# Patent

## Title
Oxo-substituted imidazo[1,2B]pyridazines, their preparation and use as pharmaceuticals

## Abstract

The invention relates to novel inhibitors of kinases of the general formula (I):




in which Q and R1 are defined in the claims, method for preparing such inhibitors, intermediates for preparing such inhibitors and uses of such inhibitors.

## Background
This application claims the benefit of the filing date of U.S. Provisional Application Ser. No. 60/815,252, filed Jun. 21, 2006, which is incorporated by reference herein.


The present invention relates to novel oxo-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, especially for inhibiting kinases of the PKC subfamily, very especially for inhibiting the PKC theta kinase (PKC θ 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; this includes immunological and general inflammatory processes and oncological processes, but also disorders such as, for example, diabetes of type II and asthma, and transplantations; preferably inflammatory processes and immune responses which exhibit the clinical appearance of acute dermatitis, of contact dermatitis but also of psoriasis.
Activation of T cells depends on a series of interactions between antigen-presenting cells (APC) and T cells. Of central importance in this connection is presentation of antigen via MHC (major histon compatibility complex) molecules on APC to the T-cell receptor (TCR) on T cells. In addition, further molecules such as the so-called costimulatory molecules (e.g. CD28) are required for complete activation of T cells. The various activation signals in total eventually lead to regulation of the transcription of genes which code for example for cell messengers (=cytokines). A cytokine of central importance in the cell response is interleukin 2 (IL-2) which in turn stimulates other T cells to proliferate and advances the adaptive immune response further.
The T-cell system is regulated in healthy individuals by a large number of mechanisms. This leads to an immune response to foreign antigen and a suppression of an immune response to self antigen. In addition, an immune response is downregulated again after effector functions have succeeded. If control of these mechanisms is inadequate, dysregulated T-cell responses may contribute to the development of a number of disorders such as autoimmune diseases, inflammatory diseases, and transplant rejections. T-cell responses also play a central part in the pathological event in inflammatory skin disorders such as psoriasis, atopic dermatitis, contact allergy.
Investigations in recent years atest that the protein kinase C (PKC) family has an important part in T-cell activation and T-cell response (Newton 1997. Regulation of protein kinase C. Curr. Opin. Cell Biol. 9:161-167; Altman et al. 1990. Molecular events mediating T cell activation. Adv. Immunol. 48:227-360). Inhibition of PKC leads to an inhibition of T-cell activation and T-cell response. It has also been possible to show that a PKC deficiency in T cells allows only inadequate TCR-triggered proliferation of T cells.
The PKC family is divided into a plurality of isoforms. A particular central role in the regulation of T-cell activation is played by the Ca2+-dependent isoform PKC-θ. This is selectively expressed in T cells and to a small extent in cells of skeletal muscles (Meller et al. 1998. New perspectives on PKCθ, a member of the novel subfamily of protein kinase C. Stem Cells 16:178-192; Altman et al. 2000. Protein kinase C θ: a new essential superstar on the T-cell stage. Immunol. Today 21:567-573; Arendt et al. 2002. Protein kinase C-theta: signaling from the center of the T cell synapse. Current Opinion in Immunology. 14: 323-330). Whereas 7 different PKC isoforms (α, δ, ε, ζ, η, θ and ι) are expressed in primary human T cells, only PKC-θ (but not the other isoforms) shows the ability to regulate the central transcription factors AP-1 and NF-kappaB. Stimulation of the TCR and CD28 is followed by localization of PKC-θ (but not other PKC isoforms) in so-called ‘lipid rafts’ in the center of the immunological synapse, it being directly involved in the transmission of the activation signal from the TCR to further target molecules of the T cell (via phosphorylations of these molecules) as far as transcription factors (Baier-Bitterlich et al. 1996. Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes. Mol. Cell. Biol. 16:1842-1850; Lin et al. 2000. Protein kinase C θ-participates in NF-kB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase B. Mol. Cell. Biol. 20:2933-2940; Coudronniere et al. 2000. NF-kB activation induced by T cell receptor/CD28 costimulation is mediated by protein kinase C-θ. Proc. Natl. Acad. Sci. USA 97:3394-3399).
Because of this close linkage to the TCR signaling pathway, PKC-θ represents an interesting molecule in the search for novel therapeutic approaches to regulating the adaptive immune response.
It has been possible to provide a functional demonstration of the central role of this of PKC-θ in the T-cell response in particular by generating so-called knockout mice (Sun et al. 2000. PKCθ is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Nature 404: 402-407; Pfeifhofer et al. 2003. Protein Kinase C theta affects calcium mobilization and NFAT cell activation in primary mouse T cells. J. Exp. Med. 197:1525-1535; Marsland et al. 2004. Protein Kinase C theta is critical for the development of in vivo T helper (TH)2 cell but not Th1 cell responses. J. Exp. Med. 200:181-189; Lin et al. 2000. Protein kinase C θ-participates in NF-kB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase B. Mol. Cell. Biol. 20:2933-2940).
These mice are characterized by a particular phenotype:

    1) reduced ability to mount an optimal T-cell response. T cells show a strongly nonreactive phenotype, even including immunosuppression.
    2) on stimulation of the T cells via the TCR, the subsequent activation of transcription factors is greatly reduced. IL-2 as key cytokine in the T-cell response is produced to only a reduced extent. In addition, the ability of the T cells to proliferate is significantly inhibited.
    3) defects relate only to mature T cells, because immature T cells in the thymus exhibit a normal phenotype.
    4) these animals are characterized by a greatly reduced in vivo T-cell response of the T helper (TH) type 2 (TH2 response=characterized for example by a typical TH2 cytokine IL-4) shown in TH2 models to infection with nematodes, asthma models and models of skin inflammation.
    5) these mice otherwise showed a normal phenotype and are not generally immunosuppressed. In addition, the ability to reproduce is not impaired.


On the basis of these special properties of knockout mice, it is to be expected that a specific inhibition of PKC-θ by selective inhibitors will inhibit only one arm of the adaptive immune response (T cells), whereas a second arm of the adaptive immune system, the B cells, will be unaffected. This would represent an advantage by comparison with classical immunosuppressants (e.g. cyclosporin A) in the therapy of inflammatory disorders with T-cell involvement (TH2-dependent disorders [atopic dermatitis, asthma, etc] and because of the central role of PKC-θ in the TCR signaling pathway also TH1 disorders [psoriasis, rheumatoid arthritis, transplant rejection, inflammatory bowel disorders etc.]) in the pathogenesis.
A single publication (Bioorg. Med. Chem. Lett. 2004, 14, 2249-2252.) of Astra Zeneca discloses pyrimidine derivatives having an attached imidazo-[1,2b]pyridazine residue as kinase inhibitors. These compounds differ from the compounds of the invention through their structure, especially on the imidazo[1,2b]pyridazine ring. Only methoxy and trifluoroethoxy radicals are mentioned. In addition, all the compounds mentioned by Astra Zeneca in WO 2002/066481 (A1) also comprise a pyrimidine ring which—owing to the synthesis—is directly linked to the imidazo[1,2b]pyridazine basic structure.
Although WO 2006/015737 describes by formula IX compounds which are similar in the basic structure to those disclosed herein, they are not comparable in the choice and number of the substituents.
WO 2005/041971 likewise describes imidazo[1,2b]pyridazines similar to the compounds disclosed herein. However, no example of this class of substances is specifically disclosed, nor is a synthetic route permitting adequate preparation of compounds of this class of substances described.
There continues to be a great need for effective pharmaceuticals for the treatment of immunological and also cell-proliferative disorders.
It has now been found that oxo-substituted imidazo[1,2b]pyridazines of the general formula I represent excellent PKC-θ inhibitors. They are compounds of the general formula (I),




    
    
        in which
    
    
    Q is an aryl or heteroaryl radical which may be linked at any position to the imidazo[1,2b]pyridazine residue and which may optionally be substituted independently of one another by
    
        1-3 hydroxy groups, halogen atoms, nitro groups or cyano groups
        1-3 C1-C6-alkyl or C3-C8-cycloalkyl groups which may optionally be substituted by 1-3 hydroxy and/or 1-3 halogen or cyano groups and/or 1-3 (C1-C5)-alkoxy groups and/or 1-3 COOR6 groups and/or 1-3 NHR6 groups and/or 1-3 NHCOR6 groups and/or 1-3 N(R2)2 groups or be interrupted by 1-3 keto groups,
        1-3 C1-C6-fluoroalkyl groups which may optionally be substituted by 1-3 hydroxy and/or 1-3 optionally fluorinated (C1-C5)-alkoxy groups and/or 1-3 COOR2 groups,
        1-3 pyrrolidine groups,
        1-3 (CH2)u—SO2—R2 groups in which u is the numbers 1, 2 or 3,
        1-3 R2 groups,
        1-3 O—CO—R6 groups,
        1-3 CO—O—R6 groups,
        1-3 CO—N(R6)2 groups,
        1-3 NH—CO—R6 groups,
        1-3 CONR7R8 groups,
        1-3 (CH2)n—NR7R8 groups,
        1-3 NH—CONHR6 groups,
        1-3 OR6 groups,
        1-3 SO2—R2 groups,
        1-3 SO2—OR2 groups,
        1-3 SO2—N(R2)2 groups,
        1-3 NHSO2R2 groups,
        and/or
        1-3 SR2 groups,

in which R2 is in each case independently of one another

        a hydrogen atom, a phenyl radical, an optionally partly or completely fluorinated C1-C5-alkyl radical or
        a C1-C5-alkyl radical which is in turn optionally substituted 1-5 times by hydroxy radicals, cyano groups, phenyl groups, C3-C7-cycloalkyl radicals, SO2(C1-C3-alkyl) radicals, NH(C1-C3-alkyl) radicals, N[(C1-C3-alkyl)]2 radicals, and/or C1-C5-alkoxy radicals,
        or a C3-C7-cycloalkyl radical,

in which R6 is in each case independently of one another either

        a radical R2,
        an aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups and/or C1-C5-alkoxy radicals,
        a radical —(CH2)u-Qs in which u is the numbers 1, 2 or 3, and in which QS is an aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups and/or C1-C5-alkoxy radicals,
        where the vicinal hydroxy groups present in the aryl or heteroaryl group may also be condensed with aldehydes or ketones or halogenated aldehydes or halogenated ketones,
        and in which
    
    
    R1 is a C1-C6-alkyl radical which may be substituted 1-3 times by —R2, —NR3R4, —NR7R8 or —OR2 in which R2 has the abovementioned meaning and R3, R4, R7 and R8 has the meaning specified hereinafter,
    
        is a C1-C6-alkenyl radical which may be substituted 1-3 times by —R2, —NR3R4, —NR7R8 or —OR2 in which R2 has the abovementioned meaning and R3, R4, R7 and R8 has the meaning specified hereinafter,
        is a C1-C6-alkynyl radical which may be substituted 1-3 times by —R2, —NR3R4, —NR7R8 or —OR2 in which R2 has the abovementioned meaning and R3, R4, R7 and R8 has the meaning specified hereinafter,
        a —(CH2)n—NR3R4 radical where n is a number 2-6 and in which R3 and R4 are independently of one another a hydrogen atom, a —COR6 radical, a —SO2R2 radical, or a C1-C5-alkyl radical which is in turn optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R2, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
        a —(CH2)t—Z—(CH2)m—NR3R4 radical,
        where Z is a group —O—, —S—, —NR2—, —CHR5— or —C(R5)2—,
        m is a number 0, 1 or 2, t is a number 0, 1, 2 or 3, and in which R3 and R4 has the abovementioned meaning,
        and in which R5 is a C1-C3-alkyl, C2-C3-alkenyl, C2-C3-alkynyl, a phenyl or a C3-C6-cycloalkyl radical,
        a —(CH2)n—NR7R8 radical where n is a number 1-6 and in which R7 and R8 together form a 3-7-membered ring, where the 3-7-membered ring may comprise a further heteroatom, and where the 3-7-membered ring is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2, or is interrupted by 0-3 keto groups,
        a —(CH2)n—(CH)R7R8 radical where n, R7 and R8 have the abovementioned meaning,
        a —(CH2)t—Z—(CH2)m—NR7R8 radical,
        where t, m, Z, R7 and R8 have the abovementioned meaning,
        a —(CH2)t—Z—(CH2)m—(CH)R7R8 radical,
        where t, m, Z, R7 and R8 have the abovementioned meaning,
        a —(CH2)r—Y1 radical where r is a number 0-3, and Y1 is a piperidine or pyrrolidine ring, where the piperidine or pyrrolidine ring is optionally substituted 1-3 times independently of one another by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
        a —(CH2)t—Z—(CH2)m—Y1 radical
        in which t, m, z, Y1 have the abovementioned meaning,
        a —(CH2)r—Y2 radical where r is a number 0-3, and Y2 is a morpholine ring, where the morpholine ring is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
        a —(CH2)t—Z—(CH2)m—Y2 radical
        where t, m, Z, Y2 have the abovementioned meaning,
        a —(CH2)r—Y3 radical where r is a number 0-3, and Y3 is a piperazine ring which optionally has a C1-C3-alkyl or a C1-C3-acyl group on the nitrogen atom, where the piperazine ring is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
        a —(CH2)t—Z—(CH2)m—Y3 radical
        where t, m, Z, Y3 have the abovementioned meaning,
        a —(CH2)r—Y4 radical where r is a number 0-3, and Y4 is a C3-C8-cycloalkyl ring which is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
        a —(CH2)t—Z—(CH2)m—Y4 radical
        where t, m, Z, Y4 have the abovementioned meaning,
        a —(CH2)r—Y5 radical where r is a number 0-3, and Y5 is an aryl or heteroaryl ring which is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2, a group —SO2N(R2)2, a group —NHSO2R2, a group —NHCOR6, a group —NHCONHR6 or a group —OR2,
        a —(CH2)t—Z—(CH2)m—Y5 radical
        where t, m, Z, Y5 have the abovementioned meaning,
        a —(CH2)r—Y6 radical where r is a number 0-3, and Y6 is a radical
    
    






    
    
        which may be linked at any position to the (CH2)r group,
        a —(CH2)t—Z—(CH2)m—Y6 radical
        where t, m, Z, Y6 have the abovementioned meaning
        in the form of the various stereoisomers of the compounds of the general formula I
        and the salts of the stereoisomers of the general formula I with physiologically tolerated counterions.
    
    


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, neopentyl and hexyl.
Fluoroalkyl means in each case a straight-chain or branched alkyl radical in which at least one hydrogen atom is replaced by a fluorine atom, such as, for example, fluoromethyl, difluoromethyl, trifluoroethyl, trifluoroethyl, pentafluoroethyl, perfluoropropyl and perfluoroisopropyl.
Alkoxy means in each case a straight-chain or branched alkoxy radical such as, for example, methyloxy, ethyloxy, propyloxy, isopropyloxy, 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-en-1-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-yl, but-3-en-1-yl, allyl.
Alkynyl means in each case a straight-chain or branched alkynyl radical which comprises 2-6, preferably 2-4, C atoms. The following radicals may be mentioned as examples: acetylenyl, propyn-1-yl, propyn-3-yl (propargyl), but-1-yn-1-yl, but-1-yn-4-yl, but-2-yn-1-yl, but-1-yn-3-yl, 3-methylbut-1-yn-3-yl.
C3-C6-Cycloalkyl is an alkyl ring which comprises 3-6 carbon atoms and which may optionally comprise one or more double bonds in the ring.
A heteroatom is a multivalent atom different from carbon, preferably a nitrogen, oxygen or sulfur atom.
The expression “independently of one another” means that multiple substituents may be different from one another. For example, the compound 3-(3-chloro-4-fluorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine comprises a phenyl ring substituted by two halogen atoms. The halogen atoms are, however, different from one another (fluorine and chlorine).
In the general formula I, Q can be an aryl or heteroaryl radical which may be linked at any position to the imidazo[1,2b]pyridazine residue. It is clear to the skilled worker in this connection that all synthetically accessible aryl or heteroaryl compounds which are stable under physiological conditions are meant.
Preferred radicals Q are the phenyl, thiophenyl, biphenyl, furanyl, benzofuranyl, indolyl, pyridinyl, benzothiophenyl and the naphthalenyl group
It is clear to the skilled worker that the aryl or heteroaryl groups present in Q may be substituted in many ways. Preferred substituents in Q are cyclopropylmethoxy-, fluorine, chlorine, hydroxyl-, cyano-, trifluoromethyl-, trifluoromethoxy-, methyl-, methoxy-, pyrrolidinyl-, —CO—OCH3, —CO—CH3, —CO2H, —CO—NH2, —CH2—CN, —CH2—OH, —CH2—S—CH3, —S—CH3, —SO2—CH2CH3 or —NHCOCH3. In addition, Q may be phenyl, naphthyl, tetralinyl, anthranyl, indanyl, indenyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, azaindolizinyl, furanyl, thiophenyl, oxazolyl, thiazolyl, furazanyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, phthalidyl, thiophthalidyl, indolyl, isoindolyl, indazolyl, benzothiazolyl, indolonyl, isoindolonyl, benzofuranyl, benzimidazolyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl, quinazolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, coumarinyl, isocoumarinyl, indolizinyl, isobenzofuranyl, azaindolyl, azaisoindolyl, furanopyridyl, furanopyrimidinyl, furanopyrazinyl, furanopyidazinyl, dihydrobenzofuranyl, dihydrofuranopyridyl, dihydrofuranopyrimidinyl, dihydrofuranopyrazinyl, dihydrofuranopyridazinyl, dihydrobenzofuranyl, chromenyl, isochromenyl, chromenonyl, isochromenonyl group, piperidyl, 4-aminopyridyl, 1H-pyridin-4-ylidenaminyl, chromanyl, isochromanyl, thiochromanyl, decahydroquinolinyl, tetrahydroquinolinyl, dihydroquinolinyl, 5,6,7,8-tetrahydro-1H-quinolin-4-onyl, decahydroisoquinolinyl, tetrahydroisoqunolinyl dihydroisoquinolinyl, 3,4-dihydro-2H-benz[1,4]oxazinyl, 1,2-dihydro[1,3]-benzoxazin-4-onyl, 3,4-dihydrobenz[1,4]oxazin-4-onyl, 3,4-dihydro-2H-benzo[1,4]thiazinyl, 4H-benzo[1,4]thiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1H-cinnolin-4-onyl, 3H-quinazolin-4-onyl, 1H-quinazolin-4-onyl, 3,4-dihydro-1H-quinoxalin-2-onyl, 1,2,3,4-tetrahydro[1,5]naphthyridinyl, dihydro-1H-[1,5]naphthyridyl, 1H-[1,5]naphthyrid-4-onyl, 5,6,7,8-tetrahydro-1H-naphthyridin-4-onyl, 1,2-dihydropyrido[3,2-d]-[1,3]oxazin-4-onyl, octahydro-1H-indolyl, 2,3-dihydro-1H-indolyl, octahydro-2H-isoindolyl, 1,3-dihydro-2H-isoindolyl, 1,2-dihydroindazolyl, 1H-pyrrolo[2,3-b]pyridyl, or 2,3-dihydro-1H-pyrrolo[2,3-b]pyridyl, 2,2-dihydro-1H-pyrrolo[2,3-b]pyridin-3-onyl.
The aryl or heteroaryl groups optionally present in the radical R6 may be for example the abovementioned aryl or heteroaryl systems. The aryl or heteroaryl groups optionally present in the radical R6 are preferably phenyl, thiophenyl, biphenyl, furanyl, benzofuranyl, indolyl, pyridinyl, benzothiophenyl and the napthalenyl group.
A preferred class of compounds of the general formula I is formed by those in which R1 is

