The present invention provides novel 2,3-dihydrobenzazine compounds that are useful in therapy of diseases and disorders. The novel compounds inhibit cell prolifera- tion and cell division and they also inhibit the activation of Hypoxia Inducible Factor (HIF)-mediated transcription and signaling under hypoxic conditions. In one aspect, the compounds of the present invention are useful for the preparation of a medicament for the treatment or prevention of a disease or disorder selected from the group consisting of an inflammatory disease, a hyperproliferative disease or disorder, a hypoxia-related pathology and a disease characterized by excessive vascularization. Also provided is a pharmaceutical composition, comprising a compound of the invention and a second therapeutic agent or radiation, useful for the treatment or prevention of the mentioned diseases or disorders.

BACKGROUND OF THE INVENTION

The normal response of cells to inadequate oxygen supply is mediated by the hypoxia signaling pathway. This response is important for a number of physiological functions such as tumor development and metastasis, resistance to apoptosis, induction of new blood vessel formation, and shift towards anaerobic metabolism amongst others. For a general review on hypoxia signaling see e.g. Qingdong Ke and Max Costa, Molecular Pharmacology (2006), vol. 70, no. 5.

As a result of hypoxia, augmented levels of a heterodimeric complex of transcription factors (Hypoxia Inducible Factor, HIF), most notably HIF-1 a and HIF-1 β, are observed in e.g. tumors to compensate in cooperation with additional co-factors for the reduced availability of oxygen and nutrients in this fast growing tissue type. Under anaerobic conditions, homeostasis of HIF-1 a is imbalanced by its reduced degradation, thus enabling enhanced signaling through the Hypoxia Responsive Element (HRE) and resulting in increased expression of a large number of survival and growth factors.

Hypoxic conditions are also found in non-tumor tissue. For example, retinopathy is a general term that refers to non-inflammatory damage to the retina of the eye. This condition is most commonly caused by an insufficient blood supply leading to hypoxia. Particularly people with diabetes mellitus are at risk of retinopathy. The lack of oxygen in the retina of diabetics causes fragile, new blood vessels to grow along the retina and in the clear, gel-like vitreous humor that fills the inside of the eye. Without timely treat- ment, these new blood vessels can bleed, cloud vision, and destroy the retina. Fi- brovascular proliferation can also cause fractional retinal detachment. The new blood vessels can also grow into the anterior chamber of the eye and cause neovascular glaucoma. Recently, evidence has accumulated that inhibition of HIF-1 activity could also act to prevent inflammation, by virtue of its role in the activation and infiltration of macrophages and neutrophils into affected tissues (see e.g. Giaccia et al., Drug Discovery, vol. 2, October 2003).

For the above-outlined reasons, compounds that inhibit HIF function are valuable medicaments for the treatment or prevention of a disease or disorder selected from the group consisting of an inflammatory disease, a hyperproliferative disease or disorder, a hypoxia-related pathology and a disease characterized by excessive vascularization.

Because of the importance of HIF-1 in tumor development, progression and metastasis, a considerable amount of effort has been devoted to identify HIF-1 inhibitors for cancer therapy. A number of small molecules and RNA constructs, like siRNA, have been reported to exhibit inhibition of the HIF-1 pathway, e.g. Kung AL et al., Cancer Cell (2004), vol. 6, p. 33 ff; Rapisarda A, et al. Cancer Res. (2002), vol. 62, p. 4316 ff.; Tan C.et al., Cancer Res. (2005), vol. 65, p. 605 ff.; Mabjeesh NJ, et al., Cancer Cell, (2003), vol. 3, p. 363ff;. Kong X, et al., Mol Cell Biol (2006), vol. 26, p. 2019 ff.; Kong D, et al., Cancer Res. (2005), vol. 65, p. 9047 ff.; Chau N. et al., Cancer Res. (2005), vol. 65, p. 4918 ff.; Welsh S, et al., Mol Cancer Ther (2004), vol. 3, p. 233 ff. However, these compounds often have activities other than HIF-1 inhibition, and most of them lack the desired pharmacokinetic properties or toxicity profiles required for a useful pharmaceutical agent. Furthermore, some of the compounds have the disadvantage that they can not be administered orally, such as the HIF-1 inhibitor EZN-2968, which is a locked nucleic acid antisense oligonucleotide.

WO 2004/056820 discloses 2,3-dihydrobenzazine compounds which in the 6-position carry an (azoline-2-one-3-yl)methylene radical. The compounds are mentioned to be suitable for the treatment of disorders which respond to the inhibition of phosphinositide-3-kinases including certain inflammatory diseases and certain cancer diseases.

US 2007/191603, inter alia, discloses inter alia 1 -benzenesulfonyl- 1 ,2,3,4-tetrahydroquinazoline compounds which in the 7-position carry a

(het)arylaminocarbonyl radical. The compounds are mentioned to be suitable for the treatment of disorders which respond to the inhibition of liver carnithine palmitoleyl transferase including hyperglycemia disorders and glucose tolerance disorders.

WO 2009/03599 A

wherein A is e.g. CO, CONH or S0 ₂ , Y is (CH ₂ ) _P with p = 1 , 2 or 3, Z is O, S, SO or SO2, Ri is alkyl, cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, R ² , R ³ are hydrogen or alkyl and R ⁴ is selected from COOR5, CONR5R6, aryl which is optionally substituted by 1 , 2 or 3 radicals selected from halogen, C1-C6- alkyl, Ci-C6-alkoxy, CF3 or OCF3, and heterocyclyl, which is optionally substituted by 1 , 2 or 3 radicals selected from halogen, Ci-C6-alkyl, Ci-C6-alkoxy, Cs-Cs-cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, CF3 or OCF3. The compounds bind to cannabinoid receptors CB1 or CB2 on the surface of mammalian cells thereby modulating the intracellular cAMP concentration. Therefore compounds are suggested to be useful in the treatment of cannabinoid receptor associated disorders including treatment of pain, pruritis, skin disorders, inflammatory diseases, neurodegenerative, neuroinflammatory or psychiatric disorders, lung disorders, ophthalmic disorders, cardiosvascular disorders, gastrointestinal disorders and certain cancer diseases.

WO 2010/085968 discloses N-phenyl (monocyclic heteroaryl)sulfonamide compounds which inhibit cell proliferation cell division and which inhibit the activation of Hypoxia Inducible Factor (HIF) - mediated transcription and signaling under hypoxic conditions.

WO 2010/075869 discloses N-phenyl benzenesulfonamide compounds which inhibit cell proliferation cell division and which inhibit the activation of Hypoxia Inducible Factor (HIF) - mediated transcription and signaling under hypoxic conditions.

US 61/359,1 19 (unpublished) discloses N-phenylsulfonamide compounds of the formula B

wherein Ri is optionally substituted naphthyl or C-bound bicyclic heterocyclyl, R2 is substituted phenyl or optionally substituted C- or N-bound monocyclic 5- or

6-membered heteroaryl; R3 is i.a. hydrogen, ethynyl, methyl, CH2OH, CH2O-C1-C4- alkyl, or CH20-Ci-C4-alkoxy-Ci-C4-alkyl; R4 is hydrogen, ethynyl or methyl and R ⁵ is hydrogen or Ci-C4-alkyl. The compounds are useful for the treatment or prevention of a disease or disorder selected from the group consisting of an inflammatory disease, a hyperproliferative disease or disorder, a hypoxia related pathology and a disease characterized by pathophysiological hypervascularization.

PCT/EP2009/064138 (unpublished) discloses 2,3-dihydrobenzazine compound of the formula C

where X is O, S, SO or SO2, Ri is phenyl or C-bound monocyclic 5- or 6-membered heteroaryl where the two last-mentioned radicals may be unsubstituted or carry 1 , 2 or 3 radicals. Two of said radicals which are bound to adjacent carbon atoms of phenyl or 5- or 6-membered heteroaryl, may also form a bridging moiety O-CH2-O, 0-CHF-O, O-CF2-O or O-CH2-CH2-O. R2 is phenyl or C- or N-bound monocyclic 5- or 6-membered heteroaryl, phenyl and monocyclic 5- or 6-membered heteroaryl carrying a CN radical and optionally further substituents. The compounds are useful for the treatment or prevention of a disease or disorder selected from the group consisting of an

inflammatory disease, a hyperproliferative disease or disorder, a hypoxia related pathology and a disease characterized by pathophysiological hyper-vascularisation.

US 61/422,586 (unpublished) discloses tetrahydroquinoxaline compounds of the formula D

wherein Ri is an optionally substituted aromatic radical selected from phenyl, C-bound monocyclic 5- or 6-membered heteroaryl or C-bound bicyclyl comprising a first ring which is a benzene ring or a 5- or 6-membered heteroaromatic ring and a second ring, which is fused to the first ring, where the second ring is a 5-, 6- or 7-membered carbocyclic ring or a 5-, 6- or 7-membered heterocyclic ring, where the saturated or unsaturated carbocyclic or heterocyclic second ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members; R2 is an optionally substituted aromatic radical selected from phenyl, C-bound monocyclic 5- or 6-membered heteroaryl or C-bound bicyclyl comprising a first ring which is a benzene ring or a 5- or

6- membered heteroaromatic ring and a second ring, which is fused to the first ring, where the second ring is a 5-, 6- or 7-membered carbocyclic ring or a 5-, 6- or

7- membered heterocyclic ring, where the saturated or unsaturated carbocyclic or heterocyclic second ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring member; R3 is hydrogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, or a radical C(X)Rx, wherein X is O or S and R _x is Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, C3-C8-cycloalkoxy, benzyloxy or fluorenylmethoxy. The compunds inhibit cell proliferation and cell division and they also inhibit the activation of Hypoxia Inducible Factor (HIF)-mediated transcription and signaling under hypoxic conditions.

The scientific literature cited above emphasizes the high medical need for new therapeutic agents to provide more efficient treatment of different proliferative and in- flammatory diseases or disorders, hypoxia-related pathologies and diseases characterized by excessive vascularization. It is an object of the present invention to provide novel compounds which can be used as very potent inhibitors of (i) the activation of HIF mediated transcription under hypoxic conditions and of (ii) cell proliferation. SUMMARY OF THE INVENTION

The present invention provides novel compounds capable of prevention or treatment of a disease or disorder. Data presented herein establish that compounds according to the present invention are surprisingly very potent inhibitors of (i) the activation of HIF mediated transcription under hypoxic conditions and of (ii) cell proliferation.

In a first aspect the present invention relates to 2,3-dihydrobenzazine compounds of the formula (I)

wherein

X is O or S(=0) _n with n being 0, 1 or 2; is C-bound bicyclyl comprising a first ring which is a benzene ring or a 5- or

6- membered heteroaromatic ring having either 1 , 2 or 3 nitrogen atoms as het- eroatom ring members or 1 oxygen or 1 sulfur atom and 0, 1 or 2 nitrogen atoms as heteroatom ring members, and a second ring, which is fused to the first ring, where the second ring is a 5-, 6- or 7-membered carbocyclic ring or a 5-, 6- or

7- membered heterocyclic ring having 1 , 2 or 3 heteroatom ring members selected from oxygen, sulfur and nitrogen, where sulfur atoms, if present, may be present as S, S(O) or S(0)2 and where the saturated or unsaturated carbocyclic or heterocyclic second ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members,

wherein C-bound bicyclic heterocyclyl is unsubstituted or carries 1 or more radicals R ^1a which are identical or different or 1 radical R ^1b and 0, 1 , 2, 3, 4 or 5 identical or different radicals R ^1a : is selected from the group consisting of halogen, cyano, NO2, NH2, OH, SH, Ci-Cio-alkyl, C ₂ -Cio-alkenyl, C ₂ -Cio-alkynyl, C≡C-CN, Ci-C ₆ -alkoxy, Ci-C ₆ - alkylthio, Ci-C6-alkylsulfonyl, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C2-alkoxy, fluorinated C1-C2- alkylthio, fluorinated Ci-C ₂ -alkylsulfonyl, C(0)R ³ , NR ⁴ R ⁵ , N(OR ⁶ )R ⁷ , C(0)NR ⁶ R ⁷ , C(0)OR ⁸ , and CHR ⁹ R ¹⁰ ; is selected from the group consisting of phenyl, C3-C7-cycloalkyl, 5- or 6-membered heteroaryl and 3- to 7-membered saturated or unsaturated heterocyclyl, where the aforementioned radicals are unsubstituted or carry 1 , 2, 3, 4 or 5 identical or different radicals R ^1c ;

R ^1c is selected from the group consisting of halogen, cyano, NO2, NH2, OH, SH, Ci-C ₄ -alkyl, Ci-C ₄ -alkoxy, Ci-C ₄ -alkylthio, Ci-C ₄ -alkylsulfonyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C2-alkoxy, fluorinated Ci-C2-alkylthio, fluorinated Ci-C ₂ -alkylsulfonyl, C ₂ -Cio-alkenyl, C ₂ -Cio-alkynyl, C≡C-CN, CH ₂ -CN, C(0)R ³ , NR ⁴ R ⁵ , N(OR ⁶ )R ⁷ , C(0)NR ⁶ R ⁷ , and C(0)OR ⁸ , is an aromatic radical selected from phenyl, C-bound monocyclic 5- or

6-membered heteroaryl or C-bound bicyclyl comprising a first ring which is a benzene ring or a 5- or 6-membered heteroaromatic ring and a second ring, which is fused to the first ring, where the second ring is a 5-, 6- or 7-membered carbocyc- lic ring or a 5-, 6- or 7-membered heterocyclic ring, where the saturated or unsaturated carbocyclic or heterocyclic second ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members, wherein phenyl, C-bound monocyclic 5- or 6-membered heteroaryl and C-bound bicyclyl are unsubstituted or carry 1 or more radicals R ^2a which are identical or different or 1 radical R ^2b and 0, 1 , 2, 3, 4 or 5 identical or different radicals R ^2a ; is selected from the group consisting of halogen, cyano, NO2, NH2, OH, SH, Ci-Cio-alkyl, C ₂ -Cio-alkenyl, C ₂ -Cio-alkynyl, C≡C-CN,

CH2-CN, d-Ce-alkoxy, Ci-C ₆ -alkylthio, Ci-C ₆ -alkylsulfonyl, hydroxy-Ci-C ₆ - alkyl, Ci-C ₄ -alkoxy-Ci-C ₄ -alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C2-alkoxy, fluorinated Ci-C2-alkylthio, fluorinated Ci-C2-alkylsulfonyl, C(0)R ³ , NR ⁴ R ⁵ , N(OR ⁶ )R ⁷ , C(0)NR ⁶ R ⁷ , C(0)OR ⁸ , and CHR ⁹ R ¹⁰ ; R ^2b is selected from the group consisting of phenyl, C3-C7-cycloalkyl, 5- or 6-membered heteroaryl and 3- to 7-membered saturated or unsaturated heterocyclyl, where the aforementioned radicals are unsubstituted or carry 1 , 2, 3, 4 or 5 identical or different radicals R ^2c ;

R ^2c is selected from the group consisting of halogen, cyano, NO2, NH2, OH, SH, Ci-Ci4-alkyl, Ci-C4-alkoxy, Ci-C4-alkylthio, Ci-C4-alkylsulfonyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C2-alkoxy, fluorinated Ci-C2-alkylthio, fluorinated Ci-C ₂ -alkylsulfonyl, C ₂ -Cio-alkenyl, C ₂ -Cio-alkynyl, C≡C-CN, CH ₂ -CN, C(0)R ³ , NR ⁴ R ⁵ , N(OR ⁶ )R ⁷ , C(0)NR ⁶ R ⁷ , C(0)OR ⁸ , and CHR ⁹ R ¹⁰ ; is selected from Ci-C4-alkyl and fluorinated Ci-C2-alkyl;

R ⁴ is hydrogen or Ci-C6-alkyl; is Ci-C6-alkyl, hydroxy-C2-C6-alkyl, Ci-C4-alkoxy-C2-C4-alkyl, carboxy-Ci-C4-alkyl or a radical C(Y)Ry, wherein

Y is O or S; and

Ry is Ci-C6-alkyl or fluorinated Ci-C2-alkyl; or

R ⁴ , R ⁵ together with the nitrogen atom, to which they are bound, form an N-bound, 5- or 6-membered saturated nitrogen heterocycle which is unsubstituted or which carries 1 , 2, 3 or 4 radicals selected from Ci-C4-alkyl, fluorinated Ci-C2-alkyl and C(0)NR ⁶ R ⁷ ;

R ⁶ is selected from hydrogen and Ci-C6-alkyl;

R ⁷ is selected from hydrogen and Ci-C6-alkyl; R ⁸ is selected from hydrogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, hydroxy-C2-C6- alkyl and Ci-C4-alkoxy-C2-C4-alkyl;

R ⁹ is selected from Ci-C6-alkoxy; R ¹⁰ is selected from Ci-C6-alkoxy; or R ⁹ , R ¹⁰ together with the carbon atom, to which they are bound, form an C-bound, 5- or 6-membered saturated heterocycle which is unsubstituted or which carries 1 , 2, 3 or 4 radicals selected from Ci-C4-alkyl, fluorinated Ci-C2-alkyl and C(0)NR ⁶ R ⁷ ; and the pharmaceutically acceptable salts thereof, and, if one or both of R ¹ and R ² are a nitrogen containing heterocycle, the N-oxides thereof and the pharmaceutically acceptable salts of said N-oxides, except for compounds of the formula I, where

where

# is the point of attachment to the 2,3-dihydrobenzazine ring;

is CH ₂ , CH2CH2, CHF or CF ₂ ; and is phenyl or C-bound monocyclic 5- or 6-membered heteroaryl, and

R ² is phenyl or C- or N-bound monocyclic 5- or 6-membered heteroaryl,

wherein phenyl and monocyclic 5- or 6-membered heteroaryl carry a CN radical and may additionally carry 1 , 2 or 3 radicals R ^2a .

In a further aspect the invention relates to use of the compounds of the formula (I), the pharmaceutically acceptable salts thereof, and, if one or both of R ¹ and R ² are a nitrogen containing heterocycle, the N-oxides thereof or the pharmaceutically acceptable salts of said N-oxides in therapy, in particular in therapy of a disease or disorder selected from the group consisting of inflammatory diseases, a hyperproliferative disease or disorders, a hypoxia related pathology and a disease characterized by patho- physiological hyper-vascularization.

In a further aspect the present invention relates to a pharmaceutical composition comprising at least one compound of the formula (I), the pharmaceutically acceptable salts thereof, and, if one or both of R ¹ and R ² are a nitrogen containing heterocycle, the N-oxides thereof or the pharmaceutically acceptable salts of said N-oxides optionally together with at least one physiologically acceptable carrier or auxiliary substance.

In a further aspect the present invention relates to a method for treatment or prevention of a disease or disorder selected from the group consisting of an inflammatory disease, a hyperproliferative disease or disorder, a hypoxia related pathology and a disease characterized by pathophysiological hypervascularization, said method comprising administering an effective amount of at least one compound of the formula (I), the pharmaceutically acceptable salts thereof, and, if one or both of R ¹ and R ² are a nitrogen containing heterocycle, the N-oxides thereof or the pharmaceutically acceptable salts of said N-oxides to a subject in need thereof.

In a further aspect the present invention relates to the use of a compound of the formula (I), the pharmaceutically acceptable salts thereof, and, if one or both of R ¹ and R ² are a nitrogen containing heterocycle, the N-oxides thereof or the pharmaceutically acceptable salts of said N-oxides in the manufacture of a medicament for therapy of a disorder or disease wherein the disorder or disease is selected from the group consisting of an inflammatory disease, a hyperproliferative disease or disorder, a hypoxia related pathology and a disease characterized by pathophysiological hypervascularization.

DETAILED DESCRIPTION OF THE INVENTION

It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined other- wise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art.

Preferably, the terms used herein are defined as described in "A multilingual glossary of biotechnological terms: (lUPAC Recommendations)", Leuenberger, H.G.W., Nagel, B. and Klbl, H. Eds. (1995), Helvetica Chimica Acta, CH-4010 Basel, Switzer- land).

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

Several documents are cited throughout the text of this specification. Each of the documents cited herein (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.), whether supra or infra, are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.

Provided the compounds of the formula (I) of a given constitution may exist in different spatial arrangements, for example if they possess one or more centers of asymmetry, polysubstituted rings or double bonds, or as different tautomers, the inven- tion also relates to enantiomeric mixtures, in particular racemates, diastereomeric mixtures and tautomeric mixtures, preferably, however, the respective essentially pure enantiomers (enantiomerically pure), diastereomers and tautomers of the compounds of formula (I) and/or of their salts and/or their N-oxides. Racemates obtained can be resolved into the isomers mechanically or chemically by methods known per se. Diastereomers are preferably formed from the racemic mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfo- nic acids, such as D- or L-camphorsulfonic acid. Also advantageous is enantiomer resolution with the aid of a column filled with an optically active resolving agent (for example dinitrobenzoylphenylglycine); an example of a suitable eluent is a hexane/- isopropanol/acetonitrile mixture. The diastereomer resolution can also be carried out by standard purification processes, such as, for example, chromatography or fractional crystallization. It is also possible to obtain optically active compounds of formula (I) by the methods described below by using starting materials which are already optically active.

The invention also relates to "pharmaceutically acceptable salts" of the compounds of the formula (I), especially acid addition salts with physiologically tolerated, i.e. pharmaceutically acceptable acids. Examples of suitable physiologically tolerated organic and inorganic acids include, but are not limited to, hydrochloric acid, hydro- bromic acid, phosphoric acid, sulfuric acid, Ci-C4-alkylsulfonic acids, such as methane- sulfonic acid, aromatic sulfonic acids, such as benzenesulfonic acid and toluenesulfo- nic acid, carboxylic acids such as oxalic acid, malic acid, maleic acid, fumaric acid, lactic acid, tartaric acid, adipic acid, mandelic acid, salicylic acid, phenylpropionic acid, nicotinic acid, benzoic acid acetate, alginic acid, ascorbic acid, aspartic acid, tannic acid, butyric acid, camphoric acid, citric acid, clavulanic acid, cyclopentanepropionic acid, gluconic acid, formic acid, acetic acid, propionic acid, pivalic acid, valeric acid, hexoic acid, heptoic acid, oleic acid, palmitic acid, pantothenic acid, pectinic acid, stearic acid, hexylresorcinic acid, hydroxynaphthoic acid, lactobionic acid and mucic acid. Other utilizable acids are described in Fortschritte der Arzneimittelforschung [Advances in drug research], Volume 10, pages 224 ff., Birkhauser Verlag, Basel and Stuttgart, 1966 and in Berge, S. M., et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977, 66, 1 -19. Illustrative examples of pharmaceutically acceptable salts include but are not limited to: acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, bu- tyrate, calcium edetate, camphorate, camphorsulfonate, camsylate, carbonate, chloride, citrate, clavulanate, cyclopentanepropionate, digluconate, dihydrochloride, dode- cylsulfate, edetate, edisylate, estolate, esylate, ethanesulfonate, formiate, fumarate, gluceptate, glucoheptonate, gluconate, glutamate, glycerophosphate, glycolylarsani- late, hemisulfate, heptanoate, hexanoate, hexylresorcinate, hydrabamine, hydrobro- mide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, hydroxynaphthoate, iodide, isothionate, lactate, lactobionate, laurate, lauryl sulfate, malate, maleate, malo- nate, mandelate, mesylate, methanesulfonate, methylsulfate, mucate, 2-naphthalene- sulfonate, napsylate, nicotinate, nitrate, N-methylglucamine ammonium salt, oleate, oxalate, pamoate (embonate), palmitate, pantothenate, pectinate, persulfate,

3-phenylpropionate, phosphate/diphosphate, picrate, pivalate, polygalacturonate, propionate, salicylate, stearate, sulfate, subacetate, succinate, tannate, tartrate, teoclate, tosylate, triethiodide, undecanoate, valerate, and the like. Certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. Furthermore, where the compound of the invention carries an acidic moiety, suitable pharmaceutically acceptable salts thereof may include alkali metal salts (e.g., sodium or potassium salts); alkaline earth metal salts (e.g., calcium or magnesium salts); and salts formed with suitable organic ligands (e.g., ammonium, quaternary ammonium and amine cations formed using counteranions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, alkyl sulfonate and aryl sulfonate).

The neutral forms of the compounds may be regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents, but otherwise the salts are equivalent to the parent form of the compound for the purposes of the present invention.

The invention also relates to N-oxides of the compounds of the formula (I), pro- vided that those compounds contain a basic nitrogen atom, such as the nitrogen atom of a nitrogen containing heterocycle which may be present in R ¹ and/or R ² . Examples of nitrogen containing heterocycle, where the nitrogen may be present in the form of an N-oxide, include pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolyl, oxa- zolyl, oxadiazolyl, triazolyl and the like.

In addition to salt forms, the N-oxides and the salts of the N-oxides, the present invention provides compounds which are in a prodrug form. Prodrugs of the compounds described herein are those compounds that readily undergo chemical changes under physiological conditions to provide a compound of general formula (I). A prodrug is a pharmacologically active or inactive compound that is modified chemically through in vivo physiological action, such as hydrolysis, metabolism and the like, into a compound of this invention following administration of the prodrug to a patient. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme. The suitability and techniques involved in making and using prodrugs are well known by those skilled in the art. For a general discussion of prodrugs involving esters, see Svensson and Tunek, Drug Metabolism Reviews 16.5 (1988), and Bundgaard, Design of Prodrugs, Elsevier (1985). Examples of a masked acidic anion include a variety of esters, such as alkyl (for example, methyl, ethyl), cycloalkyl (for example, cyclohexyl), aralkyl (for example, benzyl, p-methoxy- benzyl), and alkylcarbonyloxyalkyi (for example, pivaloyloxymethyl). Amines have been masked as arylcarbonyloxymethyl substituted derivatives which are cleaved by esterases in vivo releasing the free drug and formaldehyde (Bungaard J. Med. Chem. 2503 (1989)). Also, drugs containing an acidic NH group, such as imidazole, imide, indole and the like, have been masked with N-acyloxymethyl groups (Bundgaard Design of Prodrugs, Elsevier (1985)). Hydroxy groups have been masked as esters and ethers. EP 0 039 051 (Sloan and Little, Apr. 1 1 , 1981 ) discloses Mannich-base hydrox- amic acid prodrugs, their preparation and use.

Certain compounds of the present invention can exist in unsolvated forms as well as in solvated forms, including hydrated forms. In general, the solvated forms are equivalent to unsolvated forms and are intended to be encompassed within the scope of the present invention. Certain compounds of the present invention may exist in multiple crystalline or amorphous forms. In general, all physical forms are equivalent for the uses contemplated by the present invention and are intended to be within the scope of the present invention.

The compounds of the present invention may also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. An isotopic variation of an agent of the present invention or a pharmaceutically acceptable salt thereof is defined as one in which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the atomic mass usually found in nature. Examples of isotopes that can be incorporated into the agent and pharmaceutically acceptable salts thereof include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine such as ² H, ³ H, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁷ 0, ¹⁸ 0, ³¹ P, ³² P, ³⁵ S, ¹⁸ F and ³⁶ CI, respectively. Certain isotopic variations of the agent and pharmaceutically acceptable salts thereof, for example, those in which a radioactive isotope such as ³ H or ¹⁴ C is incorporated, are useful in drug and/or substrate tissue distribution studies. Tritiated, i.e., ³ H, and carbon-14, i.e., ¹⁴ C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with iso- topes such as deuterium, i.e., ² H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements and hence may be preferred in some circumstances. Isotopic variations of the agent of the present invention and pharmaceutically acceptable salts thereof of this invention can generally be prepared by conventional procedures using appropriate isotopic variations of suitable reagents. All isotopic variations of the compounds and compositions of the present invention, whether radioactive or not, are intended to be encompassed within the scope of the present invention.

In the following definitions of the terms: alkyl, aryl, heteroaryl, alkenyl, alkynyl, hydroxyalkyl and alkoxyalkyl are provided. These terms will in each instance of its use in the remainder of the specification have the respectively defined meaning and preferred meanings. Nevertheless in some instances of their use throughout the specification preferred meanings of these terms are indicated.

The organic moieties mentioned in the above definitions of the variables are - like the term halogen - collective terms for individual listings of the individual group members. The prefix C _n -C _m indicates in each case the possible number of carbon atoms in the group. If two or more radicals can be selected independently from each other, then the term "independently" means that the radicals may be the same or may be different.

The term "halogen" denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.

The term "Ci-Cio-alkyl" denotes a straight-chain or branched alkyl group having from 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms. Examples of an alkyl group are methyl, ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, pentyl,

1 - methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 -ethylpropyl, hexyl, 1 ,1 -dimethylpropyl, 1 ,2-dimethylpropyl, 1 -methylpentyl, 2-methylpentyl, 3-methylpentyl,

4-methylpentyl, 1 ,1 -dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl,

2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2-ethylbutyl, 1 ,1 ,2-trimethylpropyl, 1 ,2,2-trimethylpropyl, 1 -ethyl-1 -methylpropyl, 1 -ethyl-

2- methylpropyl, heptyl, octyl, nonyl and decyl.

The term "fluorinated C1-C2 alkyl" denotes an alkyl group having 1 or 2 carbon atoms as defined above, wherein at least one hydrogen atom, e.g. 1 , 2, 3, 4 or 5 hydrogen atoms, are replaced by fluorine. Examples of such a group include fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1 ,1 ,2,2-tetrafluoroethyl and 1 ,1 ,2,2,2-pentafluoroethyl.

The term "pentafluorosulfanyl" (also referred to as pentafluorothio) relates to the radical SF ₅ .

The term "hydroxy-Ci-C6-alkyl" denotes a straight-chain or branched alkyl group having from 1 to 6, especially 1 to 4 carbon atoms (=hydroxy-Ci-C4 alkyl), wherein one of the hydrogen atoms is replaced by a hydroxy group, such as in hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, 3-hydroxypropyl, hydroxy-iso-propyl, 1 -hydroxybutyl or 2-hydroxybutyl.

The term "hydroxy-C2-C6-alkyl" denotes a straight-chain or branched alkyl group having from 2 to 6, especially 2 to 4 carbon atoms (=hydroxy-C2-C4 alkyl), wherein one of the hydrogen atoms, which is preferably not located at Ci , is replaced by a hydroxy group, such as in 2-hydroxyethyl or 3-hydroxypropyl. The term "C1 " refers to the carbon atom by which hydroxy-C2-C6-alkyl is bound to the remainder of the molecule.

