WO2012130306A1 - Composés bicycliques de 2,3-dihydrobenzazine destinés à une utilisation thérapeutique - Google Patents

Composés bicycliques de 2,3-dihydrobenzazine destinés à une utilisation thérapeutique Download PDF

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WO2012130306A1
WO2012130306A1 PCT/EP2011/054959 EP2011054959W WO2012130306A1 WO 2012130306 A1 WO2012130306 A1 WO 2012130306A1 EP 2011054959 W EP2011054959 W EP 2011054959W WO 2012130306 A1 WO2012130306 A1 WO 2012130306A1
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benzo
dihydro
sulfonyl
methylbenzo
thiazin
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PCT/EP2011/054959
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English (en)
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Bernd Janssen
Douglas Thomson
Marcel MÜLBAIER
Jorge Alonso
Arantxa ENCINAS-LOPEZ
Bernd Wendt
Christoph Schultes
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Elara Pharmaceuticals Gmbh
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Priority to PCT/EP2011/054959 priority Critical patent/WO2012130306A1/fr
Publication of WO2012130306A1 publication Critical patent/WO2012130306A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Definitions

  • the present invention provides novel 2,3-dihydrobenzazine compounds that are useful in therapy of diseases and disorders.
  • 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.
  • 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.
  • 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.
  • hypoxia signaling pathway 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.
  • hypoxia signaling see e.g. Qingdong Ke and Max Costa, Molecular Pharmacology (2006), vol. 70, no. 5.
  • HIF-1 a 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 ⁇ , 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.
  • HIF-1 a 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.
  • HRE Hypoxia Responsive Element
  • 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.
  • HIF-1 inhibition 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).
  • 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.
  • 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;.
  • 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.
  • (het)arylaminocarbonyl radical (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.
  • A is e.g. CO, CONH or S0 2
  • 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
  • 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.
  • HIF Hypoxia Inducible Factor
  • 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.
  • HIF Hypoxia Inducible Factor
  • Ri is optionally substituted naphthyl or C-bound bicyclic heterocyclyl
  • R2 is substituted phenyl or optionally substituted C- or N-bound monocyclic 5- or
  • 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
  • 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.
  • 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.
  • 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
  • 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.
  • HIF Hypoxia Inducible Factor
  • 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.
  • the present invention relates to 2,3-dihydrobenzazine compounds of the formula (I)
  • 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
  • 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,
  • 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 -alkyl
  • 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
  • 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
  • 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
  • Ry is Ci-C6-alkyl or fluorinated Ci-C2-alkyl
  • 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
  • # is the point of attachment to the 2,3-dihydrobenzazine ring
  • R 2 is phenyl or C- or N-bound monocyclic 5- or 6-membered heteroaryl
  • phenyl and monocyclic 5- or 6-membered heteroaryl carry a CN radical and may additionally carry 1 , 2 or 3 radicals R 2a .
  • 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.
  • 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.
  • the present invention relates to a pharmaceutical composition
  • 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.
  • 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.
  • 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
  • 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.
  • 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).
  • 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.
  • optically active 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.
  • 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.
  • 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
  • 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, hex
  • 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.
  • 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).
  • alkali metal salts e.g., sodium or potassium salts
  • alkaline earth metal salts e.g., calcium or magnesium salts
  • 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 sul
  • 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 .
  • 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 .
  • 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.
  • 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.
  • 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.
  • prodrugs involving esters
  • 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.
  • 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.
  • isotopic variations of the agent and pharmaceutically acceptable salts thereof 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.
  • 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.
  • alkyl 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.
  • halogen denotes in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.
  • Ci-Cio-alkyl denotes a straight-chain or branched alkyl group having from 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms.
  • alkyl group examples include methyl, ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, pentyl,
  • 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.
  • pentafluorosulfanyl also referred to as pentafluorothio
  • pentafluorothio relates to the radical SF 5 .
  • C1 refers to the carbon atom by which hydroxy-C2-C6-alkyl is bound to the remainder of the molecule.
  • 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.
  • alkoxy group examples include methoxy, ethoxy, n-propoxy, iso- propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert-butyloxy, pentyloxy,
  • 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,
  • 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,
  • C1-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
  • C1 refers to the carbon atom by which Ci-C4-alkoxy-C2-C4- alkyl is bound to the remainder of the molecule.
  • 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-).
  • 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,
  • n-propylsulfonyl isopropylsulfonyl, t-butylsulfonyl, n-pentylsulfonyl and n-hexylsulfonyl.
  • 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,
  • 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.
  • 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,
  • C3-C7-cycloalkyl 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.
  • 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.
  • 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-o
  • 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.
  • 5- or 6-membered heteroaromatic radicals examples include 2-pyridinyl,
  • 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.
  • the fused 5-, 6- or 7-membered carbocycle may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members.
  • 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.
  • the fused-on heterocyclic ring may also have 1 or 2 carbonyl groups or thiocarbonyl groups as ring members.
  • 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.
  • 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.
  • 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 .
  • 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.