    3-dimethylaminopropyl-
    3-diethylaminopropyl-
    3-piperidin-1-ylpropyl-
    2-dimethylaminoethyl-
    2-diethylaminoethyl-
    1-methylpiperidin-3-ylmethyl-
    1-methylpyrrolidin-2-ylethyl-
    4-diethylamino-1-methylbutyl-
    or
    3-(4-methyl)piperazin-1-ylpropyl.


A further preferred class of compounds of the general formula I is formed by those compounds in which R1 is a
—(CH2)n—NR3R4 radical where n is 3 or 4, and in which
R3 and R4 are independently of one another a C1-C3 alkyl radical.
A further preferred class of compounds of the general formula I is formed by those compounds in which R1 is a
—(CH2)n—NR7R8 radical where n is 3 or 4, and in which
R7 and R8 together form a 5-7-membered ring.
It is clear to the skilled worker that the compounds of the general formula I may exist in various stereoisomeric forms. It is therefore clear that the compounds of the general formula I include all such stereoisomeric compounds, especially all enantiomers and diastereomers, both in pure form and as racemates.
The term stereoisomers further includes also all possible regioisomers and tautomers (e.g. keto-enol tautomers) in which the stereoisomers of the invention may be present, which are thus likewise an aspect of the invention.
The compounds of the invention may also be in the form of salts with pharmacologically acceptable cations or anions, for example in the form of the sodium salt, potassium salt, magnesium salt, ammonium salt, N-methylglucamine salt, N,N-dimethylglucamine salt, of the hydrochloride, sulfate, nitrate, phosphate, pivalate, maleate, fumarate, tartrate, benzoate, mesylate, citrate or succinate.
Pharmacologically acceptable derivatives or prodrugs of the compounds of the general formula I are also encompassed by the invention. Derivatives or prodrugs refer for example to esters, ethers or amides of the compounds of the general formula I or other compounds which metabolize in the body to compounds of the general formula I. Suitable compounds are listed for example in Hans Bundgaard (ed.), Design of Prodrugs, Elsevier, Amsterdam 1985.
Uses of the Compounds of the Invention
Compounds of the invention are suitable as kinase inhibitors, especially of tyrosine and serine/threonine 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 derived from a dysfunction of the kinase. However, a disorder derived from the dysfunction of the kinase can also be treated or prevented with the kinase inhibitor.
The invention therefore relates further 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 especially for inhibiting kinases of the PKC subfamily, very particularly 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, especially of such a cellular kinase. Disorders of this type are in particular inflammatory disorders, oncological disorders and autoimmune diseases. The compounds of the invention are likewise suitable for preparing compounds for immunosuppression. The compounds of the invention are very particularly suitable for producing pharmaceuticals for the treatment of diabetes of type II, asthma, dermatitis, psoriasis, rheumatoid arthritis, contact dermatitis, atopic dermatitis, contact allergy, multiple sclerosis, inflammatory bowel disorders or transplant rejections. The present compounds can additionally, however, also be employed for modulating an immune response, for example after 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 the desired dosage form.
A suitable physiologically effective dose is for example an amount of from 1 to 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 manufacturing of a pharmaceutical composition of the invention can take place in a manner known in the art. Examples of suitable counterions for ionic compounds are Na+, K+, Li+ or cyclohexylammonium, and Cl−, Br−, acetate, trifluoroacetate, propionate, lactate, oxalate, malonate, maleate, citrate, benzoate, salicylate etc. Suitable solid or liquid pharmaceutical presentations are for example granules, powders, coated tablets, tablets, (micro)capsules, suppositories, syrups, solutions, ointments, suspensions, emulsions, drops or solutions for injection (i.v., i.p., i.m., s.c.) or atomization (aerosols), transdermal systems, and products with protracted release of active ingredient, in the production of which conventional aids such as carriers, disintegrants, binders, coated agents, swelling agents, glidants or lubricants, and preservatives, stabilizers, wetting agents or emulsifiers; salts to alter the osmotic pressure or buffers, flavorings, sweeteners and solubilizers, are used. It is also possible to use as carrier systems 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 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 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 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 cellular kinase, where a pharmaceutical composition comprising a physiologically effective dose of a compound of the general formula I is administered to a person suffering from or under threat of suffering from the disorder.
Preparation Method (Synthesis Scheme):
The inventions can be prepared by the synthesis scheme depicted below.
The invention therefore further relates also to a method for preparing a compound of the invention with the following stages of the method:




In the synthesis diagram, R1 and Q have the meanings specified in claim 1. Hal and X are the halogen atoms chlorine, bromine and iodine.
A further aspect of the present invention places a compound of the general formula IIb




in which R1 has the meaning defined in claim 1, and in which Hal is a chlorine, bromine or iodine atom.

Preferred compounds of the formula IIb are 3-bromo-6-(3-morpholin-4-ylpropoxy)imidazo[1,2-b]pyridazine, 3-bromo-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine, 3-bromo-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine, 3-bromo-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine, 3-bromo-6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine, [3-(3-bromoimidazo[1,2-b]pyridazin-6-yloxy)propyl]diethylamine, 3-bromo-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2b]pyridazine, [4-(3-bromoimidazo[1,2-b]pyridazin-6-yloxy)butyl]dimethylamine, [4-(3-bromoimidazo[1,2-b]pyridazin-6-yloxy)pentyl]diethylamine, 3-bromo-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine and 3-bromo-6-phenoxyimidazo[1,2b]pyridazine.
A further aspect of the invention is formed by the reaction of the compounds of the general formula IIb with an aryl or heteroaryl derivative in an optionally metal-catalyzed cross-coupling reaction to give a compound of the general formula I.
Methods of this type are described for example in King, Yasuda: Topics Organomet Chem (2004) δ: 205-245.


EXAMPLES
Preparation of the compounds of the invention is illustrated in the following examples without the examples being intended to be limiting.
The naming of the compounds drawn using ISIS/draw 2.4 in accordance with a IUPAC nomenclature took place using the AutoNom 2000 software from MDL.
Preparation of the Starting Materials
6-Chloroimidazo[1,2-b]pyridazine




5.0 g (38.6 mmol) of 3-amino-6-chloropyridazine were heated together with 4.7 ml (40 mmol) of chloracetaldehyde (55% strength in water) in 15 ml of n-butanol at 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 desired product were isolated in the form of an amorphous white solid.
1H-NMR (CDCl3, stored over molecular sieves): δ=7.06 (d, 1H); 7.79 (d, 1H); 7.92, (d, 1H); 7.96 (d, 1H) ppm.
3-Bromo-6-chloroimidazo[1,2-b]pyridazine




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 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 an amorphous white solid which was employed without further chromatographic purification in subsequent reactions.
1H-NMR (CDCl3, stored over molecular sieves): δ=7.12 (d, 1H); 7.79 (s, 1H); 7.90, (d, 1H) ppm.
Preparation of the Intermediates of the Invention
Intermediate A
3-Bromo-6-(3-morpholin-4-ylpropoxy)imidazo[1,2-b]pyridazine
Variant 1




1.36 g (5.18 mmol) of 6-chloroimidazo[1,2-b]pyridazine were dissolved in 40 ml of chloroform under argon and, after addition of 1.11 g (6.22 mmol, 1.2 eq.) of N-bromo-succinimide, the reaction mixture was stirred at RT overnight.
For working up the reaction mixture is mixed with water 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 in each case once with saturated sodium dithionite solution and saturated sodium chloride solution and dried over sodium sulfate. In the final purification by chromatography on silica gel, 1.08 g (61%) of the desired product were isolated.
1H-NMR (CDCl3, stored over molecular sieves): δ=1.98-2.14 (m, 2H); 2.45-2.64 (m, 6H); 3.75 (m, 4H); 4.48 (m, 2H); 6.71 (d, 1H); 7.60 (s, 1H); 7.77 (d, 1H) ppm.
MS (Cl+): m/z=341/343 [M+H]+ 100%
Intermediate B
3-Bromo-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine
Variant 2




3.7 g (25.8 mmol) of 1-piperidinepropanol are added dropwise to a suspension of 620 mg (25.8 mmol) of sodium hydride in 30 ml of tetrahydrofuran while cooling in an ice bath. After the addition is complete, the reaction mixture is stirred for 15 minutes and then 3.0 g (12.9 mmol) of 3-bromo-6-chloroimidazo[1,2-b]pyridazine are put into the reaction mixture, which is stirred at RT overnight.
The reaction mixture was then with a little saturated ammonium chloride solution and, after addition of water, the phases were separated. The aqueous phase was extracted twice more 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, 1.75 g (40%) of the desired product were isolated.
1H-NMR (CDCl3, stored over molecular sieves): δ=1.98-2.14 (m, 2H); 2.45-2.64 (m, 6H); 3.75 (m, 4H); 4.48 (m, 2H); 6.71 (d, 1H); 7.60 (s, 1H); 7.77 (d, 1H) ppm.
MS (Cl+): m/z=341/343 [M+H]+ 100%
The following were prepared in an analogous manner:










TABLE 1








Mol.





weight/


Inter-


MS (ESI)


mediate
Structure and name of the main isomer
1H-NMR
[M +]+







C



 3-Bromo-6-[2-(1-methyl-pyrrolidin-2-yl)- ethoxy]-imidazo[1,2-b]pyridazine
(CDCl3, stored over molecular sieves): δ = 1.55-1.90(m, 4H); 2.07(m, 1H); 2.14-2.33 (m, 3H) 2.38 (s, 3H); 3.12 (m, 1H); 4.46 (m, 2H); 6.68 (d, 1H); 7.58 (s, 1H); 7.74 (d, 1H) ppm.
MW: 325.21 MS (ES+) [M + 1]+: 325/327 (100%)


 


D



 3-Bromo-6-(1-methyl-piperidin-3- ylmethoxy)-imidazo[1,2-b]pyridazine
(CDCl3, stored over molecular sieves): δ = 1.12 (m, 1H); 1.62-1.95 (m, 4H); 2.01 (m, 1H); 2.32 (s, 3H); 2.82 (br s, 1H); 2.98 (br s, 1H); 4.18 (m, 2H); 6.66 (d, 1H); 7.59 (s, 1H); 7.77 (d, 1H) ppm.
MW: 325.21 MS (ES+) [M + 1]+: 325/327 (100%)


 


E



 3-Bromo-6-(1-ethyl-pyrrolidin-3- yloxy)-imidazo[1,2-b]pyridazine
(CDCl3, stored over molecular sieves): δ = 1.18 (t, 3H); 2.09 (m, 1H); 2.48-2.67 (m, 4H); 2.96 (m, 3H); 5.48 (m, 1H); 6.72 (d, 1H); 7.60 (s, 1H); 7.76 (d, 1H) ppm.
MW: 311.18 MS (ES+) [M + 1]+: 311/313 (100%)


 


F



 [3-(3-Bromo-imidazo[1,2-b]pyridazin- 6-yloxy)-propyl]-diethyl-amine
(CDCl3, stored over molecular sieves): δ = 1.05 (t, 6H); 2.03 (m, 2H); 2.52-2.70 (m, 6H); 4.46 (m, 1H); 6.70 (d, 1H); 7.59 (s, 1H); 7.75 (d, 1H) ppm.
MW: 327.23 MS (ES+) [M + 1]+: 327/329 (100%)


 


G



 3-Bromo-6-[3-(4-methyl-piperazin-1-yl)- propoxy]-imidazo[1,2-b]pyridazine
(CDCl3, stored over molecular sieves): δ = 2.05 (m, 2H); 2.33 (s, 3H); 2.45-2.65(m, 10H); 6.69 (d, 1H); 7.58 (s, 1H); 7.75 (d, 1H) ppm.
MW: 354.25 MS (ES+) [M + 1]+: 354/356 (62%); 141 (100%)


 


H



 [4-(3-Bromo-imidazo[1,2-b]pyridazin- 6-yloxy)-butyl]-dimethyl-amine
(CDCl3, stored over molecular sieves): δ = 1.88(m,2H); 2.27 (s, 6H); 2.39 (m, 2H); 4.42 (t, 2H); 6.69 (d, 1H); 7.58 (s, 1H); 7.75 (d, 1H) ppm.
MW: 313.20 MS (ES+) [M + 1]+: 313/315 (53%); 100 (100%)


 


I



 [4-(3-Bromo-imidazo[1,2-b]pyridazin- 6-yloxy)-pentyl]-dimethyl-amine
(CDCl3, stored over molecular sieves): δ = 1.05 (m, 6H); 1.42 (d, 3H); 1.56-1.76 (m, 4H); 2.41-2.62 (m, 6H); 5.22 (m, 1H); 6.67 (d, 1H); 7.58 (s, 1H); 7.74 (d, 1H) ppm.
MW: 355.28 MS (ES+) [M + 1]+: 355/357 (67%); 160 (100%)


 


J



 3-Bromo-6-(1-methyl-piperidin-3- yloxy)-imidazo[1,2-b]pyridazine
(CDCl3, stored over molecular sieves): δ = 1.64-1.82 (m, 2H); 1.86-2.04 (m,2H); 2.34 (s, 3H); 2.45 (m, 2H); 2.61 (m, 1H); 2.82 (m, 1H); 5.27 (m, 1H); 6.77 (d, 1H); 7.57 (s, 1H); 7.76 (d, 1H) ppm.
MW: 311.18 MS (ES+) [M + 1]+: 311/313 (100%)


 


K




(DMSO-D6): δ = 1.25-1.40 (m, 2H); 1.45-1.65 (m, 2H); 1.77-1.93 (m, 2H); 2.04-2.20 (m, 2H); 3.48 (d, 1H); 4.83-4.99 (m, 1H); 6.86 (d, 1H); 7.69 (s, 1H); 7.98 (d, 1H)
MW: 312.17 MS (ES+) [M + 1]+: 312/314


 


L




(DMSO-D6): δ = 5.39 (s, 1H); 6.99 (d, 1H); 7.35-7.44 (m, 2H); 7.48-7.50 (m, 1H); 7.63 (s, 1H); 7.72 (s, 1H); 8.05 (d, 1H) ppm.
MW: 338.6 MS (ES+) [M + 1]+: 340


 


M




(DMSO-D6): δ = 3.10 (t, 2H); 4.53 (t, 2H); 6.89 (d, 1H); 7.25-7.32 (m, 3H); 7.52 (s, 1H); 7.70 (s, 1H); 8.00 (s, 1H) ppm.
MW: 352.62 MS (ES+) [M + 1]+: 354


 


N




(DMSO-D6): δ = 1.17-1.44 (m, 3H); 1.46-1.61 (m, 3H); 1.65-1.79 (m, 2H); 1.94-2.11 (m, 2H); 4.96 (septet, 1H); 6.87 (d, 1H); 7.68 (s, 1H); 7.98 (d, 1H) ppm.
MW: 296.17 MS (ES+) [M + 1]+: 296/2984