The term "Ci-C6-alkoxy" denotes a straight-chain or branched alkyl group having 1 , 2, 3, 4, 5 or 6 carbon atoms, which is bound to the remainder of the molecule via an oxygen atom. Examples of an alkoxy group are methoxy, ethoxy, n-propoxy, iso- propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert-butyloxy, pentyloxy,

1 -methylbutyloxy, 2-methylbutyloxy, 3-methylbutyloxy, 2,2-dimethylpropyloxy,

1 -ethylpropyloxy, hexyloxy, 1 ,1 -dimethylpropyloxy, 1 ,2-dimethylpropyloxy,

1 -methylpentyloyx, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy,

1 ,1 -dimethylbutyloyx, 1 ,2-dimethylbutyloxy, 1 ,3-dimethylbutyloxy, 2,2-dimethylbutyloxy, 2,3-dimethylbutyloyx, 3,3-dimethylbutyloxy, 1 -ethylbutyloxy, 2-ethylbutyloxy,

1 ,1 ,2-trimethylpropyloxy, 1 ,2,2-trimethylpropyloxy, 1 -ethyl-1 -methylpropyloxy and 1 -ethyl-2-methylpropyloxy.

The term "fluorinated Ci-C2-alkoxy" denotes an alkoxy group having 1 or 2 carbon atoms, wherein at least one hydrogen atom, e.g. 1 , 2, 3, 4 or 5 hydrogen atoms, are replaced by fluorine. Examples of such a group include fluoromethoxy, difluorometh- oxy, trifluoromethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy,

1 ,1 ,2,2-tetrafluoroethoxy and 1 ,1 ,2,2,2-pentafluoroethoxy.

The term "Ci-C4-alkoxy-Ci-C4-alkyl" denotes a straight-chain or branched alkyl group having from 1 to 4 carbon atoms, wherein one of the hydrogen atoms is replaced by a C1-C4 alkoxy group, such as in methoxymethyl, ethoxymethyl, propoxymethyl,

1 - methoxyethyl, 1 -ethoxyethyl, 2-methoxyethyl, 2-ethoxyethyl, 2-methoxypropyl,

2- ethoxypropyl, 3-methoxypropyl or 3-ethoxypropyl.

The term "Ci-C4-alkoxy-C2-C4-alkyl" denotes a straight-chain or branched alkyl group having from 2 to 4 carbon atoms, wherein one of the hydrogen atoms, which is preferably not located at C1 , is replaced by a C1-C4 alkoxy group, such as in

2- methoxyethyl, 2-ethoxyethyl, 2-methoxypropyl, 2-ethoxypropyl, 3-methoxypropyl or

3- ethoxypropyl. The term "C1 " refers to the carbon atom by which Ci-C4-alkoxy-C2-C4- alkyl is bound to the remainder of the molecule.

The term "Ci-C6-alkylthio" (also referred to as alkylsulfanyl) denotes a straight- chain or branched alkyl groups having 1 to 6 carbon atoms (as mentioned above) which are attached to the skeleton via a sulfur atom (-S-).

The term "fluorinated Ci-C2-alkylthio" denotes an alkylsulfanyl group having 1 or 2 carbon atoms, wherein at least one hydrogen atom, e.g. 1 , 2, 3, 4 or 5 hydrogen atoms, are replaced by fluorine. Examples of such a group include fluoromethylsulfanyl, di- fluoromethylsulfanyl, trifluoromethylsulfanyl, 2-fluoroethylsulfanyl,

2,2-difluoroethylsulfanyl, 2,2,2-trifluoroethylsulfanyl, 1 ,1 ,2,2-tetrafluoroethylsulfanyl and 1 ,1 ,2,2,2-pentafluoroethylsulfanyl. The term "Ci-C6-alkylsulfonyl" refers to straight-chain or branched alkyl group having 1 to 6 carbon atoms (as defined above) bonded through a -S(=0)2 moiety, at any position in the alkyl group, for example methylsulfonyl, ethylsulfonyl,

n-propylsulfonyl, isopropylsulfonyl, t-butylsulfonyl, n-pentylsulfonyl and n-hexylsulfonyl.

The term "fluorinated Ci-C2-alkylsulfonyl" denotes an alkylsulfonyl group having

1 or 2 carbon atoms, wherein at least one hydrogen atom, e.g. 1 , 2, 3, 4 or 5 hydrogen atoms, are replaced by fluorine. Examples of such a group include fluoromethanesul- fonyl, difluoromethanesulfonyl, trifluoromethanesulfonyl, 2-fluoroethanesulfonyl, 2,2-difluoroethanesulfonyl, 2,2,2-trifluoroethanesulfonyl,

1 ,1 ,2,2-tetrafluoroethanesulfonyl and 1 ,1 ,2,2,2-pentafluoroethanesulfonyl.

The term "C2-Cio-alkenyl" denotes a straight-chain or branched hydrocarbon groups having 2 to 4, 6, 8 or 10 carbon atoms and one or more, e.g. 2 or 3, carbon- carbon double bonds in any position, preferably one carbon-carbon double bond, e.g. vinyl, allyl (2-propen-1 -yl), 1 -propen-1 -yl, 2-propen-2-yl, methallyl (2-methylprop-2-en- 1 -yl), 2-buten-1 -yl, 3-buten-1 -yl, 2-penten-1 -yl, 3-penten-1 -yl, 4-penten-1 -yl, 1 -methyl- but-2-en-1 -yl, 2-ethylprop-2-en-1 -yl, hexenyl, heptenyl or octenyl.

The term "C2-C10 alkynyl" denotes a straight-chain or branched hydrocarbon groups having 2 to 4, 6, 8 or 10 carbon atoms and one or more, e.g. 2 or 3, carbon- carbon triple bonds in any position, preferably one carbon-carbon triple bond, for ex- ample ethynyl, 1 -propynyl, 2-propynyl, 1 -butynyl, 2-butynyl, 3-butynyl, 1 -methyl-2- propynyl, 1 -pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1 -methyl-2-butynyl, 1 -methyl- 3-butynyl, 2-methyl-3-butynyl, 3-methyl-1 -butynyl, 1 ,1 -dimethyl-2-propynyl, 1 -ethyl-2- propynyl, 1 -hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1 -methyl-2-pentynyl, 1 -methyl-3-pentynyl, 1 -methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-1 -pentynyl, 3-methyl-4-pentynyl, 4-methyl-1 -pentynyl, 4-methyl-2-pentynyl, 1 ,1 -dimethyl-2-butynyl, 1 ,1 -dimethyl-3-butynyl, 1 ,2-dimethyl-3-butynyl, 2,2-dimethyl- 3-butynyl, 3,3-dimethyl-1 -butynyl, 1 -ethyl-2-butynyl, 1 -ethyl-3-butynyl, 2-ethyl-3-butynyl and 1 -ethyl-1 -methyl-2-propynyl, heptynyl, octynyl, nonynyl or decynyl.

The term "C3-C7-cycloalkyl" as used herein denotes in each case a monocyclic radical having from 3 to 7 carbon atoms as ring members, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

The term "3- to 7-membered heterocyclyl" includes 3-, 4-, 5-, 6- or 7-membered, in particular 5-, 6- or 7-membered monocyclic heterocyclic non-aromatic radicals, which may be saturated or unsaturated. The monocyclic heterocyclic non-aromatic radicals usually comprise 1 , 2, 3 or 4 heteroatoms, in particular 1 or 2 heteroatoms selected from N, O and S as ring members, where S-atoms as ring members may be present as S, SO or SO2. Examples of saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered heterocyclic radicals comprise saturated or unsaturated, non-aromatic heterocyclic rings, such as oxiranyl, oxetanyl, thietanyl, thietanyl-S-oxid (S-oxothietanyl), thietanyl-S- dioxid (S-dioxothiethanyl), pyrrolidinyl, pyrazolinyl, imidazolinyl, pyrrolinyl, pyrazolinyl, imidazolinyl, tetrahydrofuranyl, dihydrofuranyl, 1 ,3-dioxolanyl, dioxolenyl, thiolanyl, S-oxothiolanyl, S-dioxothiolanyl, dihydrothienyl, S-oxodihydrothienyl, S-dioxodihydro- thienyl, oxazolidinyl, isoxazolidinyl, oxazolinyl, isoxazolinyl, thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazolidinyl, oxathiolanyl, piperidinyl, piperazinyl, pyranyl, dihydro- pyranyl, tetrahydropyranyl, 1 ,3- and 1 ,4-dioxanyl, thiopyranyl, S-oxothiopyranyl, S-dioxothiopyranyl, dihydrothiopyranyl, S-oxodihydrothiopyranyl, S-dioxodihydro- thiopyranyl, tetrahydrothiopyranyl, S-oxotetrahydrothiopyranyl, S-dioxotetrahydro- thiopyranyl, morpholinyl, thiomorpholinyl, S-oxothiomorpholinyl, S-dioxothiomorpholinyl, thiazinyl and the like. Examples for heterocyclic rings also comprising 1 or 2 carbonyl groups as ring members comprise pyrrolidin-2-onyl, pyrrolidin-2,5-dionyl, imidazolidin-

2- onyl, oxazolidin-2-onyl, thiazolidin-2-onyl and the like.

The term "C- or N-bound monocyclic 5- or 6-membered heteroaryl" (also referred to as C- or N-bound monocyclic 5- or 6-membered hetaryl) denotes a monocyclic 5- or 6-membered heteroaromatic radical comprising as ring members in addition to carbon atom(s) in general 1 , 2, 3 or 4 heteroatoms independently of each other selected from N, O and S. C-bound heteroaryl denotes a heteroaromatic radical which is bound via a carbon ring atom to the skeleton while N-bound heteroaryl denotes a heteroaromatic radical which is bound via a nitrogen ring atom to the skeleton.

Examples of 5- or 6-membered heteroaromatic radicals include 2-pyridinyl,

3- pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl,

5-pyrimidinyl, 2-pyrazinyl, 1 ,3,5-triazin-2-yl, 1 ,2,4-triazin-3-yl, 2-furyl, 3-furyl, 2-thienyl,

3- thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl,

4- isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl,

4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 1 ,2,4-oxadiazol-3-yl, 1 ,2,4-oxadiazol-5-yl, 1 ,2,4-thiadiazol-3-yl, 1 ,2,4-thiadiazol-5-yl, 1 ,2,4-triazol-3-yl, 1 ,3,4-oxadiazol-2-yl, 1 ,3,4-thiadiazol-2-yl and 1 ,3,4-triazol-2-yl and 1 H- or 2H-tetrazolyl. Preference is given to 5- to 6-membered heteroaryl radicals having one or two heteroatoms independently of each other selected from of N, O and S, for example furyl, thienyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, imidazolyl, pyridyl, pyrimidinyl, pyridazinyl and pyrazinyl.

With regard to the term "a 5-, 6- or 7-membered carbocyclic ring fused to the first ring" means a hydrocarbon ring which shares two adjacent carbon atoms with the first ring, where these two adjacent carbon atoms are connected by a C=C-bond, and where the second ring may contain a further double bound or may be an aromatic ring, examples being cyclopentene, cyclopentadiene, cyclohexene, 1 ,3-cyclohexadiene, 1 ,4-cyclohexadiene, cycloheptene, 1 ,3-cycloheptadiene, 1 ,4-cycloheptadiene and benzene. The fused 5-, 6- or 7-membered carbocycle may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members. With regard to the term "a 5-, 6- or 7-membered heterocyclic ring fused to the first ring" means a heterocyclic ring which comprises as ring members in addition to carbon atom(s) 1 , 2, 3 or 4 heteroatoms independently of each other being selected from nitrogen, oxygen and sulfur, where sulfur may be present as S, S(O) or S(02), where the 5-, 6- or 7-membered heterocyclic ring shares two adjacent carbon atoms with the first ring, where these two adjacent carbon atoms are trigonal carbon atoms (i.e. sp ² hybridized C-atoms), and where the second ring may contain a further double bound or may be an aromatic ring. Examples for fused 5-, 6- or 7-membered heterocyclic rings having up to four heteroatoms from the group of nitrogen, oxygen and sulfur are

2,3-dihydrofuran, 2,3-dihydrothiophen, 3,4-dihydrofuran, 3,4-dihydrothiophen,

2.3- pyrroline, 3,4-pyrroline 3,4-pyrazoline, 4,5-imidazoline, 4,5-oxazoline,

4.5- thiazoline, 1 ,3-dioxole, 3,4-dihydropyran, 3,6-dihydropyran, 3,4-dihydrothiopyran,

3.6- dihydrothiopyran, 1 ,2,3,4-tetrahydropyridine, 1 ,2,3,6-tetrahydropyridine,

1 ,2,3,4-tetrahydropyrimidine, 1 ,2,3,4-tetrahydropyrazine, 2,3-dihydro-[1 ,4]-dioxin, 2,3-dihydro-[1 ,4]-oxathiin, 2,3-dihydro-[1 ,4]-dithiin, 3,4-dihydro-2H-[1 ,4]-oxazin,

3.4- dihydro-2H-[1 ,4]-thiazin, 4H-1 ,3-dioxine, 4H-1 ,3-dithiin, 4H-1 ,3-oxathiin,

4H-1 ,3-oxazin, 4H-1 ,3-thiazin, furane, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, 1 ,2,3-triazole, 1 ,2,3-oxadiazole, 1 ,2,3-thiadiazole, 1 ,2,5-oxadiazole, 1 ,2,5-thiadiazole, pyridine, pyrimidine, pyrazine, pyridazine, 1 ,2,4-triazine and

1 ,2,3,4-tetrazine. The fused-on heterocyclic ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members.

The term "N-bound, 5- or 6- membered saturated nitrogen heterocycle" denotes a saturated heteromonocyclic radical containing one nitrogen atom as a ring member, which is attached to the remainder of the molecule, and optionally one or more, e.g. 1 or 2 further heteroatoms such as O, S or N as ring member, having a total of 5 or 6 ring member atoms. Examples for "N-bound, 5- or 6-membered saturated nitrogen hetero- cycles" are pyrrolidin-1 -yl, piperidin-1 -yl, piperazin-1 -yl, 4-methylpiperazin-1 -yl, mor- pholin-4-yl, thiomorpholin-4-yl, imidazolidin-1 -yl, oxazolidin-3-yl or thiazolidin-3-yl, especially pyrrolidin-1 -yl, piperazin-1 -yl, 4-methylpiperazin-1 -yl, piperidin-1 -yl and mor- pholin-4-yl.

Hereinafter particular embodiments of the compounds according to the present invention are explained by giving particular or preferred meanings of the variables R ¹ , R ^a , R2, R ^2a , R ^2b , R ^2c , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , X and Y. It is well understood by a skilled person that any particular or preferred meaning of any of these variables can be combined with the general definition or a particular or preferred meaning of any other variables, e.g. any definition of a particular or preferred embodiment of R ¹ can be combined with any particular or preferred meaning of R ² .

According to a first embodiment, the present invention relates to the compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein X is O. These compounds are hereinafter also denominated as dihydrobenzoxazines or compounds of the formula 1.1 .

According to a second embodiment, the present invention relates to the compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein X is S. These compounds are hereinafter also denominated as dihydroben- zothiazines or compounds of the formula 1.2.

According to a third embodiment, the present invention relates to the compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein X is S=0. These compounds are hereinafter also denominated as dihydrobenzothiaz- ine oxides or compounds of the formula 1.3.

According to a fourth embodiment, the present invention relates to the compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein X is S(=0)2. These compounds are hereinafter also denominated as dihydro- benzothiazine dioxides or compounds of the formula 1.4.

Particular preference is given to the first embodiment, i.e. to compounds of the formula 1.1 . Likewise, particular preference is given to the second embodiment, i.e. to compounds of the formula 1.2.

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ¹ is a C-bound bicyclic radical, which is unsubsti- tuted or which carries 1 , 2, 3 or 4 radicals R ^1a which are identical or different or carries 1 radical R ^1b and 0, 1 , 2 or 3 identical radicals R ^1a .

The radicals R ^1a , if present, have the aforementioned meanings and are preferably selected from halogen, OH, SH, CN, NO2, C1-C4 alkyl, especially methyl, ethyl or isopropyl, C2-C4 alkenyl, especially ethenyl, C2-C4 alkynyl, especially ethynyl, C1-C4- alkoxy, especially methoxy or ethoxy, Ci-C4-alkylthio, especially methylthio or ethylthio, fluorinated Ci-C2-alkyl, especially difluoromethyl or trifluoromethyl, SF ₅ , fluorinated Ci-C2-alkoxy, especially difluoromethoxy or trifluoromethoxy, NH2, hydroxy-Ci-C4-alkyl, especially hydroxym ethyl, 1-hydroxyethyl or 2-hydroxyethyl, Ci-C4-alkoxy-Ci-C4-alkyl, especially methoxymethyl, ethoxymethyl, 1 -methoxyethyl or 2-methoxyethyl, C(0)R ³ , especially acetyl or propionyl, NR ⁴ R ⁵ , especially methylamino, dimethylamino,

2-methoxyethylamino, N(CH3)(CH2CH20CH3), (carboxymethyl)amino or (carboxy- methyl)(methyl)amino, N(OR ⁶ )R ⁷ , especially (methoxy)(methyl)amino, and C(0)OR ⁸ , especially methoxycarbonyl, ethoxycarbonyl. Especially, the radicals R ^1a , if present, are selected from the group consisting of halogen, in particular fluorine, chlorine or bro- mine, CN (= cyano), NO2 (nitro), OH, SH, Ci-C4-alkyl, in particular methyl, ethyl or iso- propyl, Ci-C4-alkoxy, in particular methoxy or ethoxy, NH2, NR ⁴ R ⁵ , in particular

NH(CH3), N(CH3)2, methoxyethylamino, (carboxymethyl)amino or (carboxymethyl)- methylamino, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, SF ₅ , fluorinated Ci-alkoxy, in particular difluoromethoxy or trifluoromethoxy and N(OR ⁶ )R ⁷ , especially (methoxy)(methyl)amino.

The radical R ^1b , if present, has the aforementioned meanings and is prefereably selected from phenyl, 5-membered heteroaryl comprising as ring members in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms selected from N, O and S, 6-membered heteroaryl comprising as ring members in addition to carbon atom 1 , 2 or 3 nitrogen atoms as ring members and 5-, 6- or 7-membered saturated or unsaturated heterocyclyl comprising in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms selected from N, O, S as ring members, where S-atoms as ring members may be present as S, SO or SO2, wherein phenyl, 5-memberd heteroaryl, 6-membered heteroaryl and 5- to 7-membered heterocyclyl are unsubstituted or substituted by 1 , 2 or 3 radicals R ^1c . 5-membered het- eroaryl and 5- to 7-memberd heterocyclyl can be bound via a carbon or nitrogen atom to the remainder of the molecule.

In particular, R ^1b , if present, is phenyl, which is unsubstituted or substituted by 1 or 2 identical or different radicals R ^1c . According to another embodiment, in particular R ^1b , if present, is 5-membered heteroaryl comprising as ring members in addition to carbon atoms 1 or 2 heteroatoms selected from N, O and S wherein heteroaryl is unsubstituted or substituted by 1 or 2 identical or different radicals R ^1c . Preferred examples for 5-membered heteroaryl are furyl, thienyl, pyrazolyl, imidazol, oxazolyl, thiazolyl, pyrrolyl and isoxazolyl. Likewise, in particular R ^1b , if present, is 6-membered heteroaryl comprising as ring members in addition to carbon atoms 1 or 2 nitrogen atom, wherein heteroaryl is unsubstituted or substituted by 1 or 2 identical or different radicals R ^1c . A preferred example for 6-membered heteroaryl is pyridyl. According to another embodiment, in particular, R ^1b , if present is 5-, 6- or 7-membered saturated heterocyclyl comprising in addition to carbon atoms 1 or 2 heteroatoms selected from N, O, S as ring members, where S-atoms as ring members may be present as S, SO or SO2, and wherein heterocyclyl is unsubstituted or substituted by 1 or 2 identical or different radicals R ^1c . Preferred examples for 5-, 6- or 7-membered saturated heterocyclyl are pyr- rolidinyl, thiomorpholinyl and morpholinyl.

R ^1c has one of the meanings given above and is preferably halogen, cyano, nitro, OH, SH, Ci-C ₄ -alkyl, Ci-C ₄ -alkoxy, NH ₂ , NR ⁴ R ⁵ , fluorinated Ci-alkyl, SF ₅ , fluorinated Ci-alkoxy, and C(0)NR ⁶ R ⁷ .

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ¹ is a C-bound bicyclic radical having one of the formulae R1 -0, R1 -1 , R1 -2 or R1 -3

*

(R1 -0) (R1 -1 )

(R1 -2)

(R1 -3) where ^* indicates the point of attachment to the sulfonyl group;

A is O, S, NH or N(Ci-C ₄ -alkyl);

B is N or CH;

B' is N or CH;

D, D' and D" are independently of each other selected from N and C-R ^D ;

E, E' and E" are independently of each other selected from N and C-R ^E ;

G is N or C-R ^G ;

L, L' and L" are independently of each other selected from N and C-R ^L ; n is 0, 1 or 2;

M is O, S, S(0), S(0) ₂ , N-R ^M1 or C(R ^M2 R ^M3 );

Q is O, S, S(0), S(0) ₂ , N-R« ¹ or C(R ^Q2 R ^Q3 );

T is O, S, S(0), S(0) ₂ , N-R ^T1 or C(R ^T2 R ^T3 ); U is O, S, S(0), S(0) ₂ , N-R ^U or C(R ^U2 R ^U3 );

R ^D is selected from the group consisting of hydrogen and the radical R ^1a ;

R ^E is selected from the group consisting of hydrogen and the radical R ^1a ;

R ^G is selected from the group consisting of hydrogen and the radical R ^1a ;

R ^L is selected from the group consisting of hydrogen and the radical R ^1a ; R ^M1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated C1-C2- alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C2-C6-alkenyl, C2-C6- alkynyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , or,

if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^M1 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^M1 together with R ^T1 or together with R ^T2 may form a bond;

R ^M2 is selected from the group consisting of hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, fluorinated Ci-C2-alkoxy, Ci-C4-alkylthio, fluorinated Ci-C ₂ -alkylthio, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ³ and NR ⁴ R ⁵ , or if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^M2 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^M2 together with R ^T1 or together with R ^T2 may form a bond;

R ^M3 is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl and C(0)R ³ ; R ^Q1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated C1-C2- alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C2-C6-alkenyl, C2-C6- alkynyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , or,

if n is 1 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^Q1 together with R ^M1 or together with R ^M2 may form a bond, or

if n is 1 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^Q1 together with R ^T1 or together with R ^T2 may form a bond;

R ^Q2 is selected from the group consisting of hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, fluorinated Ci-C2-alkoxy, Ci-C4-alkylthio, fluorinated Ci-C ₂ -alkylthio, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ³ and NR ⁴ R ⁵ , or if n is 1 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^Q2 together with R ^M1 or together with R ^M2 may form a bond, or

if n is 1 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^Q2 together with R ^T1 or together with R ^T2 may form a bond;

R ^Q3 is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl and C(0)R ³ ; R ^T1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated C1-C2- alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C2-C6-alkenyl, C2-C6- alkynyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , or,

if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^T1 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^T1 together with R ^M1 or together with R ^M2 may form a bond, or

if U is N-R ^U1 or C(R ^U2 R ^U3 ), R ^T1 together with R ^U1 or together with R ^U2 may form a bond;

R ^T2 is selected from the group consisting of hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, fluorinated Ci-C2-alkoxy, Ci-C4-alkylthio, fluorinated Ci-C ₂ -alkylthio, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ³ and NR ⁴ R ⁵ , or if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^T2 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^T2 together with R ^M1 or together with R ^M2 may form a bond, or

if U is N-R ^U1 or C(R ^U2 R ^U3 ), R ^T2 together with R ^U1 or together with R ^U2 may form a bond;

R ^T3 is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, C2-C6-alkenyl, C2-C6-alkynyl and a radical C(0)R ³ ; R ^U1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated C1-C2- alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C2-C6-alkenyl, C2-C6- alkynyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , or,

if T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^U1 together with R ^T1 or together with R ^T2 may form a bond,

R ^U2 is selected from the group consisting of hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, fluorinated Ci-C2-alkoxy, Ci-C4-alkylthio, fluorinated Ci-C ₂ -alkylthio, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ³ and NR ⁴ R ⁵ , or if T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^U2 together with R ^T1 or together with R ^T2 may form a bond,

R ^U3 is selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl and C(0)R ³ ; where one or two of the moieties C(R ^M2 R ^M3 ), C(R ^Q2 R ^Q3 ), C(R ^T2 R ^T3 ) and C(R ^U2 R ^U3 ) may also be C=0 or C=S; or the moiety -M-(Q) _n -T-U- together with the carbon atoms to which it is attached forms a fused 1 ,2,5-thiadiazole ring or a 1 ,2,5-oxadiazole ring; where R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are as defined above,

provided that in formula R1 -2 and R1 -3 two or more adjacent ring members M, Q, T and U are neither oxygen nor sulfur at the same time.

R ^D , R ^E , R ^G and R ^L are, independently of each other, preferably selected from the group consisting of hydrogen, halogen, OH, SH, CN, NO2, C≡C-CN, d-Ce-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C ₄ -alkoxy- Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ .

Preferably, the radical R ¹ is a radical of the formulae R1 -1 or R1 -2.

More preferably, R ¹ is C-bound bicyclic comprising a first ring which is a benzene ring or a 5- or 6-membered heteroaromatic ring having either 1 , 2 or 3 nitrogen atoms as heteroatom ring members or 1 oxygen or 1 sulfur atom and 0, 1 or 2 nitrogen atoms as heteroatom ring members, and a second ring, which is fused to the first ring, where the second ring is a 5-, 6- or 7-membered carbocyclic ring or a 5-, 6- or 7-membered heterocyclic ring having 1 , 2 or 3 heteroatom ring members selected from oxygen, sul- fur and nitrogen, where sulfur atoms, if present, may be present as S, S(O) or S(0)2 and where the saturated or unsaturated carbocyclic or heterocyclic second ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members, provided that at least one of the first or second ring is a heterocyclic ring, wherein C-bound bicyclic heterocyclyl is unsubstituted or carries 1 or more, e.g. 1 , 2, 3 or 4 radicals R ^1a which are identical or different. In this embodiment, R ¹ is also referred to as C-bound bicyclic heterocyclyl.

Amongst the compounds of the present invention, where R ¹ in the formulae I, 1.1 , 1.2, 1.3 or 1.4 is C-bound bicyclic heterocyclyl, preference is given to those, wherein R ¹ is a radical of the formula R1 -1. In particular, R ¹ is a radical R1 -1 , wherein D is C-R ^D , E is C-R ^E , G is C-R ^G and L is C-R ^L wherein R ^D , R ^E , R ^G and R ^L independently of each other are as defined above and in particular have one of the preferred meanings. In this embodiment the six-membered second ring which is fused to the 5-membered first ring is a benzene ring.

Likewise, preference is given to those radicals R1 -1 , wherein one or two of the ring members D, E, G or L are nitrogen and the other ring members D, E, G or L are selected from C-R ^D , C-R ^E , C-R ^G and C-R ^L wherein R ^D , R ^E , R ^G and R ^L are as defined above. In this embodiment, the 6-membered second ring which is fused to the

5-membered first ring is a 6-membered hetaryl ring comprising one or two nitrogen atoms as ring members. The 6-membered second ring which is fused to the

5-membered first ring is in particular a pyridine ring.

Examples are the radicals of the formulae R1 -1 a, R1 -1 b, R1 -1 c, R1 -1 d and -1 e, which individually represent particular embodiments for R ¹ in formula I:

(R1 -1 c) (R1 -1 d) (R1 -1 e) wherein

A and B are as defined above,

k is 0, 1 or 2 and

R has one of the meanings indicated for R ^1a , preferably is selected from halogen, OH, SH, CN, N0 ₂ , C≡C-CN, d-Ce-alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, Ci-C ₆ - alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , wherein R ³ , R ⁴ and R ⁵ have the aforementioned meanings and in particular have one of the preferred meanings.

In the formulae R1 -1 a, R1 -1 b, R1 -1 c, R1 -1 d and R1 -1 e, the radical R, if present, is more preferably selected from halogen, in particular fluorine, chlorine, bromine or iodine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy, Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy. If k is 2, R may be the same or may be different. Preferably, k is 0 or 1.

More preferably, R ¹ is a radical of the formulae R1-1a.1, R1-1a.2, R1-1a.3, R1-1a.4, R1-1a.5, R1-1a.6, R1-1b.1, R1-1c.1 orR1-1d.1:

(R1-1b.1) (R1-1C.1) (R1-1d.1) wherein

^* indicated the point of attachment to the sulfonyl group

k isO, 1 or2;

R ^* is hydrogen or Ci-C4-alkyl; and

R has one of the meanings indicated for R ^1a , preferably is selected from halogen, OH, SH, CN, d-Ce-alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, Ci-C ₆ -alkoxy, Ci-C ₆ - alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ ; wherein R ³ , R ⁴ and R ⁵ have the aforementioned meanings and in particular have one of the preferred meanings.

Preferably, R ^* is hydrogen or Ci-C2-alkyl, especially hydrogen or methyl.

Preferably, R, if present, is selected from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy. If k is 2, R may be the same or may be different. Preferably, k is 0 or 1. Examples for a radical R1-1a.1 are benzofuran-2-yl, 5-methylbenzofuran-2-yl, 6-methylbenzofuran-2-yl, especially benzofuran-2-yl.

Examples for a radical R1-1a.2 are benzo[b]thiophen-2-yl,

5-methylbenzo[b]thiophen-2-yl, 6-methylbenzo[b]thiophen-2-yl, in particular benzo[b]thiophen-2-yl, especially benzo[b]thiophen-2-yl and

5-methylbenzo[b]thiophene-2-yl.

Examples for a radical R1-1a.3 are 1 H-indol-2-yl, 1-methyl-1 H-indol-2-yl,

5- methyl-1H-indol-2-yl, 1,5-dimethyl-1H-indol-2-yl, 6-methylindol-2-yl and 1,6-dimethyl- 1 H-indol-2-yl, especially 1 H-indol-2-yl, 1-methyl-1H-indol-2-yl and 5-methyl-1 H-indol- 2-yl.

