US20140135323A1

US20140135323A1 - Oxo-substituted imidazo[1,2b]pyridazines, their preparation and use as pharmaceuticals

Info

Publication number: US20140135323A1
Application number: US14/157,901
Authority: US
Inventors: Olaf Prien; Knut Eis; Benjamin Bader; Judith Guenther; Arne Von Bonin
Original assignee: Bayer Intellectual Property GmbH
Current assignee: Bayer Intellectual Property GmbH
Priority date: 2006-06-21
Filing date: 2014-01-17
Publication date: 2014-05-15
Also published as: CA2656413C; WO2007147646A1; DE102006029447A1; US20090093475A1; JP2009541241A; US8653076B2; JP5583968B2; CA2656413A1; EP2044071A1

Abstract

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

in which Q and R¹are defined in the claims, method for preparing such inhibitors, intermediates for preparing such inhibitors and uses of such inhibitors.

Description

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 β. 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 β. 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 COOR⁶groups and/or 1-3 NHR⁶groups and/or 1-3 NHCOR⁶groups and/or 1-3 N(R²)₂groups 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 COOR²groups,
- 1-3 pyrrolidine groups,
- 1-3 (CH₂)_u—SO₂—R²groups in which u is the numbers 1, 2 or 3,
- 1-3 R²groups,
- 1-3 O—CO—R⁶groups,
- 1-3 CO—O—R⁶groups,
- 1-3 CO—N(R⁶)₂groups,
- 1-3 NH—CO—R⁶groups,
- 1-3 CONR⁷R⁸groups,
- 1-3 (CH₂)_n—NR⁷R⁸groups,
- 1-3 NH—CONHR⁶groups,
- 1-3 OR⁶groups,
- 1-3 SO₂—R²groups,
- 1-3 SO₂—OR²groups,
- 1-3 SO₂—N(R²)₂groups,
- 1-3 NHSO₂R²groups,
- and/or
- 1-3 SR²groups,
  in which R²is 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)]₂radicals, and/or C₁-C₅-alkoxy radicals,
- or a C₃-C₇-cycloalkyl radical,
  in which R⁶is 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-Q^sin which u is the numbers 1, 2 or 3, and in which Q^sis 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
  R¹is a C₁-C₆-alkyl radical which may be substituted 1-3 times by —R², —NR³R⁴, —NR⁷R⁸or —OR²in which R²has the abovementioned meaning and R³, R⁴, R⁷and R⁸has the meaning specified hereinafter,
- is a C₁-C₆-alkenyl radical which may be substituted 1-3 times by —R², —NR³R⁴, —NR⁷R⁸or —OR²in which R²has the abovementioned meaning and R³, R⁴, R⁷and R⁸has the meaning specified hereinafter,
- is a C₁-C₆-alkynyl radical which may be substituted 1-3 times by —R², —NR³R⁴, —NR⁷R⁸or —OR²in which R²has the abovementioned meaning and R³, R⁴, R⁷and R⁸has the meaning specified hereinafter,
- a —(CH₂)_n—NR³R⁴radical where n is a number 2-6 and in which R³and R⁴are independently of one another a hydrogen atom, a —COR⁶radical, a —SO₂R²radical, 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 —SO₂R²or a group —OR²,
- a —(CH₂)_t—Z—(CH₂)_m—NR³R⁴radical,
- 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 R³and R⁴has the abovementioned meaning,
- and in which R⁵is a C₁-C₃-alkyl, C₂-C₃-alkenyl, C₂-C₃-alkynyl, a phenyl or a C₃-C₆-cycloalkyl radical,
- a —(CH₂)_n—NR⁷R⁸radical where n is a number 1-6 and in which R⁷and R⁸together 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 —SO₂R²or a group —OR², or is interrupted by 0-3 keto groups,
- a —(CH₂)_n—(CH)R⁷R⁸radical where n, R⁷and R⁸have the abovementioned meaning,
- a —(CH₂)_t—Z—(CH₂)_m—NR⁷R⁸radical,
- where t, m, Z, R⁷and R⁸have the abovementioned meaning,
- a —(CH₂)_t—Z—(CH₂)_m—(CH)R⁷R⁸radical,
- where t, m, Z, R⁷and R⁸have the abovementioned meaning,
- a —(CH₂)_r—Y¹radical where r is a number 0-3, and Y¹is 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 —SO₂R²or a group —OR²,
- a —(CH₂)_t—Z—(CH₂)_m—Y¹radical
- in which t, m, Z, Y¹have the abovementioned meaning,
- a —(CH₂)_r—Y²radical where r is a number 0-3, and Y²is 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 —SO₂R²or a group —OR²,
- a —(CH₂)_t—Z—(CH₂)_m—Y²radical
- where t, m, Z, Y²have the abovementioned meaning,
- a —(CH₂)_r—Y³radical where r is a number 0-3, and Y³is 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 —SO₂R²or a group —OR²,
- a —(CH₂)_t—Z—(CH₂)_m—Y³radical
- where t, m, Z, Y³have the abovementioned meaning,
- a —(CH₂)_r—Y⁴radical where r is a number 0-3, and Y⁴is 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 —SO₂R²or a group —OR²,
- a —(CH₂)_t—Z—(CH₂)_m—Y⁴radical
- where t, m, Z, Y⁴have the abovementioned meaning,
- a —(CH₂)_r—Y⁵radical where r is a number 0-3, and Y⁵is 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 —NHCONHR⁶or a group —OR²,
- a —(CH₂)_t—Z—(CH₂)_m—Y⁵radical
- where t, m, Z, Y⁵have the abovementioned meaning,
- a —(CH₂)_r—Y⁶radical where r is a number 0-3, and Y⁶is a radical