Intermediate P
3-Bromo-6-(3-chlorophenoxy)imidazo[1,2-b]pyridazine
Variant 3




5 g (21.5 mmol) of 3-bromo-6-chloroimidazo[1,2-b]pyridazine, 3 g (23.7 mmol) of 3-chlorophenyl, 246 mg (0.27 mmol) of tris(dibenzylidineacetone)dipalladium, 500 mg of rac-BINAP and 4.1 g of sodium tert-butoxide are stirred in a mixture of 100 ml of dimethylformamide and 200 ml of tetrahydrofuran at 100° C. under a protective gas atmosphere for 12 h.
The reaction mixture is then mixed with saturated sodium chloride solution. The aqueous phase is extracted with ethyl acetate. The organic phase is washed twice with dilute aqueous NaCl solution and once with saturated aqueous NaCl solution and dried over sodium sulfate. In the final purification by chromatography on silica gel, 2.78 g (40%) of the desired product were isolated.
1H-NMR (DMSO-D6): δ=7.22 (d, 1H); 7.31-7.42 (m, 2H); 7.51 (d, 1H); 7.55 (t, 1H); 7.83 (s, 1H); 8.25 (d, 1H) ppm.
MS (ESI): m/z=324/326 [M+H]+
Intermediate Q
6-Chloro-3-(3-chlorophenyl)imidazo[1,2-b]pyridazine




A mixture of 4.18 g (18 mmol) of 3-bromo-6-chloroimidazo[1,2-b]pyridazine, 2.95 g (18.9 mmol) of 3-chlorophenylbronic acid, 0.83 g (0.72 mmol) of tetrakis(triphenylphosphine)palladium (0) and 32.3 ml of 2 M aqueous sodium carbonate solution are heated to boiling under in 188 ml of 1,4-dioxane for 12 h.
The reaction mixture obtained in this way is mixed with sat. aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed with sat. aqueous sodium chloride solution and dried over sodium sulfate, and the solvent is evaporated off. In the final purification by chromatography on silica gel, 3.46 g (73%) of the desired product were isolated.
1H-NMR (DMSO-D6): δ=7.43 (d, 1H); 7.44 (dd, 1H); 7.53 (t, 1H); 8.05 (dt, 1H); 8.16 (t, 1H); 8.29 (d, 1H); 8.38 (s, 1H) ppm.
MS (ESI+): m/z=264 [M+H]+
The following were prepared in an analogous manner:










TABLE 2








Mol.





weight/


Inter-


MS (ESI)


mediate
Structure of the main isomer
1H-NMR
[M + 1]+







R




(DMSO-D6 ): δ = 7.35-7.40 (m, 1H); 7.44 (d, 1H); 7.65 (t, 1H); 8.11 (dt, 1H); 8.14 (s, 1H); 8.30 (d, 1H); 8.42 (s, 1H) ppm.
MW: 313.67 MS (ES+) [M + 1]+: 314


 


S




(DMSO-D6 ): δ = 7.39 (d, 1H); 7.72 (dd, 1H); 7.78 (dd, 1H); 8.27 (d, 1H); 8.30 (dd, 1H); 8.32 (s, 1H) ppm.
MW: 235.7 MS (ES+) [M + 1]+: 236









Intermediate T
6-(3-Morpholin-4-ylpropoxy)imidazo[1,2-b]pyridazine




3.8 g (26.05 mmol) of 1-morpholinopropanol are added dropwise to a suspension of 1.04 g (26.05 mmol) of sodium hydride in 18 ml of tetrahydrofuran while cooling in an ice bath. After the addition is complete, the reaction mixture is stirred for 15 minutes and then 2.0 g (13.02 mmol) of 6-chloroimidazo[1,2-b]pyridazine are put into the reaction mixture, which is stirred at RT overnight.
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 times more 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, 1.36 g (40%) of the desired product were obtained.
1H-NMR (CDCl3, stored over molecular sieves): δ=2.04 (m, 2H); 2.51 (m, 6H); 3.74 (m, 4H); 4.37 (m, 2H); 6.67 (d, 1H); 7.60, (d, 1H); 7.72 (d, 1H); 7.78 (d, 1H) ppm.
The following is prepared in an analogous manner:










TABLE 3








Mol.





weight/


Inter-


MS (ESI)


mediate
Structure and name of the main isomer
1H-NMR
[M + 1]+







U



 6-(1-Methyl-piperidin-3-ylmethoxy)- imidazo[1,2-b]pyridazine
(CDCl3, stored over molecular sieves): δ = 1.12(m, 1H); 1.6-1.92 (m, 4H); 1.99 (m, 1H); 2.22 (m, 1H); 2.31 (s, 3H); 2.81 (d, 1H); 2.97 (d, 1H); 4.18 (m, 2H); 6.67 (d, 1H); 7.58 (s, 1H); 7.71 (s, 1H); 7.78 (d, 1H) ppm.










Preparation of the Final Products of the Invention
Variant A
Example 1
3-(3-Chlorophenyl)-6-(3-morpholin-4-ylpropoxy)imidazo[1,2-b]pyridazine




1.08 g (3.17 mmol) of 3-bromo-6-(3-morpholin-4-ylpropoxy)imidazo[1,2-b]pyridazine were introduced into 20 ml of dimethoxyethane under argon. 544 mg (3.48 mmol, 1.1 eq.) of m-chlorophenylboronic acid, 364 mg (0.63 mmol, 0.2 eq.) of bis(dibenzylideneacetone)palladium(0) and 193 mg (0.63 mmol, 0.2 eq.) of tri-o-tolyl-phosphine, and 4.8 ml of saturated sodium bicarbonate solution, were successively added, and the reaction mixture was heated under reflux for 4 hours.
The mixture was mixed with saturated sodium bicarbonate solution and diluted with water. The aqueous phase was extracted three times more with ethyl acetate. The combined organic phases were then washed once with saturated sodium chloride solution and dried over sodium sulfate. In the final purification by chromatography of the crude product on silica gel, 200 mg (17%) of the desired product were isolated.
1H-NMR (CDCl3, stored over molecular sieves): δ=2.03 (m, 2H); 2.46 (m, 4H); 2.052 (m, 2H); 3.70 (m, 4H); 4.43 (m, 2H); 6.70 (d, 1H); 7.28 (m, 1H); 7.37 (m, 1H); 7.82 (m, 2H); 7.89 (s, 1H); 8.19 (m, 1H) ppm.
As alternative to the management of the reaction described above, the final compounds of the invention can also be prepared by parallel synthesis, for example in an automatic synthesizer.
Example 2
6-[3-(4-Methylpiperazin-1-yl)propoxy]-3-thiophen-2-ylimidazo[1,2-b]pyridazine




Firstly a solution of 38.4 mg (0.3 mmol) of thiophen-3-ylboronic acid in 0.73 ml of THF were added to a solution of 48.8 mg (0.15 mmol) in 1 ml of a mixture of THF and DMF (1:1) under an argon atmosphere. Subsequently, a mixture of 8.9 mg (0.02 mmol) of 1,3-bis(2,6-dipropylphenyl)imidazolium chloride and 9.6 mg (0.01 mmol) of tris(dibenzylideneacetone)palladium dissolved in 0.91 ml of THF was added. Addition of 147 mg (0.45 mmol) of cesium carbonate dissolved in 0.25 ml of water was followed by shaking the reaction mixture at 80° C. for 12 h. Addition of 1 ml of water and 3 ml of ethyl acetate is followed by extraction of the reaction mixture. The organic phase is separated off and the solvent is distilled off.
The crude product obtained in this way was purified by preparative HPLC. 40 mg (75%) of a solid were obtained.
HPLC-MS (analytical) of the purified product:
(Detection: UV=254 nM; column: Purospher STAR RP18e, 125×4 mm, 5μ (Merck KgGa, Darmstadt); eluent: A: H2O/0.1% TFA, B: CH3CN/0.1% TFA, gradient: 5 to 95% B in 10 min; flow rate: 1 ml/min):
Retention time of the product=4.17 min; MS of the product: m/z=358 ([M+H]+)
The following are prepared in the manner described:














EXAMPLE

Retention

MW


No.
STRUCTURE
time [min]
MW calc.
found



















3




4.89
419.0
420.0



3-(2,4-Dichloro-phenyl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo[1,2-b]






pyridazine





 


4




4.67
365.0
366.0



6-[3-(4-Methyl-piperazin-1-yl)-propoxy]-






3-m-tolyl-imidazo[1,2-b]pyridazine





 


5




4.77
385.0
386.0



3-(3-Chloro-phenyl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


6




5.15
407.0
408.0



3-Benzo[b]thiophen-2-yl-6-






[3-(4-methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazine





 


7




4.39
369.0
370.0



3-(4-Fluoro-phenyl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


8




4.32
351.0
352.0



6-[3-(4-Methyl-piperazin-1-yl)-propoxy]-






3-phenyl-imidazo[1,2-b]pyridazine





 


9




4.85
397.0
398.0



6-[3-(4-Methyl-piperazin-1-yl)-propoxy]-






3-(4-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


10




4.82
385.0
386.0



3-(4-Chloro-phenyl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


11




4.24
393.0
394.0



1-(3-{6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazin-






3-yl}-phenyl)-ethanone





 


12




4.57
397.0
398.0



6-[3-(4-Methyl-piperazin-1-yl) propoxy]-






3-(2-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


13




5.17
435.0
436.0



6-[3-(4-Methyl-piperazin-1-yl)-propoxy]-






3-(3-trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


14




5.42
427.0
428.0



3-Biphenyl-3-yl-6-[3-(4-methyl-piperazin-






1-yl)-propoxy]-imidazo[1,2-b]pyridazine





 


15




3.84
381.0
382.0



(3-{6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazin-






3-yl}-phenyl)-methanol





 


16




4.84
397.0
398.0



6-[3-(4-Methyl-piperazin-1-yl)-propoxy]-






3-(3-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


17




4.5
385.0
386.0



3-(2-Chloro-phenyl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


18




5.24
435.0
436.0



6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-3-(4-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazine





 


19




4.97
399.0
400.0



3-(3-Chloro-4-methyl-phenyl)-6-[3-






(4-methyl-piperazin-1-yl)-propoxy]-






imidazo[1,2-b]pyridazine





 


20




3.54
355.0
356.0



3-(5-Methyl-furan-2-yl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


21




4.55
399.0
400.0



3-(3-Fluoro-4-methoxy-phenyl)-6-[3-






(4-methyl-piperazin-1-yl)-propoxy]-






imidazo[1,2-b]pyridazine





 


22




4.44
365.0
366.0



6-[3-(4-Methyl-piperazin-1-yl)-propoxy]-






3-o-tolyl-imidazo[1,2-b]pyridazine





 


23




4.84
403.0
404.0



3-(3-Chloro-4-fluoro-phenyl)-6-[3-






(4-methyl-piperazin-1-yl)-propoxy]-






imidazo[1,2-b]pyridazine





 


24




4.78
391.0
392.0



3-(5-Chloro-thiophen-2-yl)-6-[3-






(4-methyl-piperazin-1-yl)-propoxy]-






imidazo[1,2-b]pyridazine





 


25




4.35
376.0
377.0



3-{6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazin-3-






yl}-benzonitrile





 


26




4.59
371 .0
372.0



6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-3-(4-methyl-thiophen-






2-yl)-imidazo[1,2-b]pyridazine





 


27




4.22
390.0
391.0



(4-{6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazin-3-






yl}-phenyl)-acetonitrile





 


28




4.55
409.0
410.0



3-{6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazin-3-






yl}-benzoic acid methyl ester





 


29




4.28
390.0
391.0



3-(1H-Indol-4-yl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


30




5.15
391.0
392.0



3-Benzofuran-2-yl-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


31




4.59
365.0
366.0



6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-3-p-tolyl-imidazo[1,2-b]






pyridazine





 


32




4.47
369.0
370.0



3-(3-Fluoro-phenyl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


33




4.94
407.0
408.0



3-Benzo[b]thiophen-3-yl-6-[3-






(4-methyl-piperazin-1-yl)-propoxy]-






imidazo[1,2-b]pyridazine





 


34




4.82
385.0
386.0



3-(4-Chloro-phenyl)-6-[3-(4-methyl-






piperazin-1-yl)-propoxy]-imidazo






[1,2-b]pyridazine





 


35




4.22
384.0
385.0



3-(6-Fluoro-5-methyl-pyridin-3-yl)-






6-[3-(4-methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazine





 


36




3.94
400.0
401.0



3-(2-Chloro-6-methyl-pyridin-3-yl)-






6-[3-(4-methyl-piperazin-1-yl)-






propoxy]-imidazo[1,2-b]pyridazine





 


37




4.94
435.0
436.0



6-[3-(4-Methyl-piperazin-1-yl)-propoxy]-






3-(2-trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


38




4.5
443.0
444.0



3-(4-Ethanesulfonyl-phenyl)-6-[3-(4-






methyl-piperazin-1-yl)-propoxy]-






imidazo[1,2-b]pyridazine





 


39




4.75
420.0
421.0



6-[3-(4-Methyl-piperazin-1-yl)-






propoxy]-3-(3-pyrrolidin-1-yl-phenyl)-






imidazo[1,2-b]pyridazine





 


40




5.17
421.0
422.0



3-(4-Cyclopropylmethoxy-phenyl)-6-






[3-(4-methyl-piperazin-1-yl)-propoxy]






-imidazo[1,2-b]pyridazine





41




5.15
358.0
359.0



Diethyl-[4-(3-thiophen-3-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-pentyl]-






amine





 


42




5.78
420.0
421.0



{4-[3-(2,4-Dichloro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-pentyl}-






diethyl-amine





 


43




5.53
366.0
367.0



Diethyl-[4-(3-m-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-pentyl]-amine





 


44




5.7
386.0
387.0



{4-[3-(3-Chloro-phenyl)-imidazo[1,2-b]






pyridazin-6-yloxy]-pentyl}-diethyl-






amine





45




6.12
408.0
409.0



[4-(3-Benzo[b]thiophen-2-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-pentyl]-






diethyl-amine





 


46




5.3
370.0
371.0



Diethyl-{4-[3-(4-fluoro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-pentyl}-






amine





 


47




5.72
398.0
399.0



Diethyl-{4-[3-(4-methylsulfanyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-pentyl}-






amine





 


48




5.72
386.0
387.0



{4-[3-(4-Chloro-phenyl)-imidazo[1,2-b]






pyridazin-6-yloxy]-pentyl}-diethyl-






amine





 


49




5.07
394.0
395.0



1-{3-[6-(4-Diethylamino-1-methyl-






butoxy)-imidazo[1,2-b]pyridazin-






3-yl]-phenyl)-ethanone





 


50




5.42
398.0
399.0



Diethyl-{4-[3-(2-methylsulfanyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl]-amine





 


51




6.07
436.0
437.0



Diethyl-{4-[3-(3-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-pentyl}-amine





 


52




6.27
428.0
429.0



[4-(3-Biphenyl-3-yl-imidazo[1,2-b]






pyridazin-6-yloxy)-pentyl]-diethyl-






amine





 


53




4.59
382.0
383.0



{3-[6-(4-Diethylamino-1-methyl-butoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-methanol





 


54




5.69
398.0
399.0



Diethyl-{4-[3-(3-methylsulfanyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl]-amine





 


55




5.6
420.0
421.0



Diethyl-{4-[3-(2-trifluoromethyl-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy[-pentyl}-amine





 


56




5.39
386.0
387.0



{4-[3-(2-Chloro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-pentyl}-






diethyl-amine





 


57




6.03
436.0
437.0



Diethyl-{4-[3-(4-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-pentyl}-amine





 


58




5.95
400.0
401.0



{4-[3-(3-Chloro-4-methyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl}-diethyl-amine





 


59




4.85
356.0
357.0



Diethyl-{4-[3-(5-methyl-furan-2-yl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl}-amine





 


60




5.42
400.0
401.0



Diethyl-{4-[3-(3-fluoro-4-methoxy-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-pentyl}-amine





 


61




5.27
366.0
367.0



Diethyl-[4-(3-o-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-pentyl]-amine





 


62




5.84
404.0
405.0



{4-[3-(3-Chloro-4-fluoro-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl}-diethyl-amine





63




5.78
392.0
393.0



{4-[3-(5-Chloro-thiophen-2-yl)-imidazo






[1,2-b]pyridazin-6-yloxy]-pentyl}-






diethyl-amine





64




5.27
377.0
378.0



3-[6-(4-Diethylamino-1-methyl-butoxy)-






imidazo[1,2-b]pyridazin-3-yl]-benzonitrile





 


65




5.44
372.0
373.0



Diethyl-{4-[3-(4-methyl-thiophen-2-yl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl}-amine





66




5.15
391.0
392.0



{4-[6-(4-Diethylamino-1-methyl-butoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-acetonitrile





 


67




5.4
410.0
411.0



3-[6-(4-Diethylamino-1-methyl-butoxy)-






imidazo[1,2-b]pyridazin-3-yl]-benzoic






acid methyl ester





 


68




5.12
391.0
392.0



Diethyl-{4-[3-(1H-indol-4-yl)-imidazo






[1,2-b]pyridazin-6-yloxy]-pentyl}-amine





 