An example for a radical R1-1a.4 is benzoxazol-2-yl.

Examples for radicals R1-1-a.5 are benzothiazol-2-yl, 5-cyanobenzothiazol-2-yl,

6- cyanobenzothiazol-2-yl, 5-methylbenzothiazol-2-yl, 6-methylbenzothiazol-2-yl, 5-methoxybenzothiazol-2-yl, 6-methoxybenzothiazol-2-yl, 5-fluorobenzothiazol-2-yl, 6-fluorobenzothiazol-2-yl, 5-chlorobenzothiazol-2-yl, 6-chlorobenzothiazol-2-yl, 5,6-difluorobenzothiazol-2-yl and 5,6-dichlorobenzothiazol-2-yl.

Examples for a radical R1 -1a.6 are 1 H-benzimidazol-2-yl and 1-methyl-1H- benzimidazol-2-yl

Examples for a radical R1-1b.1 are 7-chlorothieno[3,2-c]pyridin-2-yl and thieno[3,2-c]pyridin-2-yl.

Examples for a radical R1-1c.1 are thieno[3,2-b]pyridin-2-yl and

7- chlorothieno[3,2-b]pyridin-2-yl.

An example for a radical R1-1d.1 is thieno[2,3-b]pyridin-2-yl.

An especially preferred embodiment relates to compounds of the formula (I), to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ¹ is a radical of the formula R1-1a. In particular, R ¹ is a radical of the formulae R1-1a.1, R1-1a.2, R1-1a.3, with particular preference givewn to R1-1a.2, especially benzo[b]thiophen- 2-yl.

According to another preferred embodiment, the radical R ¹ is a bicyclic heterocy- clyl radical of the formulae R1-2 or R1-3 with n being 1. Preferred embodiments of the radicals of the formulae R1 -2 or R1 -3 with n being 1 are the radicals of the formulae R1-2a, R1-3a, R1-2b, R1-3b, R1-2c, R1-3c, R1-2d, R1-3d, R1-2e, R1-3e, R1-2f and R1-3f, which individually represent particular embodiments for R ¹ in formula I:

(R1-3a) where

^* indicated the point of attachment to the sulfonyl group;

k is O, 1 or 2,

R has one of the meanings indicated for R ^1a ;

where

A, B, M, Q, T, U, R ^M2 , R ^M3 , R« ² , R« ³ , R ^T2 , R ^T3 , R ^U2 and R ^U3 are as defined above; provided that at least one of M, Q, T and U in formulae R1 -2a, R1 -2c, R1 -2d, R1 -3a, R1 -3c, R1 -3d, is selected from O, S, S(O), S(0) ₂ , N-R ^# , where R ^# , depending on its position, has one of the meanings given for R ^M1 , R ^Q1 , R ^T1 or R ^U1 , respectively. In the formulae R1-2a or R1-3a, R ^Q3 , R ^Q2 , R ^T2 and R ^T1 in each case are different from hydrogen, when R ² is phenyl or C- or N-bound monocyclic 5- or 6-membered het- eroaryl, wherein phenyl and monocyclic 5- or 6-membered heteroaryl carry a CN radical and may additionally carry 1 , 2 or 3 radicals R ^2a .

In the formulae R1-2a, R1-3a, R1-2b, R1-3b, R1-2c, R1-3c, R1-2e and R1-3e, M is preferably O, S, N-R ^M1 or C(R ^M2 R ^M3 ), wherein R ^M1 , R ^M2 and R ^M3 are as defined above.

In the formulae R1-2a, R1-3a, R1-2b, R1-3b, R1-2d, R1-3d, R1-2fand R1-3f, U is preferably O, S, N-R ^U1 or C(R ^U2 R ^U3 ), wherein R ^U1 , R ^U2 and R ^U3 are as defined above.

In the formulae R1-2c, R1-3c, R1-2e and R1-3e, T is preferably N-R ^T1 or

C(R ^T2 R ^T3 ), wherein R ^T1 , R ^T2 and R ^T3 are as defined above.

In the formulae R1-2d and R1-3d, R1-2f and R1-3f, Q is preferably N-R ^Q1 or C(R ^Q2 R ^Q3 ), wherein R ^Q1 , R ^Q2 and R ^Q3 are as defined above.

In the formulae R1-2a, R1-3a, R1-2b, R1-3b, R1-2c, R1-3c, R1-2d, R1-3d, R1-2e, R1-3e, R1-2f and R1-3f, the radical R, if present, is preferably selected from halogen, cyano, N0 ₂ , NH ₂ , OH, SH, Ci-Cio-alkyl, C ₂ -Cio-alkenyl, C ₂ -Cio-alkynyl, C≡C-CN, Ci-C ₆ - alkoxy, Ci-C6-alkylthio, Ci-C6-alkylsulfonyl, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4- alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, fluorinated Ci-C ₂ -alkylthio, fluorinated Ci-C ₂ -alkylsulfonyl, C(0)R ³ , NR ⁴ R ⁵ , N(OR ⁶ )R ⁷ , C(0)NR ⁶ R ⁷ , C(0)OR ⁸ , and CHR ⁹ R ¹⁰ . More preferably, R, if present, is selected from halogen, in particular fluorine, chlorine or iodine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy, Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl ortrifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy. If k is 2, R may be the same or may be different. Preferably, k is 0 or 1. Amongst the compounds of the formula I, where R ¹ is a radical of the formulae R1-2 or R1-3 with n being 1 , a particular embodiment relates to compounds of the formula I, where R ¹ is a radical R1-2a or R1-2b.

Particularly preferred embodiments of the radicals of the formulae R1-2 or R1-3 with n being 1 are the radicals of the formulae R1-2a.1, R1-3a.1, R1-2a.2, R1-3a.2, R1-2a.3, R1-3a.3, R1-2a.4, R1-3a.4, R1-2a.5, R1-3a.5, R1-2a.6, R1-3a.6, R1-2a.7, R1-3a.7, R1-2a.8, R1-3a.8, R1-2a.9, R1-3a.9, R1-2a.10, R1-3a.10, R1-2a.11,

R1-3a.11, R1-2a.12, R1-3a.12, R1-2a.13, R1-3a.13, R1-2a.14, R1-3a.14, R1-2a.15, R1-3a.15, R1-2a.16, R1-3a.16, R1-2a.17, R1-3a.17, R1-2a.18, R1-3a.18, R1-2a.19, R1-3a.19, R1-2b.1, R1-3b.1, R1-2b.2, R1-3b.2, R1-2b.3, R1-3b.3, R1-2c.1, R1-3c.1, R1-2d.1, R1-3d.1, R1-2e.1, R1-3e.1, R1-2f.1 and R1-3f.1 , listed below, which individually represent particular embodiments for R ¹ in formula I:

(R1-2a.1) (R1-3a.1) (R1-2a.2)

(R1-3a.2) (R1-2a.3) (R1-3a.3)

(R1-2a.7) (R1-3a.7) (R1-2a.8)

R1-2a.15

R1-2a.17

R1-3a.16 R1-3a.17

indicated the point of attachment to the sulfonyl group;

is 0, 1 or 2, preferably 0 or 1 , where R may be the same or different, if k is 2; is 0, 1 or 2, preferably 0 or 1 , where R' may be the same or different, if m is 2; has one of the meanings indicated for R ^1a , preferably is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ¹³ and NR ¹⁴ R ¹⁵ , more preferably selected from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

has one of the meanings indicated for R ^1a , preferably is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , more preferably from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

R ^a , R ^b are independently of each other selected from the group consisting of hy- drogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S);

preferably hydrogen, methyl or ethyl or R ^a and R ^b together with the carbon atom to which they are attached form a carbonyl group;

R ^d , R ^e are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl, and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S);

preferably hydrogen, methyl or ethyl or R ^d and R ^e together with the carbon atom to which they are attached form a carbonyl group;

Ra, R ^h are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S),

preferably hydrogen, methyl or ethyl, or Rs and R ^h together with the carbon atom to which they are attached form a carbonyl group;

or one of the radicals R ^a , R ^b , R ^d , R ^e , Rs, R ^h may also be a radical selected from the group consisting of Ci-C4-alkoxy, fluorinated Ci-C2-alkoxy, C(0)R ³ and NR ⁴ R ⁵ , preferably C1-C2 alkoxy, especially methoxy or ethoxy, fluorinated Ci-alkoxy, especially difluoromethoxy or trifluoromethoxy, and NR ⁴ R ⁵ , especially NHC(0)Ci-C4-alkyl;

R ^c , R ^f , are independently of each other selected from the group consisting of hydrogen, Ci-C4-alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , preferably from the group consisting of hydrogen, methyl, ethyl, C(0)R ³ , in particular acetyl or propionyl, Ci-C2-alkylsulfonyl, such as methylsul- fonyl, C(0)NR ⁶ R ⁷ , in particular C(0)NH ₂ or C(0)N(CH ₃ ) ₂ , more preferably from the group consisting of hydrogen, Ci-C2-alkyl, C(0)R ³ , especially acetyl or propionyl and methylsulfonyl, in particular from the group consisting of hydrogen, methyl, ethyl, acetyl, propionyl and methylsulfonyl.

In the radicals R1 -2a.1 or R1 -3a.1 , R ^a , R ^b , R ^d and R ^e in each case are different from hydrogen, when R ² is phenyl or C- or N-bound monocyclic 5- or 6-membered heteroaryl, wherein phenyl and monocyclic 5- or 6-membered heteroaryl carry a CN radical and may additionally carry 1 , 2 or 3 radicals R ^2a . Amongst the compounds of the formula I, where R ¹ is a radical of the formulae R1 -2 or R1 -3 with n being 1 , a particular embodiment relates to compounds of the formula I, where R ¹ is selected from the radicals of the formulae R1 -2a and R1 -2b, in particular from the radicals of the formulae R1 -2a.3, R1 -2a.4, R1 -2a.10, R1 -2a.12, R1 -2a.14 and R1 -2b.2.

Examples for R ¹ being selected from radicals of the formulae R1 -2 with n being 1 are in particular 4-methyl-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl (radical R1 -2a.3), chroman-6-yl (radical R1 -2a.10), 2-oxo-2H-chromen-6-yl (radical R1 -2a.14), 4-methyl- 2-oxo-2H-chromen-6-yl (radical R1 -2a.14), 2-(2,2,2-trifluoroacetyl)-1 ,2,3,4-tetrahydro- isoquinolin-7-yl (R1 -2a.19) and 4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1 ,4]oxazin-7-yl (radical R1 -2b.2).

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein the radical R ¹ is a C-bound bicyclic heterocyclyl radi- cal of the formulae R1 -2 or R1 -3 with n being 0, in particular a radical of the formulae R1 -2g, R1 -3g, R1 -2h, R1 -3h, R1 -2i, R1 -3i, R1 -2k and R1 -3k, listed below, which individually represent preferred embodiments for R ¹ in formula I:

where

^* indicated the point of attachment to the sulfonyl group; k is 0, 1 or 2, in particular 0 or 1 , where R may be the same or different, if k is 2, R has one of the meanings indicated for R ^1a , preferably is selected from the group consisting of halogen, OH, SH, CN, N0 ₂ , C≡C-CN, Ci-C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C ₄ -alkoxy- Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and

NR ⁴ R ⁵ , in particular from the group consisting of hydrogen, halogen, especially fluorine, chlorine, bromine or iodine, CN, Ci-C ₄ -alkyl, especially methyl or ethyl, Ci-C ₄ -alkoxy, especially methoxy or ethoxy, Ci-C ₄ -alkylthio, especially methylthio or ethylthio, fluorinated Ci-alkyl, especially difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy, especially trifluoromethoxy;

T' in formulae R1 -2g and R1 -3g is O or S,

R ^M2 , R ^M3 indenpendently of each other are H or have one of the meanings indicated for R ^1a ;

R ^T1 , R ^T2 indenpendently of each other are H or have one of the meanings indicated for R ^1a ;

R ^U2 , R ^U3 indenpendently of each other are H or have one of the meanings indicated for R ^1a and

M, T and U, have the aforementioned meanings;

provided that at least one of M, T and U in formulae R1 -2h and R1 -3h is selected from O, S, S(O), S(0) ₂ and N-R ^# , where R ^# , depending on its position, has one of the meanings given for R ^M1 , R ^T1 or R ^U1 , respectively.

In the radical R1 -2h, if M and U are both oxygen and T is selected from CH ₂ , CHF and CF ₂ , R ² is different from phenyl or C- or N-bound monocyclic 5- or

6-membered heteroaryl, wherein phenyl and monocyclic 5- or 6-membered heteroaryl carry a CN radical and may additionally carry 1 , 2 or 3 radicals R ^2a .

In this embodiment, R ^M1 , R ^T1 and R ^U1 , independently of each other, are in particular selected from the group consisting of hydrogen, Ci-C ₄ -alkyl, especially methyl or ethyl, fluorinated Ci-C ₂ -alkyl, especially difluoromethyl, trifluoromethyl, 2,2-difluoroethyl or 2,2,2-trifluoroethyl, C(0)-Ci-C ₄ -alkyl such as acetyl or propionyl, S(0) ₂ -Ci-C ₄ -alkyl, such as methylsulfonyl, fluorinated S(0) ₂ -Ci-C ₂ -alkyl such as trifluoromethylsulfonyl, and C(0)NH-Ci-C ₄ -alkyl.

In this embodiment, R ^M2 , R ^M3 , R ^T1 , R ^T2 , R ^U2 and R ^U3 , independently of each other, are in particular selected from the group consisting of hydrogen, Ci-C ₄ -alkyl, especially methyl or ethyl or fluorinated Ci-C ₂ -alkyl.

In the formulae R1 -2g, R1 -3g, R1 -2h, R1 -3h, R1 -2i, R1 -3i, R1 -2k and R1 -3k, M is preferably O, S, N-R ^M1 or C(R ^M2 R ^M3 ), wherein R ^M1 , R ^M2 and R ^M3 are as defined above and preferably have one of the preferred meanings.

In the formulae R1 -2g, R1 -3g, R1 -2h, R1 -3h, R1 -2i, R1 -3i, R1 -2k and R1 -3k, T is preferably C(R ^T2 R ^T3 ), wherein R ^T2 and R ^T3 are as defined above. In the formulae R1-2g, R1-3g, R1-2h, R1-3h, R1-2i, R1-3i, R1-2k and R1-3k, U is preferably O, S, N-R ^U1 or C(R ^U2 R ^U3 ), wherein R ^U1 , R ^U2 and R ^U3 are as defined above and preferably have one of the preferred meanings.

Example of the radicals of the formulae R1-2g and R1-3g are the radicals of the formulae R1-2g.1, R1-3g.1, R1-2g.2 and R1-3g.2

Examples of the radical of the formulae R1-2h and R1-3h are the radicals of the formulae R1-2h.1, R1-3h.1, R1-2h.2, R1-3h.2, R1-2h.3, R1-3h.3, R1-2h.4, R1-3h.4, R1-2h.5, R1-3h.5, R1-2h.6, R1-3h.6, R1-2h.7, R1-3h.7, R1-2h.8, R1-3h.8, R1-2h.9, R1-3h.9, R1-2h.10, R1-3h.10, R1-2h.11, R1-3h.11, R1-2h.12, R1-3h.12, R1-2h.13, R1-3h.13, R1-2h.14 and R1-3h.14, with particular preference given to those of the formulae R1-2h.9, R1-2h.11, R1-2h.12 and R1-2h.13

-2h.1) -3h.1) -2h.2)

R1-2h.4 R1-2h.5 R1-2h.6

R1-3h.11 R1-2 2 R1-3 2

indicated the point of attachment to the sulfonyl group;

is 0, 1 or 2, preferably 0 or 1 ;

has one of the meanings indicated for R ^1a , preferably is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ¹³ and NR ¹⁴ R ¹⁵ , preferably selected from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

R ^b are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S)

preferably hydrogen, C1-C2 alkyl;

R ^e are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S),

preferably independently of each other selected from hydrogen, halogen, especially fluorine, Ci-C2-alkyl or R ^d and R ^e together with the carbon atom to which they are attached form a carbonyl group;

R ^h are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S), preferably independently of each other selected from hydrogen, Ci-C2-alkyl or Rs and R ^h together with the carbon atom to which they are attached form a carbonyl group;

or one of the radicals R ^a , R ^b , R ^d , R ^e , Rs, R ^h may also be a radical selected from the group consisting of Ci-C4-alkoxy, fluorinated Ci-C2-alkoxy, C(0)R ³ and NR ⁴ R ⁵ , preferably C1-C2 alkoxy, especially methoxy or ethoxy, fluorinated Ci-alkoxy, especially difluoromethoxy or trifluoromethoxy, and NR ¹⁴ R ¹⁵ , especially NHC(0)Ci-C4-alkyl; and R ^c , R ^f are independently of each other selected from the group consisting of hydrogen, Ci-C ₄ -alkyl, Ci-C ₂ -alkylsulfonyl, fluorinated Ci-C ₂ -alkylsulfonyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , preferably from the group consisting of hydrogen, methyl, ethyl,

C(0)R ³ , in particular acetyl or propionyl, Ci-C2-alkylsulfonyl, such as methylsul- fonyl, C(0)NR ⁶ R ⁷ , in particular C(0)NH ₂ or C(0)N(CH ₃ ) ₂ , more preferably from the group consisting of hydrogen, Ci-C2-alkyl, C(0)R ³ , especially acetyl or propionyl and methylsulfonyl, in particular from the group consisting of hydrogen, methyl, ethyl, acetyl, propionyl and methylsulfonyl;

Examples are 1 -methyl-2-oxoindolin-5-yl (radical of the formula R1 -2h.9), 2-oxoindolin- 5-yl (radical of the formula R1 -2h.9), 1 ,3-dimethyl-2-oxo-2,3-dihydro-1 H-benzo[d]- imidazol-5-yl (radical of the formula R1 -2h.1 1 ), 2-oxo-2,3-dihydro-1 H-benzo[d]imidazol- 5-yl (radical of the formula R1 -2h.1 1 ), 2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl (radical of the formula R1 -2h.12), and 2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl (radical of the formula R1 -2h.13).

According to another particularly preferred embodiment, the radical R ¹ is a radical of the formulae R1 -2h or R1 -3h,

where

M is O, S, N-R ^M1 or C(R ^M2 R ^M3 );

T is C(R ^T2 R ^T3 );

U is O, S, N-R ^U or C(R ^U2 R ^U3 );

R has one of the meanings indicated for R ^1a ;

k is O, 1 or 2; and where R ^M1 , R ^M2 , R ^M3 , R ^T2 , R ^T3 , R ^U1 , R ^U2 and R ^U3 are as defined above,

provided that one of M and U is different from O and S, further provided that at least one of M and U is selected from O, S and N-R ^M1 or N-R ^U1 , respectively; and that R ^T2 together with one of R ^M1 , R ^M2 , R ^U1 or R ^U2 forms a bond.

Particularly preferred embodiments of the radicals of the formulae R1 -2h or R1 -3h are the radicals of the formulae R1 -2h.15, R1 -3h.15, R1 -2h.16, R1 -3h.16, R1 -2h.17, R1 -3h.17, R1 -2h.18, R1 -3h.18, R1 -2h.19, R1 -3h.19, R1 -2h.20, R1 -3h.20, R1 -2h.21 , R1 -3h.21 , R1 -2h.22, R1 -3h.22, R1 -2h.23, R1 -3h.23, R1 -2h.24, R1 -3h.24, R1-2h.25, R1-3h.25, R1-2h.26, R1-3h.26, R1-2h.27, R1-3h.27, R1-2h.28 and R1-3h.28 listed below, which individually represent particular embodiments for R ¹ in formula I

(R1-2h.15) (R1-2h.16) (R1-2h.17)

(R1-2h.21) (R1-2h.22) (R1-2h.23)

(R1-3h.21) (R1-3h.22) (R1-3h.23)

(R1-2h.24) (R1-2h.26)

indicated the point of attachment to the sulfonyl group;

is 0 or 1 ;

is 0, 1 or 2, preferably 0 or 1 ;

has one of the meanings indicated for R ^1a , preferably is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , more preferably selected from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

has one of the meanings indicated for R ^1a , preferably is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , more preferably from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated

Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy; R' has one of the meanings indicated for R ^1a , preferably is selected from the group consisting of halogen, CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6- alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , more preferably hydrogen, Ci-C4-alky, especially methyl or ethyl;

R ^k is selected from the group consisting of hydrogen, Ci-C4-alkyl, C1-C2- alkylsulfonyl, fluorinated Ci-C ₂ -alkylsulfonyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , preferably hydrogen, Ci-C4-alkyl, especially methyl or ethyl; Preferred embodiments are the radicals of the formulae R1 -2h.20, R1 -2h.21 ,

R1 -2h.22, R1 -2h.23, R1 -2h.24 and R1 -2h.27. Particularly preferred examples are 1 -methyl-1 H-indol-5-yl (radical of the formula R1 -2h.20), 2-methylbenzo[d]oxazol-6-yl (radical of the formula R1 -2h.21 ), 2-methylbenzo[d]thiazol-6-yl (radical of the formula R1 -2h.22), 2-methyl-1 H-benzo[d]imidazol-6-yl (radical of the formula R1 -2h.23), 2-methylbenzo[d]oxazol-5-yl, (radical of the formula R1 -2h.24), and benzo[d]isoxazol- 5-yl (radical of the formula R1 -2h.27).

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ¹ is C-bound bicyclyl comprising a first ring which is a benzene ring and a second ring, which is fused to the first ring, where the second ring is a 5, 6 or 7 membered carbocyclic ring, where the saturated or unsaturated car- bocyclic second ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members, wherein C-bound bicyclyl is unsubstituted or carries 1 or more, e.g.1 , 2, 3, 4, 5, 6, 7 or 8, radicals R ^1a which are identical or different or 1 radical R ^1b and 0, 1 , 2, 3, 4, 5, 6, 7 or 8 identical or different radicals R ^1a . In this embodiment, R ¹ is a radical of the formula R1 -2, wherein D' is C-R ^D , E' is C-R ^E , L' is C-R ^L , M is CR ^M2 R ^M3 , T is

CR ^T2 CR ^T3 , U is CR ^U2 R ^U3 and Q, if present, is CR ^Q2 CR ^Q3 , with n = 0 or 1 or a radical of the formula R1 -3, where D" is C-R ^D , E" is C-R ^E , L" is C-R ^L , M is CR ^M2 R ^M3 , T is

CR ^T2 CR ^T3 , U is CR ^U2 R ^U3 and Q, if present, is CR ^Q2 CR ^Q3 , with n = 0 or 1. Examples are the radicals of the formulae R1 -2a.20, R1 -3a.20, R1 -2a.21 , R1 -3a.21 , R1 -2h.29 and given to R1 -2a.20, R1 -2a.21 and R1 -2h.29.

R1-2a.20 (R) _k — II A -W ^R1"3a - ²⁰

(R1 -2h.29) (R1 -3h.29) wherein

k is O, 1 or 2;

m is 0, 1 or 2;

p is 0, 1 , 2, 3, 4, 5, 6, 7 or 8; preferably 0, 1 , 2, 3 or 4;

q is 0, 1 , 2, 3, 4, 5 or 6; preferably 0, 1 , 2, 3 or 4

R has one of the meanings indicated for R ^1a ; and

R' has one of the meanings indicated for R ^1a .

In this embodiment, R, if present, is preferably Ci-C4-alkyl, such as methyl or ethyl, Ci-C4-alkoxy such as methoxy or ethoxy, Nhb or NR ⁴ R ⁵ with R ⁴ being hydrogen or Ci-C4-alkyl and R ⁵ being Ci-C4-alkyl. In this embodiment, R', if present, is preferably Ci-C4-alkyl, such as methyl or ethyl, Ci-C4-alkoxy such as methoxy or ethoxy, Nhb or NR ⁴ R ⁵ with R ⁴ being hydrogen or Ci-C4-alkyl and R ⁵ being Ci-C4-alkyl. In a preferred embodiment, R ¹ is naphthyl which is unsubstituted or carries one radical R ^1a .

Examples are naphtalen-1 -yl, (radical R1 -3a.20), naphthalene-2-yl (radical R1 -2a.20), 5-dimethylaminonaphthalen-2-yl (radical R1 -2a.21 ), 5,5,8,8-tetramethyl- 5,6,7,8-tetrahydronaphthalen-2-yl (radcial R1 -21 .a), 5,6,7,8-tetrahydronaphthalen-2-yl (radical R1 -21.a) and 2,3-dihydro-1 H-inden-5-yl (radical R1 -2h.29).

Preferred examples of radicals R ¹ are given in the following table A, which individually are particularly preferred embodiments of R ¹ in the compounds according to the present invention.

Table A:

In particular, R ¹ is selected from the group consisting of 2-benzo[b]thienyl, 1 -methyl-1 H-indol-5-yl, 2-methylbenzo[d]oxazol-5-yl, 2-methylbenzo[d]oxazol-6-yl and 2-methyl-benzo[d]thiazol-6-yl.

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is phenyl, which carries 1 , 2 or 3 radicals R ^2a which are identical or different or which carries 1 radical R ^2b and 0, 1 or 2 identical or different radicals R ^2a . The radical R ^2a may be located at any position of the phenyl ring. Amongst these compounds, those are preferred, wherein the carbon ring atom(s) which are located in the ortho position with respect to the point of attachment to the 2,3-dihydrobenzazine core of (I) do not carry a radical R ^2a . Preferably, one radical R ^2a is located in the para-position with respect to the point of attachment to the

2,3-dihydrobenzazine core of (I).

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is a 6-membered heteroaryl, which is unsubsti- tuted or which carries 1 , 2 or 3 radicals R ^2a which are identical or different or which carries 1 radical R ^2b and 0, 1 or 2 identical or different radicals R ^2a . 6-membered heteroaryl comprises as ring members in addition to carbon atoms preferablyl , 2 or 3 nitrogen atoms. Amongst these compounds, those are preferred, wherein the carbon ring atom(s) which are located in the ortho position with respect to the point of attachment to the 2,3-dihydrobenzazine core of (I) do not carry a radical R ^2a or a radical R ^2b . Preferably, one radical R ^2a or R ^2b , if present, is located in the para-position with respect to the point of attachment to the 2,3-dihydrobenzazine core of (I).

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is 5-membered C-bound heteroaryl, which is un- substituted or which carries 1 , 2 or 3 radicals R ^2a which are identical or different or carries 1 radical R ^2b and 0, 1 or 2 identical radicals R ^2a . 5-membered C-bound heteroaryl comprises as ring members in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms se- lected from N, O and S. Amongst these compounds, those are preferred, wherein the carbon ring atom(s) which are located in the ortho position with respect to the point of attachment to the phenyl core do not carry a radical R ^2a .

According to a further particular embodiment, the present invention relates to the compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is C-bound bicyclyl, which is unsubstituted or which carries 1 , 2 or 3 radicals R ^2a which are identical or different or carries 1 radical R ^2b and 0, 1 or 2 identical radicals R ^2a .

In these embodiments, the radicals R ^2a , if present, have the aforementioned meanings and are preferably selected from halogen, OH, SH, CN, NO2, C1-C4 alkyl, especially methyl, ethyl, isopropyl or tert-butyl, C2-C4 alkenyl, especially ethenyl, C2-C4 alkynyl, especially ethynyl, Ci-C4-alkoxy, especially methoxy or ethoxy, Ci-C4-alkylthio, especially methylthio or ethylthio, NH2, fluorinated Ci-C2-alkyl, especially difluoromethyl or trifluoromethyl, SF ₅ , fluorinated Ci-C2-alkoxy, especially difluoromethoxy or trifluoromethoxy, hydroxy-Ci-C4-alkyl, especially hydroxymethyl, 1 -hydroxyethyl or 2-hydroxyethyl, Ci-C4-alkoxy-Ci-C4-alkyl, especially methoxymethyl, ethoxymethyl,

1 - methoxyethyl or 2-methoxyethyl, C(0)R ³ , especially acetyl or propionyl, NR ⁴ R ⁵ , especially methylamino or dimethylamino, N(OR ⁶ )R ⁷ , especially meth- oxy(methyl)amino, and C(0)OR ⁸ ; especially methoxycarbonyl, ethoxycarbonyl or COOH. Especially, the radicals R ^2a , if present, are selected from the group consisting of halogen, in particular fluorine or chlorine, CN, NO2, OH, SH, Ci-C4-alkyl, in particular methyl, ethyl, isopropyl or tert-butyl, C2-C4 alkynyl, especially ethynyl, Ci-C4-alkoxy, in particular methoxy or ethoxy, NH2, NR ⁵ R ⁶ , in particular NH(CHs), or N(CHs)2,

N(OR ⁶ )R ⁷ , especially methoxy(methyl)amino, fluorinated Ci-alkyl, in particular di- fluoromethyl or trifluoromethyl, SF ₅ , fluorinated Ci-alkoxy, in particular difluoromethoxy or trifluoromethoxy. Particularly preferably, R ^2a is selected from the group consisting of halogen, OH, CN, methyl, methoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy and ethynyl.

In these embodiments, the radical R ^2b , if present, has the aforementioned mean- ings and is preferably selected from phenyl, 5-membered heteroaryl comprising as ring members in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms selected from N, O and S, 6-membered heteroaryl comprising as ring members in addition to carbon atom 1 , 2 or 3 nitrogen atoms as ring members and 5-, 6- or 7-membered saturated or unsaturated heterocyclyl comprising in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms se- lected from N, O, S as ring members, where S-atoms as ring members may be present as S, SO or S02, wherein phenyl, 5-memberd heteroaryl, 6-membered heteroaryl and 5- to 7-membered saturated and unsaturated heterocyclyl are unsubstituted or substituted by 1 , 2 or 3 radicals R ^2c . 5-membered heteroaryl and 5- to 7-memberd heterocyclyl can be bound via a carbon or nitrogen atom to the remainder of the molecule. In particular, R ^2b is 5- or 6-membered heteroaryl or 5- or 6-membered saturated heterocyclyl comprising as ring members in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms selected from N, O and S, in particular 1 nitrogen atom and 0, 1 , 2 or 3 further heteroatoms selected from N, O and S. Preferred examples include oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-5-yl, isoxazol-4-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5- yl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1 -pyrrolyl, 3-pyrrolyl, 3-pyrrolyl, imidazol-1 -yl, imidazol-

2- yl, imidazol-4-yl, pyrazol-1 -yl, pyrazol-3-yl, pyrazol-4-yl, 1 H-tetrazol-5-yl, morpholin-4- yl, thiomorpholin-4-yl, pyrrolidin-1 -yl, piperidin-1 -yl, piperazin-1 -yl and 4- methylpiperazin-1 -yl.