- which may be linked at any position to the (CH₂)_rgroup,
- a —(CH₂)_t—Z—(CH₂)_m—Y⁶radical
- where t, m, Z, Y⁶have 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 is 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—CH₂CH₃or —NHCOCH₃.
The aryl or heteroaryl groups optionally present in the radical R⁶may be for example the abovementioned aryl or heteroaryl systems. The aryl or heteroaryl groups optionally present in the radical R⁶are preferably phenyl, thiophenyl, biphenyl, furanyl, benzofuranyl, indolyl, pyridinyl, benzothiophenyl and the naphthalenyl group.
A preferred class of compounds of the general formula I is formed by those in which R¹is

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 R¹is a

—(CH₂)_n—NR³R⁴radical where n is 3 or 4, and in which
R³and R⁴are independently of one another a C₁-C₃alkyl radical.

—(CH₂)_n—NR⁷R⁸radical where n is 3 or 4, and in which
R⁷and R⁸together 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 R¹has the meaning defined in claim 1, and in which Hal is a chlorine, bromine or iodine atom.
Preferred compounds of the formula Ib 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-bromosuccuinimide 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-bromosuccinimide, 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 + 1]⁺

C		(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		(CDCl₃, stored over molecular sieves): δ = 1.12 (m, 1H); 1.62-1.95 (m, 4H); 2.01 (m, 1H); 2.23 (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		(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		(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		(CDCl₃, stored over molecular sieves): δ = 2.05 (m, 2H); 2.33 (s, 3H); 2.45-2.65 (m, 10H); 4.46 (t, 2H); 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		(CDCl₃, stored over molecular sieves): δ = 1.70 (m, 2H); 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		(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		(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, 2 H); 3.48 (d, 1H); 4.83-4.99 (m, 1H); 6.86 (d, 1H); 7.69 (s, 1H); 7.98 (d, 1H) ppm.	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, 2 H); 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 to 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/
			MS (ESI)
Intermediate	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/
			MS (ESI)
Intermediate	Structure of the main isomer	¹H-NMR	[M + 1]⁺

U		(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 to 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 to 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