69




6.07
392.0
393.0



[4-(3-Benzofuran-2-yl-imidazo[1,2-b]






pyridazin-6-yloxy)-pentyl]-diethyl-






amine





 


70




5.53
366.0
367.0



Diethyl-[4-(3-p-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-pentyl]-amine





 


71




5.42
370.0
371.0



Diethyl-{4-[3-(3-fluoro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-pentyl}-amine





 


72




5.75
408.0
409.0



[4-(3-Benzo[b]thiophen-3-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-pentyl]-






diethyl-amine





 


73




5.64
386.0
387.0



{4-[3-(4-Chloro-phenyl)-imidazo[1,2-b]






pyridazin-6-yloxy]-pentyl}-diethyl-amine





 


74




5.17
385.0
386.0



Diethyl-{4-[3-(6-fluoro-5-methyl-pyridin-






3-yl)-imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl}-amine





 


75




5.78
436.0
437.0



Diethyl-{4-[3-(2-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-pentyl}-






amine





 


76




5.75
421.0
422.0



Diethyl-{4-[3-(3-pyrrolidin-1-yl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl]-amine





 


77




8.97
388.0
389.0



{5-[6-(4-Diethylamino-1-methyl-butoxy)-






imidazo[1,2-b]pyridazin-3-yl]-thiophen-






2-yl}-methanol





 


78




6.0
422.0
423.0



{4-[3-(4-Cyclopropylmethoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






pentyl}-diethyl-amine





 


79




4.5
328.1
329.1



6-[2-(1-Methyl-pyrrolidin-2-yl)-ethoxy]-






3-thiophen-3-yl-imidazo[1,2-b]pyridazine





 


80




5.3
390.1
391.1



3-(2,4-Dichloro-phenyl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo-






[1,2-b]pyridazine





 


81




5.03
336.2
337.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-ethoxy]-






3-m-tolyl-imidazo[1,2-b]pyridazine





 


82




5.17
356.1
357.1



3-(3-Chloro-phenyl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo[1,2-b]






pyridazine





 


83




5.65
378.2
379.2



3-Benzo[b]thiophen-2-yl-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo[1,2-b]






pyridazine





 


84




4.77
340.2
341.2



3-(4-Fluoro-phenyl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidaza[1,2-b]






pyridazine





 


85




4.67
322.2
323.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-ethoxy]-






3-phenyl-imidazo[1,2-b]pyridazine





 


86




5.24
368.2
369.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-ethoxy]-






3-(4-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


87




5.22
356.1
357.1



3-(4-Chloro-phenyl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo






[1,2-b]pyridazine





 


88




4.59
364.2
365.2



1-(3-{6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazin-3-yl}-






phenyl)-ethanone





 


89




4.9
368.2
369.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-ethoxy]-






3-(2-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


90




5.62
406.2
407.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-ethoxy]-






3-(3-trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


91




5.85
398.2
399.2



3-Biphenyl-3-yl-6-[2-(1-methyl-pyrrolidin-






2-yl)-ethoxy]-imidazo[1,2-b]pyridazine





 


92




4.09
352.2
353.2



(3-{6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazin-






3-yl}-phenyl)-methanol





 


93




5.2
368.2
369.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-3-(3-methylsulfanyl-






phenyl)-imidazo[1,2-b]pyridazine





 


94




5.1
390.2
391.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-3-(2-trifluoromethyl-






phenyl)-imidazo[1,2-b]pyridazine





 


95




4.84
356.1
357.1



3-(2-Chloro-phenyl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo






[1,2-b]pyridazine





 


96




5.6
406.2
407.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-3-(4-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazine





 


97




5.47
370.2
371.2



3-(3-Chloro-4-methyl-phenyl)-6-






[2-(1-methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazine





 


98




4.9
370.2
371.2



3-(3-Fluoro-4-methoxy-phenyl)-6-






[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-






imidazo[1,2-b]pyridazine





 


99




4.72
336.2
337.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-3-o-tolyl-imidazo[1,2-b]






pyridazine





 


100




5.32
374.1
375.1



3-(3-Chloro-4-fluoro-phenyl)-6-






[2-(1-methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazine





 


101




4.7
347.2
348.2



3-{6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazin-






3-yl}-benzonitrile





 


102




4.9
342.2
343.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-3-(4-methyl-thiophen-






2-yl)-imidazo[1,2-b]pyridazine





 


103




4.62
361.2
362.2



(4-{6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazin






-3-yl}-phenyl)-acetonitrile





 


104




4.92
380.2
381.2



3-{6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazin-






3-yl}-benzoic acid methyl ester





 


105




4.55
361.2
362.2



3-(1H-Indol-4-yl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo






[1,2-b]pyridazine





 


106




4.02
341.2
342.2



3-(2-Fluoro-pyridin-3-yl)-6-[2-(1-






methyl-pyrrolidin-2-yl)-ethoxy]-






imidazo[1,2-b]pyridazine





 


107




5.67
362.2
363.2



3-Benzofuran-2-yl-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo






[1,2-b]pyridazine





 


108




5.05
336.2
337.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-ethoxy]-






3-p-tolyl-imidazo[1,2-b]pyridazine





 


109




4.87
340.2
341.2



3-(3-Fluoro-phenyl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo[1,2-b]






pyridazine





 


110




5.2
378.2
379.2



3-Benzo[b]thiophen-3-yl-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo[1,2-b]






pyridazine





 


111




5.24
356.1
357.1



3-(4-Chloro-phenyl)-6-[2-(1-methyl-






pyrrolidin-2-yl)-ethoxy]-imidazo[1,2-b]






pyridazine





 


112




4.62
355.2
356.2



3-(6-Fluoro-5-methyl-pyridin-3-yl)-






6-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-






imidazo[1,2-b]pyridazine





 


113




4.32
371.2
372.2



3-(2-Chloro-6-methyl-pyridin-3-yl)-






6-[2-(1-methyl-pyrrolidin-2-yl)-ethoxy]-






imidazo[1,2-b]pyridazine





 


114




5.24
406.2
407.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-3-(2-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazine





 


115




4.62
414.2
415.2



3-(4-Ethanesulfonyl-phenyl)-6-[2-






(1-methyl-pyrrolidin-2-yl)-ethoxy]-






imidazo[1,2-b]pyridazine





 


116




5.2
391.2
392.2



6-[2-(1-Methyl-pyrrolidin-2-yl)-






ethoxy]-3-(3-pyrrolidin-1-yl-






phenyl)-imidazo[1,2-b]pyridazine





 


117




5.5
392.2
393.2



3-(4-Cyclopropyl methoxy-phenyl)-






6-[2-(1-methyl-pyrrolidin-2-yl)-






ethoxy]-imidazo[1,2-b]pyridazine





 


118




4.64
328.1
329.1



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-thiophen-3-yl-imidazo[1,2-b]






pyridazine





 


119




5.47
390.1
391.1



3-(2,4-Dichloro-phenyl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


120




5.24
356.1
357.1



3-(3-Chloro-phenyl)-6-(1 -methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


121




5.62
378.2
379.2



3-Benzo[b]thiophen-2-yl-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


122




4.92
340.2
341.2



3-(4-Fluoro-phenyl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


123




4.74
322.2
323.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-phenyl-imidazo[1,2-b]pyridazine





 


124




5.28
368.2
369.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(4-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


125




5.2
356.1
357.1



3-(4-Chloro-phenyl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


126




4.69
364.2
365.2



1-{3-[6-(1-Methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazin-3-yl]-phenyl}-






ethanone





 


127




4.99
368.2
369.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(2-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


128




5.7
406.2
407.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(3-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazine





 


129




5.8
398.2
399.2



3-Biphenyl-3-yl-6-(1-methyl-piperidin-






3-ylmethoxy)-imidazo[1,2-b]pyridazine





 


130




4.25
352.2
353.2



{3-[6-(1-Methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazin-3-yl]-phenyl}-






methanol





 


131




5.28
368.2
369.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(3-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


132




5.17
390.2
391.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(2-trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


133




4.84
356.1
357.1



3-(2-Chloro-phenyl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


134




5.74
406.2
407.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(4-trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


135




5.55
370.2
371.2



3-(3-Chloro-4-methyl-phenyl)-6-






(1-methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazine





 


136




4.15
326.2
327.2



3-(5-Methyl-furan-2-yl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


137




4.9
370.2
371.2



3-(3-Fluoro-4-methoxy-phenyl)-6-






(1-methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazine





 


138




4.89
336.2
337.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-o-tolyl-imidazo[1,2-b]pyridazine





 


139




5.4
374.1
375.1



3-(3-Chloro-4-fluoro-phenyl)-6-






(1-methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazine





 


140




5.27
362.1
363.1



3-(5-Chloro-thiophen-2-yl)-6-






(1-methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazine





 


141




4.7
347.2
348.2



3-[6-(1-Methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazin-3-yl]-benzonitrile





 


142




5.03
342.2
343.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(4-methyl-thiophen-2-yl)-imidazo






[1,2-b]pyridazine





 


143




4.69
361.2
362.2



{4-[6-(1-Methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazin-3-yl]-phenyl}-






acetonitrile





 


144




4.97
380.2
381.2



3-[6-(1-Methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazin-3-yl]-benzoic






acid methyl ester





 


145




4.55
361.2
362.2



3-(1H-Indol-4-yl)-6-(1-methyl-piperidin-






3-ylmethoxy)-imidazo[1,2-b]pyridazine





 


146




4.17
341.2
342.2



3-(2-Fluoro-pyridin-3-yl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


147




5.7
362.2
363.2



3-Benzofuran-2-yl-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


148




5.09
336.2
337.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-p-tolyl-imidazo[1,2-b]pyridazine





 


149




4.85
340.2
341.2



3-(3-Fluoro-phenyl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


150 




5.37
378.2
379.2



3-Benzo[b]thiophen-3-yl-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo[1,2-b]






pyridazine





 


151




5.3
356.1
357.1



3-(4-Chloro-phenyl)-6-(1-methyl-






piperidin-3-ylmethoxy)-imidazo






[1,2-b]pyridazine





 


152




4.8
355.2
356.2



3-(6-Fluoro-5-methyl-pyridin-3-yl)-






6-(1-methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazine





 


153




5.37
406.2
407.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(2-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazine





 


154




4.67
414.2
415.2



3-(4-Ethanesulfonyl-phenyl)-6-






(1-methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazine





 


155




5.27
391.2
392.2



6-(1-Methyl-piperidin-3-ylmethoxy)-






3-(3-pyrrolidin-1-yl-phenyl)-imidazo






[1,2-b]pyridazine





 


156




5.49
392.2
393.2



3-(4-Cyclopropylmethoxy-phenyl)-6-






(1-methyl-piperidin-3-ylmethoxy)-






imidazo[1,2-b]pyridazine





 


157




4.64
330.0
331.0



Diethyl-[3-(3-thiophen-3-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-propyl]-amine





 


158




5.24
374.0
375.0



Diethyl-[3-(3-naphthalen-1-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-propyl]-amine





 


159




4.9
354.0
355.0



Diethyl-{3-[3-(4-methoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-amine





 


160




5.12
338.0
339.0



Diethyl-[3-(3-m-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-propyl]-amine





 


161




5.19
358.0
359.0



{3-[3-(3-Chloro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-propyl}-






diethyl-amine





 


162





380.0
381.0



[3-(3-Benzo[b]thiophen-2-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-propyl]-






diethyl-amine





 


163




4.94
342.0
343.0



Diethyl-{3-[3-(4-fluoro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-propyl}-amine





 


164




4.74
324.0
325.0



Diethyl-[3-(3-phenyl-imidazo[1,2-b]






pyridazin-6-yloxy)-propyl]-amine





 


165




5.24
370.0
371.0



Diethyl-{3-[3-(4-methylsulfanyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






-propyl}-amine





 


166




5.32
358.0
359.0



{3-[3-(4-Chloro-phenyl)-imidazo[1,2-b]






pyridazin-6-yloxy]-propyl}-diethyl-amine





 


167




4.74
366.0
367.0



1-{3-[6-(3-Diethylamino-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-phenyl}-






ethanone





 


168




5.0
370.0
371.0



Diethyl-{3-[3-(2-methylsulfanyl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


169




5.62
408.0
409.0



Diethyl-{3-[3-(3-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


170




5.59
392.0
393.0



Diethyl-{3-[3-(3-trifluoromethyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-amine





 


171




5.95
400.0
401.0



[3-(3-Biphenyl-3-yl-imidazo[1,2-b]






pyridazin-6-yloxy)-propyl]-diethyl-






amine





 


172




4.25
354.0
355.0



{3-[6-(3-Diethylamino-propoxy)-imidazo






[1,2-b]pyridazin-3-yl]-phenyl}-methanol





 


173




5.22
370.0
371.0



Diethyl-{3-[3-(3-methylsulfanyl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


174




5.22
392.0
393.0



Diethyl-{3-[3-(2-trifluoromethyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-propyl}-






amine





 


175




4.97
358.0
359.0



{3-[3-(2-Chloro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-propyl}-






diethyl-amine





 


176




5.77
408.0
409.0



Diethyl-{3-[3-(4-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


177




5.64
392.0
393.0



Diethyl-{3-[3-(4-trifluoromethyl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


178




5.59
372.0
373.0



{3-[3-(3-Chloro-4-methyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-diethyl-amine





 


179




4.2
328.0
329.0



Diethyl-{3-[3-(5-methyl-furan-2-yl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-amine





 


180




5.02
372.0
373.0



Diethyl-{3-[3-(3-fluoro-4-methoxy-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


181




4.84
338.0
339.0



Diethyl-[3-(3-o-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-propyl]-amine





 


182




5.44
376.0
377.0



{3-[3-(3-Chloro-4-fluoro-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-diethyl-amine





 


183




4.95
354.0
355.0



Diethyl-{3-[3-(3-methoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-amine





 


184




5.34
364.0
365.0



{3-[3-(5-Chloro-thiophen-2-yl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-diethyl-amine





 


185




4.75
349.0
350.0



3-[6-(3-Diethylamino-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






benzonitrile





 


186




5.1
344.0
345.0



Diethyl-{3-[3-(4-methyl-thiophen-2-yl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-amine





 


187




4.72
363.0
364.0



{4-[6-(3-Diethylamino-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-acetonitrile





 


188




5.0
382.0
383.0



3-[6-(3-Diethylamino-propoxy)-imidazo






[1,2-b]pyridazin-3-yl]-benzoic acid






methyl ester





 


189




4.27
381.0
382.0



N-{3-[6-(3-Diethylamino-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-phenyl}-






acetamide





 


190




4.69
363.0
364.0



Diethyl-{3-[3-(1H-indol-4-yl)-imidazo






[1,2-b]pyridazin-6-yloxy]-propyl}-amine





 


191




5.74
364.0
365.0



[3-(3-Benzofuran-2-yl-imidazo[1,2-b]






pyridazin-6-yloxy)-propyl]-diethyl-






amine





 


192




5.05
338.0
339.0



Diethyl-[3-(3-p-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-propyl]-amine





 


193




4.97
342.0
343.0



Diethyl-{3-[3-(3-fluoro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-propyl}-amine





 


194




5.44
380.0
381.0



[3-(3-Benzo[b]thiophen-3-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-propyl]-






diethyl-amine





 


195




5.32
358.0
359.0



{3-[3-(4-Chloro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-propyl}-






diethyl-amine





 


196




4.65
357.0
358.0



Diethyl-{3-[3-(6-fluoro-5-methyl-






pyridin-3-yl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


197




5.44
408.0
409.0



Diethyl-{3-[3-(2-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-propyl}-






amine





 


198




4.75
416.0
417.0



{3-[3-(4-Ethanesulfonyl-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-diethyl-amine





 


199




5.22
393.0
394.0



Diethyl-{3-[3-(3-pyrrolidin-1-yl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-propyl}-amine





 


200




5.69
394.0
395.0



{3-[3-(4-Cyclopropylmethoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






propyl}-diethyl-amine





 


201




4.42
314.0
315.0



6-(1-Methyl-piperidin-3-yloxy)-






3-thiophen-3-yl-imidazo[1,2-b]






pyridazine





 


202




5.05
358.0
359.0



6-(1-Methyl-piperidin-3-yloxy)-3-






naphthalen-1-yl-imidazo[1,2-b]






pyridazine





 


203




4.72
338.0
339.0



3-(4-Methoxy-phenyl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


204




5.34
376.0
377.0



3-(2,4-Dichloro-phenyl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


205




4.92
322.0
323.0



6-(1-Methyl-piperidin-3-yloxy)-3-m-






tolyl-imidazo[1,2-b]pyridazine





 


206




5.0
342.0
343.0



3-(3-Chloro-phenyl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


207




5.6
364.0
365.0



3-Benzo[b]thiophen-2-yl-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


208




4.75
326.0
327.0



3-(4-Fluoro-phenyl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


209




4.78
354.0
355.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(2-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


210




5.47
392.0
393.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(3-trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


211




5.42
376.0
377.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(3-trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


212




5.78
384.0
385.0



3-Biphenyl-3-yl-6-(1-methyl-piperidin-






3-yloxy)-imidazo[1,2-b]pyridazine





 


213




4.05
338.0
339.0



{3-[6-(1-Methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-methanol





 


