WO2007115805A2

WO2007115805A2 - Aurora kinase inhibitors

Info

Publication number: WO2007115805A2
Application number: PCT/EP2007/003136
Authority: WO
Inventors: Joe Lewis
Original assignee: European Molecular Biology Laboratory (Embl)
Priority date: 2006-04-05
Filing date: 2007-04-05
Publication date: 2007-10-18
Also published as: WO2007115805A3

Abstract

The present invention provides novel compounds that inhibit cell proliferation, in particular by inhibiting Aurora kinase activity and uses of these compounds for treating, ameliorating or preventing diseases, conditions or disorders benefiting from the inhibition of Aurora kinase activity, in particular hyperproliferative diseases.

Description

AURORA KINASE INHIBITORS

The present invention provides novel compounds that inhibit cell proliferation, in particular by inhibiting Aurora A kinase activity and uses of these compounds for treating, ameliorating or preventing diseases, conditions or disorders benefiting from the inhibition of aurora activity, in particular hyperproliferative diseases.

BACKGROUND OF THE INVENTION

Mitosis is a fundamental mode of nuclear division of eukaryotic cells and a highly coordinated process by which eukaryotic cells assure the fidelity of chromosome segregation. The number of chromosomes is often a multiple of the basic number unique to the species, but errors during mitosis result in an individual having one to several chromosomes added to or deleted from the multiple (aneuploid), which may cause cell death or oncogenesis.

Aurora (Glover et al. (1995) Cell 81:95-105) identified in Drosophila melanogaster and its most closely related homolog IPL-I (Francisco et al. (1994) MoI. Cell Biol. 14:4731-40) in budding yeast (Saccharomyces cerevisiae) are members of serine/threonine kinase family involved in controlling cell growth, differentiation and regulation of the cell cycle. These kinases are thought to participate in M phase of mitosis and are thought to be required for high-fidelity chromosome segregation. Homologous proteins have been identified in vertebrates termed Aurora kinases A (also known as Aurora, Aurora-2, AIK, AIR-I, AIRKl, AYKl, BTAK, Eg2, MmIAKl and STKl 5), Aurora B (also known as Aurora-1, AIM-I, AIK2, AIR-2, AIRK-2, ARK2, IAL-I and STK 12) and Aurora C (also known as AIK3). These protein kinases participate in several biological processes, including cytokinesis and dysregulated chromosome segregation. These important regulators of mitosis are over-expressed in diverse solid tumors including prostate, colorectal, ovarian and gastric cancers. Overexpression of Aurora A kinase is found in >95% of all invasive adenocarcinomas. Consistently, amplification of this locus correlates strongly with poor clinical prognosis suggesting that inhibition of Aurora A kinase activity could inhibit tumour cell growth (Keen, N. & Taylor, S. (2004) Aurora-kinase inhibitors as anticancer agents. Nature Reviews Cancer 4, 927-936). The effectiveness of Aurora A kinase inhibitors in the suppression of tumor growth in vivo has been described for a compound named VX-680 (see, e.g. Harrington E.A. et. al. (2004) 10: 262-7 and Doggrell S.A. (2004) 13: 1 199- 1201).

Accordingly, there is a need in the art to identify novel inhibitors of Aurora kinases, in particular of Aurora A kinase. The present invention provides a novel compound class capable of inhibiting Aurora kinase activity.

SUMMARY OF THE INVENTION

The present invention provides compounds capable of inhibiting Aurora kinase activity, in particular Aurora A kinase activity. Data presented herein establishes that compounds of formula (I) can inhibit Aurora kinase, in particular Aurora A kinase activity.

In a first aspect the present invention relates to a compound of formula (I)

(I) wherein R¹ is alkyl, cycloalkyl, heterocycloalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted;

R², R³, and R⁴ are independent of each other selected from H; halogen; OH; CN; NO₂; NR'R"; - OOC-R⁶; -COO-R^6'; alkyl, alkyloxy, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein R' and R" are independent of each other hydrogen, alkyl, alkenyl, alkynyl, or together form a heteroaryl; optionally substituted; R⁶ is alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted

R⁶ is H, alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted; R⁵ is H, NR⁷R⁸, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein R⁷ and R⁸ are independently selected from the group consisting of H, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; or R⁷ and R⁸ are taken together to form a heterocycloalkyl, an alicyclic system or heteroaryl moiety; optionally substituted;

X and Y are independently selected from O and S; and p is 0, 1, or 2 and pharmaceutically acceptable salts thereof.

In a preferred embodiment of this invention the compound has a structure according to formula (IV)

(IV).