4		4.67	365.0	366.0

5		4.77	385.0	386.0

6		5.15	407.0	408.0

7		4.39	369.0	370.0

8		4.32	351.0	352.0

9		4.85	397.0	398.0

10		4.82	385.0	386.0

11		4.24	393.0	394.0

12		4.57	397.0	398.0

13		5.17	435.0	436.0

14		5.42	427.0	428.0

15		3.84	381.0	382.0

16		4.84	397.0	398.0

17		4.5	385.0	386.0

18		5.24	435.0	436.0

19		4.97	399.0	400.0

20		3.54	355.0	356.0

21		4.55	399.0	400.0

22		4.44	365.0	366.0

23		4.84	403.0	404.0

24		4.78	391.0	392.0

25		4.35	376.0	377.0

26		4.59	371.0	372.0

27		4.22	390.0	391.0

28		4.55	409.0	410.0

29		4.28	390.0	391.0

30		5.15	391.0	392.0

31		4.59	365.0	366.0

32		4.47	369.0	370.0

33		4.94	407.0	408.0

34		4.82	385.0	386.0

35		4.22	384.0	385.0

36		3.94	400.0	401.0

37		4.94	435.0	436.0

38		4.5	443.0	444.0

39		4.75	420.0	421.0

40		5.17	421.0	422.0

41		5.15	358.0	359.0

42		5.78	420.0	421.0

43		5.53	366.0	367.0

44		5.7	386.0	387.0

45		6.12	408.0	409.0

46		5.3	370.0	371.0

47		5.72	398.0	399.0

48		5.72	386.0	387.0

49		5.07	394.0	395.0

50		5.42	398.0	399.0

51		6.07	436.0	437.0

52		6.27	428.0	429.0

53		4.59	382.0	383.0

54		5.69	398.0	399.0

55		5.6	420.0	421.0

56		5.39	386.0	387.0

57		6.03	436.0	437.0

58		5.95	400.0	401.0

59		4.85	356.0	357.0

60		5.42	400.0	401.0

61		5.27	366.0	367.0

62		5.84	404.0	405.0

63		5.78	392.0	393.0

64		5.27	377.0	378.0

65		5.44	372.0	373.0

66		5.15	391.0	392.0

67		5.4	410.0	411.0

68		5.12	391.0	392.0

69		6.07	392.0	393.0

70		5.53	366.0	367.0

71		5.42	370.0	371.0

72		5.75	408.0	409.0

73		5.64	386.0	387.0

74		5.17	385.0	386.0

75		5.78	436.0	437.0

76		5.75	421.0	422.0

77		8.97	388.0	389.0

78		6.0	422.0	423.0

79		4.5	328.1	329.1

80		5.3	390.1	391.1

81		5.03	336.2	337.2

82		5.17	356.1	357.1

83		5.65	378.2	379.2

84		4.77	340.2	341.2

85		4.67	322.2	323.2

86		5.24	368.2	369.2

87		5.22	356.1	357.1

88		4.59	364.2	365.2

89		4.9	368.2	369.2

90		5.62	406.2	407.2

91		5.85	398.2	399.2

92		4.09	352.2	353.2

93		5.2	368.2	369.2

94		5.1	390.2	391.2

95		4.84	356.1	357.1

96		5.6	406.2	407.2

97		5.47	370.2	371.2

98		4.9	370.2	371.2

99		4.72	336.2	337.2

100		5.32	374.1	375.1

101		4.7	347.2	348.2

102		4.9	342.2	343.2

103		4.62	361.2	362.2

104		4.92	380.2	381.2

105		4.55	361.2	362.2

106		4.02	341.2	342.2

107		5.67	362.2	363.2

108		5.05	336.2	337.2

109		4.87	340.2	341.2

110		5.2	378.2	379.2

111		5.24	356.1	357.1

112		4.62	355.2	356.2

113		4.32	371.2	372.2

114		5.24	406.2	407.2

115		4.62	414.2	415.2

116		5.2	391.2	392.2

117		5.5	392.2	393.2

118		4.64	328.1	329.1

119		5.47	390.1	391.1

120		5.24	356.1	357.1

121		5.62	378.2	379.2

122		4.92	340.2	341.2

123		4.74	322.2	323.2

124		5.28	368.2	369.2

125		5.2	356.1	357.1

126		4.69	364.2	365.2

127		4.99	368.2	369.2