214




5.05
354.0
355.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(3-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


215




5.03
376.0
377.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(2-trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


216




4.75
342.0
343.0



3-(2-Chloro-phenyl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


217




5.62
392.0
393.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(4-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazine





 


218




5.5
376.0
377.0



6-(1-Methyl-piperidin-3-yloxy)-






3-(4-trifluoromethyl-phenyl)-






imidazo[1,2-b]pyridazine





 


219




5.4
356.0
357.0



3-(3-Chloro-4-methyl-phenyl)-6-






(1-methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazine





 


220




3.97
312.0
313.0



3-(5-Methyl-furan-2-yl)-6-






(1-methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazine





 


221




4.82
356.0
357.0



3-(3-Fluoro-4-methoxy-phenyl)-6-






(1-methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazine





 


222




4.62
322.0
323.0



6-(1-Methyl-piperidin-3-yloxy)-3-






o-tolyl-imidazo[1,2-b]pyridazine





 


223




5.25
360.0
361.0



3-(3-Chloro-4-fluoro-phenyl)-6-






(1-methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazine





 


224




4.75
338.0
339.0



3-(3-Methoxy-phenyl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


225




5.15
348.0
349.0



3-(5-Chloro-thiophen-2-yl)-6-(1-






methyl-piperidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


226




4.57
333.0
334.0



3-[6-(1-Methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






benzonitrile





 


227




4.89
328.0
329.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(4-methyl-thiophen-2-yl)-imidazo






[1,2-b]pyridazine





 


228




4.52
347.0
348.0



{4-[6-(1-Methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-acetonitrile





 


229




4.82
366.0
367.0



3-[6-(1-Methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






benzoic acid methyl ester





 


230




4.1
365.0
366.0



N-{3-[6-(1-Methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-acetamide





 


231




4.47
347.0
348.0



3-(1H-Indol-4-yl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


232




5.62
348.0
349.0



3-Benzofuran-2-yl-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


233




4.92
322.0
323.0



6-(1-Methyl-piperidin-3-yloxy)-3-p-






tolyl-imidazo[1,2-b]pyridazine





 


234




4.67
326.0
327.0



3-(3-Fluoro-phenyl)-6-(1-methyl-piperidin-






3-yloxy)-imidazo[1,2-b]pyridazine





 


235




5.24
364.0
365.0



3-Benzo[b]thiophen-3-yl-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


236




5.15
342.0
343.0



3-(4-Chloro-phenyl)-6-(1-methyl-






piperidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


237




4.49
341.0
342.0



3-(6-Fluoro-5-methyl-pyridin-3-yl)-






6-(1-methyl-piperidin-3-yloxy)-






imidazo[1,2-b]pyridazine





 


238




5.24
392.0
393.0



6-(1-Methyl-piperidin-3-yloxy)-3-(2-






trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


239




4.57
400.0
401.0



3-(4-Ethanesulfonyl-phenyl)-6-






(1-methyl-piperidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


240




5.1
377.0
378.0



6-(1-Methyl-piperidin-3-yloxy)-3-






(3-pyrrolidin-1-yl-phenyl)-imidazo






[1,2-b]pyridazine





 


241




5.52
378.0
379.0



3-(4-Cyclopropylmethoxy-phenyl)-






6-(1-methyl-piperidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


242




4.3
314.0
315.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






thiophen-3-yl-imidazo[1,2-b]






pyridazine





 


243




4.97
358.0
359.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






naphthalen-1-yl-imidazo[1,2-b]






pyridazine





 


244




4.62
338.0
339.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-






3-(4-methoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


245




5.25
376.0
377.0



3-(2,4-Dichloro-phenyl)-6-






(1-ethyl-pyrrolidin-3-yloxy)-






imidazo[1,2-b]pyridazine





 


246




4.9
342.0
343.0



3-(3-Chloro-phenyl)-6-(1-ethyl-






pyrrolidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


247




5.57
364.0
365.0



3-Benzo[b]thiophen-2-yl-6-(1-ethyl-






pyrrolidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


248




4.65
326.0
327.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(4-fluoro-phenyl)-imidazo[1,2-b]






pyridazine





 


249




4.44
308.0
309.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






phenyl-imidazo[1,2-b]pyridazine





 


250




5.02
354.0
355.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(4-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


251




5.07
342.0
343.0



3-(4-Chloro-phenyl)-6-(1-ethyl-






pyrrolidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


252




4.47
350.0
351.0



1-{3-[6-(1-Ethyl-pyrrolidin-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-ethanone





 


253




4.72
354.0
355.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(2-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


254




5.42
392.0
393.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-(3-






trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


255




5.34
376.0
377.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(3-trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


256




5.75
384.0
385.0



3-Biphenyl-3-yl-6-(1-ethyl-pyrrolidin-






3-yloxy)-imidazo[1,2-b]pyridazine





 


257




3.98
338.0
339.0



{3-[6-(1-Ethyl-pyrrolidin-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-methanol





 


258




4.97
354.0
355.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(3-methylsulfanyl-phenyl)-imidazo






[1,2-b]pyridazine





 


259




4.97
376.0
377.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(2-trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


260




4.67
342.0
343.0



3-(2-Chloro-phenyl)-6-(1-ethyl-






pyrrolidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


261




5.57
392.0
393.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(4-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazine





 


262




5.44
376.0
377.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(4-trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


263




5.34
356.0
357.0



3-(3-Chloro-4-methyl-phenyl)-6-






(1-ethyl-pyrrolidin-3-yloxy)-






imidazo[1,2-b]pyridazine





 


264




5.17
360.0
361.0



3-(3-Chloro-4-fluoro-phenyl)-6-






(1-ethyl-pyrrolidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


265




4.65
338.0
339.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-






3-(3-methoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


266




5.09
348.0
349.0



3-(5-Chloro-thiophen-2-yl)-6-(1-ethyl-






pyrrolidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


267




4.45
333.0
334.0



3-[6-(1-Ethyl-pyrrolidin-3-yloxy)-imidazo






[1,2-b]pyridazin-3-yl]-benzonitrile





 


268




4.82
328.0
329.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(4-methyl-thiophen-2-yl)-imidazo






[1,2-b]pyridazine





 


269




4.78
366.0
367.0



3-[6-(1-Ethyl-pyrrolldln-3-yloxy)-






imidazo[1,2-b]pyridazin-3-yl]-






benzoic acid methyl ester





 


270




4.12
365.0
366.0



N-{3-[6-(1-Ethyl-pyrrolidin-3-y-






imidazo[1,2-b]pyridazin-3-yl]-






acetamide





 


271




4.32
347.0
348.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-(1H-






indol-4-yl)-imidazo[1,2-b]pyridazine





 


272




5.59
348.0
349.0



3-Benzofuran-2-yl-6-(1-ethyl-pyrrolidin-






3-yloxy)-imidazo[1,2-b]pyridazine





 


273




4.85
322.0
323.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






p-tolyl-imidazo[1,2-b]pyridazine





 


274




4.65
326.0
327.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(3-fluoro-phenyl)-imidazo[1,2-b]






pyridazine





 


275




5.09
342.0
343.0



3-(4-Chloro-phenyl)-6-(1-ethyl-






pyrrolidin-3-yloxy)-imidazo[1,2-b]






pyridazine





 


276




4.44
341.0
342.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(6-fluoro-5-methyl-pyridin-3-yl)-






imidazo[1,2-b]pyridazine





 


277




5.09
392.0
393.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(2-trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


278




4.52
400.0
401.0



3-(4-Ethanesulfonyl-phenyl)-6-






(1-ethyl-pyrrolidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


279




5.02
377.0
378.0



6-(1-Ethyl-pyrrolidin-3-yloxy)-3-






(3-pyrrolidin-1-yl-phenyl)-imidazo






[1,2-b]pyridazine





 


280




5.39
378.0
379.0



3-(4-Cyclopropylmethoxy-phenyl)-






6-(1-ethyl-pyrrolidin-3-yloxy)-imidazo






[1,2-b]pyridazine





 


281




4.74
342.0
343.0



6-(3-Piperidin-1-yl-propoxy)-3-






thiophen-3-yl-imidazo[1,2-b]






pyridazine





 


282




5.4
386.0
387.0



3-Naphthalen-1-yl-6-(3-piperidin-1-






yl-propoxy)-imidazo[1,2-b]pyridazine





 


283




4.97
366.0
367.0



3-(4-Methoxy-phenyl)-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-b]pyridazine





 


284




5.19
350.0
351.0



6-(3-Piperidin-1-yl-propoxy)-3-m-






tolyl-imidazo[1,2-b]pyridazine





 


285




5.35
370.0
371.0



3-(3-Chloro-phenyl)-6-(3-piperidin-1-yl-






propoxy)-imidazo[1,2-b]pyridazine





 


286




5.8
392.0
393.0



3-Benzo[b]thiophen-2-yl-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-bipyridazine





 


287




4.94
354.0
355.0



3-(4-Fluoro-phenyl)-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-b]






pyridazine





 


288




4.84
336.0
337.0



3-Phenyl-6-(3-piperidin-1-yl-propoxy)-






imidazo[1,2-b]pyridazine





 


289




5.4
382.0
383.0



3-(4-Methylsulfanyl-phenyl)-6-(3-






piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


290




5.35
370.0
371.0



3-(4-Chloro-phenyl)-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-b]pyridazine





 


291




4.72
378.0
379.0



1-{3-[6-(3-Piperidin-1-yl-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-ethanone





 


292




5.07
382.0
383.0



3-(2-Methylsulfanyl-phenyl)-6-






(3-piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


293




5.77
420.0
421.0



6-(3-Piperidin-1-yl-propoxy)-3-






(3-trifluoromethoxy-phenyl)-






imidazo[1,2-b]pyridazine





 


294




5.7
404.0
405.0



6-(3-Piperidin-1-yl-propoxy)-3-(3-






trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


295




5.92
412.0
413.0



3-Biphenyl-3-yl-6-(3-piperidin-1-yl-






propoxy)-imidazo[1,2-b]pyridazine





 


296




4.34
366.0
367.0



{3-[6-(3-Piperidin-1-yl-propoxy)-






imidazo[1,2-b]pyridazin-3-y]-






phenyl}-methanol





 


297




5.37
382.0
383.0



3-(3-Methylsulfanyl-phenyl)-6-






(3-piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


298




5.27
404.0
405.0



6-(3-Piperidin-1-yl-propoxy)-3-






(2-trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


299




4.94
370.0
371.0



3-(2-Chloro-phenyl)-6-(3-piperidin-1-yl-






propoxy)-imidazo[1,2-b]pyridazine





 


300




5.85
420.0
421.0



6-(3-Piperidin-1-yl-propoxy)-3-(4-






trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


301




5.78
404.0
405.0



6-(3-Piperidin-1-yl-propoxy)-3-(4-






trifluoromethyl-phenyl)-imidazo






[1,2-b]pyridazine





 


302




5.62
384.0
385.0



3-(3-Chloro-4-methyl-phenyl)-6-






(3-piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


303




4.17
340.0
341.0



3-(5-Methyl-furan-2-yl)-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-b]pyridazine





 


304




5.09
384.0
385.0



3-(3-Fluoro-4-methoxy-phenyl)-6-






(3-piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


305




4.99
350.0
351.0



6-(3-Piperidin-1-yl-propoxy)-3-o-






tolyl-imidazo[1,2-b]pyridazine





 


306




5.47
388.0
389.0



3-(3-Chloro-4-fluoro-phenyl)-6-






(3-piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


307




4.92
366.0
367.0



3-(3-Methoxy-phenyl)-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-b]






pyridazine





 


308




5.39
376.0
377.0



3-(5-Chloro-thiophen-2-yl)-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-b]pyridazine





 


309




4.89
361.0
362.0



3-[6-(3-Piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazin-3-yl]-benzonitrile





 


310




5.19
356.0
357.0



3-(4-Methyl-thiophen-2-yl)-6-






(3-piperidin-1-yl-propoxy)-






imidazo[1,2-b]pyridazine





 


311




4.7
375.0
376.0



{4-[6-(3-Piperidin-1-yl-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-acetonitrile





 


312




5.07
394.0
395.0



3-[6-(3-Piperidin-1-yl-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






benzoic acid methyl ester





 


313




4.4
393.0
394.0



N-{3-[6-(3-Piperidin-1-yl-propoxy)-






imidazo[1,2-b]pyridazin-3-yl]-






phenyl}-acetamide





 


314




4.74
375.0
376.0



3-(1H-Indol-4-yl)-6-(3-piperidin-1-yl-






propoxy)-imidazo[1,2-b]pyridazine





 


315




5.78
376.0
377.0



3-Benzofuran-2-yl-6-(3-piperidin-1-






yl-propoxy)-imidazo[1,2-b]pyridazine





 


316




5.2
350.0
351.0



6-(3-Piperidin-1-yl-propoxy)-3-p-






tolyl-imidazo[1,2-b]pyridazine





 


317




5.02
354.0
355.0



3-(3-Fluoro-phenyl)-6-(3-piperidin-1-yl-






propoxy)-imidazo[1,2-b]pyridazine





 


318




5.37
392.0
393.0



3-Benzo[b]thiophen-3-yl-6-(3-






piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


319




5.39
370.0
371.0



3-(4-Chloro-phenyl)-6-(3-piperidin-






1-yl-propoxy)-imidazo[1,2-b]






pyridazine





 


320




4.8
369.0
370.0



3-(6-Fluoro-5-methyl-pyridin-3-yl)-6-






(3-piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


321




5.39
420.0
421.0



6-(3-Piperidin-1-yl-propoxy)-3-(2-






trifluoromethoxy-phenyl)-imidazo






[1,2-b]pyridazine





 


322




4.8
428.0
429.0



3-(4-Ethanesulfonyl-phenyl)-6-(3-






piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


323




5.37
405.0
406.0



6-(3-Piperidin-1-yl-propoxy)-3-






(3-pyrrolidin-1-yl-phenyl)-imidazo






[1,2-b]pyridazine





 


324




5.64
406.0
407.0



3-(4-Cyclopropylmethoxy-phenyl)-6-






(3-piperidin-1-yl-propoxy)-imidazo






[1,2-b]pyridazine





 


325




4.59
316.0
317.0



Dimethyl-[4-(3-thiophen-3-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-butyl]-amine





 


326




5.17
360.0
361.0



Dimethyl-[4-(3-naphthalen-1-yl-imidazo






[1,2-b]pyridazin-6-yloxy)-butyl]-amine





 


327




4.87
340.0
341.0



{4-[3-(4-Methoxy-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-butyl}-






dimethyl-amine





 


328




5.09
324.0
325.0



Dimethyl-[4-(3-m-tolyl-imidazo[1,2-






b]pyridazin-6-yloxy)-butyl]-amine





 


329




4.9
328.0
329.0



{4-[3-(4-Fluoro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-butyl}-






dimethyl-amine





 


330




4.74
310.0
311.0



Dimethyl-[4-(3-phenyl-imidazo[1,2-b]






pyridazin-6-yloxy)-butyl]-amine





 


331




5.27
356.0
357.0



Dimethyl-{4-[3-(4-methylsulfanyl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-butyl}-amine





 


332




5.17
344.0
345.0



{4-[3-(4-Chloro-phenyl)-imidazo






[1,2-b]pyridazin-6-yloxy]-butyl}-






dimethyl-amine





 


333




4.67
352.0
353.0



1-{3-[6-(4-Dimethylamino-butoxy)-






imidazo[1,2-b]pyridazin-3-yl]-phenyl}-






ethanone





 


334




4.97
356.0
357.0



Dimethyl-{4-[3-(2-methylsulfanyl-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-butyl}-amine





 


335




5.6
394.0
395.0



Dimethyl-{4-[3-(3-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-butyl}-amine





 


336




5.4
378.0
379.0



Dimethyl-{4-[3-(3-trifluoromethyl-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-butyl}-amine





 


337




5.89
386.0
387.0



[4-(3-Biphenyl-3-yl-imidazo[1,2-b]






pyridazin-6-yloxy)-butyl]-dimethyl-






amine





 


338




4.22
340.0
341.0



{3-[6-(4-Dimethylamino-butoxy)-imidazo






[1,2-b]pyridazin-3-yl]-phenyl}-methanol





 


339




5.24
356.0
357.0



Dimethyl-{4-[3-(3-methylsulfanyl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-butyl}-amine





 


340




5.07
378.0
379.0



Dimethyl-{4-[3-(2-trifluoromethyl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-butyl}-amine





 


341




5.7
394.0
395.0



Dimethyl-{4-[3-(4-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-butyl}-amine





 


342




5.6
378.0
379.0



Dimethyl-{4-[3-(4-trifluoromethyl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-butyl}-amine





 


343




4.99
358.0
359.0



{4-[3-(3-Fluoro-4-methoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-






butyl}-dimethyl-amine





 


344




4.89
324.0
325.0



Dimethyl-[4-(3-o-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-butyl]-amine





 


345




4.9
340.0
341.0



{4-[3-(3-Methoxy-phenyl)-imidazo






[1,2-b]pyridazin-6-ylIoxy]-butyl}-






dimethyl-amine





 