R ^2c has one of the meanings given above and is preferably halogen, cyano, nitro, OH, SH, Ci-C ₄ -alkyl, Ci-C ₄ -alkoxy, NH ₂ , NR ⁵ R ⁶ , fluorinated Ci-alkyl, SF ₅ , fluorinated Ci-alkoxy, and C(0)NR ⁷ R ⁸ .

According to a preferred embodiment, R ² in the formulae I, 1.1 , 1.2, 1.3 and 1.4 is a radical of the formula Ar2:

wherein # indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I),

X ¹ is N or CH;

X ² is N or C-R ²¹ ;

X ³ is N or C-R ²² ;

X ⁴ is N or C-R ²³ ;

X ⁵ is N or C-R ^23a

wherein R ²¹ , R ²² and R ²³ , independently of each other, are hydrogen or have one of the meanings given for R ^2a or where R ²² may also have one of the meanings given for R ^2b , provided that if X ¹ and X ⁵ are CH, X ² is C-R ²¹ , X ³ is C-R ²² and X ⁴ is C-R ²³ , at least one of R ²¹ , R ²² or R ²³ is different from H.

More preferably, R ² is selected from radicals of the formulae Ar2.1 , Ar2.2, Ar2.3, Ar2.4, Ar2.5, Ar2.6, Ar2.7, Ar2.8, Ar2.9, Ar2.10, Ar2.1 1 and Ar2.12,

Ar2.7 Ar2.8 Ar2.9

Ar2.10 Ar2.1 1 Ar2.12 wherein # indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I), and wherein R ²¹ , R ²² , R ²³ and R ^23a , independently of each other, are hydrogen or have one of the meanings given for R ^2a or where the radical R ²² may also have one of the meanings given for R ² .

An even more preferred embodiment of the invention relates to compounds of the formulae I, 1.1 , I.2, 1.3 and I.4, where R ² is a radical of the formulae Ar2.1 , Ar2.2, Ar2.3, Ar2.4, Ar2.5, Ar2.6, Ar2.7, Ar2.8, Ar2.9, Ar2.10, Ar2.1 1 , or Ar2.12, wherein the variables R ²¹ , R ²² , R ²³ and R ^23a , if present, individually or in particular in combination have the following meanings:

R ²¹ , if present, is selected from the group consisting of hydrogen, halogen, OH, CN, C1-C4 alkyl, especially methyl, ethyl or isopropyl, Ci-C4-alkoxy, especially meth- oxy or ethoxy, fluorinated Ci-C2-alkyl, especially difluoromethyl or trifluoromethyl, fluorinated Ci-C2-alkoxy, especially difluoromethoxy and trifluoromethoxy, hy- droxy-Ci-C4-alkyl, especially hydroxym ethyl, 1 -hydroxyethyl or 2-hydroxyethyl, and Ci-C4-alkoxy-Ci-C4-alkyl, especially methoxymethyl, ethoxymethyl,

1 -methoxyethyl or 2-methoxyethyl.

R ²² if present, is selected from the group consisting of hydrogen, halogen, OH , CN,

NH2, cyanomethyl, SF ₅ , C2-C4-ethynyl, especially ethynyl, C1-C4 alkyl, especially methyl, ethyl or isopropyl, Ci-C4-alkoxy, especially methoxy or ethoxy, C1-C4- alkylthio, especially methylthio or ethylthio, Ci-C4-alkylsulfonyl, especially methyl- sulfonyl, N(OR ⁷ )R ⁸ , especiallay methoxy((methyl)amino, tetrazolyl, fluorinated Ci-C2-alkyl, especially difluoromethyl, trifluoromethyl, fluorinated Ci-C2-alkoxy, especially difluoromethoxy and trifluoromethoxy, hydroxy-Ci-C4-alkyl, especially hydroxymethyl, 1 -hydroxyethyl or 2-hydroxyethyl, and Ci-C4-alkoxy-Ci-C4-alkyl, especially methoxymethyl, ethoxymethyl, 1 -methoxyethyl or 2-methoxyethyl and a radical R ^2b . R ^2b is preferably a 5-memberd C-bound heteroaryl comprising in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms independently of each other selected from O, S and N, especially tetrazolyl.

R ²³ , if present, is selected from the group consisting of hydrogen, halogen, OH, CN, C1-C4 alkyl, especially methyl, ethyl or isopropyl, Ci-C4-alkoxy, especially methoxy or ethoxy, fluorinated Ci-C2-alkyl, especially difluoromethyl or trifluoromethyl, fluorinated Ci-C2-alkoxy, especially difluoromethoxy and trifluoromethoxy, hy- droxy-Ci-C4-alkyl, especially hydroxym ethyl, 1 -hydroxyethyl or 2-hydroxyethyl, and Ci-C4-alkoxy-Ci-C4-alkyl, especially methoxymethyl, ethoxymethyl,

1 -methoxyethyl or 2-methoxyethyl.

R ^23a , if present, is selected from the group consisting of hydrogen and halogen, in par- ticular hydrogen and fluorine.

Particular embodiments of the invention relate to compounds of the formulae I,

1.1 , I.2, 1.3 or I.4, where R ² is a radical of the formulae Ar2.1 , Ar2.2, Ar2.3, Ar2.4, Ar2.5, Ar2.6, Ar2.7, Ar2.8, Ar2.9, Ar2.10, Ar2.1 1 , or Ar2.12, wherein the variables R ²¹ , R ²² , R ²³ and R ^23a , if present, individually or in particular in combination have the following meanings:

R ²¹ , if present, is selected from hydrogen, halogen, CN, OH, C1-C4 alkyl, especially methyl, ethyl or isopropyl, Ci-C4-alkoxy, especially methoxy or ethoxy, C1-C4- alkylthio, especially methylthio or ethylthio, fluorinated Ci-alkyl, especially di- fluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy, especially difluoro- methoxy or trifluoromethoxy;

R ²² , if present, is hydrogen, halogen, CN, NH2, OH, SF ₅ , C2-C4-ethynyl, especially

ethynyl, Ci-C4-alkyl, especially methyl, Ci-C4-alkoxy, especially methoxy, C1-C4- alkylsulfonyl, espcially methylsulfonyl, N(0-Ci-C4-alkyl)(Ci-C4-alkyl), especially, methoxy(methyl)amino, or 5-membered heteroaryl, comprising in addition to carbon atoms 1 , 2, 3 or 4 heteroatoms independently selected from O, S and N as ring members, especially 1 H-tetrazol-5-yl;

R ²³ , if present, is selected from hydrogen, halogen, OH, CN, C1-C4 alkyl, especially methyl, ethyl or isopropyl, Ci-C4-alkoxy, especially methoxy or ethoxy, C1-C4- alkylthio, especially methylthio or ethylthio, fluorinated Ci-alkyl, especially di- fluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy, especially difluoro- methoxy or trifluoromethoxy.

R ^23a , if present, is selected from the group consisting of hydrogen and halogen, in particular hydrogen and fluorine.

Special embodiments of the invention relate to compounds of the formulae 1, 1.1 ,

1.2, 1.3 or 1.4, where R ² is a radical of the formulae Ar2.1 , Ar2.2, Ar2.3, Ar2.4, Ar2.5, Ar2.6, Ar2.7, Ar2.8, Ar2.9, Ar2.10, Ar2.1 1 , or Ar2.12, in particular a radical of the formulae formulae Ar2.1 , Ar2.3, Ar2.4, Ar2.5 or Ar2.12, wherein the variables R ²¹ , R ²² , R ²³ and R ^23a , if present, individually or in particular in combination have the following mean- ings:

R ²¹ is selected from the group consisting of hydrogen, halogen, especially fluorine, OH, CN, methyl, methoxy, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy; R ²² is hydrogen, halogen, especially fluorine, CN, NH2, SF ₅ , ethynyl, methoxy, me- thylsulfonyl, methoxy(methyl)amino, tetrazolyl, trifluoromethyl or methyl;

R ²³ is selected from the group consisting of hydrogen, halogen, OH, CN, methyl, methoxy, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy. R ^23a if present, is selected from the group consisting of hydrogen and fluorine.

Preferred examples are: 4-methylphenyl, 4-cyanophenyl, pyridin-2-yl,

5- methylpyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-cyanopyridin-2-yl, pyridin-3-yl,

6- methylpyridin-3-yl, 6-cyanopyridin-3-yl, 6-fluoropyridin-3-yl, pyridin-4-yl,

2-methylpyridin-4-yl, 2-fluoropyridin-4-yl, 2 , 3-d if I uoro py rid i n-4-y I , pyrimdin-2-yl,

5-methylpyrimidin-2-yl, 5-cyanopyrimidin-2-yl, pyrimidin-5-yl, 2-methylpyrimidin-5-yl, 2-methoxypyrimidin-5-yl, 2-cyanopyrimidin-5-yl or 2-aminopyrimidin-5-yl.

A further preferred embodiment relates to compounds of the formula I, 1.1 , 1.2, 1.3 and I.4, where R ² is a 5-membered C-bound heteroaryl, which is unsubstituted or which carries 1 , 2 or 3 radicals R ^2a which are identical or different or which carries 1 radical R ^2b and 0, 1 or 2 identical or different radicals R ^2a . Amongst these compounds, preference is given to those compounds, wherein R ² in the formula (I) is a radical of the formulae

(Ar3) (Ar3')

wherein # indicates the point of attachment of R ² to the 2,3-dihydrobenzazine ring of (I).

Y is N or C-R ²⁴ ,

Y ¹¹ is N or C-R ²⁵ ,

Y ² is N or C-R ²⁶ ,

Y ³ is N or C-R ²⁷ ,

Y ⁴ is O, S or N-R ²⁸ ,

Y ¹⁴ is O, S or N-R ²⁹ ,

wherein R ²⁴ , R ²⁵ , R ²⁶ and R ²⁷ , independently of each other, are hydrogen or have one of the meanings given for R ^2a , where either R ²⁶ or R ²⁷ may also be a radical R ^2b , and wherein R ²⁸ and R ²⁹ are selected from the group consisting of hydrogen, cyano, NH2, OH, Ci-Cio-alkyl, in particular Ci-C4-alkyl, especially methyl, ethyl, isopropyl or tert- butyl, C2-Cio-alkenyl, in particular C2-C4-alkenyl, especially ethenyl or 3-propenyl, C2-Cio-alkynyl, in particular C2-C4-alkynyl, especially ethynyl or 3-propynyl, C1-C6- alkoxy, in particular Ci-C4-alkoxy, especially methoxy or ethoxy, hydroxy-C2-C6-alkyl, in particular hydroxy-C2-C4-alkyl, especially 2-ethoxyethyl, Ci-C4-alkoxy-C2-C4-alkyl, especially methoxymethyl, ethoxymethyl, 1 -methoxyethyl or 2-methoxyethyl, fluorinated Ci-C2-alkyl, especially difluoromethyl or trifluoromethyl, fluorinated Ci-C2-alkoxy, especially difluoromethoxy or trifluoromethoxy, C(0)R ³ , in particular acetyl or propionyl, NR ⁴ R ⁵ , especially methylamino or dimethylamino, and C(0)OR ⁸ , especially COOH, methoxycarbonyl or ethoxycarbonyl.

A particularly prefered embodiment of the invention relates to compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is selected from radicals of the formulae Ar3.1 , Ar3.2, Ar3.3, Ar3.4, Ar3.5, Ar3.6, Ar3.7, Ar3.8, Ar3.9, Ar3.10, Ar3.1 1 , Ar3.12, Ar3.13, Ar3.14, Ar3.15, Ar3.16, Ar3.17, Ar3.18, Ar3.19, Ar3.20, Ar3.21 , Ar3.22, Ar3'.1 , Ar3'.2, Ar3'.3, Ar3'.4, Ar3'.5, Ar3'.6, Ar3'.7, Ar3'.8, Ar3'.9, Ar3'.10, Ar3'.1 1 , Ar3'.12, Ar3'.13, Ar3'.14 and Ar3'.15, with particular preference given to the formulae Ar3.1 , Ar3.2, Ar3.3, Ar3.4, Ar3.10, Ar3.1 1 , Ar3'.1 , Ar3'.2, Ar3'.3 and Ar3'.4:

Ar3.1 Ar3.2 Ar3.3 Ar3.4

Ar3.5 Ar3.6 Ar3.7 3.8

Ar3.9 Ar3.10 Ar3.1 1 Ar3.12

Ar3.13 Ar3.14 Ar3.15 Ar3.16

Ar3.20 Ar3.21 Ar3.22

Ar3'.1 Ar3'.2 Ar3'.3 Ar3'.4

Ar3'.5 Ar3'.6 Ar3'.7 Ar3'.8

Ar3M 3 Ar3M 4 wherein

# indicates the point of attachment of R ² to the 2,3-dihydrobenzazine ring of (I), R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ and R ²⁹ have the meanings indicated above.

In the compounds of the formula (I), where R ² is selected from radicals of the formulae Ar3.1 , Ar3.2, Ar3.3, Ar3.4, Ar3.5, Ar3.6, Ar3.7, Ar3.8, Ar3.9, Ar3.10, Ar3.1 1 , Ar3.12, Ar3.13, Ar3.14, Ar3.15, Ar3.16, Ar3.17, Ar3.18, Ar3.19, Ar3.20, Ar3.21 , Ar3.22, Ar3'.1 , Ar3'.2, Ar3'.3, Ar3'.4, Ar3'.5, Ar3'.6, Ar3'.7, Ar3'.8, Ar3'.9, Ar3'.10, Ar3'.1 1 , Ar3'.12, Ar3'.13, Ar3'.14 and Ar3'.15, particular embodiments of the invention relate to compounds, wherein the variables R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ and R ²⁹ , if present, individually or in particular in combination have the following meanings

R ²⁴ if present, is hydrogen or Ci-C4-alkyl, in particular methyl or ethyl;

_R 25 if present, is hydrogen or Ci-C4-alkyl, in particular methyl or ethyl;

R26 if present, is selected from the group consisting of hydrogen, halogen, OH, SH, CN, NO2, C1-C4 alkyl, or isopropyl, C2-C4 alkenyl, in particular ethenyl or pro- penyl, C2-C4 alkynyl, in particular ethynyl or propynyl, Ci-C4-alkoxy, in particular methoxy or ethoxy, Ci-C4-alkylthio, in particular methylthio or ethylthio, fluori- nated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, fluorinated

Ci-alkoxy, NH2, hydroxy-Ci-C4-alkyl, especially hydroxymethyl or 2-hydroxyethyl, Ci-C4-alkoxy-Ci-C4-alkyl, especially 1 -methoxyethyl or 2-methoxyethyl, C(0)R ³ , especially acetyl or propionyl and NR ⁴ R ⁵ , especially methylamino or dimethyl- amino;

R ²⁷ if present, is selected from the group consisting of hydrogen, halogen, OH, SH, CN, NO2, C1-C4 alkyl, in particular methyl, ethyl or isopropyl, C2-C4 alkenyl, in particular ethenyl or propenyl, C2-C4 alkynyl, in particular ethynyl or propynyl, C1-C4- alkoxy, in particular methoxy or ethoxy, Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, fluori- nated Ci-alkoxy, in particular difluoromethoxy or trifluoromethoxy, NH2, hydroxy- Ci-C4-alkyl, especially hydroxymethyl or 2-hydroxyethyl, Ci-C4-alkoxy-Ci-C4-alkyl, especially 1 -methoxyethyl or 2-methoxyethyl, C(0)R ³ , especially acetyl or propionly and NR ⁴ R ⁵ , especially methylamino or dimethylamino;

R ²⁸ if present, is selected from the group consisting of hydrogen, CN, C1-C4 alkyl, in particular methyl, ethyl or isopropyl, C2-C4 alkenyl, in particular ethenyl or pro- penyl, C2-C4 alkynyl, in particular ethynyl or propynyl, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, Ci-C4-alkoxy-C2-C4-alkyl, especially 1 -methoxyethyl or 2-methoxyethyl, and hydroxy-C2-C4 alkyl, especially hydroxy- methyl or 2-hydroxyethyl; and

R ²⁹ if present, is selected from the group consisting of hydrogen, CN, C1-C4 alkyl, in particular methyl, ethyl or isopropyl,C2-C4 alkenyl, in particular ethenyl or pro- penyl, C2-C4 alkynyl, in particular ethynyl or propynyl, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, Ci-C4-alkoxy-C2-C4-alkyl, especially 1 -methoxyethyl or 2-methoxyethyl, and hydroxy-C2-C4 alkyl, especially hydroxymethyl or 2-hydroxyethyl.

Particular embodiments of the invention relate to compounds of the formula I, 1.1 , 1.2, 1.3 or 1.4, where R ² is selected from radicals of the formulae Ar3.1 , Ar3.2, Ar3.3, Ar3.4, Ar3.5, Ar3.6, Ar3.7, Ar3.8, Ar3.9, Ar3.10, Ar3.1 1 , Ar3.12, Ar3.13, Ar3.14, Ar3.15, Ar3.16, Ar3.17, Ar3.18, Ar3.19, Ar3.20, Ar3.21 , Ar3.22, Ar3'.1 , Ar3'.2, Ar3'.3, Ar3'.4, Ar3'.5, Ar3'.6, Ar3'.7, Ar3'.8, Ar3'.9, Ar3'.10, Ar3'.1 1 , Ar3'.12, Ar3'.13, Ar3'.14 and Ar3'.15, wherein the variables R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ , R ²⁸ and R ²⁹ , if present, individually or in particular in combination have the following meanings:

R ²⁴ is hydrogen or methyl;

R ²⁵ is hydrogen or methyl;

R ²⁶ is selected from the group consisting of hydrogen, halogen, in particular fluorine or chlorine, OH, CN, methyl, methoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy and ethynyl, especially hydrogen;

R ²⁷ is selected from the group consisting of hydrogen, halogen, in particular fluorine or chlorine, OH, CN, methyl, methoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy and ethynyl, especially hydrogen, methyl or cyano; R ²⁸ is hydrogen or C1-C4 alkyl, especially hydrogen or methyl;

R ²⁹ is hydrogen or C1-C4 alkyl, especially hydrogen or methyl.

Preferred examples are: 5-cyanothiophen-2-yl, 5-cyanothiophen-3-yl, furan-2-yl, 5-methylfuran-2-yl, 5-cyanofuran-2-yl, 1 H-pyrrol-2-yl, 5-methyl-1 H-pyrrol-2-yl, 5-cyano- 1 H-pyrrol-2-yl, 3,5-dimethylisoxazol-4-yl, 5-cyanothiazol-2-yl and oxazol-5-yl.

More preferably, R ² is selected from radicals of the formulae Ar3.2 and Ar3'.2, in particular 5-cyanothiophen-2-yl and 5-cyanothiophen-3-yl. Another particular embodiment of the invention relates to compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, where R ² is a C-bound bicyclic radical, which is unsubstituted or which carries 1 , 2 or 3 radicals R ^2a which are identical or different or which carries 1 radical R ^2b and 0, 1 or 2 identical or different radicals R ^2a , preference is given to those compounds, wherein R ² is a radical of

where

# indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I);

A is O, S, NH or N(Ci-C ₄ -alkyl);

B is N or CH;

B' is N or CH;

D, D' and D" are independently of each other selected from N and C-R ^D ;

E, E' and E" are independently of each other selected from N and C-R ^E ;

G is N or C-R ^G ;

L, L' and L" are independently of each other selected from N and C-R ^L ;

n is 0, 1 or 2;

M is O, S, S(O), S(0) ₂ , N-R ^M1 or C(R ^M2 R ^M3 );

Q is O, S, S(O), S(0) ₂ , N-R« ¹ or C(R ^Q2 R ^Q3 );

T is O, S, S(O), S(0) ₂ , N-R ^T1 or C(R ^T2 R ^T3 );

U is O, S, S(O), S(0) ₂ , N-R ^U or C(R ^U2 R ^U3 );

R ^D is selected from the group consisting of hydrogen and the radical R ^2a , preferably is selected from hydrogen, halogen, OH, SH, CN, N0 ₂ , C≡C-CN, d-Ce-alkyl, C ₂ -C6-alkenyl, C ₂ -C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C2-alkoxy, C(0)R ³ and NR ⁴ R ⁵ ;

R ^E is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, halogen, OH, SH, CN, NO2, C≡C-CN, d-Ce-alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, Ci-Ce-alkoxy, Ci-Ce-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ ;

R ^G is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, halogen, OH, SH, CN, NO2, C≡C-CN, Ci-Ce-alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, Ci-Ce-alkoxy, Ci-Ce-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ ;

R ^L is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, halogen, OH, SH, CN, NO2, C≡C-CN, Ci-Ce-alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, Ci-Ce-alkoxy, Ci-Ce-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ ;

R ^M1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated C1-C2- alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C2-C6-alkenyl, C2-C6- alkynyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , or,

if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^M1 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^M1 together with R ^T1 or together with R ^T2 may form a bond;

R ^M2 is selected from the group consisting of hydrogen and the radical R ^2a , preferably hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, fluorinated Ci-C2-alkoxy, Ci-C4-alkylthio, fluorinated Ci-C2-alkylthio, C2-C6-alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ³ and NR R ⁵ , or

if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^M2 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^M2 together with R ^T1 or together with R ^T2 may form a bond;

R ^M3 is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl and C(0)R ³ ;

R ^Q1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated C1-C2- alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C2-C6-alkenyl, C2-C6- alkynyl, C(0)R ⁴ and C(0)NR ⁷ R ⁸ , or, if n is 1 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^Q1 together with R ^M1 or together with R ^M2 may form a bond, or

if n is 1 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^Q1 together with R ^T1 or together with R ^T2 may form a bond;

R ^Q2 is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, fluorinated Ci-C2-alkoxy, Ci-C4-alkylthio, fluorinated Ci-C ₂ -alkylthio, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ⁴ and NR ⁵ R ⁶ , or if n is 1 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^Q2 together with R ^M1 or together with R ^M2 may form a bond, or

if n is 1 and T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^Q2 together with R ^T1 or together with R ^T2 may form a bond;

R ^Q3 is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl and C(0)R ³ ;

R ^T1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated Ci-C ₂ - alkyl, Ci-C ₂ -alkylsulfonyl, fluorinated Ci-C ₂ -alkylsulfonyl, C ₂ -C6-alkenyl, C ₂ -C6- alkynyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , or,

if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^T1 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^T1 together with R ^M1 or together with R ^M2 may form a bond, or

if U is N-R ^U1 or C(R ^U2 R ^U3 ), R ^T1 together with R ^U1 or together with R ^U2 may form a bond;

R ^T2 is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, Ci-C6-alkoxy, fluorinated Ci-C ₂ -alkoxy, Ci-C4-alkylthio, fluorinated Ci-C ₂ -alkylthio, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ³ and NR ⁴ R ⁵ , or if n is 1 and Q is N-R ^Q1 or C(R ^Q2 R ^Q3 ), R ^T2 together with R ^Q1 or together with R ^Q2 may form a bond, or

if n is 0 and M is N-R ^M1 or C(R ^M2 R ^M3 ), R ^T2 together with R ^M1 or together with R ^M2 may form a bond, or

if U is N-R ^U1 or C(R ^U2 R ^U3 ), R ^T2 together with R ^U1 or together with R ^U2 may form a bond;

R ^T3 is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl and a radical C(0)R ³ ; R ^U1 is selected from the group consisting of hydrogen, Ci-C6-alkyl, fluorinated C1-C2- alkyl, Ci-C2-alkylsulfonyl, fluorinated Ci-C2-alkylsulfonyl, C2-C6-alkenyl, C2-C6- alkynyl, C(0)R ⁴ and C(0)NR ⁷ R ⁸ , or,

if T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^U1 together with R ^T1 or together with R ^T2 may form a bond,

R ^U2 is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, OH, halogen, Ci-C6-alkyl, fluorinated Ci-C2-alkyl, Ci-C6-alkoxy, fluorinated Ci-C2-alkoxy, Ci-C4-alkylthio, fluorinated Ci-C ₂ -alkylthio, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, C(0)R ³ and NR ⁴ R ⁵ , or if T is N-R ^T1 or C(R ^T2 R ^T3 ), R ^U2 together with R ^T1 or together with R ^T2 may form a bond,

R ^U3 is selected from the group consisting of hydrogen and the radical R ^2a , preferably selected from the group consisting of hydrogen, halogen, Ci-C6-alkyl, fluorinated Ci-C ₂ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl and C(0)R ³ ; where one or two of the moieties C(R ^M2 R ^M3 ), C(R ^Q2 R ^Q3 ), C(R ^T2 R ^T3 ) and C(R ^U2 R ^U3 ) may also be C=0 or C=S;

or the moiety -M-(Q) _n -T-U- together with the carbon atoms to which it is attached forms a fused 1 ,2,5-thiadiazole ring or a 1 ,2,5-oxadiazole ring; where R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are as defined above or have one of the preferred meanings, provided that in formula R2-2 and R2-3 two or more adjacent ring members M, Q, T and U are neither oxygen nor sulfur at the same time.

According to a particular embodiment, the radical R ² is a radical of the formulae R2-0 or R2-1 , wherein D is C-R ^D , E is C-R ^E , G is C-R ^G and L is C-R ^L wherein R ^D , R ^E , R ^G and R ^L are as defined above, i.e. the six-membered second ring which is fused to the 5-membered first ring is a benzene ring.

According to another particular embodiment, the radical R ² is a radical of the formulae R2-0 or R2-1 , wherein one or two of the ring members D, E, G or L are nitrogen and the other ring members D, E, G or L are selected from C-R ^D , C-R ^E , C-R ^G and C-R ^L wherein R ^D , R ^E , R ^G and R ^L are as defined above. In this embodiment, the six- membered second ring which is fused to the 5-membered first ring is a 6-membered heteroaryl ring comprising one or two nitrogen atoms as ring members. In this embodiment, the six-membered second ring which is fused to the 5-membered first ring is in particular a pyridine ring. Preferred embodiments of the radical of the formulae R2-0 or R2-1 are the radicals of the formulae R2-0a, R2-1 a, R2-0b, R2-1 b, R2-0c, R2-1 c, R2-0d, R2-1 d, R2-0e and R2-1 e, which individually represent particular embodiments for R ² in formula I:

wherein A, B' and B are as defined above,

# indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I) k is 0, 1 or 2 and

R has one of the meanings indicated for R ^2a , preferably halogen, OH, SH, CN, NO2, C≡C-CN, d-Ce-alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, Ci-C ₆ -alkoxy, Ci-C ₆ -alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluori- nated Ci-C ₂ -alkoxy, C(0)R ⁴ and NR ⁵ R ⁶ , wherein R ⁴ , R ⁵ and R ⁶ have the aforementioned meanings.

In the formulae R2-0a, R2-1 a, R2-0b, R2-1 b, R2-0c, R2-1 c, R2-0d, R2-1 d, R2-0e and R2-1 e, the radical R, if present, is preferably selected from halogen, in particular fluorine, chlorine, bromine or iodine, CN, Ci-C4-alkyl, in particular methyl or ethyl,

Ci-C4-alkoxy, in particular methoxy or ethoxy, Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluori- nated Ci-alkoxy in particular trifluoromethoxy. If k is 2, R may be the same or may be different. Preferably, k is 0 or 1.

Particularly preferred embodiments of the radical of the formulae R2-0 and R2-1 are the radicals of the formulae R2-0a.1, R2-0a.2, R2-0a.3, R2-0a.4, R2-0a.5, R2-0a.6, R2-0b.1, R2-0C.1 or R2-0d.1 R2-1a.1 , R2-1a.2, R2-1a.3, R2-1a.4, R2-1a.5, R2-1a.6, R2-1b.1, R2-1c.1 or R2-1d.1, which individually represent particular embodiments for R ² in formula I:

wherein

# indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I) k is 0, 1 or 2; and R has one of the meanings indicated for R ^2a , preferably halogen, OH, SH, CN,

Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy- Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ ; wherein R ³ , R ⁴ and R ⁵ have the aforemen- tioned meanings, preferably those being preferred.

Preferably, R, if present, is selected from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated

Ci-alkoxy in particular trifluoromethoxy. If k is 2, R may be the same or may be different. Preferably, k is 0 or 1 .

Examples for a radical R2-0 are benzofuran-3-yl, 5-methylbenzofuran-3-yl, 6-methylbenzofuran-3-yl, benzo[b]thiophen-3-yl, 5-methylbenzo[b]thiophen-3-yl, 6-methylbenzo[b]thiophen-3-yl, 1 H-indol-3-yl, 5-methyl-1 H-indol-3-yl 6-methylindol-3-yl, benzisoxazol-3-yl, benzisothiazol-3-yl, 1 H-indazol-3-yl, 7-chlorothieno[3,2-c]pyridin- 3-yl, thieno[3,2-c]pyridin-3-yl, thieno[3,2-b]pyridin-3-yl and 7-chlorothieno[3,2-b]pyridin- 3-yl.

Examples for a radical R2-1 are benzofuran-2-yl, 5-methylbenzofuran-2-yl, 6-methylbenzofuran-2-yl, benzo[b]thiophen-2-yl, 5-methylbenzo[b]thiophen-2-yl, 6-methylbenzo[b]thiophen-2-yl, 1 H-indol-2-yl, 5-methyl-1 H-indol-2-yl, 6-methylindol- 2-yl, benzoxazol-2-yl, benzothiazol-2-yl, 5-cyanobenzothiazol-2-yl,

6-cyanobenzothiazol-2-yl, 5-methylbenzothiazol-2-yl, 6-methylbenzothiazol-2-yl,

5- methoxybenzothiazol-2-yl, 6-methoxybenzothiazol-2-yl, 5-fluorobenzothiazol-2-yl,

6- fluorobenzothiazol-2-yl, 5-chlorobenzothiazol-2-yl, 6-chlorobenzothiazol-2-yl, 5,6-difluorobenzothiazol-2-yl, 5,6-dichlorobenzothiazol-2-yl, 1 H-benzimidazol-2-yl,

7- chlorothieno[3,2-c]pyridin-2-yl, thieno[3,2-c]pyridin-2-yl, thieno[3,2-b]pyridin-2-yl, 7-chlorothieno[3,2-b]pyridin-2-yl and thieno[2,3-b]pyridin-2-yl.