128		5.7	406.2	407.2

129		5.8	398.2	399.2

130		4.25	352.2	353.2

131		5.28	368.2	369.2

132		5.17	390.2	391.2

133		4.84	356.1	357.1

134		5.74	406.2	407.2

135		5.55	370.2	371.2

136		4.15	326.2	327.2

137		4.9	370.2	371.2

138		4.89	336.2	337.2

139		5.4	374.1	375.1

140		5.27	362.1	363.1

141		4.7	347.2	348.2

142		5.03	342.2	343.2

143		4.69	361.2	362.2

144		4.97	380.2	381.2

145		4.55	361.2	362.2

146		4.17	341.2	342.2

147		5.7	362.2	363.2

148		5.09	336.2	337.2

149		4.85	340.2	341.2

150		5.37	378.2	379.2

151		5.3	356.1	357.1

152		4.8	355.2	356.2

153		5.37	406.2	407.2

154		4.67	414.2	415.2

155		5.27	391.2	392.2

156		5.49	392.2	393.2

157		4.64	330.0	331.0

158		5.24	374.0	375.0

159		4.9	354.0	355.0

160		5.12	338.0	339.0

161		5.19	358.0	359.0

162			380.0	381.0

163		4.94	342.0	343.0

164		4.74	324.0	325.0

165		5.24	370.0	371.0

166		5.32	358.0	359.0

167		4.74	366.0	367.0

168		5.0	370.0	371.0

169		5.62	408.0	409.0

170		5.59	392.0	393.0

171		5.95	400.0	401.0

172		4.25	354.0	355.0

173		5.22	370.0	371.0

174		5.22	392.0	393.0

175		4.97	358.0	359.0

176		5.77	408.0	409.0

177		5.64	392.0	393.0

178		5.59	372.0	373.0

179		4.2	328.0	329.0

180		5.02	372.0	373.0

181		4.84	338.0	339.0

182		5.44	376.0	377.0

183		4.95	354.0	355.0

184		5.34	364.0	365.0

185		4.75	349.0	350.0

186		5.1	344.0	345.0

187		4.72	363.0	364.0

188		5.0	382.0	383.0

189		4.27	381.0	382.0

190		4.69	363.0	364.0

191		5.74	364.0	365.0

192		5.05	338.0	339.0

193		4.97	342.0	343.0

194		5.44	380.0	381.0

195		5.32	358.0	359.0

196		4.65	357.0	358.0

197		5.44	408.0	409.0

198		4.75	416.0	417.0

199		5.22	393.0	394.0

200		5.69	394.0	395.0

201		4.42	314.0	315.0

202		5.05	358.0	359.0

203		4.72	338.0	339.0

204		5.34	376.0	377.0

205		4.92	322.0	323.0

206		5.0	342.0	343.0

207		5.6	364.0	365.0

208		4.75	326.0	327.0

209		4.78	354.0	355.0

210		5.47	392.0	393.0

211		5.42	376.0	377.0

212		5.78	384.0	385.0

213		4.05	338.0	339.0

214		5.05	354.0	355.0

215		5.03	376.0	377.0

216		4.75	342.0	343.0

217		5.62	392.0	393.0

218		5.5	376.0	377.0

219		5.4	356.0	357.0

220		3.97	312.0	313.0

221		4.82	356.0	357.0

222		4.62	322.0	323.0

223		5.25	360.0	361.0

224		4.75	338.0	339.0

225		5.15	348.0	349.0

226		4.57	333.0	334.0

227		4.89	328.0	329.0

228		4.52	347.0	348.0

229		4.82	366.0	367.0

230		4.1	365.0	366.0

231		4.47	347.0	348.0

232		5.62	348.0	349.0

233		4.92	322.0	323.0

234		4.67	326.0	327.0

235		5.24	364.0	365.0

236		5.15	342.0	343.0

237		4.49	341.0	342.0

238		5.24	392.0	393.0

239		4.57	400.0	401.0

240		5.1	377.0	378.0

241		5.52	378.0	379.0

242		4.3	314.0	315.0

243		4.97	358.0	359.0

244		4.62	338.0	339.0

245		5.25	376.0	377.0

246		4.9	342.0	343.0