346




5.09
330.0
331.0



Dimethyl-{4-[3-(4-methyl-thiophen-






2-yl)-imidazo[1,2-b]pyridazin-6-






yloxy]-butyl}-amine





 


347




4.59
349.0
350.0



{4-[6-(4-Dimethylamino-butoxy)-imidazo






[1,2-b]pyridazin-3-yl]-phenyl}-acetonitrile





 


348




4.95
368.0
369.0



3-[6-(4-Dimethylamino-butoxy)-imidazo






[1,2-b]pyridazin-3-yl]-benzoic acid methyl






ester





 


349




4.2
367.0
368.0



N-{3-[6-(4-Dimethylamino-butoxy)-imidazo






[1,2-b]pyridazin-3-yl]-phenyl}-acetamide





 


350




4.65
349.0
350.0



{4-[3-(1H-Indol-4-yl)-imidazo[1,2-b]






pyridazin-6-yloxy]-butyl}-dimethyl-






amine





 


351




5.09
324.0
325.0



Dimethyl-[4-(3-p-tolyl-imidazo[1,2-b]






pyridazin-6-yloxy)-butyl]-amine





 


352




5.35
394.0
395.0



Dimethyl-{4-[3-(2-trifluoromethoxy-






phenyl)-imidazo[1,2-b]pyridazin-6-






yloxy]-butyl}-amine





 


353




5.17
379.0
380.0



Dimethyl-{4-[3-(3-pyrrolidin-1-yl-






phenyl)-imidazo[1,2-b]pyridazin-






6-yloxy]-butyl}-amine





 


354




5.62
380.0
381.0



{4-[3-(4-Cyclopropylmethoxy-phenyl)-






imidazo[1,2-b]pyridazin-6-yloxy]-butyl}-






dimethyl-amine









The following are prepared in the manner described:
















Retention




EXAMPLE

time
MW
MW


No.
Structure
[min]
calc.
found



















355




7.51
369
370


 


356




7.03
393
394


 


357




7.56
410
411


 


358




7.5
374
375


 


359




10.16
389
390


 


340




6.92
413
413


 


341




7.01
351
352


 


342




6.85
351
352


 


343




7.04
351
352


 


344




7.56
428
429


 


345




7.07
406
407


 


346




6.83
365
366


 


347




8.87
459
460


 


348




7.68
366
367


 


349




7.67
379
380


 


350




8.48
460
461


 


351




9.68
337
338


 


352




6.72
392
393


 


353




7.73
325
326


 


354




7.95
355
356


 


355




8.01
341
342


 


356




8.98
405
406


 


357




8.02
454
455


 


358




8.38
354
355


 


359




9.7
341
342


 


360




8.99
361
362


 


361




9.5
370
370


 


362




8.02
335
336


 


363




7.25
418
419


 


364




7.71
413
414


 


365




8.13
365
366


 


366




5.98
373
374


 


367




4.66
366
367


 


368




5.56
329
330


 


369




5.43
315
316


 


370




6.29
379
380


 


371




5.51
428
429


 


372




4.91
328
329


 


373




5.37
351
352


 


374




6.61
309
310


 


375




6.64
364
365


 


376




6.4
323
324


 


377




8.71
454
455


 


378




5.83
294
295


 


379




5.29
392
393


 


380




8.59
400
400


 


381




9.63
419
420


 


382




11.19
405
406


 


383




11.01
356
356


 


384




9.48
321
322


 


385




7.86
404
405


 


386




8.2
399
400


 


387




4.7
325
326


 


388




10.32
433
434


 


389




7.88
323
324


 


390




7.27
383
384


 


391




8.02
383
384


 


392




8.66
391
392


 


393




9.52
351
352


 


394




8.25
414
415


 


395




10.18
387
388


 


396




9.16
352
353


 


397




7.03
378
379


 


398




7.22
407
408


 


399




8.14
424
425


 


400




7.58
388
389


 


401




10.97
403
404


 


402




7.47
427
427


 


403




8.18
365
366


 


404




9.63
446
447


 


405




10.55
391
392


 


406




9.17
340
341


 


407




8.68
460
461


 


408




6.86
365
366


 


409




6.73
365
366


 


410




7.16
365
366


 


411




6.98
406
407


 


412




7.47
420
421


 


413




9.77
327
328


 


414




9.83
511
511


 


415




5.7
448
449


 


416




5.58
463
464


 


417




4.93
343
344


 


418




5.13
343
344


 


419




5.14
351
352


 


420




4.96
384
385


 


421




5.38
348
349


 


422




9.36
414
414


 


423




7.09
406
407


 


424




8.1
339
340


 


425




8.53
369
370


 


426




8.65
355
356


 


427




6.62
363
364


 


428




5.53
420
421


 


429




4.81
325
326


 


430




4.76
325
326


 


431




9.73
375
376


 


432




10.61
384
384


 


433




8.77
349
350


 


434




7.52
432
433


 


435 




8.17
427
428


 


436




8.93
379
380


 


437




4.83
325
326


 


438




4.58
366
367


 


439




4.76
380
381


 


440




4.7
339
340


 


441




6.58
470
471


 


442




4.0
310
311


 


443




8.27
355
356


 


444




8.96
363
364


 


445




7.55
379
380


 


446




8.18
396
397


 


447




8.08
360
361


 


448




11.26
375
376


 


449




7.92
442
443


 


450




9.41
415
416


 


451




9.13
473
474


 


452




8.54
380
381


 


453




4.02
408
409


 


454




4.13
423
424


 


455




4.31
311
312


 


456




5.78
373
374


 


457




7.4
399
399


 


458




9.35
432
433


 


459




6.82
337
338


 


460




6.92
337
338


 


461




7.51
337
338


 


462




4.9
299
300


 


463




5.38
329
330


 


464




5.12
315
316


 


465




6.42
393
394


 


466




6.05
335
336


 


467




6.08
343
344


 


468




5.28
407
408


 


469




6.66
295
296


 


470




8.45
357
358


 


471




7.79
313
314


 


472




6.26
339
340


 


473




9.86
355
356


 


474




6.66
327
328


 


475




7.47
335
336


 


476




6.6
351
352


 


477




7.04
368
369


 


478




5.23
309
310


 


479




4.82
392
393


 


480




5.0
387
388


 


481




5.48
339
340


 


482




7.77
299
300


 


483




9.24
377
378


 


484




8.75
319
320


 


485




9.61
327
328


 


486




7.82
293
294


 


487




7.05
371
372


 


488




7.23
332
333


 


489




10.36
347
348


 


490




8.69
362
363


 


491




7.5
404
405


 


492




6.67
309
310


 


493




6.51
309
310


 


494




5.84
375
376


 


495




6.57
433
434


 


496




4.96
340
341


 


497




5.35
353
354


 


498




5.88
434
435


 


499




6.95
386
387


 


500




0.0
359
360


 


501




8.58
417
418


 


502




7.43
324
325


 


503




7.37
337
338


 


504




5.22
343
344


 


505




5.26
351
352


 


506




4.98
367
368


 


507




4.99
384
385


 


508




5.6
348
349


 


509




6.62
363
364


 


510




6.16
343
344


 


511




5.51
309
310


 


512




4.94
392
393


 


513




4.93
387
388


 


514




5.59
339
340


 


515




8.86
363
364


 


516




8.11
312
313


 


517




7.47
335
336


 


518




5.68
420
421


 


519




4.78
325
326


 


520




4.77
366
367


 


521




5.08
402
403


 


522




5.94
375
376


 


523




6.55
433
434


 


524




5.09
340
341


 


525




5.67
353
354


 


526




7.71
392
393


 


527




7.18
351
352


 


528




5.25
420
421


 


529




4.82
380
381


 


530




4.62
339
340


 


531




6.45
470
471


 


532




4.06
310
311


 


533




3.96
408
409


 


534




4.02
423
424


 


535




5.98
434
435


 


536




6.33
379
380


 


537




5.47
428
429


 


538




4.97
328
329


 


539




5.38
351
352


 


540




5.29
435
436


 


541




7.39
378
379


 


542




9.08
311
312


 


543




9.46
341
342


 


544




5.18
299
300


 


545




6.61
393
394


 


546




4.61
366
367


 


547




5.0
402
403


 


548




6.98
379
380


 


549




11.07
347
348


 


550




4.92
353
354


 


551




7.77
393
394


 


552




7.18
327
328


 


553




6.42
370
371


 


554




6.32
350
351


 


555




8.8
401
402


 


556




6.17
350
351


 


557




6.56
376
377


 


558




7.93
418
419









Variant B
This variant for preparing the final compounds can likewise be carried out with parallel syntheses, for example in an automatic synthesizer.
Example 559
6-Benzyloxy-3-(3-chlorophenyl)imidazo[1,2-b]pyridazine




12 mg (0.26 mmol) of sodium hydride (60% in liquid paraffin) are suspended in 2 ml of THF under a protective gas atmosphere. Then 0.031 ml of benzyl alcohol (0.3 mmol) in 0.5 ml THF are added. After 15 min, 47 mg (0.15 mmol) of 6-chloro-3-(3-chlorophenyl)imidazo[1,2-b]pyridazine are added. The reaction mixture is shaken for 12 h.
Addition of a half-saturated aqueous sodium chloride solution is followed by extraction of the resulting mixture with ethyl acetate. The organic phase is separated off and the solvent is evaporated off. The crude product obtained in this way is purified by preparative HPLC. 20 mg (40%) of the desired product are obtained.
HPLC-MS (analytical) of the purified product:
(Detection: UV=254 nM; column: Purospher STAR RP18e, 125×4 mm, 5μ (Merck KgGa, Darmstadt); eluent: A: H2O/0.1% TFA, B: CH3CN/0.1% TFA, gradient: 5 to 95% B in 10 min; flow rate: 1 ml/min):
Retention time of the product=8.66 min; MS of the product: m/z=355 ([M+H+])
The following were prepared analogously:














Example

Retention
MW
MW


No.
Structure
time [min]
calc.
found



















560




7.22
353
354


 


561




5.75
420
421


 


562




9.77
433
434


 


563




5.64
394
395


 


564




8.45
402
403


 


565




5.8
420
421


 


566




5.81
414
415


 


567




8.61
349
350


 


568




10.24
379
380


 


569




4.26
344
345


 


570




4.97
437
438


 


571




5.17
390
391


 


572




7.46
307
308


 


573




4.17
330
331


 


574




6.22
255
256


 


575




4.4
308
309


 


576




4.64
322
323


 


577




7.51
321
322


 


578




4.11
343
344


 


579




9.85
433
434


 


580




9.74
419
420


 


581




8.45
349
350


 


582




10.8
391
392


 


583




8.82
391
392


 


584




0
414
415


 


585




5.73
414
415


 


586




9.8
413
414


 


587




9.96
433
434


 


588




10.72
454
454


 


589




5.47
422
423


 


590




5.92
515
516


 


591




6.22
468
469


 


592




7.27
283
284


 


593




5.34
350
351


 


594




4.65
371
372


 


595




10.58
327
328


 


596




5.1
350
351


 


597




5.31
370
371


 


598




55
339
340


 


599




9.58
384
384


 


600




10.17
404
404


 


601




9.41
414
414


 


602




8.43
327
328


 


603




5.12
344
345


 


604




5.2
350
351


 


605




5.39
370
371


 


606




5.3
364
365


 


607




8.21
299
300


 


608




9.56
384
384


 


609




9.27
370
370


 


610




10.6
341
342


 


611




8.39
341
342


 


612




5.26
364
365


 


613




5.36
364
365


 


614




9.55
363
364


 


615




9.45
384
384


 


616




5.1
372
373


 


617




8.71
353
354


 


618




5.61
386
387


 


619




5.57
465
466


 


620




5.91
418
419


 


621




8
299
300


 


622




4.54
344
345


 


623




4.47
328
329


 


624




4.44
322
323


 


625




5.8
275
276


 


626




4.81
342
343


 


627




4.32
311
312


 


628




8.17
355
356


 


629




8.76
376
376


 


630




8
386
386


 


631




67
301
302


 


632




5.57
404
405


 


633




7.11
299
300


 


634




4.6
316
317


 


635




7.16
324
325


 


636




4.65
322
323


 


637




4.77
342
343


 


638




4.76
336
337


 


639




72
271
272


 


640




8.38
301
302


 


641




8.24
355
356


 


642




7.88
341
342


 


643




6.87
271
272


 


644




8.78
313
314


 


645




7.49
313
314


 


646




4.57
336
337


 


647




9.11
385
386


 


648




5.37
408
409


 


649




5.64
386
387


 


650




5.68
400
401


 


651




10.67
454
454


 


652




9.91
464
464


 


653




7.5
379
380


 


654




6.39
482
483


 


655




8.97
377
378


 


656




5.68
394
395


 


657




4.66
336
337


 


658




8.42
335
336


 


659




9.55
376
376


 


660




5.15
421
422


 


661




5.72
422
423


 


662




5.76
406
407


 


663




5.55
400
401


 


664




9.1
403
404


 


665




7.94
325
326


 


666




5.12
336
337


 


667




82
299
300


 


668




4.51
316
317


 


669




8.61
355
356


 


670




87
352
353


 


671




5.27
356
357









The following examples describe the biological effect of the compounds of the invention:
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 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 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 μl of antibody solution in PBS 0.1 μg/ml 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 μl 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 1×10−6-1×10−12 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 μl 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












Inhibition of
IC50 [mol/l] (concentration


Example

PKC theta
for 50% inhibition of IL-2)


No.
Structure
IC50 [mol/l]
inhibition at 10 μM





1




4.1 × 10−6
1.3 × 10−6, >95% inhibition at 10 μM



3-(3-Chloro-phenyl)-6-(3-morpholin-4-yl-



propoxy)-imidazo[1,2-b]pyridazine









PKC-Theta Kinase Assay

Inhibition of the enzymic activity of the protein kinase C theta was determined with the aid of the PKC-theta HTRF assay.
Recombinant PKC-theta protein was purchased from ProQinase (Freiburg). The kinase substrate used was the biotinylated peptide having the amino acid sequence biotin-RFARKGSLRQKNVHEVK, which was purchased from Biosynthan (Berlin).
PKC-theta [0.7 nM in the assay mixture, assay volume 5 μl] was incubated at 22° C. for 15 min in the presence of various concentrations of test substances (0 μM, and 10 measurement points within the range 0.001-20 μM in duplicates) in assay buffer [50 mM Hepes/NaOH pH 7.4, 1.0 mM MnCl2, 10.0 mM MgCl2, 1.0 mM dithiothreitol, 0.1 mM sodium orthovanadate, 10 μM adenosine triphosphate (ATP), 0.5 μM substrate peptide, 0.1 mg/ml phosphatidyl serine, 0.01 mg/ml diacylglycerol, 1% (v/v) dimethyl sulfoxide]. The reaction was stopped by adding 5 μl of an EDTA/detection solution [50 mM Hepes/NaOH pH 7.4, 400 mM KF, 40 mM EDTA, 0.1% bovine serum albumin, 100 nM streptavidin-XLlent (from Cisbio, #611SAXLB), 1.8 nM anti-phospho PKC substrate crypate conjugate antibody (CisBio: #61P03KAZ)]. After incubation at 22° C. for 60 minutes, during which formation of the trimeric complex of biotinylated and phosphorylated substrate peptide, streptavidin-XLlent and anti-phospho PKC substrate europium crypate conjugate antibody took place, the time-resolved fluorescence of the assay mixtures was determined in a Rubystar HTRF measuring instrument (from BMG Labsystems) after excitation with light of wavelength 350 nM at the wavelength of 620 nm (Europium cryptate fluorescence) and 665 nm (fluorescence resonance energy transfer from Europium cryptate to streptavidin-XLlent). The degree of phosphorylation of the substrate peptide is in this case proportional to the ratio of the emissions at 665 nm and 620 nm.
The measured data were normalized to 0% inhibition (enzyme reaction without inhibitor) and 100% inhibition (assay components without enzyme). The IC50 values were determined by means of a 4-parameter fit using the company's software.

## Claims

1. A compound of the formula (I),



in which
Q is an aryl or heteroaryl radical linked through a carbon atom thereof to the imidazo[1,2b]pyridazine residue and which may optionally be substituted independently of one another by 1-3
hydroxy groups, halogen atoms, nitro groups or cyano groups,
C1-C6-alkyl or C3-C8-cycloalkyl groups which may optionally be substituted by 1-3 hydroxy, halogen, cyano, (C1-C5)-alkoxy, COOR6, NHR6, NHCOR6, N(R2)2 groups,
C1-C6-fluoroalkyl groups which may optionally be substituted by 1-3 hydroxy, optionally fluorinated (C1-C5)-alkoxy, or COOR2 groups,
pyrrolidinyl groups,
(CH2)u—SO2—R2 groups in which u is 1, 2 or 3,
R2 groups or O—CO—R6 groups,
CO—O—R groups,
CO—N(R6)2 groups,
NH—CO—R6 groups,
CONR7R8 groups,
(CH2)n—NR7R8 groups,
NH—CONHR6 groups,
OR6 groups,
SO2—R2 groups,
SO2—OR2 groups,
SO2—N(R2)2 groups,
NHSO2R2 groups,
or
SR2 groups,

in which R2 is in each case independently of one another
a hydrogen atom, a phenyl radical, an optionally partly or completely fluorinated C1-C5-alkyl radical or
a C1-C5-alkyl radical which is in turn optionally substituted 1-5 times by hydroxy radicals, cyano groups, phenyl groups, C3-C7-cycloalkyl radicals, SO2(C1-C3-alkyl) radicals, NH(C1-C3-alkyl) radicals, N[(C1-C3-alkyl)]2 radicals, and/or C1-C5-alkoxy radicals,
or a C3-C7-cycloalkyl radical,

in which R6 is in each case independently of one another either
a radical R2,
an aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups or C1-C5-alkoxy radicals,
a radical —(CH2)u-Q8 in which u is 1, 2 or 3, and in which Qs is an aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups or C1-C5-alkoxy radicals,


and in which R1 is a
3-dimethylaminopropyl,
3-diethylaminopropyl,
3-piperidin-1-ylpropyl,
2-dimethylaminoethyl,
2-diethylaminoethyl,
1-methylpiperidin-3-ylmethyl,
1-methylpyrrolidin-2-ylethyl,
4-diethylamino-1-methylbutyl, or
3-(4-methyl)piperazin-1-ylpropyl radical,

or a stereoisomer, or a salt or salt of the stereoisomer thereof with physiologically tolerated counterions.