According to another preferred embodiment, the radical R ² is a radical of the formulae R2-2 or R2-3 with n being 1 . Preferred embodiments of the radicals of the for- mulae R2-2 or R2-3 with n being 1 are the radicals of the formulae R2-2a, R2-3a,

R2-2b, R2-3b, R2-2c, R2-3c, R2-2d, R2-3d, R2-2e, R2-3e, R2-2f and R2-3f, which individually represent particular embodiments for R ² in formula I:

(R1 -3a)

where

# indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I);

k is 0, 1 or 2,

R has one of the meanings given for R ^2a , preferably halogen, OH, SH, CN, NO2,

C≡C-CN, d-Ce-alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, Ci-C ₆ -alkoxy, Ci-C ₆ -alkylthio, hydroxy-Ci-Ce-alkyl, Ci-C4-alkoxy-Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , wherein R ³ , R ⁴ and R ⁵ have the aforementioned meanings, preferably those being preferred;

M, Q, T, U, R ^M2 , R ^M3 , R ^Q2 , R ^Q3 , R ^T2 , R ^T3 , R ^U2 and R ^U3 are as defined above; provided that at least one of M, Q, T and U in formulae R2-2a, R2-2c, R2-2d, R2-3a, R2-3c and R2-3d is selected from O, S, S(O), S(0) ₂ , N-R ^# , where R ^# , depending on its position, has one of the meanings given above for R ^M1 , R ^Q1 , R ^T1 or R ^U1 , respectively. In the formulae R2-2a, R2-3a, R2-2b, R2-3b, R2-2c, R2-3c, R2-2e and R2-3e, M is preferably O, S, N-R ^M1 or C(R ^M2 R ^M3 ), wherein R ^M1 , R ^M2 and R ^M3 are as defined above.

In the formulae R2-2a, R2-3a, R2-2b, R2-3b, R2-2d, R2-3d, R2-2f and R2-3f, U is preferably O, S, N-R ^U1 or C(R ^U2 R ^U3 ), wherein R ^U1 , R ^U2 and R ^U3 are as defined above.

In the formulae R2-2c, R2-3c, R2-2e and R2-3e, T is preferably N-R ^T1 or

C(R ^T2 R ^T3 ), wherein R ^T1 , R ^T2 and R ^T3 are as defined above.

In the formulae R2-2d and R2-3d, R2-2f and R2-3f, Q is preferably N-R ^Q1 or C(R ^Q2 R ^Q3 ), wherein R ^Q1 , R ^Q2 and R ^Q3 are as defined above.

In the formulae R2-2a, R2-3a, R2-2b, R2-3b, R2-2c, R2-3c, R2-2d, R2-3d, R2-2e,

R2-3e, R2-2f and R2-3f, the radical R, if present, is preferably selected from halogen, in particular fluorine, chlorine or iodine, CN, Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy, Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluori- nated Ci-alkoxy in particular trifluoromethoxy. If k is 2, R may be the same or may be different. Preferably, k is 0 or 1 .

Particularly preferred embodiments of the radicals of the formulae R2-2 or R2-3 with n being 1 are the radicals of the formulae R2-2a.1 , R2-3a.1 , R2-2a.2, R2-3a.2, R2-2a.3, R2-3a.3, R2-2a.4, R2-3a.4, R2-2a.5, R2-3a.5, R2-2a.6, R2-3a.6, R2-2a.7, R2-3a.7, R2-2a.8, R2-3a.8, R2-2a.9, R2-3a.9, R2-2a.10, R2-3a.10, R2-2a.1 1 ,

R2-3a.1 1 , R2-2a.12, R2-3a.12, R2-2a.13, R2-3a.13, R2-2a.14, R2-3a.14, R2-2a.15, R2-3a.15, R2-2a.16, R2-3a.16, R2-2a.17, R2-3a.17, R2-2a.18, R2-3a.18, R2-2a.19, R2-3a.19, R2-2b.1 , R2-3b.1 , R2-2b.2, R2-3b.2, R2-2b.3, R2-3b.3, R2-2c.1 , R2-3c.1 , R2-2d.1 , R2-3d.1 , R2-2e.1 , R2-3e.1 , R2-2f.1 and R2-3f.1 , listed below, which individu- all re resent articular embodiments for R ² in formula I:

(R2-3a.2) (R2-2a.3) (R2-3a.3)

(R2-3a.4)

(R2-2a.7) (R2-3a.7) (R2-2a.8)

(R2-2a.13) (R2-3a.13)

R2-2b.1 R2-3b.1

R2-2b.2 R2-3b.2

R2-2b.3 R2-3b.3

(R2-3C.1 )

(R2-3e.1 )

where

# indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I);

k is 0, 1 or 2, preferably 0 or 1 , where R may be the same or different, if k is 2; mm is 0, 1 or 2, preferably 0 or 1 , where R' may be the same or different, if m is 2;

R is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, C1-C4- alkoxy-Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , preferably selected from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C ₄ -alkyl, in particular methyl or ethyl, Ci-C ₄ -alkoxy, in particular methoxy or ethoxy or Ci-C ₄ -alkylthio, in particular methylthio or ethyl- thio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

R' is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, C1-C4- alkoxy-Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and N R ⁴ R ⁵ , preferably from the group consisting of halogen, in particular fluorine or chlorine, CN , Ci-C4-alkyl, in particular methyl or ethyl, Ci-C4-alkoxy, in particular methoxy or ethoxy or Ci-C4-alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

R ^a , R ^b are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S);

preferably hydrogen, methyl or ethyl or R ^a and R ^b together with the carbon atom to which they are attached form a carbonyl group;

R ^d , R ^e are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl, and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S);

or R ^d together with Rs forms a bond;

preferably hydrogen, methyl or ethyl or R ^d and R ^e together with the carbon atom to which they are attached form a carbonyl group;

Ra, R ^h are independently of each other selected from the group consisting of hy- drogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S),

preferably hydrogen, methyl or ethyl, or Rs and R ^h together with the carbon atom to which they are attached form a carbonyl group;

or one of the radicals R ^a , R ^b , R ^d , R ^e , Rs, R ^h may also be a radical selected from the group consisting of Ci-C4-alkoxy, fluorinated Ci-C2-alkoxy, C(0)R ³ and N R ⁴ R ⁵ , preferably C1-C2 alkoxy, especially methoxy or ethoxy, fluorinated Ci-alkoxy, especially difluoromethoxy or trifluoromethoxy, and N R ⁴ R ⁵ , especially N HC(0)Ci-C4-alkyl;

R ^c , R ^f , are independently of each other selected from the group consisting of hy- drogen, Ci-C ₄ -alkyl, Ci-C ₂ -alkylsulfonyl, fluorinated Ci-C ₂ -alkylsulfonyl, C(0)R ³ and C(0)N R ⁶ R ⁷ preferably from the group consisting of hydrogen, methyl, ethyl, C(0)R ³ , in particular acetyl, 2,2,2-trifluoroacetyl or propionyl, Ci-C2-alkylsulfonyl, such as methylsulfonyl, C(0)N R ⁵ R ⁶ , in particular C(0)NH ₂ or C(0)N(CH ₃ ) ₂ , more preferably from the group consisting of hydrogen, Ci-C2-alkyl, C(0)R ³ , especially acetyl, 2,2,2-trifluoroacetyl, or propionyl, and methylsulfonyl, in particular from the group consisting of hydrogen, methyl, ethyl, acetyl, 2,2,2-trifluoroacetyl, propionyl and methylsulfonyl.

Another particular embodiment of the invention relates to compounds of the formulae I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is naphthyl, i.e. a radical of the formulae R2-2a.19 or R2-3a.19, which is unsubstituted or which carry 1 , 2, 3, 4, 5 or 6 identical or different radicals R ^2a or 1 radical R ^2b and 0, 1 , 2, 3, 4 or 5 identical or different radicals R ^2a . In this embodiment, R ^2a , if present, is preferably Ci-C4-alkyl, such as methyl or ethyl, Ci-C4-alkoxy such as methoxy or ethoxy or NR ⁴ R ⁵ with R ⁵ being hydrogen or Ci-C4-alkyl and R ⁵ being hydrogen or Ci-C4-alkyl. R ^2b , if present, is as defined above, preferably imidazolyl, pyrazolyl, phenyl, furyl, oxazolyl, isoxazolyl and pyridyl, where the 7 last mentioned radicals are unsubstituted or carry 1 or 2 radicals selected from halogen, C1-C4 alkyl, Ci-C4-alkoxy, fluorinated Ci-alkyl and fluorinated Ci-alkoxy.

Preferred embodiments of the radicals of the formulae R2-2 or R2-3 with n being 0 are the radicals of the formulae R2-2g, R2-3g, R2-2h, R2-3h, R2-2i, R2-3i, R2-2k and R2-3k, listed below, which individually represent preferred embodiments for R ² in formula I:

where

# indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I);

k is 0, 1 or 2, in particular 0 or 1 , where R may be the same or different, if k is 2, R is selected from the group consisting of halogen, OH, SH, CN, NO2, C≡C-CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy- Ci-C6-alkyl, Ci-C4-alkoxy-Ci-C4-alkyl, fluorinated Ci-C2-alkyl, SF ₅ , fluorinated Ci-C2-alkoxy, C(0)R ³ and NR ⁴ R ⁵ , in particular from the group consisting of hydrogen, halogen, especially fluorine, chlorine, bromine or iodine, CN, Ci-C4-alkyl, especially methyl or ethyl, Ci-C4-alkoxy, especially methoxy or ethoxy, C1-C4- alkylthio, especially methylthio or ethylthio, fluorinated Ci-alkyl, especially di- fluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy, especially trifluoro- methoxy;

T' in formulae R2-2g and R2-3g is O or S, and where

M, T and U, have the aforementioned meanings;

provided that at least one of M, T and U in formulae R2-2h and R2-3h is selected from O, S, S(O), S(0)2, N-R ^# , where R ^# , depending on its position, has one of the meanings given for R ^M1 , R ^Q1 , R ^T1 or R ^U1 , respectively, and R ^M1 , R ^Q1 , R ^T1 or R ^u are as defined above and where R ^M1 , R ^Q1 , R ^T1 and R ^u , independently of each other, are in particular selected from the group consisting of hydrogen, Ci-C4-alkyl, especially methyl or ethyl, fluorinated Ci-C2-alkyl, especially difluoromethyl, trifluoromethyl, 2,2-difluoroethyl or 2,2,2-trifluoroethyl, C(0)-Ci-C4-alkyl such as acetyl or propionyl, S(0)2-Ci-C4-alkyl, such as methylsulfonyl, fluorinated S(0)2-Ci-C2-alkyl such as trifluoromethylsulfonyl, and C(0)NH-Ci-C ₄ -alkyl.

In particular, R ² is a radical R2-2h.

Particularly embodiments of the radicals of the formulae R2-2 or R2-3 with n be- ing 0 are the radicals of the formulae R2-2g.1 , R2-3g.1 , R2-2g.2, R2-3g.2, R2-2h.1 , R2-3h.1 , R2-2h.2, R2-3h.2, R2-2h.3, R2-3h.3, R2-2h.4, R2-3h.4, R2-2h.5, R2-3h.5, R2-2h.6, R2-3h.6, R2-2h.7, R2-3h.7, R2-2h.8, R2-3h.8, R2-2h.9, R2-3h.9, R2-2h.10, R2-3h.10, R2-2h.1 1 , R2-3h.1 1 , R2-2h.12, R2-3h.12, R2-2h.13, R2-3h.13, R2-2h.14, R2-3h.14, R2-2h.15, R2-3h.15, R2-2h.16, R2-3h.16, R2-2h.17, R2-3h.17, R2-2h.18, R2-3h.18, R2-2h.19, R2-3h.19, R2-2h.20, R2-3h.20, R2-2h.21 , R2-3h.21 , R2-2h.22, R2-3h.22, R2-2h.23, R2-3h.23, R2-2h.24, R2-3h.24, R2-2h.25, R2-3h.25, R2-2h.26, R2-3h.26, R2-2h.27, R2-3h.27, R2-2h.28, R2-3h.28, R2-2h.29, R2-3h.29, R2-2h.30, R2-3h.30, R2-2h.31 and R2-3h.31 and listed below, which individually represent particular embodiments for R ² in formula I:

(R2-2g.1 ) (R2-2g.2) (R2-3g.1 ) (R2-3g.2)

(R2-2h.1 ) (R2-3h.1 ) (R2-2h.2)

(R2-3h.2) (R2-2h.3) (R2-3h.

(R2-2h.4) (R2-2h.5) (R2-2h.6)

(R2-2h.7) (R2-2h.8) (R2-2h.9)

(R2-3h.13) (R2-3 4) (R2-3 5)

(R2-3h.16) (R2-3h.17)

R2-3h.21 R2-3h.22 R2-3h.23

R2-2h.28 R2-3h.28

indicates the point of attachment to the 2,3-dihydrobenzazine ring of (I);

is 0 or 1 ;

is 0, 1 or 2, preferably 0 or 1 ;

is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, C1-C4- alkoxy-Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , preferably selected from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C ₄ -alkyl, in particular methyl or ethyl, Ci-C ₄ -alkoxy, in particular methoxy or ethoxy or Ci-C ₄ -alkylthio, in particular methylthio or ethyl- thio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

is selected from the group consisting of halogen, OH, SH, CN, Ci-C6-alkyl, C2-C6- alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, C1-C4- alkoxy-Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , preferably from the group consisting of halogen, in particular fluorine or chlorine, CN, Ci-C ₄ -alkyl, in particular methyl or ethyl, Ci-C ₄ -alkoxy, in particular methoxy or ethoxy or Ci-C ₄ -alkylthio, in particular methylthio or ethylthio, fluorinated Ci-alkyl, in particular difluoromethyl or trifluoromethyl, and fluorinated Ci-alkoxy in particular trifluoromethoxy;

are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C ₄ -alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S)

preferably hydrogen, C1-C2 alkyl; R ^d , R ^e are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S),

preferably independently of each other selected from hydrogen, halogen, especially fluorine, Ci-C2-alkyl or R ^d and R ^e together with the carbon atom to which they are attached form a carbonyl group;

R9, R ^h are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or

together with the carbon atom to which they are attached form a carbonyl (C=0) or thiocarbonyl group (C=S),

preferably independently of each other selected from hydrogen, Ci-C2-alkyl or Rs and R ^h together with the carbon atom to which they are attached form a carbonyl group;

or one of the radicals R ^a , R ^b , R ^d , R ^e , Rs, R ^h may also be a radical selected from the group consisting of Ci-C4-alkoxy, fluorinated Ci-C2-alkoxy, C(0)R ³ and NR ⁴ R ⁵ , preferably C1-C2 alkoxy, especially methoxy or ethoxy, fluorinated Ci-alkoxy, especially difluoromethoxy or trifluoromethoxy, and NR ⁴ R ⁵ , especially NHC(0)Ci-C4-alkyl;

R' is selected from the group consisting of halogen, CN, Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, Ci-C6-alkoxy, Ci-C6-alkylthio, hydroxy-Ci-C6-alkyl, Ci-C4-alkoxy-

Ci-C ₄ -alkyl, fluorinated Ci-C ₂ -alkyl, SF ₅ , fluorinated Ci-C ₂ -alkoxy, C(0)R ³ and NR ⁴ R ⁵ , preferably hydrogen, Ci-C4-alky, especially methyl or ethyl;

R ^c , R ^f are independently of each other selected from the group consisting of hydrogen, Ci-C ₄ -alkyl, Ci-C ₂ -alkylsulfonyl, fluorinated Ci-C ₂ -alkylsulfonyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , preferably from the group consisting of hydrogen, methyl, ethyl,

C(0)R ³ , in particular acetyl or propionyl, Ci-C2-alkylsulfonyl, such as methylsul- fonyl, C(0)NR ⁶ R ⁷ , in particular C(0)NH ₂ or C(0)N(CH ₃ ) ₂ , more preferably from the group consisting of hydrogen, Ci-C2-alkyl, C(0)R ³ , especially acetyl or propionyl and methylsulfonyl, in particular from the group consisting of hydrogen, methyl, ethyl, acetyl, propionyl and methylsulfonyl;

R ^k is selected from the group consisting of hydrogen, Ci-C4-alkyl, C1-C2- alkylsulfonyl, fluorinated Ci-C ₂ -alkylsulfonyl, C(0)R ³ and C(0)NR ⁶ R ⁷ , preferably hydrogen, Ci-C4-alkyl, especially methyl or ethyl;

In these embodiments, if k is 2, R may be the same or different.

In this embodiment, a more preferred embodiment relates to compounds of the formula I, 1.1 , 1.2, 1.3 and 1.4, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is a radical of the formulae R2-2h.7 such as benzofuran-5-yl, R2-2h.9 such as 1 H-indol-5-yl or 1 -methyl-1 H-indol-5-yl, R2-2h.25, such as 2-oxo- 2,3-dihydrobenzo[d]imidazol-5-yl, R2-2h.26. An especially preferred embodiment relates to compounds of the formula (I), to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ² is selected from 5-cyanothiophen-2-yl, 5-cyanothiophen-3-yl, furan-2-yl, 5-methylfuran-2-yl,

5- cyanofuran-2-yl, 1 H-pyrrol-2-yl, 5-methyl-1 H-pyrrol-2-yl, 5-cyano-1 H-pyrrol-2-yl, 3,5-dimethylisoxazol-4-yl, 5-cyanothiazol-2-yl, oxazol-5-yl, pyridin-2-yl, 5-methylpyridin- 2-yl, 5-trifluoromethylpyridin-2-yl, 5-cyanopyridin-2-yl, pyridin-3-yl, 6-methylpyridin-3-yl,

6- cyanopyridin-3-yl, 6-fluoropyridin-3-yl, pyridin-4-yl, 2-methylpyridin-4-yl,

2-fluoropyridin-4-yl, 2 ,3-d if luoropyrid i n-4-yl , pyrimdin-2-yl, 5-methylpyrimidin-2-yl, 5-cyanopyrimidin-2-yl, pyrimidin-5-yl, 2-methylpyrimidin-5-yl, 2-methoxypyrimidin-5-yl, 2-cyanopyrimidin-5-yl, 2-aminopyrimidin-5-yl, benzofuran-5-yl, 1 -methyl-1 H-indol-5-yl, 2-0X0-2, 3-d ihydro-1 H-benzo[d]imidazol-5-yl, 2-oxo-2,3-dihydrobenzooxazol-5-yl,

4- methylphenyl and 4-cyanophenyl.

Most preferably, R ² is selected from the group consisting of 5-cyanothiophen-2-yl,

5- cyanothiophen-3-yl, pyridin-3-yl, 6-methylpyridin-3-yl, 6-cyanopyridin-3-yl,

6-fluoropyridin-3-yl, pyridin-4-yl, 2-methylpyridin-4-yl, 2-fluoropyridin-4-yl,

2,3-difluoropyridin-4-yl, pyrimidin-2-yl, 5-methylpyrimidin-2-yl, pyrimidin-5-yl,

2-methylpyrimidin-5-yl, 2-cyanopyrimidin-5-yl, and 4-cyanophenyl.

With regard to the radical C(0)R ³ the following meanings are particular embodiments: R ⁴ is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert. -butyl or trifluoro- methyl. In particular the radical C(0)R ³ is selected from acetyl or propionyl.

With regard to the radical NR ⁴ R ⁵ the following meanings are particular embodiments of R ⁴ : hydrogen or Ci-C4-alkyl, in particular hydrogen, methyl, ethyl, n-propyl, isopropyl or n-butyl. The following meanings are particular embodiments of R ⁵ : C1-C4- alkyl, in particular methyl, ethyl, n-propyl, isopropyl or n-butyl. In other embodiments, R ⁴ and R ⁵ together with the nitrogen atom, to which they are bound, form an N-bound, 5- or 6-membered saturated nitrogen heterocycle, such as pyrrolidin-1 -yl, morpholin-4-yl, thiomorpholin-4-yl, piperazin-1 -yl or 4-methylpiperazin-1 -yl. In particular, the radical NR ⁴ R ⁵ is selected from methylamino, ethylamino, n-propylamino, isopropylamino, di- methylamino, diethylamino, N-methyl-N-ethylamino, N-methyl-N-isopropylamino, N-methyl-N-propylamino, pyrrolidin-1 -yl, morpholin-4-yl, thiomorpholin-4-yl, piperazin- 1 -yl and 4-methylpiperazin-1 -yl.

With regard to the radical N(OR ⁶ )R ⁷ and C(0)NR ⁶ NR ⁷ the following meanings are particular embodiments of R ⁶ : hydrogen or Ci-C4-alkyl, in particular hydrogen, methyl, ethyl, n-propyl, isopropyl or n-butyl. hydrogen or Ci-C4-alkyl, in particular hydrogen, methyl, ethyl, n-propyl, isopropyl or n-butyl.

With regard to the radical C(0)OR ⁸ the following meanings are particular embodiments of R ⁸ : Ci-C4-alkyl, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert. -butyl. In particular the radical C(0)OR ⁸ is selected from methoxycar- bonyl, ethoxycarbonyl, n-propoxycarbonyl, n-butoxycarbonyl or tert.-butoxycarbonyl. With regard to the radical CHR ⁹ R ¹⁰ the following meanings are particular embodiments of R ⁹ : methoxy, ethoxy, propoxy, isopropoxy, n-butoxy or tert butoxy. The following meanings are particular embodiments of R ¹⁰ : methoxy, ethoxy, propoxy, isopropoxy, n-butoxy or tert butoxy; or R ⁹ and R ¹⁰ form a bridging moiety O-Alk-0, wherein Alk is selected from CH ₂ , CH ₂ CH ₂ and CH2CH2CH2, and where 1 , 2, 3, or 4 hydrogen atoms of Alk may be replaced by Ci-C2-alkyl or fluorinated Ci-C2-alkyl.

With regard to the radical C(Y)R ^y the following meanings are particular embodiments of R ^y ; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert. -butyl ortrifluoro- methyl; Y is preferably oxygen.

A particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1-1, in particular a radical of the formulae R1-1a.1,

R1-1a.2 or R1-1a.3, most preferably R1-1a.2;

R ² is a radical of the formula Ar2, in particular a radical of the formulae Ar2.1 , Ar2.2,

Ar2.3, Ar2.4, Ar2.5 or Ar2.12; and

X isO.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1-1, in particular a radical of the formulae R1-1a.1,

R1-1a.2 or R1-1a.3, most preferably R1-1a.2;

R ² is a radical of the formula Ar2, in particular a radical of the formulae Ar2.1 , Ar2.3,

Ar2.4, Ar2.5 or Ar2.12; and

X isS.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1 -2, in particular a radical of the formulae R1 -2a.3, R1-2a.10, R1-2a.14, R1-2a.19, R1-2a.20, R1-2a.21, R1-2b.2, R1-2h.9, R1-2h.11,

R1-2h.12, R1-2h.13, R1-2h.20, R1-2h.21, R1-2h.23, R1-2h.24, R1-2h.27, R1-2h.29, most preferably R1-2h.20, R1-2h.21, R1-2h.24;

R ² is a radical of the formula Ar2, in particular a radical of the formulae Ar2.1 , Ar2.2, Ar2.3, Ar2.4, Ar2.5 or Ar2.12; and

X is O.

A further particular embodiment of the invention relates to compounds of the for- mula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ¹ is a radical of the formula R1 -2, in particular a radical of the formulae R1 -2a.3, R1-2a.10, R1-2a.14, R1-2a.19, R1-2a.20, R1-2a.21, R1-2b.2, R1-2h.9, R1-2h.11, R1-2h.12, R1-2h.13, R1-2h.20, R1-2h.21, R1-2h.23, R1-2h.24, R1-2h.27, R1-2h.29, most preferably R1-2h.20, R1-2h.21, R1-2h.24;

R ² is a radical of the formula Ar2, in particular a radical of the formulae Ar2.1 , Ar2.2, Ar2.3, Ar2.4, Ar2.5 or Ar2.12; and

X isS.

A particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1-1, in particular a radical of the formulae R1-1a.1,

R1-1a.2 or R1-1a.3, most preferably R1-1a.2;

R ² is a radical of the formula Ar3, in particular a radical of the formulae Ar3.1 , Ar3.2, Ar3.3, Ar3.4, Ar3.10, Ar3.11 , Ar3'.1 , Ar3'.2, Ar3'.3 and Ar3'.4, most preferably Ar3.2 and Ar3'.2; and

X isO.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1-1, in particular a radical of the formulae R1-1a.1,

R1-1a.2 or R1-1a.3, most preferably R1-1a.2;

R ² is a radical of the formula Ar3, in particular a radical of the formulae Ar3.1 , Ar3.2,

Ar3.3, Ar3.4, Ar3.10, Ar3.11 , Ar3'.1 , Ar3'.2, Ar3'.3 and Ar3'.4, most preferably

Ar3.2 and Ar3'.2; and

X isS.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1 -2, in particular a radical of the formulae R1 -2a.3, R1-2a.10, R1-2a.14, R1-2a.19, R1-2a.20, R1-2a.21, R1-2b.2, R1-2h.9, R1-2h.11,

R1-2h.12, R1-2 3, R1-2h.20, R1-2h.21, R1-2h.23, R1-2h.24, R1-2h.27,

R1-2h.29, most preferably R1-2h.20, R1-2h.21, R1-2h.24;

R ² is a radical of the formula Ar3, in particular a radical of the formulae Ar3.1 , Ar3.2,

Ar3.3, Ar3.4, Ar3.10, Ar3.11 , Ar3'.1 , Ar3'.2, Ar3'.3 and Ar3'.4, most preferably Ar3.2 and Ar3'.2; and

X isO.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein R ¹ is a radical of the formula R1 -2, in particular a radical of the formulae R1 -2a.3, R1-2a.10, R1-2a.14, R1-2a.19, R1-2a.20, R1-2a.21, R1-2b.2, R1-2h.9, R1-2h.11, R1-2h.12, R1-2h.13, R1-2h.20, R1-2h.21, R1-2h.23, R1-2h.24, R1-2h.27, R1-2h.29, most preferably R1-2h.20, R1-2h.21, R1-2h.24;

R ² is a radical of the formula Ar3, in particular a radical of the formulae Ar3.1 , Ar3.2, Ar3.3, Ar3.4, Ar3.10, Ar3.11 , Ar3'.1 , Ar3'.2, Ar3'.3 and Ar3'.4, most preferably Ar3.2 and Ar3'.2; and

X isS.

A particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1-1, in particular a radical of the formulae R1-1a.1,

R1-1a.2 or R1-1a.3, most preferably R1-1a.2;

R ² is a radical of the formula R2-2, in particular a radical of the formulae R2-2h.7,

R2-2h.9 or R2-2h.25; and

X isO.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1-1, in particular a radical of the formulae R1-1a.1,

R1-1a.2 or R1-1a.3, most preferably R1-1a.2;

R ² is a radical of the formula R2-2, in particular a radical of the formulae R2-2h.7,

R2-2h.9 or R2-2h.25; and

X isS.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1 -2, in particular a radical of the formulae R1 -2a.3,

R1-2a.10, R1-2a.14, R1-2a.19, R1-2a.20, R1-2a.21, R1-2b.2, R1-2h.9, R1-2h.11,

R1-2h.12, R1-2 3, R1-2h.20, R1-2h.21, R1-2h.23, R1-2h.24, R1-2h.27,

R1-2h.29, most preferably R1-2h.20, R1-2h.21, R1-2h.24;

R ² is a radical of the formula R2-2, in particular a radical of the formulae R2-2h.7,

R2-2h.9 or R2-2h.25; and

X isO.

A further particular embodiment of the invention relates to compounds of the formula I, to their salts, to their N-oxides and to the salts of the N-oxides, wherein

R ¹ is a radical of the formula R1 -2, in particular a radical of the formulae R1 -2a.3,

R1-2a.10, R1-2a.14, R1-2a.19, R1-2a.20, R1-2a.21, R1-2b.2, R1-2h.9, R1-2h.11, R1 -2 2, R1 -2h.13, R1 -2h.20, R1 -2h.21 , R1 -2h.23, R1 -2h.24, R1 -2h.27, R1 -2h.29, most preferably R1 -2h.20, R1 -2h.21 , R1 -2h.24;

R ² is a radical of the formula R2-2, in particular a radical of the formulae R2-2h.7, R2-2h.9 or R2-2h.25; and

X is S.

Examples of suitable compounds according to the present invention are the compounds of the formula (I) as given in the following tables 1 to 37, 38 to 74, 75 to 1 1 1 and 1 12 to 148, their pharmaceutically acceptable salts, their N-oxides and the pharmaceutically acceptable salts of said N-oxides.