  • These compounds are hereinafter also denominated as dihydrobenzothiaz- ine oxides or compounds of the formula 1.3.
  • These compounds are hereinafter also denominated as dihydro- benzothiazine dioxides or compounds of the formula 1.4.
  • first embodiment i.e. to compounds of the formula 1.1 .
  • second embodiment i.e. to compounds of the formula 1.2.
  • 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-C
  • 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
  • R 1b if present, is phenyl, which is unsubstituted or substituted by 1 or 2 identical or different radicals R 1c .
  • 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.
  • R 1b 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.
  • 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 .
  • 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
  • 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,
  • R M1 together with R Q1 or together with R Q2 may form a bond, or
  • 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
  • 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,
  • R Q1 together with R M1 or together with R M2 may form a bond, or
  • 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
  • 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,
  • R T1 together with R Q1 or together with R Q2 may form a bond, or
  • R T1 together with R M1 or together with R M2 may form a bond, or
  • 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
  • R T2 together with R M1 or together with R M2 may form a bond, or
  • 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,
  • 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 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 .
  • the radical R 1 is a radical of the formulae R1 -1 or R1 -2.
  • 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,
  • R 1 in the formulae I, 1.1 , 1.2, 1.3 or 1.4 is C-bound bicyclic heterocyclyl
  • 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.
  • the six-membered second ring which is fused to the 5-membered first ring is a benzene ring.
  • 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.
  • 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.
  • R1 -1 a 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:
  • a and B are as defined above,
  • k 0, 1 or 2
  • 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.
  • the radical R 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.
  • R may be the same or may be different.
  • k is 0 or 1.
  • 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:
  • k isO, 1 or2;
  • R * is hydrogen or Ci-C4-alkyl
  • 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.
  • R * is hydrogen or Ci-C2-alkyl, especially hydrogen or methyl.
  • 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.
  • R may be the same or may be different.
  • 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,
  • Examples for a radical R1-1a.3 are 1 H-indol-2-yl, 1-methyl-1 H-indol-2-yl,
  • R1-1a.4 An example for a radical R1-1a.4 is benzoxazol-2-yl.
  • 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
  • R1-1d.1 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.
  • 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.
  • 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:
  • k O, 1 or 2
  • R has one of the meanings indicated for R 1a ;
  • 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.
  • 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 .
  • 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.
  • 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.
  • T is preferably N-R T1 or
  • Q is preferably N-R Q1 or C(R Q2 R Q3 ), wherein R Q1 , R Q2 and R Q3 are as defined above.
  • the radical R 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
  • R 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.
  • k is 2
  • R may be the same or may be different.
  • k is 0 or 1.
  • 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.
  • 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,
  • 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,
  • R 1a 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
  • 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
  • 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
  • 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
  • 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.
  • R 1 -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 .
  • 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.
  • 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).
  • 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:
  • R 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
  • 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.
  • 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 .
  • R M1 , R T1 and R U1 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.
  • Ci-C 4 -alkyl especially methyl or ethyl
  • fluorinated Ci-C 2 -alkyl especially difluoromethyl, trifluoromethyl, 2,2-difluoroeth
  • R M2 , R M3 , R T1 , R T2 , R U2 and R U3 are in particular selected from the group consisting of hydrogen, Ci-C 4 -alkyl, especially methyl or ethyl or fluorinated Ci-C 2 -alkyl.
  • 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.
  • T is preferably C(R T2 R T3 ), wherein R T2 and R T3 are as defined above.
  • 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
  • radicals 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
  • R 1a 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
  • R b are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or
  • R e are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C4-alkyl and fluorinated Ci-C2-alkyl, or
  • 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
  • C carbonyl
  • S thiocarbonyl group
  • 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).
  • the radical R 1 is a radical of the formulae R1 -2h or R1 -3h,
  • 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 ;
  • R M1 , R M2 , R M3 , R T2 , R T3 , R U1 , R U2 and R U3 are as defined above,
  • 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.
  • 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
  • R 1a 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 ethylthi
  • R 1a 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
  • 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 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).
  • 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 .
  • R 1 is a radical of
  • 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.
  • k O, 1 or 2;
  • n 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 ;
  • R' has one of the meanings indicated for R 1a .
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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 .
  • R 2a may be located at any position of the phenyl ring.
  • 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.
  • 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 .
  • 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).
  • 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 .
  • 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 .
  • 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
  • the radicals R 2a 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.
  • R 2a is selected from the group consisting of halogen, OH, CN, methyl, methoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy and ethynyl.
  • the radical R 2b 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.
  • 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-
  • 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 .
  • R 2 in the formulae I, 1.1 , 1.2, 1.3 and 1.4 is a radical of the formula Ar2:
  • 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
  • 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.
  • 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,
  • 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 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,
  • R 22 if present, is selected from the group consisting of hydrogen, halogen, OH , CN,
  • R 23 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,