247		5.57	364.0	365.0

248		4.65	326.0	327.0

249		4.44	308.0	309.0

250		5.02	354.0	355.0

251		5.07	342.0	343.0

252		4.47	350.0	351.0

253		4.72	354.0	355.0

254		5.42	392.0	393.0

255		5.34	376.0	377.0

256		5.75	384.0	385.0

257		3.98	338.0	339.0

258		4.97	354.0	355.0

259		4.97	376.0	377.0

260		4.67	342.0	343.0

261		5.57	392.0	393.0

262		5.44	376.0	377.0

263		5.34	356.0	357.0

264		5.17	360.0	361.0

265		4.65	338.0	339.0

266		5.09	348.0	349.0

267		4.45	333.0	334.0

268		4.82	328.0	329.0

269		4.78	366.0	367.0

270		4.12	365.0	366.0

271		4.32	347.0	348.0

272		5.59	348.0	349.0

273		4.85	322.0	323.0

274		4.65	326.0	327.0

275		5.09	342.0	343.0

276		4.44	341.0	342.0

277		5.09	392.0	393.0

278		4.52	400.0	401.0

279		5.02	377.0	378.0

280		5.39	378.0	379.0

281		4.74	342.0	343.0

282		5.4	386.0	387.0

283		4.97	366.0	367.0

284		5.19	350.0	351.0

285		5.35	370.0	371.0

286		5.8	392.0	393.0

287		4.94	354.0	355.0

288		4.84	336.0	337.0

289		5.4	382.0	383.0

290		5.35	370.0	371.0

291		4.72	378.0	379.0

292		5.07	382.0	383.0

293		5.77	420.0	421.0

294		5.7	404.0	405.0

295		5.92	412.0	413.0

296		4.34	366.0	367.0

297		5.37	382.0	383.0

298		5.27	404.0	405.0

299		4.94	370.0	371.0

300		5.85	420.0	421.0

301		5.78	404.0	405.0

302		5.62	384.0	385.0

303		4.17	340.0	341.0

304		5.09	384.0	385.0

305		4.99	350.0	351.0

306		5.47	388.0	389.0

307		4.92	366.0	367.0

308		5.39	376.0	377.0

309		4.89	361.0	362.0

310		5.19	356.0	357.0

311		4.7	375.0	376.0

312		5.07	394.0	395.0

313		4.4	393.0	394.0

314		4.74	375.0	376.0

315		5.78	376.0	377.0

316		5.2	350.0	351.0

317		5.02	354.0	355.0

318		5.37	392.0	393.0

319		5.39	370.0	371.0

320		4.8	369.0	370.0

321		5.39	420.0	421.0

322		4.8	428.0	429.0

323		5.37	405.0	406.0

324		5.64	406.0	407.0

325		4.59	316.0	317.0

326		5.17	360.0	361.0

327		4.87	340.0	341.0

328		5.09	324.0	325.0

329		4.9	328.0	329.0

330		4.74	310.0	311.0

331		5.27	356.0	357.0

332		5.17	344.0	345.0

333		4.67	352.0	353.0

334		4.97	356.0	357.0

335		5.6	394.0	395.0

336		5.4	378.0	379.0

337		5.89	386.0	387.0

338		4.22	340.0	341.0

339		5.24	356.0	357.0

340		5.07	378.0	379.0

341		5.7	394.0	395.0

342		5.6	378.0	379.0

343		4.99	358.0	359.0

344		4.89	324.0	325.0

345		4.9	340.0	341.0

346		5.09	330.0	331.0

347		4.59	349.0	350.0

348		4.95	368.0	369.0

349		4.2	367.0	368.0

350		4.65	349.0	350.0

351		5.09	324.0	325.0

352		5.35	394.0	395.0

353		5.17	379.0	380.0

354		5.62	380.0	381.0

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 1×10⁻⁶-1×10⁻¹²M.
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

			IC50 [mol/l]
		Inhibition of	(concentration for 50%
Example		PKC theta	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