Table 1 Compounds of the formula (I), wherein X is O and R ² is 4-cyanophenyl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-1 to I-28);

Table 2 Compounds of the formula (I), wherein X is O and R ² is 4-methylphenyl and wherein R ¹ has one of the meanings given in rows 1 to 212 of table A (Compounds I-29 to I-56);

Table 3 Compounds of the formula (I), wherein X is O and R ² is 5-cyanothiophen- 3-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-57 to I-84);

Table 4 Compounds of the formula (I), wherein X is O and R ² is 5-cyanothiophen- 3-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-85 to 1-1 12);

Table 5 Compounds of the formula (I), wherein X is O and R ² is furan-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-1 13 to 1-140);

Table 6 Compounds of the formula (I), wherein X is O and R ² is 5-methylfuran- 2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-141 to 1-168);

Table 7 Compounds of the formula (I), wherein X is O and R ² is 5-cyanofuran-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-169 to 1-196);

Table 8 Compounds of the formula (I), wherein X is O and R ² is 1 H-pyrrol-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-197 to I-224);

Table 9 Compounds of the formula (I), wherein X is O and R ² is 5-methyl-1 H- pyrrol-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-225 to I-252); Table 10 Compounds of the formula (I), wherein X is O and R ² is 5-cyano-1 H- pyrrol-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-253 to I-280);

Table 1 1 Compounds of the formula (I), wherein X is O and R ² is 3,5- dimethylisoxazol-4-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-281 to I-308);

Table 12 Compounds of the formula (I), wherein X is O and R ² is 5-cyanothiazol- 2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-309 to I-336);

Table 13 Compounds of the formula (I), wherein X is O and R ² is oxazol-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-337 to I-364);

Table 14 Compounds of the formula (I), wherein X is O and R ² is pyridin-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-365 to I-392);

Table 15 Compounds of the formula (I), wherein X is O and R ² is 5-methylpyridin- 2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-393 to I-420);

Table 16 Compounds of the formula (I), wherein X is O and R ² is

5-trifluoromethylpyridin-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-421 to I-448);

Table 17 Compounds of the formula (I), wherein X is O and R ² is 5-cyanopyridin-

2- yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-449 to I-476);

Table 18 Compounds of the formula (I), wherein X is O and R ² is pyridin-3-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-477 to I-504);

Table 19 Compounds of the formula (I), wherein X is O and R ² is 6-methylpyridin-

3- yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-505 to I-532);

Table 20 Compounds of the formula (I), wherein X is O and R ² is 6-cyanopyridin- 3-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-533 to I-560);

Table 21 Compounds of the formula (I), wherein X is O and R ² is 6-fluoropyridin- 3-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-561 to I-588);

Table 22 Compounds of the formula (I), wherein X is O and R ² is pyridin-4-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-589 to 1-616); Table 23 Compounds of the formula (I), wherein X is O and R ² is 2-methylpyridin- 4-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-617 to I-644);

Table 24 Compounds of the formula (I), wherein X is O and R ² is 2-fluoropyridin-

4- yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-645 to I-672);

Table 25 Compounds of the formula (I), wherein X is O and R ² is

2,3-difluoropyridin-4-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-673 to I-700);

Table 26 Compounds of the formula (I), wherein X is O and R ² is pyrimdin-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-701 to I-728);

Table 27 Compounds of the formula (I), wherein X is O and R ² is

5- methylpyrimidin-2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-729 to I-756);

Table 28 Compounds of the formula (I), wherein X is O and R ² is 5-cyanopyrimidin- 2-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-757 to I-784);

Table 29 Compounds of the formula (I), wherein X is O and R ² is pyrimidin-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-785 to 1-812);

Table 30 Compounds of the formula (I), wherein X is O and R ² is

2-methylpyrimidin-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-813 to I-840);

Table 31 Compounds of the formula (I), wherein X is O and R ² is

2-methoxypyrimidin-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-841 to I-868);

Table 32 Compounds of the formula (I), wherein X is O and R ² is 2-cyanopyrimidin- 5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-869 to I-896);

Table 33 Compounds of the formula (I), wherein X is O and R ² is 2-aminopyrimidin- 5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-897 to I-924);

Table 34 Compounds of the formula (I), wherein X is O and R ² is benzofuran-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-925 to I-952);

Table 35 Compounds of the formula (I), wherein X is O and R ² is 1 -methyl-1 H- indol-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds I-953 to I-980); Table 36 Compounds of the formula (I), wherein X is O and R ² is 2-oxo-

2,3-dihydro-1 H-benzo[d]imidazol-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-981 to 1-1008); Table 37 Compounds of the formula (I), wherein X is O and R ² is 2-oxo- 2,3-dihydrobenzooxazol-5-yl and wherein R ¹ has one of the meanings given in rows 1 to 28 of table A (Compounds 1-1009 to 1-1036);

Tables 38 to 74: Compounds of the formula (I), which correspond to the compounds of tables 1 to 37, wherein X = O has been replaced by X = S (Compounds 1-1037 to I-2072).

Tables 75 to 1 1 1 : Compounds of the formula (I), which correspond to the compounds of tables 1 to 37 wherein X = O has been replaced by X = SO (Compounds I-2073 to 1-3108).

Tables 1 12 to 148: Compounds of the formula (I), which correspond to the compounds of tables 1 to 37 wherein X = O has been replaced by X = S02 (Compounds 1-3109 to 1-4144).

Examples of particular preferred compounds according to the present invention are the compounds listed below, their pharmaceutically acceptable salts, their N-oxides and the pharmaceutically acceptable salts of said N-oxides:

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)-1 H-pyrrole-2-carbonitrile;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)furan-2-carbonitrile;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)-1 H-pyrrole-2-carbonitrile;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)-1 H-pyrrole-2-carbonitrile;

5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)furan-2-carbonitrile;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)furan-2-carbonitrile;

6- (5-methyl-1 H-pyrrol-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro- 2H-benzo[b][1 ,4]thiazine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylfuran- 2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

6-(5-methyl-1 H-pyrrol-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide;

6-(5-methyl-1 H-pyrrol-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide; 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylfuran- 2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylfuran- 2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(1 H-pyrrol-2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

6-(furan-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro-2H-benzo[b]- [1 ,4]thiazine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(1 H-pyrrol-2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(1 H-pyrrol-2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

6-(furan-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro-2H-benzo[b]- [1 ,4]thiazine 1 -oxide;

6-(furan-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro-2H-benzo[b]- [1 ,4]thiazine 1 ,1 -dioxide;

4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4- ((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(p-tolyl)-3,4-dih ydro-2H-benzo[b]- [1 ,4]thiazine;

5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H-b enzo[b][1 ,4]thiazin- 6-yl)picolinonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridi n-3-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine;

6- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H-b enzo[b][1 ,4]thiazin- 6-yl)nicotinonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine;

4- ((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-(trifluorometh yl)pyridin-2-yl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine;

5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H-b enzo[b][1 ,4]thiazin- 6-yl)pyrimidine-2-carbonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyrimi din-5-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine;

6- (2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)s ulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine; 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)pyrimidin-2-amine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl )-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-3-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-2-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-4-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyridi n-4-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)pyrimidine-5-carbonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-2-yl )-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

4- ((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyrimidi n-2-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine;

5- (4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H-be nzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)thiophene-2-carbonitrile;

5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)thiophene-2-carbonitrile;

5-(4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-dihyd ro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-(naphthalen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)thiophene- 2-carbonitrile;

5-(4-(benzofuran-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)thiophene- 2-carbonitrile;

5-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)thiophene- 2-carbonitrile; 5-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(p-tolyl)-3,4-d ihydro-2H-benzo[b]- [1 ,4]thiazine 1 -oxide;

4- ((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(p-tolyl)-3,4-dih ydro-2H-benzo[b]- [1 ,4]thiazine 1 ,1 -dioxide;

5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)picolinonitrile;

5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)picolinonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridi n-3-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridi n-3-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

6- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)nicotinonitrile;

6-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)nicotinonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-(trifluorome thyl)pyridin-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide;

4- ((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-(trifluorometh yl)pyridin-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)pyrimidine-2-carbonitnle;

5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)pyrimidine-2-carbonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyrimi din-5-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyrimi din-5-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

6- (2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)s ulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide; 6-(2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl )sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

6-(2-aminopyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)s ulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide;

6-(2-aminopyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)s ulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl )-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl )-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-3-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-3-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-4-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-4-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyridi n-4-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyridi n-4-yl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)pyrimidine-5-carbonitrile;

2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)pyrimidine-5-carbonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-2-yl )-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-2-yl )-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyrimi din-2-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyrimi din-2-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-2-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-2-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide; 5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(1 -oxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(1 ,1 -dioxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-

3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(1 -oxido-4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-d ihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(1 ,1 -dioxido-4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4 -dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-(naphthalen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-

6-yl)thiophene-2-carbonitrile;

5-(4-(naphthalen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

5-(4-(benzofuran-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

5-(4-(benzofuran-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

5-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-

6-yl)thiophene-2-carbonitrile;

5-(4-((1 H-indol-2-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile; 5-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

5-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]-

[1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)benzo- nitrile;

4-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- benzonitrile;

4-(4-(benzofuran-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)benzo- nitrile;

4-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin-6-yl)- benzonitrile;

4-(4-(naphthalen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)benzo- nitrile;

4-(4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-dihyd ro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(1 -oxido-4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-d ihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile;

4-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-

6-yl)benzonitrile;

4-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile; 4-(4-(naphthalen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- benzonitrile;

4-(4-(naphthalen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]-

[1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-(benzofuran-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- benzonitrile;

4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-(benzofuran-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- benzonitrile;

4-(4-((1 H-indol-2-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b][1 ,4]thiazin- 6-yl)benzonitrile;

4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

4-(1 -oxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)benzonitrile;

4- (1 ,1 -dioxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)benzonitrile;

5- (4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

4-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)benzonitrile;

5-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)furan-2-carbonitrile; 5- (4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)-1 H-pyrrole-2-carbonitrile;

6- (4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)nicotinonitrile;

5-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)picolinonitrile;

2-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- thiazole-5-carbonitrile;

2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)thiazole-5-carbonitrile;

2-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin- 6-yl)thiazole-5-carbonitrile;

2-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin-6-yl)- thiazole-5-carbonitrile;

2-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiazole-5-carbonitrile;

4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- thiophene-2-carbonitrile;

4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile;

4- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- thiophene-2-carbonitrile;

4-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile;

3,5-dimethyl-4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]thiazin-6-yl)isoxazole;

3,5-dimethyl-4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)isoxazole;

5- ((6-(3,5-dimethylisoxazol-4-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)-yl)sulfonyl)-2- methylbenzo[d]oxazole;

4- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)-3,5- dimethylisoxazole;

5-((6-(3,5-dimethylisoxazol-4-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)-yl)sulfonyl)-1 H- benzo[d]imidazol-2(3H)-one;

5- (4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)- oxazole; 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)oxazole;

2-methyl-5-((6-(oxazol-5-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)-yl)sulfonyl)benzo[d]- oxazole;

5-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin-6-yl)- oxazole;

5- ((6-(oxazol-5-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)-yl)sulfonyl)-1 H-benzo[d]- imidazol-2(3H)-one;

2-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- thiazole-5-carbonitrile;

2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]oxazin- 6-yl)thiazole-5-carbonitrile;

2-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin- 6-yl)thiazole-5-carbonitrile;

2-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]oxazin-6-yl)- thiazole-5-carbonitrile;

2-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)thiazole-5-carbonitrile;

4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

4-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]oxazin-6-yl)- thiophene-2-carbonitrile;

4-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

6-(3,5-dimethylisoxazol-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

6- (3,5-dimethylisoxazol-4-yl)-4-((2-methylbenzo[d]thiazol-6-yl )sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazine;

6-(3,5-dimethylisoxazol-4-yl)-4-((2-methylbenzo[d]oxazol-5-y l)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazine;

4- (benzo[b]thiophen-2-ylsulfonyl)-6-(3,5-dimethylisoxazol-4-yl )-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

5- ((6-(3,5-dimethylisoxazol-4-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H- benzo[d]imidazol-2(3H)-one;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(oxazol-5-yl)-3,4-dihydro-2H-benzo[ b]-

[1 ,4]oxazine;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(oxazol-5-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]oxazine; 4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-6-(oxazol-5-yl)-3, 4-dihydro-2H- benzo[b][1 ,4]oxazine;

4- (benzo[b]thiophen-2-ylsulfonyl)-6-(oxazol-5-yl)-3,4-dihydro- 2H- benzo[b][1 ,4]oxazine;

5-((6-(oxazol-5-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H-benzo[d]- imidazol-2(3H)-one;

5- (4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- 1 H-pyrrole-2-carbonitrile;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]oxazin- 6-yl)-1 H-pyrrole-2-carbonitrile;

5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin- 6-yl)-1 H-pyrrole-2-carbonitrile;

5-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]oxazin-6-yl)-1 H- pyrrole-2-carbonitrile;

5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)-1 H-pyrrole-2-carbonitrile;

5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- furan-2-carbonitrile;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]oxazin- 6-yl)furan-2-carbonitrile;

5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin- 6-yl)furan-2-carbonitrile;

5-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]oxazin-6-yl)- furan-2-carbonitrile;

5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)furan-2-carbonitrile;

4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-6-(6-methylpyridin -3-yl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

4-(benzo[b]thiophen-2-ylsulfonyl)-6-(6-methylpyridin-3-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]oxazine;

4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-6-(pyridin-4-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]oxazine;

4- (benzo[b]thiophen-2-ylsulfonyl)-6-(pyridin-4-yl)-3,4-dihydro -2H-benzo[b]- [1 ,4]oxazine;

5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin- 6-yl)pyrimidine-2-carbonitrile;

5- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- pyrimidine-2-carbonitrile; 5- (4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)pyrimidine-2-carbonitrile;

6- (2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]oxazol-6-yl)su lfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine;

4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2-methoxypyrimidin-5-yl )-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

5- ((6-(2-methoxypyrimidin-5-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H- benzo[d]imidazol-2(3H)-one;

6- (2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)s ulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazine;

4-(benzo[b]thiophen-2-ylsulfonyl)-6-(6-fluoropyridin-3-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine;

4-(benzo[b]thiophen-2-ylsulfonyl)-6-(6-fluoropyridin-3-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]oxazine;

6-(6-fluoropyridin-3-yl)-4-((5-methylbenzo[b]thiophen-2-yl)s ulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine;

6-(6-fluoropyridin-3-yl)-4-((5-methylbenzo[b]thiophen-2-yl)s ulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazine;

4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2,3-difluoropyridin-4-y l)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2,3-difluoropyridin-4-y l)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2,3-difluoropyridin-4-y l)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide;

6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

6-(2-fluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

6-(2-fluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine;

6-(2-fluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazine; 6-(6-fluoropyridin-3-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H benzo[b][1 ,4]thiazine;

6-(6-fluoropyridin-3-yl)-4-((2-methylbenzo[d]oxazol-5-yl)sul fonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

6-(6-fluoropyridin-3-yl)-4-((2-methylbenzo[d]oxazol-6-yl)sul fonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine, and

6-((6-(2,3-difluoropyridin-4-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)-yl)sulfonyl)-2-methyl- benzo[d]oxazole. In particular preferred compounds according to the present invention are the compounds listed below, their pharmaceutically acceptable salts, their N-oxides and the pharmaceutically acceptable salts of said N-oxides:

5-(4-((4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1 ,4]oxazin-7-yl)sulfonyl)-3,4-dihydro-

2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-

6-yl)benzonitrile;

4- (4-((4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1 ,4]oxazin-7-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazin-6-yl)benzonitrile;

5- (4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H-be nzo[b][1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((4-methyl-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((2-(2,2,2-trifluoroacetyl)-1 ,2,3,4-tetrahydroisoquinolin-7-yl)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- thiophene-2-carbonitrile;

5-(4-((2-oxoindolin-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- thiophene-2-carbonitrile;

5-(4-((1 ,3-dimethyl-2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

5-(4-(benzo[d]isoxazol-5-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]oxazin-6-yl)- thiophene-2-carbonitrile;

5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile; 5-(4-((5-(dimethylamino)naphthalen-1 -yl)sulfonyl)-3,4-dihydro-2H-benzo[b]- [1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((2-oxo-2H-chromen-6-yl)sulfonyl)-3,4-dihydro-2H-benzo[ b][1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

5-(4-(naphthalen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene- 2-carbonitrile;

5-(4-(benzofuran-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene- 2-carbonitrile;

5-(4-((2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)sulfonyl)-3,4-di hydro-2H-benzo[b]- [1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

5-(4-((1 -methyl-2-oxoindolin-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][ 1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

5-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl )sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

5-(4-(chroman-6-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene- 2-carbonitrile;

5-(4-((2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)sulfonyl)-3,4-di hydro-2H-benzo[b]- [1 ,4]oxazin-6-yl)thiophene-2-carbonitrile;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(6-methylpyridin-3-yl)-3,4-dihydro- 2H- benzo[b][1 ,4]oxazine;

4- ((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridin- 3-yl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

6-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)nicotinonitrile;

5- ((6-(pyridin-4-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H-benzo[d]- imidazol-2(3H)-one;

5-((6-(benzofuran-5-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H-benzo[d]- imidazol-2(3H)-one;

5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)benzo[d]oxazol-2(3H)-one;

5- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- thiophene-2-carbonitrile;

6-(1 -methyl-1 H-indol-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4 -dihydro-

2H-benzo[b][1 ,4]oxazine;

6- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H-b enzo[b][1 ,4]oxazin- 6-yl)nicotinonitrile; 5- (4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H-b enzo[b][1 ,4]oxazin- 6-yl)picolinonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-4-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]oxazin- 6-yl)pyrimidine-2-carbonitrile;

4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- thiophene-2-carbonitrile;

4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile;

4- ((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- picolinonitrile;

6- (4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- nicotinonitrile;

5- (4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- pyrimidine-2-carbonitrile;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(pyrimidin-5-yl)-3,4-dihydro-2H-ben zo[b]- [1 ,4]oxazine;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(pyridin-4-yl)-3,4-dihydro-2H-benzo [b]- [1 ,4]oxazine;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(p-tolyl)-3,4-dihydro-2H-benzo[b]-

[1 ,4]oxazine;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(2-methylpyridin-4-yl)-3,4-dihydro- 2H- benzo[b][1 ,4]oxazine;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(2-methylpyrimidin-5-yl)-3,4-dihydr o-2H- benzo[b][1 ,4]oxazine;

6- (2-methoxypyrimidin-5-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine;

4- ((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(5-methylpyridin-2-yl)-3,4-dihydro- 2H- benzo[b][1 ,4]oxazine;

4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(5-(trifluoromethyl)pyridin-2-yl)-3 ,4-dihydro-

2H-benzo[b][1 ,4]oxazine;

5- (4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)- pyrimidin-2-amine; 5-((6-(6-methylpyridin-3-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H- benzo[d]imidazol-2(3H)-one;

5-((6-(2-methylpyrimidin-5-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H- benzo[d]imidazol-2(3H)-one,

5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H -benzo[b][1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile.

The compounds herein were named according to lUPAC standard using the software Struct=Name in ChemDraw Ultra version 10 from Cambridgesoft.

The compounds of the formula (I) according to the present invention can be prepared by various routes in analogy to prior art processes known per se for preparing 2,3-dihydrobenzazine compounds. Advantageously, they can be obtained as outlined in schemes 1 , 2 and 3.

Generally, compounds of the formula I , wherein X is oxygen or sulfur can be prepared e.g. starting from 6-halogen-3,4-dihydro-2H-benzo[b][1 ,4]oxazine II and

6-halogen-3,4-dihydro-2H-benzo[b][1 ,4]thiazine I I , respectively, or the salts thereof. Scheme 1 :

Scheme 2:

Scheme 3:

In schemes 1 , 2 and 3, R ¹ and R ² have the aforementioned meanings. X is O or S. R ^a and R ^b are hydroxyl or Ci-C4-alkoxy such as methoxy or ethoxy or R ^a and R ^b together form a moiety 0-R-O, wherein R is ethan-1 ,2-diyl, 1 ,1 ,2,2-tetramethylethan-1 ,2- diyl, propan-1 ,3-diyl, 2,2-dimethylpropan-1 ,3-diyl or 1 , 1 ,3-trimethylpropan-1 ,3-diyl. Hal and Hal' are each independently chlorine, bromine or iodine, preferably bromine or chlorine. "Pd" denominates a Pd(0) catalyst or a Pd(0) precursor compound, optionally in combination with a suitable ligand. "Base" denominates a suitable basic compound which assists in the formation of the sulfonylamide formation.

According to the first step of scheme 1 , the halogen compound II or a salt thereof, e.g. an acid addition salt such as the salt with a hydrohalic acid, is treated with a boronic compound II I , in a known manner, under conditions of a Suzuki coupling in the presence of a palladium catalyst to give a compound IV intermediate. The reaction is usually carried out in the presence of a base and a palladium catalyst, such as for example described in the following literature: Synth. Commun. Vol. 1 1 , p. 513 (1981 ); Acc. Chem. Res. Vol. 15, pp. 178-184 (1982); Chem. Rev. Vol. 95, pp. 2457-2483 (1995); Organic Letters Vol. 6 (16), p. 2808 (2004); "Metal catalyzed cross coupling reactions", 2 ^nd Edition, Wiley, VCH 2005 (Eds. De Meijere, Diederich); "Handbook of organopalladium chemistry for organic synthesis" (Eds Negishi), Wiley, Interscience, New York, 2002; "Handbook of functionalized organometallics", (Ed. P. Knochel), Wiley, VCH, 2005 or in the experimental part of this application.

Suitable catalysts are in tetrakis(triphenylphosphine)palladium(0);

bis(triphenylphosphine)palladium(ll) chloride; bis(acetonitrile)palladium(l l) chloride;

[1 , 1 '-bis(diphenylphosphino)ferrocene]-palladium(ll) chloride/methylene chloride (1 :1 ) complex; bis[bis-(1 ,2-diphenylphosphino)ethane]palladium(0);

bis(bis-(1 ,2-diphenylphosphino)butane]-palladium(l l) chloride; palladium(l l) acetate; palladium(l l) chloride; and palladium(l l) acetate/tri-o-tolylphosphine complex or mix- tures of phosphines and Pd salts or phosphines and Pd-complexes e.g. diben- zylideneacetone-palladium and tri-tert-butylphosphine (or its tetrafluoroborate), triscy- clohexylphosphine; or a polymer-bound Pd-triphenylphosphine catalyst system.

Suitable bases are, in general, inorganic compounds, such as alkali metal and al- kaline earth metal oxides, such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, sodium carbonate, potassium carbonate, caesium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, alkali metal and alkaline earth metal alkoxides, such as sodium methoxide, sodium ethoxide, po- tassium ethoxide and potassium tert.-butoxide, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines, preferably potassium carbonate.

The reaction is usually carried out in an inert organic solvent. Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, ethers, such as diisopropyl ether, tert. -butyl methyl ether, 1 ,4-dioxane, anisole and tetrahydrofuran and dimethoxyethane, alkanol, e.g. Ci-C6-alkanols such as methanol, ethanol or n- propanol, or mixtures of these solvents, particularly preferably ethers, such as dioxane or a mixture of toluene/methanol.

According to the second step of scheme 1 , the compound IV intermediate is reacted with a sulfonylchloride V in accordance with standard methods of organic chemistry and as described in the experimental part of this application. This reaction is usually carried out in an inert organic solvent. Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and petroleum ether, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as dichloro- methane, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert. -butyl methyl ether, dioxane, anisole and tetrahydrofuran.

The reaction of compound IV intermediate with compound V is customarily car- ried out in the presence of an auxiliary base. Suitable bases are inorganic bases, such as sodium carbonate or potassium carbonate, or sodium hydrogen carbonate or potassium hydrogen carbonate, and organic bases, for example trialkylamines, such as triethylamine, or pyridine compounds, such as pyridine, lutidine, 4-dimethylaminopyridine and the like. The auxiliary base is customarily employed in at least equimolar quantities, based on the amine compound IV.

If not indicated otherwise, the above-described reactions are generally carried out in a solvent at temperatures between room temperature and the boiling temperature of the solvent employed. Alternatively, the activation energy which is required for the reaction can be introduced into the reaction mixture using microwaves, something which has proved to be of value, in particular, in the case of the Suzuki coupling (with regard to reactions using microwaves, see Tetrahedron 2001 , 57, p. 9199 ff. and p. 9225 ff. and also, in a general manner, "Microwaves in Organic Synthesis", Andre Loupy (Ed.), Wiley-VCH 2002.

A skilled person will appreciate that the first step of scheme 2 can be performed under conditions as described for the second step of scheme 1 . Similarly, the second step of scheme 2 can be performed under conditions as described for the first step of scheme 1.

It may be advantageous that schemes 1 and 2 include an additional step as shown in scheme 3. According to scheme 3, compound II is first converted into the arylboronic compound I la under conditions of a Suzuki coupling. The conversion can be performed e.g. as described above for the first step of scheme 1 . Preferably, the diboron ester Ilia is bis(pinacolato)diboron, bis(neopentyl glycolato)diboron or bis(hexylene glycolato)diboron, especially bis(pinacolato)diboron. Then, compound I la can be converted into compound I either by reacting I la with an appropriate heteroaro- matic or aromatic halogenide VII to give compound IV intermediate and reacting the obtained compound IV intermediate with a sulfonylchloride V as described in scheme 1 or by reacting I la with an appropriate sulfonylchloride V to give compound Via intermediate and then reacting the obtained compound Via intermediate with a (het)arylhalide R ² Hal' (compound VII) under conditions of a Suzuki coupling as described in scheme 2.

The starting materials of the formula II required for preparing the compounds I are known from the literature or commercially available, can be prepared by the average skilled person trained in organic chemistry without undue burden following routine laboratory practice, or as described in the experimental part of this application.

Boronic compounds III and Ilia are commercially available or can be prepared according to "Science of Synthesis" Vol. 6, Thieme, 2005.

If sulfonylchlorides V are not commercially available, they can be obtained according to procedures known in the art without undue burden following routine laboratory practice.

Compounds of the formula I, wherein X is S=0, can be prepared by treating compounds I, wherein X is sulfur with an appropriate amount of an oxidizing agent, in particular an inorganic or organic peroxide or hydroperoxide, e.g. a percarboxylic acid such as 3-chloroperbenzoic acid or monoperphthalic acid or with an appropriate amount of alkali metal periodate or hydroperoxide.

Compounds of the formula I, wherein X is SO2, can be prepared by, for example, treating the compound of formula I, wherein X is S or SO, with an appropriate amount of an oxidizing agent, in particular an inorganic or organic peroxide or hydroperoxide, e.g. a percarboxylic acid such as 3-chloroperbenzoic acid or monoperphthalic acid or with an appropriate amount of alkali metal periodate or hydroperoxide. The N-oxides of compounds of formula I can be prepared by, for example, treating a compound of the formula I with an oxidizing agent, in particular an inorganic or organic peroxide or hydroperoxide, such as hydrogen peroxide, or percarboxylic acids, such as peracetic acid, perbenzoic acid or m-chloroperbenzoic acid.

Besides the guidance provided in the general procedures below, alternative synthetic transformations that may be employed in the synthesis of compounds of formula (I) and in the synthesis of intermediates involved in the synthesis of compounds of formula (I) are known by or accessible to one skilled in the art. Collections of synthetic transformations may be found in compilations, such as: J. March. Advanced Organic Chemistry, 4th ed.; John Wiley: New York (1992) R. C. Larock. Comprehensive Organic Transformations, 2nd ed.; Wiley-VCH: New York (1999); F. A. Carey; R. J.

Sundberg. Advanced Organic Chemistry, 2nd ed.; Plenum Press: New York (1984) T. W. Greene; P. G. M. Wuts. Protective Groups in Organic Synthesis, 3rd ed.; John Wiley: New York (1999). L. S. Hegedus. Transition Metals in the Synthesis of Complex Organic Molecules, 2nd ed.; University Science Books: Mill Valley, CA (1994) L. A. Paquette, Ed. The Encyclopedia of Reagents for Organic Synthesis; John Wiley: New York (1994). A. R. Katritzky; O. Meth-Cohn; C. W. Rees, Eds. Comprehensive Organic Functional Group Transformations ; Pergamon Press: Oxford, UK (1995). G. Wilkinson; F. G A. Stone; E. W. Abel, Eds. Comprehensive Organometallic Chemistry; Pergamon Press: Oxford, UK (1982). B. M. Trost; I. Fleming; Comprehensive Organic Synthesis; Pergamon Press: Oxford, UK (1991 ) A. R. Katritzky; C. W. Rees Eds. Comprehensive Heterocylic Chemistry; Pergamon Press: Oxford, UK (1984) A. R. Katritzky; C. W. Rees; E. F. V. Scriven, Eds. Comprehensive Heterocylic Chemistry; Pergamon Press : Oxford, UK (1996). C. Hansch; P. G. Sammes; J. B. Taylor, Eds. Comprehensive Me- dicinal Chemistry: Pergamon Press: Oxford, UK (1990).

In addition, recurring reviews of synthetic methodology and related topics include Organic Reactions ; John Wiley : New York; Organic Syntheses ; John Wiley: New York; Reagents for Organic Synthesis: John Wiley: New York; The Total Synthesis of Natural Products; John Wiley: New York; The Organic Chemistry of Drug Synthesis; John Wiley: New York; Annual Reports in Organic Synthesis; Academic Press: San

Diego CA; and Methoden der Organischen Chemie (Houben- Weyl); Thieme: Stuttgart, Germany. Furthermore, databases of synthetic transformations include Chemical Abstracts, which may be searched using either CAS OnLine or SciFinder, Handbuch der Organischen Chemie (Beilstein), which may be searched using Crossfire, and RE- ACCS.

As shown in the examples below, the advantageous properties of the compounds of the invention include their ability of effectively inhibiting cell proliferation and their activity as HIF inhibitors. For example, the compounds of the present invention were shown to inhibit the activation of HIF-mediated transcription under hypoxic conditions. Thus, the compounds of the invention can be used for the preparation of a medicament for the treatment of a disorder characterized by pathophysiological HIF signaling. A person skilled in the art of medical, biological and/or pharmacological science can determine with routine methodology if a disorder is characterized by undesirable HIF sig- naling. Tissues affected by such diseases will overexpress genes that are induced by activation of the HIF responsive element (HRE). HIF-1 acts by binding to HIF- responsive elements (HREs) in promoters that generally contain the sequence

NCGTG. The genes affected by HIF activity which are regulated by said promoters are well known in the art and were also described in multiple reviews (see e.g. figure 3 of Gregg L. Semenza, Nature Reviews, Oct. 2003, vol. 3).

In animal studies, HIF-1 overexpression is associated with increased tumor growth, increased vascularization, metastasis and fibrosis, e.g. renal fibrosis (see: Semenza, G., Drug Discovery Today, vol. 12, no. 19/20, October 2007; Kimura, Kuniko, et al., American Journal of Physiology (2008), 295(4, Pt. 2), F1023-F1029 and for a re- view see N. J. Mabjeesh et al., Histol. Histopathol (2007) 22:559-572). Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue. Recently, it has become clear that inhibition of HIF-1 activity also acts to prevent inflammation, by virtue of its essential role in the activation and infiltration of macrophages and neutrophils into affected tissues (see e.g. Giaccia et al., Drug Discovery, vol. 2, October 2003).

For the above mentioned reasons, a compound of the present invention can be used to treat an inflammatory disease, a hyperproliferative disease or disorder, a hypoxia related pathology and also diseases characterized by pathophysiological hyper- vascularization. Therefore, as a further aspect, the invention provides a pharmaceutical composition comprising at least one compound of the present invention, optionally together with at least one physiologically acceptable carrier or auxiliary substance.

