted into the compound according to the general formula I.

12. The method as claimed in claim 11, with the following stages of the method:
Al) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, A2) the product from stage A1 is reacted with N-bromosuccinimide to give a 3-bromo-6-haloimidazo[1,2-b]pyridazine, A3) the product from stage A2 is converted by reaction with a compound NHR1R2 in a Buchwald-Hartwig cross-coupling reaction into a(3-bromoimidazo[1,2-b]pyridazin-6-yl)-(R1)-(R2)-amine, A4) the product from stage A3 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula I, or B1) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, B2) the product from stage B1 is reacted with N-bromosuccinimide to give a 3-bromo-6-haloimidazo[1,2-b]pyridazine, B3) the product from stage B2 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula II, B4) the product from stage B3 is converted by reacting with a compound NHR1R2 in a Buchwald-Hartwig cross-coupling reaction into the compound according to the general formula I, or C1) 3-amino-6-halopyrazine is reacted with chloractetaldehyde to give 6-haloimidazo[1,2-b]pyridazine, C2) the product from stage C1 is converted by reacting with a compound NHR1R2 in a Buchwald-Hartwig cross-coupling reaction into an imidazo[1,2-b]pyridazin-6-yl)-(R1)-(R2)-amine, C3) the product from stage C2 is reacted with N-bromosuccinimide to give a(3-bromoimidazo[1,2-b]pyridazin-6-yl)-(R1)-(R2)-amine, C4) the product from stage C3 is reacted for example with a boronic acid which is optionally substituted by the radicals A and B to give the compound according to the general formula I.

13. The use of a compound as claimed in any of claims 1 to 10 for producing a pharmaceutical composition.

14. The use of a compound as claimed in any of claims 1 to 10 for inhibiting a cellular kinase.

15. The use of a compound as claimed in any of claims 1 to 10 for inhibiting a cellular kinase according to claim 14, where the kinase belongs to the group of the protein kinase C family, such as, for example, PKC theta, delta, iota, alpha and zeta.

16. The use of a compound as claimed in any of claims 1 to 9 for inhibiting a cellular kinase according to claim 15, where the kinase is from the class of the ALK family, preferably ALK1, ALK2, ALK4 or ALK5.

17. The use of a compound as claimed in any of claims 1 to 10 for producing a pharmaceutical composition for the treatment or for the prophylaxis of a disorder which is associated with overexpression or mutation of a cellular kinase according to claim 14, in particular a cellular kinase according to claim 15 or a cellular kinase according to claim 16.

18. The use as claimed in claim 13, where the disorder is a disorder from the group consisting of benign tumors, malignant tumors, leukemia such as myeloblastic leukemia, lymphoma, sarcoma, such as osteosarcoma or chondrosarcoma, neuroblastoma, Wilm's tumor, malignant neoplasms of the bladder, breast, lung, pancreas, prostate, kidney, neoplasms of epithelial origin such as carcinoma of the breast or metastases thereof.

19. The use as claimed in claim 13, where the disorder may be a disorder from the group consisting of epidermal hyperproliferation such as psoriasis, Alzheimer's, autoinflammatory disorders, fibroses, impaired wound healing, diabetic retinopathy, nephropathy, age-related macular degeneration, Crohn's disease, exaggerated immune response, contact dermatitis, atopic dermatitis, multiple sclerosis, ALS, diabetes, asthma.

20. The use as claimed in claim 13 for modulating, in particular reducing, an immune response, for example after a transplantation has taken place to avoid rejection of an organ.

21. A method for producing a pharmaceutical composition, where a physiologically effective dose of a compound as claimed in any of claims 1 to is mixed with at least one pharmaceutical excipient, and a dosage form is manufactured.

22. A method for the treatment of prophylaxis of a disorder which is associated with overexpression of a cellular kinase, where a pharmaceutical composition comprising a physiologically effective dose of a compound as claimed in any of claims 1 to 10 is administered to a person suffering from or under threat of suffering from the disorder.

23. The intermediate according to formula Ila where Y is a halogen atom, and R1 and R2 have the meaning specified in claim 1.

24. An intermediate according to general formula Ilb Q, A and B have the meaning specified in claim 1, and X is chlorine, bromine, O-SO2-CF3 or O-SO2-C4F9.