PKC-Theta Kinase Assay

Inhibition of the enzymic activity of the protein kinase C theta was determined with to 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-XLIent (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-XLIent 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-XLIent). 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 method for the treatment of a disease or disorder selected from inflammatory disorders, oncological disorders, and autoimmune disorders, or for producing immunosupression in a host in need thereof, comprising administering thereto an effective amount of 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, or N(R²)₂groups,

C₁-C₆-fluoroalkyl groups which may optionally be substituted by 1-3 hydroxy, optionally fluorinated (C₁-C₅)-alkoxy, or COOR²groups,

pyrrolidinyl groups,

(CH₂)_u—SO₂—R²groups in which u is 1, 2 or 3,

R²groups or O—CO—R⁶groups,

CO—O—R⁶groups,

CO—N(R⁶)₂groups,

NH—CO—R⁶groups,

CONR⁷R⁸groups,

(CH₂)_n—NR⁷R⁸groups,

NH—CONHR⁶groups,

OR⁶groups,

SO₂—R²groups,

SO₂—OR²groups,

SO₂—N(R²)₂groups,

NHSO₂R²groups,

or

SR²groups,

in which R²is 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)]₂radicals, and/or C₁-C₅-alkoxy radicals,

or a C₃-C₇-cycloalkyl radical,

in which R⁶is 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-Q^sin which u is 1, 2 or 3, and in which Q^sis 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 R¹is 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 method for the treatment of a disease or disorder selected from inflammatory disorders, oncological disorders, and autoimmune disorders, or for producing immunosupression in a host in need thereof, comprising administering thereto an effective amount of 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-C₅-cycloalkyl groups which may optionally be substituted by 1-3 hydroxy, halogen, cyano, (C₁-C₅)-alkoxy, COOR⁶, NHR⁶, NHCOR⁶, or N(R²)₂groups,

pyrrolidinyl groups,

(CH₂)_u—SO₂—R²groups in which u is 1, 2 or 3,

R²groups or O—CO—R⁶groups,

CO—O—R⁶groups,

CO—N(R⁶)₂groups,

NH—CO—R⁶groups,

CONR⁷R⁸groups,

(CH₂)_n—NR⁷R⁸groups,

NH—CONHR⁶groups,

OR⁶groups,

SO₂—R²groups,

SO₂—OR²groups,

SO₂—N(R²)₂groups,

NHSO₂R²groups,

or

SR²groups,

in which R²is in each case independently of one another

or a C₃-C₇-cycloalkyl radical,

in which R⁶is in each case independently of one another

either

a radical R²,

and in which R¹is

a C₁-C₆-alkyl radical which may be substituted 1-3 times by —R², —NR³R⁴, —NR⁷R⁸or —OR²,

a C₂-C₆-alkenyl radical which may be substituted 1-3 times by —R², —NR³R⁴, —NR⁷R⁸or —OR²,

a C₂-C₆-alkynyl radical which may be substituted 1-3 times by —R², —NR³R⁴, —NR⁷R⁸or —OR²,

a —(CH₂)_n—NR³R⁴radical where n is a number 2-6 and in which R³and R⁴are independently of one another a hydrogen atom, a —COR⁶radical, a —SO₂R²radical, 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 —SO₂R²or a group —OR²,

a —(CH₂)_t—Z—(CH₂)_m—NR³R⁴radical,

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 R⁵is a C₁-C₃-alkyl, C₂-C₃-alkenyl, C₂-C₃-alkynyl, a phenyl or a C₃-C₆-cycloalkyl radical,

a —(CH₂)_n′—NR⁷R⁸radical where n′ is a number 1-6 and in which R⁷and R⁸together 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 —SO₂R²or a group —OR²,

a —(CH₂)_n—(CH)R⁷R⁸radical,

a —(CH₂)_t—Z—(CH₂)_m—NR⁷R⁸radical,

a —(CH₂)_t—Z—(CH₂)_m—(CH)R⁷R⁸radical,

a —(CH₂)_r—Y¹radical where r is a number 0-3, and Y¹is 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 —SO₂R²or a group —OR²,

a —(CH₂)_t—Z—(CH₂)_m—Y¹radical,

a —(CH₂)_r—Y²radical where r is a number 0-3, and Y²is 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 —SO₂R²or a group —OR²,