As a further aspect, the invention provides a therapeutical composition which, in addition to the compound of the invention comprises at least one further pharmaceutically active compound that is useful to treat one of the aforementioned diseases or disorders. Such therapeutical compositions are useful because the therapeutic efficiency of the compounds of the invention can be amplified by the presence of said at least one further pharmaceutically active compound and vice versa. For example, it was shown that inhibiting HIF1 a activity via antisense gene therapy enhances the therapeutic efficacy of doxorubicin to combat hepatocellular carcinoma (see Liu, Feng- jun et. al., Cancer Science (2008), 99(10), 2055-2061 ).

In a further aspect, the present invention relates to a pharmaceutical composition comprising a compound according to the invention and a second therapeutic agent useful for the treatment or prevention of a disease or disorder selected from the group consisting of an inflammatory disease, a hyperproliferative disease or disorder, a hy- poxia related pathology and a disease characterized by pathophysiological hyper- vascularization, and, optionally, a pharmaceutically acceptable carrier or excipient. Such compositions are also useful to obtain synergistic therapeutic effects and also to prevent drug resistance of tumor cells, for example. It is also for these reasons, that current chemotherapy generally involves administering a cocktail of different cytotoxic and/or cytostatic compounds to improve the effectiveness of the treatment and reduce the possibility of tumor cell adaptation.

In a further aspect, the present invention relates to a pharmaceutical composition comprising a compound according to the invention in combination with radiation thera- pies.

Any composition of the present invention may be admixed with a pharmaceutically acceptable diluent, excipient or carrier, or a mixture thereof.

Even though the compounds of the present invention (including their pharmaceutically acceptable salts, their N-oxides, the salts of said N-oxides, ester derivatives and pharmaceutically acceptable solvates) can be administered alone, they will generally be administered in a mixture with a pharmaceutical carrier, excipient or diluent, particularly for human therapy. The pharmaceutical compositions may be for human or animal usage in human and veterinary medicine. Examples of such suitable excipients for the various different forms of pharmaceutical compositions described herein may be found in the "Handbook of Pharmaceutical Excipients", 2nd Edition, (1994), Edited by A

Wade and PJ Weller. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R Gennaro edit. 1985).

For preparing pharmaceutical compositions from the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dis- persible granules. A solid carrier can be one or more substances, which may also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.

In powders, the carrier is a finely divided solid, which is in a mixture with the finely divided active component. In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired.

The powders and tablets preferably contain from 1 % to 80%, more preferably from 5% to 60% of the active compound or active compounds. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term "preparation" is intended to include the formulation of the active compound with encapsulating material as a carrier provid- ing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.

For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify.

Liquid form preparations include solutions, suspensions, and emulsions, for ex- ample, water or water/propylene glycol solutions. Liquid forms are particularly preferred for topical applications to the eye. For parenteral injection, liquid preparations can be formulated in solution as in aqueous polyethylene glycol solution.

Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizers, and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents.

Also included are solid form preparations, which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

The pharmaceutical preparation is preferably in unit dosage form. In such form the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.

Interestingly, HIF inhibitors, such as the compounds of the invention, can prevent the development of tumor resistance towards chemotherapeutic drugs and can make cancer cells more sensitive towards radiotherapy (see e.g. Palayoor ST, et al., Int J Cancer. 2008 Nov 15; 123(10):2430-7 and Gregg L. Semenza, Nature Reviews, Oct. 2003, vol. 3). Thus, useful second therapeutic agents that can be combined with a compound of the invention to produce the pharmaceutical composition of the invention include, without limitation, a (further) HIF-1 inhibitor, a cytotoxic compound and cytostatic compounds. A HIF-1 inhibitor can be, e.g. selected from the group consisting of PX-478 (S-2-amino-3-[4'-A/,A/,-bis(2-chloroethyl)amino]phenyl propionic acid A/-oxide dihydro- chloride); a topoisomerase-1 inhibitor such as 8,9-Dimethoxy-5-(2-A/,A/-dimethyl- aminoethyl)-2,3-methylenedioxy-5/-/-dibenzo[c, ?][1 ,6] naphthyridin-6-one (also known as ARC-1 1 1 or topovale) or (S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1 H- pyrano[3',4':6,7] indolizino [1 ,2-£>]quinoline-3,14-(4/-/ ,12H)-dione monohydrochloride (also referred to as tropotecan); echinomycin; chetomin (NSC289491 ); cyclosporine A; 3-[2-[4-[bis(4-fluorophenyl)methylene]-1 -piperidinyl]-2,3-dihydro-2-thioxo-4(1 H)- quinazolinone (R59949); an inhibitor of the PI K3K/Akt/mTor signaling cascade, e.g., LY294002, wortmannin or rapamycin; an inhibitor of the MAPK signaling cascade, e.g. the MEK1 inhibitor PD98059; a soluble guanyl cyclase stimulator such as

3-(5'-hydroxymethyl-2'-furyl)-1 -benzylindazole (YC-1 ); a heat-shock protein 90 inhibitor, in particular radicicol, the radicicol analogue KF58333 or geldanamycin; a microtubule disrupting agent, in particular e.g. taxol, vincristine or 2-methoxyestradiol; a histone deacetylase inhibitor, e.g. FK228; a thioredoxin inhibitor, in particular PX-12 or pleu- rotin; UCNO-1 ; diphenylene iodonium, genestein and carboxyamido-triazole.

Many cytotoxic or cytostatic compounds are known to the expert artisan skilled in the therapy of hyperproliferative diseases or disorders such as a tumor or cancer disease. For example, cytotoxic and cytostatic compounds include, but are not limited to, pure or mixed anti-estrogens such as faslodex, tamoxifen or raloxifen; any inhibitors of topoisomerase I or II, such as camptothecin (topo I) or etoposide (topo II); any compound that acts through inhibiting aromatase activity, such as anastrozole or letrozole; any preparation that interferes with HER2 signaling such as herceptin; any compound that intercalates DNA, such as doxorubicin. Particularly preferred cytostatic or cytotoxic drugs, which can be combined with the compounds of the present invention are alkylating substances, anti-metabolites, antibiotics, epothilones, nuclear receptor agonists and antagonists, anti-androgenes, anti-estrogens, platinum compounds, hormones and antihormones, interferons and inhibitors of cell cycle-dependent protein kinases (CDKs), inhibitors of cyclooxygenases and/or lipoxygenases, biogeneic fatty acids and fatty acid derivatives, including prostanoids and leukotrienes, inhibitors of protein kinases, inhibitors of protein phosphatases, inhibitors of lipid kinases, platinum coordination complexes, ethyleneimenes, methylmelamines, trazines, vinca alkaloids, pyrimidine analogs, purine analogs, alkylsulfonates, folic acid analogs, anthracen- diones, substituted urea, methylhydrazin derivatives, in particular acediasulfone, acla- rubicine, ambazone, aminoglutethimide, L-asparaginase, azathioprine, bleomycin, busulfan, calcium folinate, carboplatin, carpecitabine, carmustine, celecoxib, chlorambucil, cis-platin, cladribine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin dapsone, daunorubicin, dibrompropamidine, diethylstilbestrole, docetaxel, doxorubicin, enediynes, epirubicin, epothilone B, epothilone D, estramucin phosphate, estrogen, ethinylestradiole, etoposide, flavopiridol, floxuridine, fludarabine, fluorouracil, fluoxyme- sterone, flutamide fosfestrol, furazolidone, gemcitabine, gonadotropin releasing hormone analogue, hexamethylmelamine, hydroxycarbamide, hydroxymethylnitrofuran- toin, hydroxyprogesteronecaproate, hydroxyurea, idarubicin, idoxuridine, ifosfamide, interferon γ , irinotecan, leuprolide, lomustine, lurtotecan, mafenide sulfate olamide, mechlorethamine, medroxyprogesterone acetate, megastrolacetate, melphalan, mepa- crine, mercaptopurine, methotrexate, metronidazole, mitomycin C, mitopodozide, mito- tane, mitoxantrone, mithramycin, nalidixic acid, nifuratel, nifuroxazide, nifuralazine, nifurtimox, nimustine, ninorazole, nitrofurantoin, nitrogen mustards, oleomucin, oxolinic acid, pentamidine, pentostatin, phenazopyridine, phthalylsulfathiazole, pipobroman, prednimustine, prednisone, preussin, procarbazine, pyrimethamine, raltitrexed, rapa- mycin, rofecoxib, rosiglitazone, salazosulfapyridine, scriflavinium chloride, semustine streptozocine, sulfacarbamide, sulfacetamide, sulfachlopyridazine, sulfadiazine, sul- fadicramide, sulfadimethoxine, sulfaethidole, sulfafurazole, sulfaguanidine,

sulfaguanole, sulfamethizole, sulfamethoxazole, co-trimoxazole, sulfamethoxydiazine, sulfamethoxypyridazine, sulfamoxole, sulfanilamide, sulfaperin, sulfaphenazole, sul- fathiazole, sulfisomidine, staurosporin, tamoxifen, taxol, teniposide, tenyposide, testo- lactone, testosteronpropionate, thioguanine, thiotepa, tinidazole, topotecan, tri- aziquone, treosulfan, trimethoprim, trofosfamide, UCN-01 , vinblastine, vincristine, vindesine, vinblastine, vinorelbine, and zorubicin, or their respective derivatives or analogs thereof. Several of the above indicated drugs are now administered simultaneously for cancer therapy and, consequently, it is also envisioned that more than one cytostatic and/or cytotoxic drug can be comprised in compositions of the present invention.

As mentioned above, HIF inhibitors render cancer cells more vulnerable to chemotherapy and radiation therapy. Thus, to effectively treat a hyperproliferative disease or disorder, the compounds of the present invention can be co-administered with other active medicinal agents and/or administered in conjunction with other anticancer, antitumor, or antiproliferative disease therapies. In one aspect, the invention provides a method for treating a hyperproliferative disease or disorder comprising administering a compound according to the invention to a patient prior to, during and/or after said patient was subjected to a radiation therapy, a chemotherapy, an immunotherapy, a laser/microwave thermotherapy or a gene therapy using antisense DNA and RNA (for examples see Moeller et al., Cancer Cell 2004 5429-441 ).

In a further aspect the invention provides, as already outlined above, the use of a compound according to the invention or a composition according to the invention for the preparation of a medicament for the therapy, including the treatment or prevention, of a disease or disorder selected from the group consisting of an inflammatory disease, a hyperproliferative disease or disorder, a hypoxia related pathology such as e.g. dia- betic retinopathy, ischemic reperfusion injury, ischemic myocardial and limb disease, ischemic stroke, sepsis and septic shock (see, e.g. Liu FQ, et al., Exp Cell Res. 2008 Apr 1 ;314(6): 1327-36); and a disease characterized by pathophysiological hyper- vascularization, such as e.g. angiogenesis in osteosarcoma (see, e.g.: Yang, Qing- cheng et al., Dier Junyi Daxue Xuebao (2008), 29(5), 504-508), macular degeneration, in particular, age-related macular degeneration and vasoproliferative retinopathy (see e.g. Kim JH, et al., J Cell Mol Med. 2008 Jan 19).

As was already mentioned above, HIF inhibitors, such as the compounds of the invention, are useful to treat inflammatory disease or disorder. For example, it was shown that oxygen-dependent HIF isoforms are strongly upregulated in psoriatic skin (see e.g. Rosenberger C, et al., J Invest Dermatol. 2007 Oct; 127(10):2445-52). Furthermore it was shown that a HIF inhibitor, neovastat, inhibits the airway inflammation in asthma (see e.g., Lee SY, et al., Vascul Pharmacol. 2007 Nov-Dec; 47(5-6):313-8). Furthermore, recent evidence also shows that HIF participates under hypoxic condi- tions in joint inflammation and destruction in rheumatoid arthritis (see e.g., Ahn, J. K., et al., Rheumatology (Oxford, United Kingdom) (2008), 47(6), 834-839). Thus, in a preferred embodiment of the use of the invention, the inflammatory disease is selected form the group consisting of atherosclerosis, rheumatoid arthritis, asthma, inflammatory bowel disease, psoriasis, in particular psoriasis vulgaris, psoriasis capitis, psoriasis guttata, psoriasis inversa; neurodermatitis; ichtyosis; alopecia areata; alopecia totalis; alopecia subtotalis; alopecia universalis; alopecia diffusa; atopic dermatitis; lupus ery- thematodes of the skin; dermatomyositis of the skin; atopic eczema; morphea;

scleroderma; alopecia areata Ophiasis type; androgenic alopecia; allergic dermatitis; irritative contact dermatitis; contact dermatitis; pemphigus vulgaris; pemphigus foli- aceus; pemphigus vegetans; scarring mucous membrane pemphigoid; bullous pemphigoid; mucous membrane pemphigoid; dermatitis; dermatitis herpetiformis Duhring; urticaria; necrobiosis lipoidica; erythema nodosum; prurigo simplex; prurigo nodularis; prurigo acuta; linear IgA dermatosis; polymorphic light dermatosis; erythema Solaris; exanthema of the skin; drug exanthema; purpura chronica progressiva; dihydrotic ec- zema; eczema; fixed drug exanthema; photoallergic skin reaction; and perioral dermatitis. Therefore, a further preferred embodiment of the present invention encompasses a combination of one or more compounds of the present invention and medication in current use for treating such inflammatory diseases or conditions, which can be determined by a person skilled in the art of pharmacological sciences. Such therapeutics for combination can be selected e.g. from a group of anti-inflammatory steroids, antioxidants, therapeutic antibodies or fusion proteins that sequester or bind to certain cytokines or cellular epitopes associated with inflammatory processes, or a dihydrofolate reductase inhibitor like methotrexate. The compounds of the invention show anti-proliferative effects. Furthermore, HIF inhibitors, such as the compounds of the invention are effective medicaments for the treatment of various cancer diseases (see review article by e.g. Gregg L. Semenza, Nature Reviews, Oct. 2003, vol. 3 and also review article by N.J. Mabjeesh et al., His- tol. Histopathol (2007), 22:559-572). Thus, also preferred is the use of the invention wherein the hyperproliferative disease is selected from the group consisting of a tumor or cancer disease, precancerosis, dysplasia, histiocytosis, a vascular proliferative disease and a virus-induced proliferative disease. Thus, in one preferred embodiment of the use of the invention the hyperproliferative disease is a tumor or cancer disease selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), T-cell lymphomas or leukemias, e.g., cutaneous T-cell lymphoma (CTCL), noncutaneous peripheral T-cell lymphoma, lymphoma associated with human T-cell lymphotrophic virus (HTLV), adult T- cell leukemia/lymphoma (ATLL), as well as acute lymphocytic leukemia, acute nonlymphocytic leukemia, acute myeloid leukemia, chronic lympho- cytic leukemia, chronic myelogenous leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, myeloma, multiple myeloma, mesothelioma, childhood solid tumors, glioma, bone cancer and soft-tissue sarcomas, common solid tumors of adults such as head and neck cancers (e.g., oral, laryngeal and esophageal), genitourinary cancers (e.g., prostate, bladder, renal (in particular malignant renal cell carcinoma (RCC)), uterine, ovarian, testicular, rectal, and colon), lung cancer (e.g., small cell carcinoma and non- small cell lung carcinoma, including squamous cell carcinoma and adenocarcinoma), breast cancer, pancreatic cancer, melanoma and other skin cancers, basal cell carcinoma, metastatic skin carcinoma, squamous cell carcinoma of both ulcerating and papillary type, stomach cancer, brain cancer, liver cancer, adrenal cancer, kidney cancer, thyroid cancer, medullary carcinoma, osteosarcoma, soft-tissue sarcoma, Ewing's sarcoma, veticulum cell sarcoma, and Kaposi's sarcoma, fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endo- theliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, leiomyosarcoma, rhabdomyosarcoma, squamous cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, glioblastoma, papillary adenocarcinomas, cystadenocarcinoma, bronchogenic carcinoma, seminoma, embryonal carcinoma, Wilms' tumor, small cell lung carcinoma, epithelial carcinoma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, heman- gioblastoma, acoustic neuroma, oligodendroglioma, meningioma, neuroblastoma, reti- noblastoma, glaucoma, hemangioma, heavy chain disease and metastases.

The precancerosis treatable with the compounds of the present invention are preferably selected from the group consisting of precancerosis, in particular actinic keratosis, cutaneaous horn, actinic cheilitis, tar keratosis, arsenic keratosis, x-ray keratosis, Bowen's disease, bowenoid papulosis, lentigo maligna, lichen sclerosus, and lichen rubber mucosae; precancerosis of the digestive tract, in particular erythroplakia, leukoplakia, Barrett's esophagus, Plummer-Vinson syndrome, crural ulcer, gastropathia hypertrophica gigantea, borderline carcinoma, neoplastic intestinal polyp, rectal polyp, porcelain gallbladder; gynaecological precancerosis, in particular carcinoma ductale in situ (CDIS), cervical intraepithelial neoplasia (CIN), endometrial hyperplasia (grade III), vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), hydatidiform mole; urologic precancerosis, in particular bladder papillomatosis, Queyrat's erythroplasia, testicular intraepithelial neoplasia (TIN), carcinoma in situ (CIS); precancerosis caused by chronic inflammation, in particular pyoderma, osteomyelitis, acne conglobata, lupus vulgaris, and fistula.

Dysplasia is frequently a forerunner of cancer, and is can be found in e.g. the epi- thelia; it is the most disorderly form of non-neoplastic cell growth, involving a loss in individual cell uniformity and in the architectural orientation of cells. Dysplastic cells often have abnormally large, deeply stained nuclei, and exhibit pleomorphism. Dyspla- sia characteristically occurs where there exists chronic irritation or inflammation. Dysplastic disorders which can be treated with the compounds of the present invention include, but are not limited to, anhidrotic ectodermal dysplasia, anterofacial dysplasia, asphyxiating thoracic dysplasia, atriodigital dysplasia, bronchopulmonary dysplasia, cerebral dysplasia, cervical dysplasia, chondroectodermal dysplasia, cleidocranial dys- plasia, congenital ectodermal dysplasia, craniodiaphysial dysplasia, craniocarpotarsal dysplasia, craniometaphysial dysplasia, dentin dysplasia, diaphysial dysplasia, ectodermal dysplasia, enamel dysplasia, encephalo-ophthalmic dysplasia, dysplasia epi- physialis heminelia, dysplasia epiphysialis multiplex, dysplasia epiphysalis punctata, epithelial dysplasia, faciodigitogenital dysplasia, familial fibrous dysplasia of jaws, famil- ial white folded dysplasia, fibromuscular dysplasia, fibrous dysplasia of bone, florid osseous dysplasia, hereditary renal-retinal dysplasia, hidrotic ectodermal dysplasia, hy- pohidrotic ectodermal dysplasia, lymphopenic thymic dysplasia, mammary dysplasia, mandibulofacial dysplasia, metaphysical dysplasia, Mondini dysplasia, monostotic fibrous dysplasia, mucoepithelial dysplasia, multiple epiphysial dysplasia, oculoauricu- lovertebral dysplasia, oculodentodigital dysplasia, oculovertebral dysplasia, odontogenic dysplasia, ophthalmomandibulomelic dysplasia, periapical cemental dysplasia, polyostotic fibrous dysplasia, pseudoachondroplastic spondyloepiphysial dysplasia, retinal dysplasia, septo-optic dysplasia, spondyloepiphysial dysplasia, and ventriculo- radial dysplasia.

Estrogen receptor refers to a group of receptors which are activated by the hormone 17β -estradiol (estrogen). Two types of estrogen receptor exist: ER which is a member of the nuclear hormone family of intracellular receptors and the estrogen G protein coupled receptor GPR30 (GPER), which is a G-protein coupled receptor. Estrogen and the estrogen receptors have been implicated in breast cancer, ovarian can- cer, colon cancer, prostate cancer and endometrial cancer and other diseases. As the compounds of the invention are capable of inhibiting estrogen receptor-mediated transcriptional activity, they can be used to treat said diseases.

Thus, in a further preferred embodiment, the hyperproliferative disorders treat- able according to the invention are those which benefit from a reduced estrogen receptor signaling, i.e. disorders associated with an increased estrogen receptor signaling, if compared to healthy tissue. This particular suitability of the compounds of the present invention is based on the fact, that the compounds of the present invention potentially through inhibiting cellular replication but possibly also through an additional activity of the compounds of the present invention exert an inhibition of estrogen receptor signaling. Thus, preferred diseases, conditions and/or disorders which can be treated are selected from the group consisting of mammary tumors, endometrial tumors and tumors of the uterus. Whether a disease is associated with an increased estrogen receptor activity can be measured by a variety of art known methods including determination of ER expression level in the diseased tissue by, e.g. immunological methods, which determine the amount of expressed protein, by methods determining the amount of transcribed ER encoding nucleic acids, e.g. RT-PCR, Northern-blots, nuclear run-ons etc., and determining the activity of a nucleic acid construct comprising an ER-receptor recognition element, which drives expression of a detectable reporter, e.g. CAT, luciferase, GFP etc as described in more detail in the Experimental Section below.

Preferably, the disorders which benefit from a reduced estrogen receptor signaling are those, which show in the diseased tissue an increase in estrogen receptor signaling by at least 10%, preferably by at least 20%, 30%, 40%, 50%, 60%, 70%, if compared to healthy tissue. Preferably this increase is measured on the basis of a nucleic acid comprising an ER-receptor recognition element and the increase of the expression of a reporter driven by this element.

In therapeutic use as an antagonist of estrogen receptor signaling, acting through inhibition of cellular replication, the compounds utilized in the use of the invention are administered at the initial dosage of about 0.02 mg/kg to about 20 mg/kg daily. A daily dose range of about 0.05 mg/kg to about 10 mg/kg is preferred, with a daily dose range of about 0.05 mg/kg to about 5 mg/kg being most preferred. The dosages, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treat- ment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day, if desired. A compound according to the invention can be administered by various well known routes, including oral, rectal, intragastrical, intracranial and parenteral administration, e.g. intravenous, intramuscular, intranasal, intradermal, subcutaneous, and similar administration routes. Parenteral administration and particular intravenous ad- ministration, preferably by depot injection, is preferred. Depending on the route of administration different pharmaceutical formulations are required and some of those may require that protective coatings are applied to the drug formulation to prevent degradation of a compound of the invention in, for example, the digestive tract.

Thus, preferably, a compound of the invention is formulated as a syrup, an infu- sion or injection solution, a tablet, a capsule, a caplet, lozenge, a liposome, a suppository, a plaster, a band-aid, a retard capsule, a powder, or a slow release formulation. Preferably the diluent is water, a buffer, a buffered salt solution or a salt solution and the carrier preferably is selected from the group consisting of cocoa butter and vitebe- sole.

Particular preferred pharmaceutical forms for the administration of a compound of the invention are forms suitable for injectionable use and include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. In all cases, the final solution or dispersion form must be sterile and fluid. Typically, such a solution or dispersion will include a solvent or dis- persion medium, containing, for example, water-buffered aqueous solutions, e.g. biocompatible buffers, ethanol, polyol, such as glycerol, propylene glycol, polyethylene glycol, suitable mixtures thereof, surfactants or vegetable oils. A compound of the invention can also be formulated into liposomes, in particular for parenteral administration. Liposomes provide the advantage of increased half life in the circulation, if com- pared to the free drug and a prolonged more even release of the enclosed drug.

Sterilization of infusion or injection solutions can be accomplished by any number of art recognized techniques, including but not limited to, addition of preservatives like anti-bacterial or anti-fungal agents, e.g. parabene, chlorobutanol, phenol, sorbic acid or thimersal. Further, isotonic agents, such as sugars or salts, in particular sodium chlo- ride may be incorporated in infusion or injection solutions.

Production of sterile injectable solutions containing one or several of the compounds of the invention is accomplished by incorporating the respective compound in the required amount in the appropriate solvent with various ingredients enumerated above as required followed by sterilization. To obtain a sterile powder the above solu- tions are vacuum-dried or freeze-dried as necessary. Preferred diluents of the present invention are water, physiologically acceptable buffers, physiologically acceptable buffer salt solutions or salt solutions. Preferred carriers are cocoa butter and vitebe- sole. Besides the preferred excipients mentioned already above, also the following ex- cipients can be chosen, without limitation, to be used with the various pharmaceutical forms of a compound of the invention:

a) binders such as lactose, mannitol, crystalline sorbitol, dibasic phosphates, calcium phosphates, sugars, microcrystalline cellulose, carboxymethyl cellulose, hy- droxyethyl cellulose, polyvinyl pyrrolidone and the like;

b) lubricants such as magnesium stearate, talc, calcium stearate, zinc stearate, stearic acid, hydrogenated vegetable oil, leucine, glycerids and sodium stearyl fumarates,

c) disintegrants such as starches, croscarmellose, sodium methyl cellulose, agar, bentonite, alginic acid, carboxymethyl cellulose, polyvinyl pyrrolidone and the like.

Other suitable excipients can be found in the Handbook of Pharmaceutical Ex- cipients, published by the American Pharmaceutical Association, which is herein incorporated by reference.

It is to be understood that depending on the severity and the particular type of the disorder which is treatable with one of the compounds of the invention, as well as on the respective patient to be treated, e.g. the general health status of the patient, etc., different doses of the respective compound are required to elicit a therapeutic or prophylactic effect. The determination of the appropriate dose lies within the discretion of the attending physician. It is contemplated that the average daily dosage of a com- pound of the invention in the therapeutic or prophylactic use of the invention should be in the range of about 0.1 mg to about 3 g. However, in a preferred use of the present invention a compound of the invention is administered to a subject in need thereof in an amount ranging from 1 .0 to 1000 mg, more preferably ranging from 10 to 500 mg, most preferably ranging from 20 to 200 mg. The duration of therapy and the dosing fre- quency with a compound of the invention will vary, depending on the severity of the disease being treated and the condition and idiosyncratic response of each individual patient.

As is known in the art, the pharmaceutically effective amount of a given composition will also depend on the administration route. In general the required amount will be higher, if the administration is through the gastrointestinal tract; e.g. by suppository, rectal, or by an intragastric probe, and lower if the route of administration is parenteral, e.g. intravenous. Typically, a compound of the invention will be administered in ranges of 20 mg to 3 g, preferably 20 mg to 500 mg, if rectal or intragastric administration is used and in ranges of 10 to 500 mg, if parenteral administration is used.

If a person is known to be at risk of developing a disorder treatable with a compound of the invention, a prophylactic administration of the pharmaceutical composition according to the invention may be possible. In these cases, the respective compound of the invention is preferably administered in above outlined preferred and particular preferred doses on a daily basis. This administration can be continued until the risk of developing the respective disorder has lessened. In most instances, however, a compound of the invention will be administered once a disease/disorder has been diagnosed. In these cases it is preferred that a first dose of a compound of the invention is administered one, two, three or four times daily. Preferably the administration is discon- tinued for one day, one week or one month and then repeated until the symptoms of the respective disease are no longer worsening or until they are improving.

Within the meaning of this invention, a combination of substituents or variables is permissible only if such a combination results in a stable or chemically feasible compound. A stable compound or chemically feasible compound is one that is not substan- tially altered when kept at a temperature of 40°C or less, in the absence of moisture or other chemically reactive conditions, for at least a week. This invention also envisions the quaternization of any basic nitrogen-containing groups of the compounds disclosed herein. Water or oil-soluble or dispersible products may be obtained by such quaternization.

Various modifications and variations of the invention will be apparent to those skilled in the art without departing from the scope of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in the relevant fields are intended to be covered by the present invention.

The following examples and figures are merely illustrative of the present invention and should not be construed to limit the scope of the invention, as indicated by the appended claims, in any way.

PREPARATION EXAMPLES

Synthesis of building blocks The starting materials used in the examples are either commercially available or can be synthesized by the average skilled person trained in organic chemistry without undue burden following routine laboratory practice as outlined, for example in example 1 .

E.g., sulfonyl chlorides R ¹ -S02-CI are either commercially available or have been synthesized according to literature procedures. Different methods are described in the literature for the preparation of sulfonyl chlorides, for example the direct sulfonation of the corresponding bicyclic arene with chlorosulfonic acid as described in U.S. Pat. Appl. Publ (2006), 54 pp. CODEN: USXXCO US 2006269926 A1 20031 130, oxidative chlorination of the corresponding sulfur derivatives as described in J. Org. Chem. 2006, 71 , 1080-1084, via formation of diazonium salts of the corresponding amino derivatives or chlorination of the corresponding sulfonate as described in Tetrahedron Letters, 2009, 7028-7031 or of the corresponding sulfonic acid.

The following abbreviations are used hereinafter:

EtOAc: Ethyl acetate

DMF: Dimethylformamide

Me: Methyl

MeOH: Methanol

Pd(dppf)Cl2: 1 ,1 '-Bis(diphenylphosphino)ferrocene]dichloropalladium

THF: Tetrahydrofuran

Bicyclic 2,3-Dihydrobenzazine compounds of the formula 1.1 according to the present invention have been prepared for example according to the following ap- proaches:

Additional step:

Similar approaches were used to prepare the compounds of the formula 1.2 starting from 6-bromo-3,4-dihydro-2H-1 ,4-benzo[b][1 ,4]thiazine (8) instead of compound

(1 )- The compounds of the formula 1.3 and 1.4 can be prepared by selective oxidation of the compounds of the formula 1.2 according to standard procedures as outlined in the following schemes:

The general reaction procedures indicated above are as follows:

General Procedure A: A flask charged with 6-bromo-3,4-dihydro-2H-benzo[b]- [1 ,4]oxazine hydrochloride (1 ) (1 .0 equiv), 1 ,1 '-bis(diphenylphosphino)ferro- cenepalladium(ll) chloride (=Pd(dppf)Cl2) (0.1 equiv), and the corresponding het- eroaromatic or aromatic boronic acid or boronic ester (1 .2 equiv) in 1 :1 (v/v) tolu- ene/methanol was purged with N2 under vigorous stirring, and 2.0 M aqueous K2CO3 solution (3.5 equiv) were added slowly. The mixture was heated at 88°C for 4 h. After cooling, the mixture was purified by flash column chromatography (silica gel, ethyl acetate/heptane, 1 :5 to 1 :3) to give the compounds (2) (44-82% yield).