In a further aspect the present invention relates to compounds with a structure according to formula (V)

(V) wherein

R¹³ is alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted; R¹⁴ is NR¹⁵R¹⁶, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein R¹⁵ and R¹⁶ are independently selected from the group consisting of H, alkyl, cycloalkyl, heterocycloalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; or R¹⁵ and R¹⁶ are taken together to form a heterocycloalkyl, an alicyclic system or heteroaryl moiety; optionally substituted; X' and Y' are independently O or S and pharmaceutically acceptable salts thereof. In a preferred embodiment of the present invention the compound has a structure according to formula (VII) to (IX)

(VII),

(VIII), or

(IX).

In a further aspect the present invention is directed at pharmaceutical composition comprising an effective amount of at least one compound of the present invention and a pharmaceutically acceptable carrier or excipient.

In a further aspect the present invention is directed at the use of a compound of the invention for the production of a medicament for treating, ameliorating or preventing diseases, conditions and/or disorders which benefit from a reduced aurora kinase activity. DETAILED DESCRIPTION Definitions

Before the present invention is described in detail below, it is to be understood that this invention is not limited to the particular methodology, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Preferably, the terms used herein are defined as described in "A multilingual glossary of biotechnological terms: (IUPAC Recommendations)", Leuenberger, H.G.W, Nagel, B. and Klbl, H. eds. (1995), Helvetica Chimica Acta, CH-4010 Basel, Switzerland).

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

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

In the following definitions of the terms: alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, an alicyclic system, alkenyl, cycloalkenyl, and alkynyl are provided. These terms will in each instance of its use in the remainder of the specification have the respectively defined meaning and preferred meanings. Nevertheless in some instances of their use throughout the specification preferred meanings of these terms are indicated.

The term "alkyl" refers to a saturated straight or branched carbon chain. Preferably, the chain comprises from 1 to 10 carbon atoms, e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 e.g. methyl, ethyl methyl, ethyl, propyl, wo-propyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, or octyl. Alkyl groups are optionally substituted.

The term "heteroalkyl" refers to a saturated straight or branched carbon chain. Preferably, the chain comprises from 1 to 9 carbon atoms, i.e. 1, 2, 3, 4, 5, 6, 7, 8, or 9 e.g. methyl, ethyl, propyl, zso-propyl, butyl, iso-buty\, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, or octyl, which is interrupted one or more times, e.g. 1, 2, 3, 4, or 5, with the same or different heteroatoms. Preferably the heteroatoms are selected from O₅ S, and N, e.g. CH₂-O-CH₃, CH₂-O-C₂H₅, C₂H₄- O-CH3, C₂H₄-O-C₂H₅ etc. Heteroalkyl groups are optionally substituted.

The terms "cycloalkyl" and "heterocycloalkyl", by themselves or in combination with other terms, represent, unless otherwise stated, cyclic versions of "alkyl" and "heteroalkyl", respectively, with preferably 3, 4, 5, 6, 7, 8, 9 or 10 atoms forming a ring, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl etc. The terms "cycloalkyl" and "heterocycloalkyl" are also meant to include bicyclic, tricyclic and polycyclic versions thereof. If bicyclic, tricyclic or polycyclic rings are formed it is preferred that the respective rings are connected to each other at two adjacent carbon atoms, however, alternatively the two rings are connected via the same carbon atom, i.e. they form a spiro ring system or they form "bridged" ring systems. The term "heterocycloalkyl" preferably refers to a saturated ring having five members of which at least one member is a N, O or S atom and which optionally contains one additional 0 or one additional N; a saturated ring having six members of which at least one member is a N, O or S atom and which optionally contains one additional O or one additional N or two additional N atoms; or a saturated bicyclic ring having nine or ten members of which at least one member is a N, O or S atom and which optionally contains one, two or three additional N atoms. "Cycloalkyl" and "heterocycloalkyl" groups are optionally substituted. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. Preferred examples of cycloalkyl include C₃-Ci₀-cycloalkyl, in particular cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, spiro[3,3]heptyl, spiro[3,4]octyl, spiro[4,3]octyl, spiro[3,5]nonyl, spiro[5,3]nonyl, spiro[3,6]decyl, spiro[6,3]decyl, spiro[4,5]decyl, spiro[5,4]decyl, bicyclo[4.1.0]heptyl, bicyclo[3.2.0]heptyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[5.1.0]octyl, bicyclo[4.2.0]octyl, octahydro-pentalenyl, octahydro-indenyl, decahydro-azulenyl, adamantly, or decahydro-naphthalenyl. Preferred examples of heterocycloalkyl include C₃-Ci₀- heterocycloalkyl, in particular l-(l,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3- piperidinyl, 4-morpholinyl, 3-morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1 ,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro- [5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, 1- aza-7,l l-dioxo-spiro[5,5] undecyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, or 2-piperazinyl.