a —(CH₂)_t—Z—(CH₂)_m—Y²radical,

a —(CH₂)_r—Y³radical where r is a number 0-3, and Y³is 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 —SO₂R²or a group —OR²,

a —(CH₂)_t—Z—(CH₂)_m—Y³radical,

a —(CH₂)_r—Y⁴radical where r is a number 0-3, and Y⁴is 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 —SO₂R²or a group —OR²,

a —(CH₂)_t—Z—(CH₂)_m—Y⁴radical,

a —(CH₂)_r—Y⁵radical where r is a number 0-3, and Y⁵is 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 —NHCONHR⁶or a group —OR²,

a —(CH₂)_t—Z—(CH₂)_m—Y⁵radical,

R²is in each case independently of one another

or a C₃-C₇-cycloalkyl radical,

in which R⁶is 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-Q^sin which u is the numbers 1, 2 or 3, and in which Q^sis 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,

3. The method as claimed in claim 2, in which R¹is a —(CH₂)_n—NR³R⁴radical where n is 3 or 4, and in which R³and R⁴are independently of one another a C₁-C₃alkyl radical.

4. The method as claimed in claim 2, in which R¹is a —(CH₂)_n—NR⁷R⁸radical where n is 3 or 4, and in which R⁷and R⁸together form a 5-7-membered ring.

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

6. The method 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 method for the treatment of a disease or disorder selected from inflammatory disorders, oncological disorders, and autoimmune disorders, or for producing immunosupression in a host in need thereof, comprising administering thereto an effective amount of a compound selected from:

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-1-yl)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-1-yl)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-1-yl)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-1-yl)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]pyridazin-3-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-1-yl)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[1,2b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-[3-(4-methylpiperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; diethyl-[4-(3-thiophen-3-ylimidazo[1,2b]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[1,2-b]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[1,2-b]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-1 methylbutoxy)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-(3-pyrrolidin-1-ylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]pentyl}amine; {5-[6-(4-diethylamino-1-methylbutoxy)imidazo[1,2-b]pyridazin-3-yl]thiophen-2-yl}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-m-tolylimidazo[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-methylpyrrolidin-2-yl)ethoxy]-3-phenylimidazo[1,2-b]pyridazine; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(4-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 3-(4-chlorophenyl)-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; 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-3-yl}benzonitrile; 6-[2-(1-methylpyrrolidin-2-yl)ethoxy]-3-(4-methylthiophen-2-yl)imidazo[1,2-b]pyridazine; (4-{6-[2-(1-methylpyrrolidin-2-yl)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[1,2b]pyridazine; 3-(2-fluoropyridin-3-yl)-6-[2-(1-methylpyrrolidin-2-yl)ethoxy]imidazo[1,2-b]pyridazine; 3-benzofuran-2-yl-6-[2-(1-methylpyrrolidin-2-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-3-yl]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-biphenyl-3-yl-6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazine; {3-[6-(1 methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}methanol; 6(1-methylpiperidin-3-ylmethoxy)-3-(3-methylsulfanylphenyl)imidazo[1,2b]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-methylfuran-2-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[1,2b]pyridazine; 3-[6-(1-methylpiperidin-3-ylmethoxy)imidazo[1,2-b]pyridazin-3-yl]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-indol-4-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[1,2-b]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]pyridazin-6-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]pyridazin-6-yloxy)propyl]diethylamine; diethyl-{3-[3-(4-fluorophenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; diethyl-[3-(3-phenylimidazo[1,2-b]pyridazin-6-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-(3-diethylaminopropoxy)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-(5-chlorothiophen-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-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-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-3-yl)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[1,2-b]pyridazin-6-yloxy]propyl}diethylamine; 6-(1-methylpiperidin-3-yloxy)-3-thiophen-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-(3-methylsulfanylphenyl)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-O— tolylimidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-(1-methylpiperidin-3-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-methylpiperidin-3-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-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; N-{3-[6-(1 methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetamide; 3-(1H-indol-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-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}ethanone; 6-(1-ethylpyrrolidin-3-yloxy)-3-(2-methylsulfanylphenyl)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 6-(1-ethylpyrrolidin-3-yloxy)-3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-biphenyl-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-methylsulfanyl phenyl)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-3-yloxy)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-(1-ethylpyrrolidin-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; 3-benzofuran-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-ethylpyrrolidin-3-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-(4-ethanesulfonylphenyl)-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[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-thiophen-3-ylimidazo[1,2b]pyridazine; 3-naphthalen-1-yl-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(4-methoxyphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2b]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; 3-benzo[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-phenyl-6-(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[1,2-b]pyridazin-3-yl]phenyl}methanol; 3-(3-methylsulfanylphenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3-(2-trifluoromethylphenyl)imidazo[1,2-b]pyridazine; 3-(2-chlorophenyl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-3(4-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 6-(3-piperidin-1-ylpropoxy)-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-(3-methoxyphenyl)-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-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]benzonitrile; {4-[6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazin-3-yl]phenyl}acetonitrile; 3-[6-(3-piperidin-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-3-yl]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-fluoro-5-methylpyridin-3-yl)-6-(3-piperidin-1-ylpropoxy)imidazo[1,2-b]pyridazine; 6-(3-piperidin-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]pyridazin-6-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-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; dimethyl-{4-[3-(3-trifluoromethylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; [4-(3-biphenyl-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-(3-methoxyphenyl)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-3-yl]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-1-ylphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}amine; {4-[3-(4-cyclopropylmethoxyphenyl)imidazo[1,2-b]pyridazin-6-yloxy]butyl}dimethylamine; and 6-phenoxy-3-m-tolylimidazo[1,2b]pyridazine.