  • R 23a if present, is selected from the group consisting of hydrogen and halogen, in par- ticular hydrogen and fluorine.
  • 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 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 is hydrogen, halogen, CN, NH2, OH, SF 5 , C2-C4-ethynyl, especially
  • 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 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.
  • 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,
  • 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 .
  • R 2 in the formula (I) is a radical of the formulae
  • 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 ,
  • 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-
  • 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, Ar
  • R 24 , R 25 , R 26 , R 27 , R 28 and R 29 have the meanings indicated above.
  • 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
  • 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 -
  • 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.
  • 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.
  • 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
  • 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 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,
  • R M1 together with R Q1 or together with R Q2 may form a bond, or
  • 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
  • R M2 together with R Q1 or together with R Q2 may form a bond, or
  • 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
  • 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
  • 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,
  • R T1 together with R Q1 or together with R Q2 may form a bond, or
  • R T1 together with R M1 or together with R M2 may form a bond, or
  • 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
  • R T2 together with R M1 or together with R M2 may form a bond, or
  • 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,
  • 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 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.
  • 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.
  • 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.
  • 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.
  • the six-membered second ring which is fused to the 5-membered first ring is in particular a pyridine ring.
  • 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:
  • 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.
  • the radical R 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
  • fluori- nated Ci-alkoxy in particular trifluoromethoxy.
  • R may be the same or may be different.
  • k is 0 or 1.
  • 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:
  • # 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.
  • 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- 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,
  • 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:
  • k 0, 1 or 2
  • R has one of the meanings given for R 2a , preferably halogen, OH, SH, CN, NO2,
  • 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.
  • 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.
  • 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.
  • T is preferably N-R T1 or
  • Q is preferably N-R Q1 or C(R Q2 R Q3 ), wherein R Q1 , R Q2 and R Q3 are as defined above.
  • the radical R 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.
  • R may be the same or may be different.
  • k is 0 or 1 .
  • 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:
  • 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
  • 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 di
  • 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
  • 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
  • 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
  • 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
  • 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 .
  • 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 .
  • R 2a 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.
  • 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:
  • 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
  • T' in formulae R2-2g and R2-3g is O or S, and where
  • R 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 methylsulfon
  • R 2 is a radical R2-2h.
  • 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
  • Ci-C6-alkyl 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, fluor
  • Ci-C6-alkyl 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
  • Ci-C 4 -alkyl are independently of each other selected from the group consisting of hydrogen, halogen, Ci-C 4 -alkyl and fluorinated Ci-C2-alkyl, or
  • 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
  • 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
  • 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;
  • R may be the same or different.
  • 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.
  • 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,
  • R 2 is selected from the group consisting of 5-cyanothiophen-2-yl
  • R 4 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert. -butyl or trifluoro- methyl.
  • R 4 is selected from acetyl or propionyl.
  • R 4 hydrogen or Ci-C4-alkyl, in particular hydrogen, methyl, ethyl, n-propyl, isopropyl or n-butyl.
  • R 5 C1-C4- alkyl, in particular methyl, ethyl, n-propyl, isopropyl or n-butyl.
  • 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.
  • 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.
  • R 6 hydrogen or Ci-C4-alkyl, in particular hydrogen, methyl, ethyl, n-propyl, isopropyl or n-butyl.
  • Ci-C4-alkyl in particular hydrogen, methyl, ethyl, n-propyl, isopropyl or n-butyl.
  • R 8 Ci-C4-alkyl, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert. -butyl.
  • the radical C(0)OR 8 is selected from methoxycar- bonyl, ethoxycarbonyl, n-propoxycarbonyl, n-butoxycarbonyl or tert.-butoxycarbonyl.
  • R 9 R 10 the following meanings are particular embodiments of R 9 : methoxy, ethoxy, propoxy, isopropoxy, n-butoxy or tert butoxy.
  • 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.
  • 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,
  • R 2 is a radical of the formula Ar2, in particular a radical of the formulae Ar2.1 , Ar2.2,
  • 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,
  • R 2 is a radical of the formula Ar2, in particular a radical of the formulae Ar2.1 , Ar2.3,
  • 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,
  • 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;
  • 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;
  • 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,
  • 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
  • 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,
  • R 2 is a radical of the formula Ar3, in particular a radical of the formulae Ar3.1 , Ar3.2,
  • 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.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,
  • 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
  • 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,
  • R 2 is a radical of the formula R2-2, in particular a radical of the formulae R2-2h.7,
  • 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,
  • R 2 is a radical of the formula R2-2, in particular a radical of the formulae R2-2h.7,
  • 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,
  • R1-2h.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,
  • 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,
  • 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;
  • X is S.
  • 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 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 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 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 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 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 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 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-
  • 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:

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Abstract

La présente invention concerne des nouveaux composés de 2,3-dihydrobenzazine de formule I et leurs sels. Les composés inhibent la prolifération cellulaire et la division cellulaire; ils inhibent également l'activation de la transcription induite par le facteur inductible par l'hypoxie (HIF) et de la signalisation dans des conditions d'hypoxie. Dans la formule (I) X représente O ou S(=O)n ; n vaut 0, 1 ou 2; R1 représente bicyclyle lié par C éventuellement substitué comprenant un premier cycle qui est un cycle benzène ou un cycle hétéroaromatique à 5 ou 6 chaînons présentant 1, 2 ou 3 atomes d'azote comme éléments de cycle hétéroatomiques ou 1 atome d'oxygène ou 1 atome de soufre et 0, 1 ou 2 atomes d'azote comme éléments de cycle hétéroatomiques, et un deuxième cycle qui est condensé sur le premier cycle. Le deuxième cycle est un cycle carbocyclique à 5, 6 ou 7 chaînons ou un cycle hétérocyclique à 5, 6 ou 7 chaînons comportant 1, 2 ou 3 éléments de cycle hétéroatomiques sélectionnés parmi oxygène, soufre et azote. Les atomes de soufre, s'ils sont présents, peuvent être présents sous forme de S, S(O) ou S(O)2 et le deuxième cycle carbocyclique ou hétérocyclique saturé ou insaturé peut également comporter 1 ou 2 groupes carbonyle ou groupes thiocarbonyle comme éléments de cycle; R2 représente un radical aromatique éventuellement substitué sélectionné parmi phényle, hétéroaryle à 5 ou 6 chaînons monocyclique lié par C ou un bicyclyle lié par C comprenant un premier cycle qui est un cycle benzène ou un cycle hétéroaromatique à 5 ou 6 chaînons et un deuxième cycle, qui est condensé sur le premier cycle, le deuxième cycle représentant un cycle carbocyclique à 5, 6 ou 7 chaînons ou un cycle hétérocyclique à 5, 6 ou 7 chaînons.
PCT/EP2011/054959 2011-03-30 2011-03-30 Composés bicycliques de 2,3-dihydrobenzazine destinés à une utilisation thérapeutique WO2012130306A1 (fr)

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Publication number Priority date Publication date Assignee Title
CN105085504A (zh) * 2014-04-16 2015-11-25 北京大学 4-取代苯磺酰胺衍生物及其制备方法和应用
CN110092782A (zh) * 2018-01-30 2019-08-06 中国科学院广州生物医药与健康研究院 一种苯并六元氮杂环化合物及其制备方法和应用
US11059796B2 (en) 2015-06-11 2021-07-13 The Regents Of The University Of Michigan Aryl dihydro-2H benzo[b][1,4]oxazine sulfonamide and related compounds for use as agonists of RORγ and the treatment of disease

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105085504A (zh) * 2014-04-16 2015-11-25 北京大学 4-取代苯磺酰胺衍生物及其制备方法和应用
US11059796B2 (en) 2015-06-11 2021-07-13 The Regents Of The University Of Michigan Aryl dihydro-2H benzo[b][1,4]oxazine sulfonamide and related compounds for use as agonists of RORγ and the treatment of disease
CN110092782A (zh) * 2018-01-30 2019-08-06 中国科学院广州生物医药与健康研究院 一种苯并六元氮杂环化合物及其制备方法和应用

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