The term "alicyclic system" refers to mono, bicyclic, tricyclic or polycyclic version of a cycloalkyl or heterocycloalkyl comprising at least one double and/or triple bond. However, an alicyclic system is not aromatic or heteroaromatic, i.e. does not have a system of conjugated double bonds/free electron pairs. Thus, the number of double and/or triple bonds maximally allowed in an alicyclic system is determined by the number of ring atoms, e.g. in a ring system with up to 5 ring atoms an alicyclic system comprises up to one double bond, in a ring system with 6 ring atoms the alicyclic system comprises up to two double bonds. Accordingly, the "cycloalkenyl" as defined below is a preferred embodiment of an alicyclic ring system. Alicyclic systems are optionally substituted. Preferred examples include 1,2-dihydropyridinyl, 1,2,5,6- tetrahydropyridinyl, 1,2,3,4-tetrahydropyridyl, 1,2-dihydropyrazyl, 1,2,3,4-tetrahydropyrazyl, 1- cyclohexenyl, and 3-cyclohexenyl. Furthermore, "cycloalkenyl" as defined below is a preferred embodiment of an alicyclic system. Alicyclic systems are optionally substituted.

The term "aryl" preferably refers to an aromatic monocyclic ring containing 6 carbon atoms, an aromatic bicyclic ring system containing 10 carbon atoms or an aromatic tricyclic ring system containing 14 carbon atoms. Examples are phenyl, naphthalenyl or anthracenyl. The aryl group is optionally substituted.

The term "aralkyl" refers to an alkyl moiety, which is substituted by aryl, wherein alkyl and aryl have the meaning as outlined above. An example is the benzyl radical. Preferably, in this context the alkyl chain comprises from 1 to 8 carbon atoms, i.e. 1, 2, 3, 4, 5, 6, 7, or 8, e.g. methyl, ethyl, propyl, tsø-propyl, butyl, wø-butyl, sec-butenyl, tert-butyl, pentyl, hexyl, heptyl, or octyl. The aralkyl group is optionally substituted at the alkyl and/or aryl part of the group. Preferably the aryl attached to the alkyl has the meaning phenyl, naphthalenyl or anthracenyl.

The term "heteroaryl" preferably refers to a five or six-membered aromatic monocyclic ring wherein at least one of the carbon atoms are replaced by 1, 2, or 3 (for the five membered ring) or 1, 2, 3, or 4 (for the six membered ring) of the same or different heteroatoms, preferably selected from O, N and S; an aromatic bicyclic ring system wherein 1, 2, 3, 4, 5, or 6 carbon atoms of the 8, 9, 10, 11 or 12 carbon atoms have been replaced with the same or different heteroatoms, preferably selected from O, N and S; or an aromatic tricyclic ring system wherein 1, 2, 3, 4, 5, or 6 carbon atoms of the 13, 14, 15, or 16 carbon atoms have been replaced with the same or different heteroatoms, preferably selected from O, N and S. Examples are furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3, -thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1 -benzofuranyl, 2- benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1- benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl.

The term "heteroaralkyl" refers to an alkyl moiety, which is substituted by heteroaryl, wherein alkyl and heteroaryl have the meaning as outlined above. An example is the (2- pyridinyl) ethyl, (3-pyridinyl) ethyl, or (2-pyridinyl) methyl. Preferably, in this context the alkyl chain comprises from 1 to 8 carbon atoms, i.e. 1, 2, 3, 4, 5, 6, 7, or 8, e.g. methyl, ethyl methyl, ethyl, propyl, wo-propyl, butyl, wσ-butyl, sec-butenyl, tert-hutyl, pentyl, hexyl, heptyl, octyl. The heteroaralkyl group is optionally substituted at the alkyl and/or heteroaryl part of the group. Preferably the heteroaryl attached to the alkyl has the meaning oxazolyl, isoxazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3- triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1- benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, 2,3- benzodiazinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl.