8. The method 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.

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

10. The method as claimed in claim 7, wherein the compound 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-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-biphenyl-3-yl-6-[3-(4-methylpiperazin-1-yl)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-1-yl)propoxy]imidazo[1,2-b]pyridazine; 3-(3-chloro-4-fluorophenyl)-6-[3-(4-methylpiperazin-1-yl)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-1-yl)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[1,2b]pyridazine; 3-(4-cyclopropylmethoxyphenyl)-6-[3-(4-methyl piperazin-1-yl)propoxy]imidazo[1,2-b]pyridazine; diethyl-[4-(3-thiophen-3-ylimidazo[1,2b]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[1,2-b]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-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; 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-(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-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-3-yl]phenyl}ethanone; 6-(1-methylpiperidin-3-ylmethoxy)-3-(3-trifluoromethoxyphenyl)imidazo[1,2-b]pyridazine; 3-biphenyl-3-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-3-yl]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[1,2b]pyridazine; diethyl-{3-[3-(4-methoxyphenyl)imidazo[1,2b]pyridazin-6-yloxy]propyl}amine; diethyl-[3-(3-m-tolylimidazo[1,2-b]pyridazin-6-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]pyridazin-6-yloxy)propyl]diethylamine; diethyl-{3-[3-(4-methylsulfanylphenyl)imidazo[1,2-b]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-(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-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-methylpiperidin-3-yloxy)imidazo[1,2-b]pyridazin-3-yl]benzoic acid methyl ester; 3-(4-chlorophenyl)-6-(1-ethylpyrrolidin-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-1-ylpropoxy)imidazo[1,2-b]pyridazine; 3-(3-chloro-4-methylphenyl)-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; 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-(3-piperidin-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-(3-biphenyl-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; and 6-phenoxy-3-m-tolylimidazo[1,2b]pyridazine.

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

12. The method as claimed in claim 11, 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.

13. The method 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.

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

15. The method as claimed in claim 1, wherein the disease or disorder is a solid tumor or metastesis thereof.

16. The method as claimed in claim 2, wherein the disease or disorder is a solid tumor or metastesis thereof.

17. The method as claimed in claim 7, wherein the disease or disorder is a solid tumor or metastesis thereof.

18. The method as claimed in claim 1, wherein the disease or disorder is characterized by the dysregulation of a protein kinase.

19. The method as claimed in claim 2, wherein the disease or disorder is characterized by the dysregulation of a protein kinase.

20. The method as claimed in claim 7, wherein the disease or disorder is characterized by the dysregulation of a protein kinase.