2. A compound of Formula I



in which Q is phenyl, biphenyl, naphthyl, tetralinyl, anthranyl, indanyl, indenyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, azaindolizinyl, furanyl, oxazolyl, thiazolyl, furazanyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, tetrazolyl, thiadiazolyl, phthalidyl, thiophthalidyl, benzothiophenyl, indolyl, isoindolyl, indazolyl, benzothiazolyl, indolonyl, isoindolonyl, benzofuranyl, benzimidazolyl, benzoxazinonyl, phthalazinonyl, quinolinyl, isoquinolinyl, quinolonyl, isoquinolonyl, quinazolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, 1,7- or 1,8-naphthyridinyl, coumarinyl, isocoumarinyl, indolizinyl, isobenzofuranyl, azaindolyl, azaisoindolyl, furanopyridyl, furanopyrimidinyl, furanopyrazinyl, furanopyidazinyl, chromenyl, isochromenyl, chromenonyl, isochromenonyl group, 4-aminopyridyl, chromanyl, isochromanyl, thiochromanyl, in which Q may optionally be substituted independently of one another by 1-3
hydroxy groups, halogen atoms, nitro groups or cyano groups,
C1-C6-alkyl or C3-C8-cycloalkyl groups which may optionally be substituted by 1-3 hydroxy, halogen, cyano, (C1-C5)-alkoxy, COOR6, NHR6, NHCOR6, or N(R2)2 groups
C1-C6-fluoroalkyl groups which may optionally be substituted by 1-3 hydroxy, optionally fluorinated (C1-C5)-alkoxy, or COOR2 groups,
pyrrolidinyl groups,
(CH2)u—SO2—R2 groups in which u is 1, 2 or 3,
R2 groups or O—CO—R6 groups,
CO—O—R6 groups,
CO—N(R6)2 groups,
NH—CO—R6 groups,
CONR7R8 groups,
(CH2)n—NR7R8 groups,
NH—CONHR6 groups,
OR6 groups,
SO2—R2 groups,
SO2—OR2 groups,
SO2—N(R2)2 groups,
NHSO2R2 groups,
or
SR2 groups,

in which R2 is in each case independently of one another
a hydrogen atom, a phenyl radical, an optionally partly or completely fluorinated C1-C5-alkyl radical or
a C1-C5-alkyl radical which is in turn optionally substituted 1-5 times by hydroxy radicals, cyano groups, phenyl groups, C3-C7-cycloalkyl radicals, SO2(C1-C3-alkyl) radicals, NH(C1-C3-alkyl) radicals, N[(C1-C3-alkyl)]2 radicals, and/or C1-C5-alkoxy radicals,
or a C3-C7-cycloalkyl radical,

in which R6 is in each case independently of one another either
a radical R2,
an aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups or C1-C5-alkoxy radicals,

a radical —(CH2)u-Qs in which u is 1, 2 or 3 and in which Qs is aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups or C1-C5-alkoxy radicals,
and in which R1 is
a C1-C6-alkyl radical which may be substituted 1-3 times by —R2, —NR3R4, —NR7R8 or —OR2,
a C2-C6-alkenyl radical which may be substituted 1-3 times by —R2, —NR3R4, —NR7R8 or —OR2,
a C2-C6-alkynyl radical which may be substituted 1-3 times by —R, —NR3R4, —NR7R8 or —OR2,
a —(CH2)n—NR3R4 radical where n is a number 2-6 and in which R3 and R4 are independently of one another a hydrogen atom, a —COR6 radical, a —SO2R2 radical, or a C1-C8-alkyl radical which is in turn optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R2, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
a —(CH2)t—Z—(CH2)m—NR3R4 radical,
where Z is a group —O—, —S—, —NR2—, —CHR5— or —C(R5)2—,
m is a number 0, 1 or 2, t is a number 0, 1, 2 or 3,
and in which R5 is a C1-C3-alkyl, C2-C3-alkenyl, C2-C3-alkynyl, a phenyl or a C3-C6-cycloalkyl radical,

a —(CH2)n′—NR7R8 radical where n′ is a number 1-6 and in which R7 and R8 together form a 3-7-membered ring, where the 3-7-membered ring may comprise a further heteroatom, and where the 3-7-membered ring is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
a —(CH2)n—(CH)R7R8 radical,
a —(CH2)t—Z—(CH2)m—NR7R8 radical,
a —(CH2)t—Z—(CH2)m—(CH)R7R8 radical,
a —(CH2)r—Y1 radical where r is a number 0-3, and Y1 is a piperidinyl or pyrrolidinyl ring, where the piperidinyl or pyrrolidinyl ring is optionally substituted 1-3 times independently of one another by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
a —(CH2)t—Z—(CH2)m—Y1 radical,
a —(CH2)r—Y2 radical where r is a number 0-3, and Y2 is a morpholinyl ring, where the morpholinyl ring is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
a —(CH2)t—Z—(CH2)m—Y2 radical,
a —(CH2)r—Y3 radical where r is a number 0-3, and Y3 is a piperazinyl ring which optionally has a C1-C3-alkyl or a C1-C3-acyl group on the nitrogen atom, where the piperazinyl ring is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
a —(CH2)t—Z—(CH2)m—Y3 radical,
a —(CH2)r—Y4 radical where r is a number 0-3, and Y3 is a C3-C8-cycloalkyl ring which is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group —R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2 or a group —OR2,
a —(CH2)t—Z—(CH2)m—Y4 radical,
a —(CH2)r—Y5 radical where r is a number 0-3, and Y5 is an aryl or heteroaryl ring which is optionally substituted 1-3 times by a halogen atom, a hydroxy group, a cyano group, a nitro group, a group R6, a group —NHR2, a group —N(R2)2, a group —CO2R6, a group —OCOR6, a group —SO2R2, a group —SO2N(R2)2, a group —NHSO2R2, a group —NHCOR6, a group —NHCONHR6 or a group —OR2,

a —(CH2)t—Z—(CH2)m—Y5 radical,
R2 is in each case independently of one another
a hydrogen atom, a phenyl radical, an optionally partly or completely fluorinated C1-C5-alkyl radical or
a C1-C5-alkyl radical which is in turn optionally substituted 1-5 times by hydroxy radicals, cyano groups, phenyl groups, C3-C7-cycloalkyl radicals, SO2(C1-C3-alkyl) radicals, NH(C1-C3-alkyl) radicals, N[(C1-C3-alkyl)]2 radicals, and/or C1-C5-alkoxy radicals,
or a C3-C7-cycloalkyl radical,

in which R6 is in each case independently of one another either
a radical R2,
an aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups and/or C1-C5-alkoxy radicals,
a radical —(CH2)u-Qs in which u is the numbers 1, 2 or 3, and in which Qs is an aryl or heteroaryl radical which may in turn optionally be substituted independently of one another 1-3 times by hydroxy radicals, halogen atoms, cyano groups and/or C1-C5-alkoxy radicals,

or a stereoisomer, or a salt or salt of the stereoisomer thereof with physiologically tolerated counterions.

3. The compound as claimed in claim 1, in which R1 is a —(CH2)n—NR3R4 radical where n is 3 or 4, and in which R3 and R4 are independently of one another a C1-C3 alkyl radical.

4. The compound as claimed in claim 2, in which R1 is a —(CH2)n—NR7R8 radical where n is 3 or 4, and in which R7 and R8 together form a 5-7-membered ring.

5. The compound as claimed in claim 2, in which Q is an optionally substituted phenyl, biphenyl, furanyl, benzofuranyl, indolyl, benzothiophenyl or naphthyl radical.

6. The compound as claimed in claim 5, in which the aryl or heteroaryl radical present in Q is substituted by at least one of the following radicals: cyclopropylmethoxy-fluoro, chloro, hydroxy-, cyano-, trifluoromethyl-, trifluoromethoxy-, methyl-, methoxy-, pyrrolidinyl-, —CO—OCH3, —CO2H, —CO—NH2, CH2—CN, CH2—OH, —S—CH3, —SO2—CH2CH3, or —NHCOCH3.