General Procedure B: A flask charged with amine compounds (1 ) or (2) (1 .0 equiv), the corresponding sulfonyl chloride (1 .1 equiv) and pyridine (10 equiv) in CH2CI2 was stirred at room temperature for 12 h. The reaction mixture was washed with saturated aqueous NH4CI solution, subsequently with brine and dried over MgSC . The organic solvent was evaporated and the crude product was purified by preparative HPLC or by flash column chromatography (silica gel, ethyl acetate/heptane) to give the compounds 1.1 or (3) (70% to quantitative yield).

General Procedure C: Thermal Reaction: A reaction tube charged with compound (3) (1.0 equiv), Pd(dppf)C (0.1 equiv), and the corresponding heteroaromatic or aromatic boronic acid or boronic ester (1 equiv) in methanol was purged with N2 under vigorous stirring and 2.0 M aqueous K2CO3 solution (2.5 equiv) were added slowly. The vessel was sealed and the mixture was heated in a carousel reactor block for 1 h at 85°C. After cooling, the mixture was diluted with CH2CI2, filtered through celite and eluted with CH2CI2. The organic solvent was evaporated and the crude product was purified by preparative HPLC or by flash column chromatography (silica gel, ethyl acetate/heptane,) to give the compound 1.1 (42-90% yield).

General Procedure C: Microwave reaction: A 2-5 ml microwave reaction vessel charged with compound (3) (1.0 equiv), Pd(dppf)C (0.1 equiv), and the corresponding heteroaromatic or aromatic boronic acid or boronic ester (1 equiv) in methanol was purged with N2 under vigorous stirring and 2.0 M aqueous K2CO3 solution (2.5 equiv) were added slowly. The vessel was sealed and the mixture was heated in a microwave oven for 30 min at 90°C (CEM Discover Microwave system, set to P _m ax=150W). After cooling, the mixture was diluted with CH2CI2, filtered through celite and eluted with CH2CI2. The organic solvent was evaporated and the crude product was purified by preparative HPLC or by flash column chromatography (silica gel, ethyl acetate/- heptane) to give the compounds 1.1 (42-90% yield).

General Procedure D: Bis(pinacolato)diboron (2 equiv), Pd(dppf)C (0.1 equiv), and potassium acetate (4.0 equiv) were added to a flask containing compound (1 ) (1 .0 equiv) in degassed 1 ,4-dioxane. The reaction mixture was heated to 95°C and stirred for 4 hours. Upon completion, the reaction mixture was diluted with ethyl acetate (50 ml), filtered through a short column of silica gel, and further eluted with ethyl acetate. The combined organic solvent was washed with H2O and brine, dried over anhydrous MgSC and evaporated. The resulting residue was purified by flash column chromatography (silica gel, ethyl acetate/heptane, 1 :3) to yield the boronate esters (4) (50 - 88% yield) as a cream or white-off solid. In a subsequent step, compounds (4) were transformed with a heteroaromatic or aromatic bromide to compounds 1.1 following the general procedures described above.

General procedure E: A compound of the formula 1.2 (1 .0 eq) was dissolved in CH2CI2. 3-Chloroperoxybenzoic acid (1.0 eq) was added at room temperature, and the mixture was stirred for 30 minutes. The progress of the reaction was monitored by LCMS. After completion, the reaction was quenched by addition of H2O, followed by extraction in CH2CI2 (3x). The organic layer was dried with Na2S0 ₄ and the solvent was removed under reduced pressure. The crude product was further purified by prepara- tive LCMS.

General procedure F: A compound of the formula 1.2 (1 .0 eq) was dissolved in CH2CI2. 3-Chloroperoxybenzoic acid (2.5 eq) was added at room temperature, and the mixture was stirred for 48 h. The progress of the reaction was monitored by LCMS. After completion, the reaction was quenched by addition of H2O, followed by extraction in CH2CI2 (3x). The organic layer was dried with Na2S0 ₄ and the solvent was removed under reduced pressure. The crude product was further purified by preparative LCMS.

6-Bromo-3,4-dihydro-2H-1 ,4-benzo[b][1 ,4]thiazine (8) was prepared by the method depicted in the following scheme 4:

Scheme 4:

(6)

(7) (8)

5-Bromo-2-fluoro nitrobenzene (5) (1.0 equiv) was dissolved in DMF in a round bottom flask. Thioglycolic acid (1.1 equiv) and K2CO3 (2.5 equiv) were added. The mixture was allowed to stir at room temperature and the progress of the reaction was monitored by thin layer chromatography (TLC). After 16h the reaction was complete and water was added to the reaction mixture. The thus obtained aqueous mixture was washed with CH2CI2 and acidified with diluted hydrochloric acid to pH 1 . The resulting mixture was extracted with ethylacetate. The organic layer was dried over Na2S0 ₄ and the solvent was removed in vacuo to yield compound (6) in 99% yield as a yellow solid. This material was used in the next step without any further purification.

Compound (6) (1 .0 equiv) was dissolved in glacial acetic acid in a round bottom flask and iron powder (4.0 equiv) was added. The mixture was heated under stirring to 70°C for 1 h. After completion of the reaction, the mixture was allowed to cool to room temperature and diluted with water. The aqueous mixture was extracted with ethyl acetate. The resulting organic layer was dried over Na2S0 ₄ and the solvent was removed under reduced pressure. The crude product was dissolved in toluene and the solution was evaporated. This procedure was repeated several times until the acetic acid was removed completely. No further purification was necessary. Compound (7) was obtained in 55% yield as a white to slightly yellow solid.

Compound (7) (1 .0 equiv) was dissolved in dry THF under nitrogen in a round bottom flask. Under vigorous stirring a 1 M solution of BH3 ^* THF complex (10.0 equiv) in THF was slowly added. Then the mixture was stirred for an additional 3h. After completion of the reaction, monitored by TLC, the reaction was quenched by addition of water. The resulting mixture was extracted with ethyl acetate. The organic layer was dried over Na2S0 ₄ and the solvent was removed under reduced pressure. The crude product was further purified by flash column chromatography (cyclohexane / ethyl acetate 3:1 as eluent) to yield compound (8) as a white solid in 71 % yield.

Compounds I were analyzed as follows:

HPLC/MS Method: using a Waters X-bridge Ci8-column, 5 μηη particle size, 4.6 x 150 mm (diameter x length) at a flow rate of 1.75 ml/min with a linear gradient (water to acetonitrile, 0.2% formic acid as modifier) from initially 99:1 to 1 :99 over 9.10 min, then held for 1 .80 min. Mass signals were determined using a Waters 3100 Mass Detector.

The following compounds of the formula (I) listed in table I below were prepared using the standard operation procedures described above.

Table I

Ex. lUPAC-Name Rt ^#

1 . 5-(4-((4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1 ,4]oxazin-7-yl)sulfonyl)- 7.9 3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

2. 4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- 7.74 benzo[b][1 ,4]oxazin-6-yl)benzonitrile

3. 4-(4-((4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1 ,4]oxazin-7-yl)sulfonyl)- 7.8 3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)benzonitrile

4. 5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- 7.9 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

5. 5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- 7.84 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

6. 5-(4-((4-methyl-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)sulfonyl)-3,4- 8.78 dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

7. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - 9.13 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

8. 5-(4-((2-(2,2,2-trifluoroacetyl)-1 ,2,3,4-tetrahydroisoquinolin-7- 9.37 yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2- carbonitrile

9. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- 9.26 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

10. 5- (4-((2-oxoindolin-5-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin- 8.77

6- yl)thiophene-2-carbonitrile

1 1 . 5-(4-((1 ,3-dimethyl-2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5- 7.31 yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2- carbonitrile

12. 5-(4-(benzo[d]isoxazol-5-ylsulfonyl)-3,4-dihydro-2H- 7.34 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile Ex. lUPAC-Name Rt ^#

13. 5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4- 9.15 dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

14. 5-(4-((5-(dimethylamino)naphthalen-1 -yl)sulfonyl)-3,4-dihydro-2H- 9.44 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

15. 5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-3,4-dihydro-2H- 9.01 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

16. 5-(4-((2-oxo-2H-chromen-6-yl)sulfonyl)-3,4-dihydro-2H- 7.73 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

17. 5-(4-(naphthalen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6- 8.74 yl)thiophene-2-carbonitrile

18. 5-(4-(benzofuran-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6- 8.6 yl)thiophene-2-carbonitrile

19. 5-(4-((2-oxo-2,3-dihydrobenzo[d]oxazol-6-yl)sulfonyl)-3,4-di hydro-2H- 7.22 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

20. 5-(4-((1 -methyl-2-oxoindolin-5-yl)sulfonyl)-3,4-dihydro-2H- 7.34 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

21 . 5-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl )sulfonyl)- 7.14 3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

22. 5-(4-(chroman-6-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-6- 8.48 yl)thiophene-2-carbonitrile

23. 5-(4-((2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)sulfonyl)-3,4-di hydro-2H- 7.29 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

24. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(6-methylpyridin-3-yl)-3,4- 5.98 dihydro-2H-benzo[b][1 ,4]oxazine

25. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridi n-3-yl)-3,4- 5.73 dihydro-2H-benzo[b][1 ,4]oxazine

26. 6-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4- 7 dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)nicotinonitrile

27. 5-((6-(pyridin-4-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H- 7.92 benzo[d]imidazol-2(3H)-one

28. 5-((6-(benzofuran-5-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H- 7.92 benzo[d]imidazol-2(3H)-one

29. 5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4- 6.73 dihydro-2H-benzo[b][1 ,4]oxazin-6-yl)benzo[d]oxazol-2(3H)-one

30. 5-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H- 8.83 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

31 . 6-(1 -methyl-1 H-indol-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)- 10.03 3,4-dihydro-2H-benzo[b][1 ,4]oxazine

32. 6-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - 9.21 benzo[b][1 ,4]oxazin-6-yl)nicotinonitrile Ex. lUPAC-Name Rt ^#

33. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - 9.16 benzo[b][1 ,4]oxazin-6-yl)picolinonitrile

34. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-4-yl)- 3,4-dihydro- 6.78 2H-benzo[b][1 ,4]oxazine

35. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - 9.22 benzo[b][1 ,4]oxazin-6-yl)pyrimidine-2-carbonitnle

36. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4- 8.01 dihydro-2H-benzo[b][1 ,4]oxazine

37. 4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- 9.48 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

38. 4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - 9.41 benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

39. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl )-3,4- 6.25 dihydro-2H-benzo[b][1 ,4]oxazine

40. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- 7.89 benzo[b][1 ,4]oxazin-6-yl)picolinonitrile

41 . 6-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- 7.69 benzo[b][1 ,4]oxazin-6-yl)nicotinonitrile

42. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- 7.58 benzo[b][1 ,4]oxazin-6-yl)pyrimidine-2-carbonitrile

43. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(pyrimidin-5-yl)-3,4-dihydro-2H- 6.58 benzo[b][1 ,4]oxazine

44. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(pyridin-4-yl)-3,4-dihydro-2H- 8.41 benzo[b][1 ,4]oxazine

45. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(p-tolyl)-3,4-dihydro-2H- 8.93 benzo[b][1 ,4]oxazine

46. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(2-methylpyridin-4-yl)-3,4- 8.36 dihydro-2H-benzo[b][1 ,4]oxazine

47. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(2-methylpyrimidin-5-yl)-3,4- 6.66 dihydro-2H-benzo[b][1 ,4]oxazine

48. 6-(2-methoxypyrimidin-5-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4- 7.17 dihydro-2H-benzo[b][1 ,4]oxazine

49. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(5-methylpyridin-2-yl)-3,4- 6.17 dihydro-2H-benzo[b][1 ,4]oxazine

50. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(5-(trifluoromethyl)pyridin-2-yl)- 8.53 3,4-dihydro-2H-benzo[b][1 ,4]oxazine

51 . 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- 6.02 benzo[b][1 ,4]oxazin-6-yl)pyrimidin-2-amine

52. 5-((6-(6-methylpyridin-3-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)- 4.13 1 H-benzo[d]imidazol-2(3H)-one

Ex. Example

R _t ^# retention time, (HPLC) as described above

Compounds of the formula (I), listed in table I I below, can be prepared using the standard operation procedures described above.

Table I I

Ex. l UPAC-Name R _f

55. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)-1 H-pyrrole-2-carbonitrile

56. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)furan-2-carbonitrile

57. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)-1 H-pyrrole-2-carbonitrile

58. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 , 1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)-1 H-pyrrole-2-carbonitrile

59. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)furan-2-carbonitrile

60. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 , 1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)furan-2-carbonitrile

61 . 6-(5-methyl-1 H-pyrrol-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine

62. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylfuran- 2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

63. 6-(5-methyl-1 H-pyrrol-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

64. 6-(5-methyl-1 H-pyrrol-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 , 1 -dioxide

65. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylfuran- 2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

66. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylfuran- 2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 , 1 -dioxide

67. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(1 H-pyrrol-2-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine Ex. lUPAC-Name R _f

68. 6-(furan-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro-2H- benzo[b][1 ,4]thiazine

69. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(1 H-pyrrol-2-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide

70. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(1 H-pyrrol-2-yl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

71 . 6-(furan-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide

72. 6-(furan-2-yl)-4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3, 4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide

73. 4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)benzonitrile

74. 4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

75. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(p-tolyl)-3,4-d ihydro-2H- benzo[b][1 ,4]thiazine

76. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)picolinonitrile

77. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridi n-3-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

78. 6-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)nicotinonitrile

79. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

80. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-(trifluorome thyl)pyridin-2- yl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazine

81 . 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)pyrimidine-2-carbonitnle

82. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpynmid in-5-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

83. 6-(2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl )sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine

84. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)pyrimidin-2-amine

85. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl )-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine

86. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyndin-3-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine

87. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyndin-2-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine Ex. lUPAC-Name R _f

88. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-4-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine

89. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyridi n-4-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

90. 2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)pyrimidine-5-carbonitnle

91 . 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-2-yl )-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine

92. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyrimi diri-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

93. 5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

94. 5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

95. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

96. 5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

97. 5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

98. 5-(4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-dihyd ro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

99. 5-(4-(naphthalen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)thiophene-2-carbonitrile

100. 5-(4-(benzofuran-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)thiophene-2-carbonitrile

101 . 5- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-

6- yl)thiophene-2-carbonitrile

102. 5-(4-((1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)thiophene-2-carbonitrile

103. 5-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

104. 4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

105. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(p-tolyl)-3,4-d ihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide

106. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(p-tolyl)-3,4-d ihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide

107. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)picolinonitrile Ex. lUPAC-Name R _f

108. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)picolinonitrile

109. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridi n-3-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

1 10. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(6-methylpyridi n-3-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

1 1 1 . 6-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)nicotinonitrile

1 12. 6-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)nicotinonitrile

1 13. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

1 14. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpyridi n-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

1 15. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-(trifluorome thyl)pyridin-2- yl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

1 16. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-(trifluorome thyl)pyridin-2- yl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

1 17. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)pyrimidine-2-carbonitrile

1 18. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)pyrimidine-2-carbonitnle

1 19. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpynmid in-5-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

120. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpynmid in-5-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

121 . 6-(2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl )sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

122. 6-(2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl )sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

123. 6-(2-aminopyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)s ulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

124. 6-(2-aminopyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl)s ulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

125. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl )-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide

126. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-5-yl )-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

127. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyndin-3-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide Ex. lUPAC-Name R _f

128. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyridin-3-yl)- 3,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide

129. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyndin-4-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide

130. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyndin-4-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide

131 . 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyridi n-4-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

132. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(2-methylpyridi n-4-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

133. 2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)pyrimidine-5-carbonitnle

134. 2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)pyrimidine-5-carbonitrile

135. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-2-yl )-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide

136. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyrimidin-2-yl )-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

137. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpynmid in-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 -oxide

138. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(5-methylpynmid in-2-yl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine 1 ,1 -dioxide

139. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyndin-2-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 -oxide

140. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(pyndin-2-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine 1 ,1 -dioxide

141 . 5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

142. 5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

143. 5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

144. 5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

145. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

146. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 , 1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

147. 5-(1 -oxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile Ex. lUPAC-Name R _f

148. 5-(1 ,1 -dioxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

149. 5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

150. 5-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

151 . 5-(1 -oxido-4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-d ihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

152. 5-(1 ,1 -dioxido-4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4 - dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

153. 5-(4-(naphthalen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

154. 5-(4-(naphthalen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

155. 5-(4-(benzofuran-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

156. 5-(4-(benzofuran-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

157. 5-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

158. 5-(4-((1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

159. 5-(4-((1 H-indol-2-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

160. 5-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

161 . 5-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

162. 5-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 , 1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

163. 4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

164. 4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

165. 4-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)benzonitrile

166. 4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

167. 4-(4-((1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)benzonitrile Ex. lUPAC-Name R _f

168. 4-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

169. 4-(4-(benzofuran-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)benzonitrile

170. 4-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin- 6-yl)benzonitrile

171 . 4-(4-(naphthalen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6- yl)benzonitrile

172. 4-(4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-dihyd ro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

173. 4-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

174. 4-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

175. 4-(4-((2,3-dihydro-1 H-inden-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

176. 4-(1 -oxido-4-((5,6,7,8-tetrahydronaphthalen-2-yl)sulfonyl)-3,4-d ihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)benzonitrile

177. 4-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

178. 4-(4-(benzo[b]thiophen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

179. 4-(4-(naphthalen-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

180. 4-(4-(naphthalen-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

181 . 4-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

182. 4-(4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-1 , 1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

183. 4-(4-(benzofuran-2-ylsulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

184. 4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

185. 4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-1 , 1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

186. 4-(4-(benzofuran-2-ylsulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

187. 4-(4-((1 H-indol-2-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile Ex. lUPAC-Name R _f

188. 4-(4-((1 H-indol-2-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

189. 4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

190. 4-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

191 . 4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 -oxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

192. 4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-1 ,1 -dioxido-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

193. 4-(1 -oxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)benzonitrile

194. 4-(1 ,1 -dioxido-4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]thiazin-6-yl)benzonitrile

195. 5-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

196. 4-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)benzonitrile

197. 5-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)furan-2-carbonitrile

198. 5-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)-1 H-pyrrole-2-carbonitrile

199. 6-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)nicotinonitrile

200. 5-(4-((2-methyl-1 H-benzo[d]imidazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)picolinonitrile

201 . 2-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiazole-5-carbonitrile

202. 2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)thiazole-5-carbonitrile

203. 2-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiazole-5-carbonitrile

204. 2-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin- 6-yl)thiazole-5-carbonitrile

205. 2-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)thiazole-5-carbonitrile

206. 4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

207. 4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile Ex. lUPAC-Name R _f

208. 4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

209. 4-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin- 6-yl)thiophene-2-carbonitrile

210. 4-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)thiophene-2-carbonitrile

21 1 . 3,5-dimethyl-4-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)isoxazole

212. 3,5-dimethyl-4-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3 ,4-dihydro- 2H-benzo[b][1 ,4]thiazin-6-yl)isoxazole

213. 5-((6-(3,5-dimethylisoxazol-4-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)- yl)sulfonyl)-2-methylbenzo[d]oxazole

214. 4-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]thiazin- 6-yl)-3 ,5-di methyl isoxazole

215. 5-((6-(3,5-dimethylisoxazol-4-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)- yl)sulfonyl)-1 H-benzo[d]imidazol-2(3H)-one

216. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]thiazin-6-yl)oxazole

217. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]thiazin-6-yl)oxazole

218. 2-methyl-5-((6-(oxazol-5-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)- yl)sulfonyl)benzo[d]oxazole

219. 5- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]thiazin-

6- yl)oxazole

220. 5-((6-(oxazol-5-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)-yl)sulfonyl)-1 H- benzo[d]imidazol-2(3H)-one

221 . 2-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)thiazole-5-carbonitrile

222. 2-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]oxazin-6-yl)thiazole-5-carbonitrile

223. 2-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)thiazole-5-carbonitrile

224. 2-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]oxazin- 6-yl)thiazole-5-carbonitrile

225. 2-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazin-6-yl)thiazole-5-carbonitrile

226. 4-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

227. 4-(4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b] [1 ,4]oxazin- 6-yl)thiophene-2-carbonitrile Ex. lUPAC-Name R _f

228. 4-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazin-6-yl)thiophene-2-carbonitrile

229. 6-(3,5-dimethylisoxazol-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

230. 6-(3,5-dimethylisoxazol-4-yl)-4-((2-methylbenzo[d]thiazol-6- yl)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazine

231 . 6-(3,5-dimethylisoxazol-4-yl)-4-((2-methylbenzo[d]oxazol-5-y l)sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazine

232. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(3,5-dimethylisoxazol-4- yl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

233. 5-((6-(3,5-dimethylisoxazol-4-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)- yl)sulfonyl)-1 H-benzo[d]imidazol-2(3H)-one

234. 4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-6-(oxazol-5-yl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazine

235. 4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-6-(oxazol-5-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]oxazine

236. 4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-6-(oxazol-5-yl)-3, 4-dihydro-2H- benzo[b][1 ,4]oxazine

237. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(oxazol-5-yl)-3,4-dihydr o-2H- benzo[b][1 ,4]oxazine

238. 5-((6-(oxazol-5-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)-yl)sulfonyl)-1 H- benzo[d]imidazol-2(3H)-one

239. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)-1 H-pyrrole-2-carbonitrile

240. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]oxazin-6-yl)-1 H-pyrrole-2-carbonitrile

241 . 5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)-1 H-pyrrole-2-carbonitrile

242. 5- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-

6- yl)-1 H-pyrrole-2-carbonitrile

243. 5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazin-6-yl)-1 H-pyrrole-2-carbonitrile

244. 5-(4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)furan-2-carbonitrile

245. 5-(4-((2-methylbenzo[d]thiazol-6-yl)sulfonyl)-3,4-dihydro-2H - benzo[b][1 ,4]oxazin-6-yl)furan-2-carbonitrile

246. 5-(4-((2-methylbenzo[d]oxazol-5-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)furan-2-carbonitrile

247. 5- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-

6- yl)furan-2-carbonitrile Ex. lUPAC-Name R _f

248. 5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazin-6-yl)furan-2-carbonitrile

249. 4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-6-(6-methylpyridin -3-yl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

250. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(6-methylpyridin-3-yl)-3 ,4-dihydro- 2H-benzo[b][1 ,4]oxazine

251 . 4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-6-(pyridin-4-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]oxazine

252. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(pyridin-4-yl)-3,4-dihyd ro-2H- benzo[b][1 ,4]oxazine

253. 5-(4-((2-methylbenzo[d]oxazol-6-yl)sulfonyl)-3,4-dihydro-2H- benzo[b][1 ,4]oxazin-6-yl)pyrimidine-2-carbonitrile

254. 5- (4-(benzo[b]thiophen-2-ylsulfonyl)-3,4-dihydro-2H-benzo[b][1 ,4]oxazin-

6- yl)pyrimidine-2-carbonitrile

255. 5-(4-((2-oxo-2,3-dihydro-1 H-benzo[d]imidazol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazin-6-yl)pyrimidine-2-carbonitrile

256. 6-(2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]oxazol-6-yl) sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazine

257. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2-methoxypyrimidin-5-yl )-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

258. 5-((6-(2-methoxypyrimidin-5-yl)-2H-benzo[b][1 ,4]oxazin-4(3H)- yl)sulfonyl)-1 H-benzo[d]imidazol-2(3H)-one

259. 6-(2-methoxypyrimidin-5-yl)-4-((2-methylbenzo[d]thiazol-6-yl )sulfonyl)- 3,4-dihydro-2H-benzo[b][1 ,4]oxazine

260. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(6-fluoropyridin-3-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]thiazine

261 . 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(6-fluoropyridin-3-yl)-3 ,4-dihydro-2H- benzo[b][1 ,4]oxazine

262. 6-(6-fluoropyridin-3-yl)-4-((5-methylbenzo[b]thiophen-2-yl)s ulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

263. 6-(6-fluoropyridin-3-yl)-4-((5-methylbenzo[b]thiophen-2-yl)s ulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

264. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2,3-difluoropyridin-4-y l)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine

265. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2,3-difluoropyridin-4-y l)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazine

266. 4-(benzo[b]thiophen-2-ylsulfonyl)-6-(2,3-difluoropyridin-4-y l)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine 1 -oxide

267. 6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine Ex. lUPAC-Name R _f

268. 6-(2-fluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine

269. 6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

270. 6-(2-fluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-2-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]oxazine

271 . 6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

272. 6-(2,3-difluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4- dihydro-2H-benzo[b][1 ,4]thiazine

273. 6-(2-fluoropyridin-4-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine

274. 6-(6-fluoropyridin-3-yl)-4-((1 -methyl-1 H-indol-5-yl)sulfonyl)-3,4-dihydro- 2H-benzo[b][1 ,4]thiazine

275. 6-(6-fluoropyridin-3-yl)-4-((2-methylbenzo[d]oxazol-5-yl)sul fonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

276. 6-(6-fluoropyridin-3-yl)-4-((2-methylbenzo[d]oxazol-6-yl)sul fonyl)-3,4- dihydro-2H-benzo[b][1 ,4]oxazine

277. 6-((6-(2,3-difluoropyridin-4-yl)-2H-benzo[b][1 ,4]thiazin-4(3H)-yl)sulfonyl)- 2-methylbenzo[d]oxazole

Ex. Example

# Rt retention time in minutes (HPLC)

BIOLOGY EXAMPLES

1 . General cell culture maintenance and cell proliferation assays

MCF-7 human breast adenocarcinoma cells were obtained from ATCC (LGC Promochem). The CellSensor® HRE-bla HCT1 16 cell line (colorectal carcinoma) was obtained from Invitrogen. The HeLa cervical adenocarcinoma cell line was obtained from the Chemical Biology Core Facility (EMBL).

Cells were grown under humidified 95% air, 5% CO2 at 37°C in Dulbecco's modified Eagle's medium (DMEM: MCF-7; HeLa) supplemented with 10% fetal bovine serum (FBS), 100U/ml penicillin and 100μg/ml streptomycin and 2mM L-glutamine. The HCT1 16 cell line was grown under the same atmospheric conditions in McCoy's 5A medium supplemented with 10% FBS and penicillin/streptomycin as above, in addition to blasticidin as a selection marker at a final concentration of 5μg/ml. Cell proliferation experiments were carried out in 96-well tissue culture plates with seeding of 2000 cells/well in 100μΙ of the relevant medium. Cells were subsequently incubated under the conditions mentioned for 24h prior to addition of compounds.

For the determination of compound EC50 values, 10μΙ compounds at 1 1 X concen- trations in 5.5% DMSO were added to the wells at various concentrations yielding a final constant percentage of 0.5% DMSO at the desired 1X compound concentration. As a positive control, cells were treated with 5.5% DMSO. The cells were then incubated for a further 72h prior to the measurement.

To determine the degree of inhibition of cell proliferation, cells were treated with ATPIite solution according to the manufacturer's instructions (PerkinElmer, ATPIite

1 -step Luminescence ATP Detection Assay System) and luciferase readout measured on an Envision HTS multilabel plate reader (PerkinElmer) in luminescence mode according to established protocols. Raw data were imported into an ActivityBase database (IDBS, ID Business Solutions) and EC50 values calculated using the IDBS pro- gram ActivityBase XE. The results are summarized in the following table.

Reference: < 500nM:

500 - 1000nM

> 1000nM:

Example no. MCF-7 Example no. MCF-7

1 +++ 19 +

2 +++ 20 ++

3 + 21 +

4 +++ 22 +++

5 +++ 23 +

6 ++ 24 +++

7 +++ 25 +++

8 + 26 ++

9 +++ 27 +++

10 + 28 +

1 1 +++ 29 +

12 + 30 +++

13 +++ 31 ++

14 + 32 +++

15 +++ 33 +++

16 + 34 +++

17 +++ 35 +++

18 +++ 36 +++ Example no. MCF-7 Example no. MCF-7

37 +++ 46 +++

38 +++ 47 +++

39 +++ 48 +++

40 +++ 49 +++

41 +++ 50 +++

42 +++ 51 +++

43 +++ 52 +++

44 +++ 53 +++

45 +++ 54 +++

2. HIF / HRE reporter assay

Inhibition of an activated HIF signaling response under chemically-induced hy- poxic conditions due to compound treatment was determined using the CellSensor® HRE-bla HCT-1 16 stably transfected reporter cell line from Invitrogen according to the manufacturer's instructions.

Cells were maintained as described previously and seeded into 384-well, clear- bottom plates (Corning 3712) at 15000 cells/well in 32 μΙ assay medium (Opti-MEM [Invitrogen], 0.5% FBS, 100 U/ml penicillin, 100 μg/ml streptomycin, 0.1 mM nonessential amino acids [NEAA], 1 mM sodium pyruvate, 5mM HEPES [pH 7.3]). Following a 2 h incubation period, compounds (4 μΙ) were subsequently added to the cells at 10 X concentrations in 5% DMSO and incubated under normal conditions for 30 min. To induce hypoxic conditions, 4 μΙ of a 2 mM deferoxamine (DFO) solution was added to the cells followed by 24 h incubation under standard assay conditions (as described). Control wells included wells containing only medium (no cells) and wells treated with 0.5% DMSO instead of compound.

Prior to the readout, the Substrate Loading Solution was prepared as described in the manufacturer's protocol and 10 μΙ added to each well. Following a further 2 h incubation period at room temperature and in the dark, fluorescence was measured at two wavelengths (blue channel: ex. 409 nm, em. 460 nm; green channel: ex. 409 nm, em. 530 nm) on a PerkinElmer Envision HTS. For the analysis, the average signal of the cell-free wells at 460 nm and 530 nm was first subtracted from the blue and green channel data, respectively. The blue/green emission ratios were then calculated for each well, dividing the background-corrected blue emission values by the background- corrected green emission values. IC50 values were determined from these ratios using GraphPad Prism (Prism 5, GraphPad software, Inc.). The results are summarized in the following table. Reference: ECso < 500nM: +++

500 - 1000nM ++

> 1000nM: +

Example Evaluation Example Evaluation no. no.

1 +++ 5 +++

2 +++ 9 +++

4 +++ 24 +++

The results of these experiments show that the compounds of the invention are capable of inhibiting hypoxia regulated element-mediated transcriptional activity under hypoxic conditions.