7. A compound of the formula
6-[3-(4-methylpiperazin-1-yl)propoxy]-3-thiophen-3-ylimidazo[1,2-b]pyridazine; 3-(2,4-dichlorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-m-tolylimidazo[1,2b]pyridazine; 3-(3-chlorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 3-(4-fluorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-phenylimidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(4-methylsulfanylphenyl)imidazo[1,2b]pyridazine; 3-(4-chlorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 1-(3-{6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazin-3-yl}phenyl)ethanone; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(2-methylsulfanylphenyl)imidazo[1,2b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-biphenyl-3-yl-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; (3-{6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazin-3-yl}phenyl)methanol; 6-[3-(4-methylpiperazin-1yl)propoxy]-3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 3-(2-chlorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(4-trifluoromethoxyphenyl)imidazo[1,2b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 3-(5-methylfuran-2-yl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-(3-fluoro-4-methoxyphenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-o-tolylimidazo[1,2b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-(5-chlorothiophen-2-yl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-{6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazin-3-yl}benzonitrile; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(4-methylthiophen-2-yl)imidazo[1,2b]pyridazine; (4-{6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazin3-yl}phenyl)acetonitrile; 3-{6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2b]pyridazin-3-yl}benzoic acid methyl ester; 3-(1H-indol-4-yl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-benzofuran-2-yl-6-[3 (4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-p-tolylimidazo[1,2-b]pyridazine; 3-(3-fluorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-3-yl-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2b]pyridazine; 3-(4-chlorophenyl)-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 3-(6-fluoro-5-methylpyridin-3-yl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-(2-chloro-6-methylpyridin-3-yl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-(4-ethanesulfonylphenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; diethyl-[4-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]amine; {4-[3-(2,4-dichlorophenyl)imidazo[1,2b]pyridazin-6-yloxy]pentyl}diethylamine; diethyl-[4-(3-m-tolylimidazo[1,2b]pyridazin-6-yloxy)pentyl]amine; {4-[3-(3-chlorophenyl)imidazo[1,2b]pyridazin-6-yloxy]pentyl}diethylamine; [4-(3-benzo[b]thiophen-2-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]diethylamine; diethyl-{4-[3-(4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; {4-[3-(4-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; 1-{3-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}ethanone; diethyl-{4-[3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(3-trifluoromethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]pentyl}amine; [4-(3-biphenyl-3-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]diethylamine; {3-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2b]pyridazin-3-yl]phenyl}methanol; diethyl-{4-[3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(4-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; {4-[3-(3 chloro-4-methylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; diethyl-{4-[3-(5-methylfuran-2-yl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(3-fluoro-4-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-[4-(3-o-tolylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]amine; {4-[3-(3-chloro-4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; {4-[3-(5-chlorothiophen-2-yl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; 3-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2b]pyridazin-3-yl]benzonitrile; diethyl-{4-[3-(4-methylthiophen-2-yl)imidazo[1,2b]pyridazin-6-yloxy]pentyl}amine; {4-[6-(4-diethylamino-1methylbutoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetonitrile; 3-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; diethyl-{4-[3-(1H-indol-4-yl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; [4-(3-benzofuran-2-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]diethylamine; diethyl-[4-(3-p-tolylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]amine; diethyl-{4-[3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; [4-(3-benzo[b]thiophen-3-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]diethylamine; {4-[3-(4-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; diethyl-{4-[3-(6-fluoro-5-methylpyridin-3-yl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(3pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; {5-[6-(4diethylamino-1-methylbutoxy)imidazo[1,2-b]pyridazin-3-yl]thiophen-2yl}methanol; {4-[3-(4-cyclopropylmethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-thiophen-3-ylimidazo[1,2-b]pyridazine; 3-(2,4-dichlorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-mtolylimidazo[1,2-b]pyridazine; 3-(3-chlorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(4-fluorophenyl)-6-[2-(1 methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin2-yl)ethoxy]-3-phenylimidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(4-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 3-(4chlorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 1-(3-{6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazin-3yl}phenyl)ethanone; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-biphenyl-3-yl-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; (3-{6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazin-3-yl}phenyl)methanol; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(3-methylsulfanylphenyl)imidazo[1,2b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(2-chlorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(4-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(3-fluoro-4-methoxyphenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-o-tolylimidazo[1,2-b]pyridazine; 3-(3 chloro-4-fluorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2b]pyridazine; 3-{6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazin-3yl}benzonitrile; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(4-methylthiophen-2-yl)imidazo[1,2-b]pyridazine; (4-{6-[2-(1-methylpyrrolidin-2yl)ethoxy]imidazo[1,2-b]pyridazin-3-yl}phenyl)acetonitrile; 3-{6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazin-3-yl}benzoic acid methyl ester; 3-(1H-indol-4-yl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(2-fluoropyridin-3-yl)-6-[2-(1-methylpyrrolidin-2yl)ethoxy]imidazo[1,2-b]pyridazine; 3-benzofuran-2-yl-6-[2-(1-methylpyrrolidin2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-ptolylimidazo[1,2-b]pyridazine; 3-(3-fluorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-3-yl-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6-[2(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(6-fluoro-5-methylpyridin-3-yl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2b]pyridazine; 3-(2-chloro-6-methylpyridin-3-yl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-(4-ethanesulfonylphenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazine; 3 (4-cyclopropylmethoxyphenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-ylmethoxy)-3-thiophen-3-ylimidazo[1,2-b]pyridazine; 3-(2,4-dichlorophenyl)-6-(1 methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-(3-chlorophenyl)-6-(1 methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-(4-fluorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 6-(1 methylpiperidin-3-ylmethoxy)-3-phenylimidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-ylmethoxy)-3-(4-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 3 (4-chlorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 1{3-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3yl]phenyl}ethanone; 6-(1-methylpiperidin-3-ylmethoxy)-3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-ylmethoxy)-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-biphenyl3-yl-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; {3-[6-(1methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}methanol; 6(1-methylpiperidin-3-ylmethoxy)-3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-ylmethoxy)-3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(2-chlorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-ylmethoxy)-3-(4-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-methylphenyl)6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-(5-methylfuran2-yl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-(3-fluoro-4-methoxyphenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 6(1-methylpiperidin-3-ylmethoxy)-3-o-tolylimidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3 (5-chlorothiophen-2-yl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3yl]benzonitrile; 6-(1-methylpiperidin-3-ylmethoxy)-3-(4-methylthiophen-2-yl)imidazo[1,2-b]pyridazine; {4-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2b]pyridazin-3-yl]phenyl}acetonitrile; 3-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; 3-(1H-indol4-yl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-(2-fluoropyridin-3-yl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-benzofuran-2-yl-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 6(1-methylpiperidin-3-ylmethoxy)-3-p-tolylimidazo[1,2-b]pyridazine; 3-(3-fluorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-3-yl-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2b]pyridazine; 3-(4-chlorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2b]pyridazine; 3-(6-fluoro-5-methylpyridin-3-yl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-ylmethoxy)-3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-(4-ethanesulfonylphenyl)6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 6-(1 methylpiperidin-3-ylmethoxy)-3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; diethyl-[3-(3-thiophen-3-ylimidazo[1,2b]pyridazin-6-yloxy)propyl]amine; diethyl-[3-(3-naphthalen-1-ylimidazo[1,2b]pyridazin-6-yloxy)propyl]amine; diethyl-{3-[3-(4-methoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; diethyl-[3-(3-m-tolylimidazo[1,2-b]pyridazin6-yloxy)propyl]amine; {3-[3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; [3-(3-benzo[b]thiophen-2-ylimidazo[1,2-b]pyridazin6-yloxy)propyl]diethylamine; diethyl-{3-[3-(4-fluorophenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; diethyl-[3-(3-phenylimidazo[1,2-b]pyridazin6-yloxy)propyl]amine; diethyl-{3-[3-(4-methylsulfanylphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; {3-[3-(4-chlorophenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}diethylamine; 1-{3-[6-(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}ethanone; diethyl-{3-[3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl-{3-[3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl {3-[3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; [3(3-biphenyl-3-ylimidazo[1,2-b]pyridazin-6-yloxy)propyl]diethylamine; {3-[6-(3diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}methanol; diethyl-{3[3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl-{3-[3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(2-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; diethyl-{3-[3-(4-trifluoromethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; diethyl-{3-[3-(4-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(3-chloro-4-methylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; diethyl-{3-[3-(5-methylfuran-2-yl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl-{3-[3-(3 fluoro-4-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl[3-(3-o-tolylimidazo[1,2-b]pyridazin-6-yloxy)propyl]amine; {3-[3-(3-chloro-4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; diethyl-{3-[3(3-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(5chlorothiophen-2-yl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; 3-[6(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; diethyl-{3-[3 (4-methylthiophen-2-yl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {4-[6-(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetonitrile; 3-[6-(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; N-{3-[6-(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3yl]phenyl}acetamide; diethyl-{3-[3-(1H-indol-4-yl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; [3-(3-benzofuran-2-ylimidazo[1,2-b]pyridazin-6-yloxy)propyl]diethylamine; diethyl-[3-(3-p-tolylimidazo[1,2-b]pyridazin-6-yloxy)propyl]amine; diethyl-{3-[3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; [3-(3-benzo[b]thiophen-3-ylimidazo[1,2-b]pyridazin-6-yloxy)propyl]diethylamine; {3-[3-(4-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; diethyl-{3-[3-(6-fluoro-5-methylpyridin-3yl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl-{3-[3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(4-ethanesulfonylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethyl-amine; diethyl-{3-[3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(4-cyclopropylmethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}diethylamine; 6-(1-methylpiperidin-3-yloxy)-3thiophen-3-ylimidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-naphthalen-1-ylimidazo[1,2-b]pyridazine; 3-(4-methoxyphenyl)-6-(1 methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-(2,4-dichlorophenyl)-6-(1 methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-m-tolylimidazo[1,2-b]pyridazine; 3-(3-chlorophenyl)-6-(1 methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-(4-fluorophenyl)-6-(1 methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6-(1 methylpiperidin-3-yloxy)-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-(3-trifluoromethylphenyl)imidazo[1,2b]pyridazine; 3-biphenyl-3-yl-6-(1-methylpiperidin-3-yloxy)imidazo[1,2b]pyridazine; {3-[6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}methanol; 6-(1-methylpiperidin-3-yloxy)-3-(3methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(2-chlorophenyl)-6-(1 methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-(4-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 6-(1 methylpiperidin-3-yloxy)-3-(4-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-(1-methylpiperidin-3-yloxy)imidazo[1,2b]pyridazine; 3-(5-methylfuran-2-yl)-6-(1-methylpiperidin-3-yloxy)imidazo[1,2b]pyridazine; 3-(3-fluoro-4-methoxyphenyl)-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-otolylimidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-(1-methylpiperidin3-yloxy)imidazo[1,2-b]pyridazine; 3-(3-methoxyphenyl)-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-(5-chlorothiophen-2-yl)-6-(1-methylpiperidin3-yloxy)imidazo[1,2-b]pyridazine; 3-[6-(1-methylpiperidin-3-yloxy)imidazo[1,2b]pyridazin-3-yl]benzonitrile; 6-(1-methylpiperidin-3-yloxy)-3-(4-methylthiophen-2-yl)imidazo[1,2-b]pyridazine; {4-[6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetonitrile; 3-[6-(1-methylpiperidin3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; N-{3-[6-(1methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetamide; 3-(1Hindol-4-yl)-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-benzofuran-2-yl-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1 methylpiperidin-3-yloxy)-3-p-tolylimidazo[1,2-b]pyridazine; 3-(3-fluorophenyl)6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-3-yl-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-(6-fluoro-5-methylpyridin-3-yl)-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1 methylpiperidin-3-yloxy)-3-(2-trifluoromethoxyphenyl)imidazo; [1,2b]pyridazine; 3-(4-ethanesulfonylphenyl)-6-(1-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-methylpiperidin-3-yloxy)-3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-(1 methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-thiophen-3-ylimidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3 naphthalen-1-ylimidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-(4-methoxyphenyl)imidazo[1,2-b]pyridazine; 3-(2,4-dichlorophenyl)-6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-(3-chlorophenyl)-6-(1 ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-(1 ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3 (4-fluorophenyl)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-phenylimidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-(4-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6-(1 ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 1-{3-[6-(1-ethylpyrrolidin-3yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}ethanone; 6-(1-ethylpyrrolidin-3-yloxy)-3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin3-yloxy)-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 6-(1 ethylpyrrolidin-3-yloxy)-3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3biphenyl-3-yl-6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; {3-[6-(1 ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}methanol; 6-(1 ethylpyrrolidin-3-yloxy)-3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6(1-ethylpyrrolidin-3-yloxy)-3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(2-chlorophenyl)-6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1 ethylpyrrolidin-3-yloxy)-3-(4-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-(4-trifluoromethylphenyl)imidazo[1,2b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-(1-ethylpyrrolidin-3yloxy)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-(1 ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3 (3-methoxyphenyl)imidazo[1,2-b]pyridazine; 3-(5-chlorothiophen-2-yl)-6-(1 ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 3-[6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; 6-(1-ethylpyrrolidin-3-yloxy)-3 (4-methylthiophen-2-yl)imidazo[1,2-b]pyridazine; 3-[6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; N-{3-[6-(1ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetamide; 6-(1 ethylpyrrolidin-3-yloxy)-3-(1H-indol-4-yl)imidazo[1,2-b]pyridazine; 3benzofuran-2-yl-6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-p-tolylimidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin3-yloxy)-3-(3-fluorophenyl)imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6-(1 ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3 (6-fluoro-5-methylpyridin-3-yl)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-(4ethanesulfonylphenyl)-6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 6(1-ethylpyrrolidin-3-yloxy)-3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-(1-ethylpyrrolidin-3-yloxy)imidazo[1,2b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-thiophen-3-ylimidazo[1,2-b]pyridazine; 3-naphthalen-1-yl-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(4-methoxyphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-m-tolylimidazo[1,2-b]pyridazine; 3(3-chlorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3benzo[b]thiophen-2-yl-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3(4-fluorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-phenyl6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(4-methylsulfanylphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3 (4-chlorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 1-{3-[6(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}ethanone; 3-(2-methylsulfanylphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6(3-piperidin-1-ylpropoxy)-3-(3-trifluoromethoxyphenyl)imidazo[1,2b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-biphenyl-3-yl-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; {3-[6-(3-piperidin-1-ylpropoxy)imidazo[1,2b]pyridazin-3-yl]phenyl}methanol; 3-(3-methylsulfanylphenyl)-6-(3-piperidin-1ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(2-chlorophenyl)-6-(3piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3(4-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1ylpropoxy)-3-(4-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(5-methylfuran-2-yl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(3 fluoro-4-methoxyphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-o-tolylimidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(3methoxyphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(5-chlorothiophen-2-yl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-[6(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; 3-[6-(3piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; {4-[6-(3piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetonitrile; 3-[6-(3piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; N-{3-[6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3yl]phenyl}acetamide; 3-(1H-indol-4-yl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2b]pyridazine; 3-benzofuran-2-yl-6-(3-piperidin-1-ylpropoxy)imidazo[1,2b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-p-tolylimidazo[1,2-b]pyridazine; 3(3-fluorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(6-fluoro5-methylpyridin-3-yl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3piperidin-1-ylpropoxy)-3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3 (4-ethanesulfonylphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2b]pyridazine; dimethyl-[4-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yloxy)butyl]amine; dimethyl-[4-(3-naphthalen-1-ylimidazo[1,2-b]pyridazin-6-yloxy)butyl]amine; {4-[3-(4-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; dimethyl-[4-(3-m-tolylimidazo[1,2-b]pyridazin-6-yloxy)butyl]amine; {4-[3-(4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; dimethyl-[4-(3-phenylimidazo[1,2-b]pyridazin-6-yloxy)butyl]amine; dimethyl-{4-[3-(4-methylsulfanylphenyl)imidazo[1,2b]pyridazin-6-yloxy]butyl}amine; {4-[3-(4-chlorophenyl)imidazo[1,2-b]pyridazin6-yloxy]butyl}dimethylamine; 1-{3-[6-(4-dimethylaminobutoxy)imidazo[1,2b]pyridazin-3-yl]phenyl}ethanone; dimethyl-{4-[3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; dimethyl-{4-[3-(3-trifluoro-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; dimethyl-{4-[3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; [4-(3biphenyl-3-ylimidazo[1,2-b]pyridazin-6-yloxy)butyl]dimethylamine; {3-[6-(4-dimethylaminobutoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}methanol; dimethyl-{4-[3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; dimethyl-{4-[3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; dimethyl-{4-[3-(4-trifluoromethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]butyl}amine; dimethyl-{4-[3-(4-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; {4-[3-(3-fluoro-4-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; dimethyl-[4-(3-o-tolylimidazo[1,2-b]pyridazin-6-yloxy)butyl]amine; {4-[3-(3methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; dimethyl-{4-[3-(4-methylthiophen-2-yl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; {4[6-(4-dimethylaminobutoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetonitrile; 3[6-(4-dimethylaminobutoxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; N-{3-[6-(4-dimethylaminobutoxy)imidazo[1,2-b]pyridazin-3yl]phenyl}acetamide; {4-[3-(1H-indol-4-yl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; dimethyl-[4-(3-p-tolylimidazo[1,2-b]pyridazin-6-yloxy)butyl]amine; dimethyl-{4-[3-(2-trifluoromethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]butyl}amine; dimethyl-{4-[3-(3-pyrrolidin-1ylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; {4-[3-(4-cyclopropylmethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; or 6-phenoxy-3-m-tolylimidazo[1,2b]pyridazine.

8. A method for preparing compounds of formula I, where a compound of formula IIb



in which R1 has the meaning defined in claim 1, and in which Hal is a chlorine, bromine or iodine atom, is reacted with a boronic acid in a metal-catalyzed reaction to give a compound of formula I




in which R1 and Q have the meaning given in claim 1.

9. A method for preparing compounds of formula I, where a compound of formula IIb



in which R1 has the meaning defined in claim 1, and in which Hal is a chlorine, bromine or iodine atom, is reacted with a boronic acid with a palladium catalyst to give a compound of formula I




in which R1 and Q have the meaning given in claim 1.

10. A pharmaceutical composition comprising at least one compound as claimed in claim 1 and a pharmaceutically acceptable excipient or carrier.

11. The compound as claimed in claim 2, in which Q is an optionally substituted phenyl, biphenyl, naphthyl, tetralinyl, benzothiophenyl, indolyl, indazolyl, benzothiazolyl, benzofuranyl, benzimidazolyl, benzoxazinonyl, isobenzofuranyl, azaindolyl, azaisoindolyl, furanopyridyl, furanopyrimidinyl, furanopyrazinyl, or furanopyidazinyl.

12. The compound as claimed in claim 2, in which Q is an optionally substituted phenyl, biphenyl, naphthyl, benzothiophenyl, indolyl, or benzofuranyl.

13. The compound as claimed in claim 7, which is selected from 3-(3-chlorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 3-biphenyl-3-yl-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 3-(3-fluorophenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(2-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-(4-ethanesulfonylphenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; 6-[3-(4-methylpiperazin-1-yl)propoxy]-3-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-[3-(4-methylpiperazin-1yl)propoxy]imidazo[1,2-b]pyridazine; diethyl-[4-(3-thiophen-3-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]amine; {4-[3-(2,4-dichlorophenyl)imidazo[1,2b]pyridazin-6-yloxy]pentyl}diethylamine; diethyl-[4-(3-m-tolylimidazo[1,2b]pyridazin-6-yloxy)pentyl]amine; {4-[3-(3-chlorophenyl)imidazo[1,2b]pyridazin-6-yloxy]pentyl}diethylamine; [4-(3-benzo[b]thiophen-2-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]diethylamine; diethyl-{4-[3-(4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; 1-{3-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}ethanone; diethyl-{4-[3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; diethyl-{4-[3-(3-trifluoromethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]pentyl}amine; [4-(3-biphenyl-3-ylimidazo[1,2-b]pyridazin-6-yloxy)pentyl]diethylamine; {3-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2b]pyridazin-3-yl]phenyl}methanol; diethyl-{4-[3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; {4-[3-(3 chloro-4-methylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; diethyl-{4-[3-(3-fluoro-4-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; {4-[3-(3-chloro-4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; 3-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2b]pyridazin-3-yl]benzonitrile; diethyl-{4-[3-(1H-indol-4-yl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; [4-(3-benzofuran-2-ylimidazo[1,2-b]pyridazin-6-yloxy)-pentyl]diethylamine; diethyl-{4-[3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; {4-[3-(4-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}diethylamine; 3-(3-chlorophenyl)-6-[2-(1-methylpyrrolidin-2yl)ethoxy]imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 1(3-{6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazin-3-yl}phenyl)ethanone; 3-biphenyl-3-yl-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 6[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(3-methylsulfanylphenyl)imidazo[1,2b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(3-fluoro-4-methoxyphenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(3chloro-4-fluorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2b]pyridazine; 3-{6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazin-3-yl}benzonitrile; 3-{6-[2-(1 methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazin-3-yl}benzoic acid methyl ester; 3-(3-fluorophenyl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6-[2(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-(3-chlorophenyl)-6-(1 methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 1{3-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3yl]phenyl}ethanone; 6-(1-methylpiperidin-3-ylmethoxy)-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-biphenyl3-yl-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 6(1-methylpiperidin-3-ylmethoxy)-3-(3-methylsulfanylphenyl)imidazo[1,2b]pyridazine; 3-(3-chloro-4-methylphenyl)6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; 3-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3yl]benzonitrile; 3-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; 3-(4-chlorophenyl)-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; diethyl-{3-[3-(4-methoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; diethyl-[3-(3-m-tolylimidazo[1,2-b]pyridazin6-yloxy)propyl]amine; {3-[3-(3-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; [3-(3-benzo[b]thiophen-2-ylimidazo[1,2-b]pyridazin6-yloxy)propyl]diethylamine; diethyl-{3-[3-(4-methylsulfanylphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; 1-{3-[6-(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}ethanone; diethyl-{3-[3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl {3-[3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; [3(3-biphenyl-3-ylimidazo[1,2-b]pyridazin-6-yloxy)propyl]diethylamine; diethyl-{3 [3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl-{3-[3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(2-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; diethyl-{3-[3-(4-trifluoromethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; diethyl-{3-[3-(4-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(3-chloro-4-methylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; diethyl-{3-[3-(3 fluoro-4-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; diethyl[3-(3-o-tolylimidazo[1,2-b]pyridazin-6-yloxy)propyl]amine; {3-[3-(3-chloro-4-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; diethyl-{3-[3(3-methoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; 3-[6(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; {4-[6-(3diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetonitrile; 3-[6-(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; N-{3-[6-(3-diethylaminopropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetamide; diethyl-{3-[3-(1H-indol-4-yl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; [3-(3-benzofuran-2-ylimidazo[1,2-b]pyridazin-6-yloxy)propyl]diethylamine; diethyl-{3-[3-(3-fluorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}amine; {3-[3-(4-chlorophenyl)imidazo[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; {3-[3-(4-cyclopropylmethoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}diethylamine; 3-[6-(1-methylpiperidin3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; 3-(4-chlorophenyl)-6-(1ethylpyrrolidin-3-yloxy)imidazo[1,2-b]pyridazine; 3(3-chlorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-benzo[b]thiophen-2-yl-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-(3-trifluoromethylphenyl)-imidazo[1,2-b]pyridazine; 3-(3-methylsulfanylphenyl)-6-(3-piperidin-1ylpropoxy)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-methylphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(3fluoro-4-methoxyphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-[6(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; 3-[6-(3piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; 3(3-fluorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; dimethyl-{4-[3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; [4-(3biphenyl-3-ylimidazo[1,2-b]pyridazin-6-yloxy)butyl]dimethylamine; dimethyl {4-[3-(3-methylsulfanylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; {4-[3-(4-cyclopropylmethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; or 6-phenoxy-3-m-tolylimidazo[1,2b]pyridazine.

14. The compound as claimed in claim 1, in which Q is an optionally substituted phenyl, biphenyl, furanyl, benzofuranyl, indolyl, benzothiophenyl or naphthyl radical.

15. The compound as claimed in claim 14, in which the aryl or heteroaryl radical present in Q is substituted by at least one of the following radicals: cyclopropylmethoxy-fluoro, chloro, hydroxy-, cyano-, trifluoromethyl-, trifluoromethoxy-, methyl-, methoxy-, pyrrolidinyl-, —CO—OCH3, —CO—CH3, —CO2H, —CO—NH2, —CH2—CN, —CH2—OH, —CH2—S—CH3, —S—CH3, —SO2—CH2CH3, or —NHCOCH3.

16. The compound as claimed in claim 1, in which Q is an optionally substituted phenyl, biphenyl, naphthyl, tetralinyl, benzothiophenyl, indolyl, indazolyl, benzothiazolyl, benzofuranyl, benzimidazolyl, benzoxazinonyl, isobenzofuranyl, azaindolyl, azaisoindolyl, furanopyridyl, furanopyrimidinyl, furanopyrazinyl, or furanopyidazinyl.

17. The compound as claimed in claim 1, in which Q is an optionally substituted phenyl, biphenyl, naphthyl, benzothiophenyl, indolyl, or benzofuranyl.