The terms "alkenyl" and "cycloalkenyl" refer to olefinic unsaturated carbon atoms containing chains or rings with one or more double bonds. Examples are propenyl and cyclohexenyl. Preferably, the alkenyl chain comprises from 2 to 8 carbon atoms, i.e. 2, 3, 4, 5, 6, 7, or 8, e.g. ethenyl, 1 -propenyl, 2-propenyl, wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, iso- butenyl, sec-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, hexenyl, heptenyl, octenyl. Preferably the cycloalkenyl ring comprises from 3 to 14 carbon atoms, i.e. 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13 or 14, e.g. cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctyl, cyclononenyl, cyclodecenyl, spiro[3,3]heptenyl, spiro[3,4]octenyl, spiro[4,3]octenyl, spiro[3,5]nonenyl, spiro[5,3]nonenyl, spiro[3,6]decenyl, spiro[6,3]decenyl, spiro[4,5]decenyl, spiro[5,4]decenyl, bicyclo[4.1.0]heptenyl, bicyclo[3.2.0]heptenyl, bicyclo[2.2.1]heptenyl, bicyclo[2.2.2]octenyl, bicyclo[5.1.0]octenyl, bicyclo[4.2.0]octenyl, hexahydro-pentalenyl, hexahydro-indenyl, octahydro-azulenyl, or octahydro-naphthalenyl.

The term "alkynyl" refers to unsaturated carbon atoms containing chains or rings with one or more triple bonds. An example is the propargyl radical. Preferably, the alkynyl chain comprises from 2 to 8 carbon atoms, i.e. 2, 3, 4, 5, 6, 7, or 8, e.g. ethynyl, 1-propynyl, 2- propynyl, 1 -butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, hexynyl, heptynyl, octynyl. In one embodiment, carbon atoms or hydrogen atoms in alkyl, cycloalkyl, aryl, aralkyl, alkenyl, cycloalkenyl, alkynyl radicals may be substituted independently from each other with one or more elements selected from the group consisting of O, S, N or with groups containing one ore more elements selected from the group consisting of O, S, N. Embodiments include alkoxy, cycloalkoxy, arykoxy, aralkoxy, alkenyloxy, cycloalkenyloxy, alkynyloxy, alkylthio, cycloalkylthio, arylthio, aralkylthio, alkenylthio, cycloalkenylthio, alkynylthio, alkylamino, cycloalkylamino, arylamino, aralkylamino, alkenylamino, cycloalkenylamino, and alkynylamino radicals.

Other embodiments include hydroxyalkyl, hydroxycycloalkyl, hydroxyaryl, hydroxyaralkyl, hydroxyalkenyl, hydroxycycloalkenyl, hydroxyalinyl, mercapto alkyl, mercaptocycloalkyk, mercaptoaryl, mercaptoaralkyl, mercaptoalkenyl, mercaptocycloalkenyl, mercaptoalkynyl, aminoalkyl, aminocycloalkyl, aminoaryl, aminoaralkyl, aminoalkenyl, aminocycloalkenyl, and aminoalkynyl radicals.

In another embodiment, hydrogen atoms in alkyl, cycloalkyl, aryl, aralkyl, alkenyl, cycloalkenyl, alkynyl radicals may be substituted independently from each other with one ore more halogen atoms. One radical is the trifluoromethyl radical.

If two or more radicals can be selected independently from each other, then the term "independently" means that the radicals may be the same or may be different.

The term "pharmaceutically acceptable salt" refers to a salt of the compound of the present invention. Suitable pharmaceutically acceptable salts of the compound of the present invention include acid addition salts which may, for example, be formed by mixing a solution of compounds of the present invention with a solution of a pharmaceutically acceptable acid such as hydrochloric acid, sulfuric acid, fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid, citric acid, tartaric acid, carbonic acid or phosphoric acid. Furthermore, where the compound of the invention carries an acidic moiety, suitable pharmaceutically acceptable salts thereof may include alkali metal salts (e.g., sodium or potassium salts); alkaline earth metal salts (e.g., calcium or magnesium salts); and salts formed with suitable organic ligands (e.g., ammonium, quaternary ammonium and amine cations formed using counteranions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, alkyl sulfonate and aryl sulfonate). Illustrative examples of pharmaceutically acceptable salts include but are not limited to: acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, butyrate, calcium edetate, camphorate, camphorsulfonate, camsylate, carbonate, chloride, citrate, clavulanate, cyclopentanepropionate, digluconate, dihydrochloride, dodecylsulfate, edetate, edisylate, estolate, esylate, ethanesulfonate, formate, fumarate, gluceptate, glucoheptonate, gluconate, glutamate, glycerophosphate, glycolylarsanilate, hemisulfate, heptanoate, hexanoate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, hydroxynaphthoate, iodide, isothionate, lactate, lactobionate, laurate, lauryl sulfate, malate, maleate, malonate, mandelate, mesylate, methanesulfonate, methylsulfate, mucate, 2-naphthalenesulfonate, napsylate, nicotinate, nitrate, N-methylglucamine ammonium salt, oleate, oxalate, pamoate (embonate), palmitate, pantothenate, pectinate, persulfate, 3-phenylpropionate, phosphate/diphosphate, picrate, pivalate, polygalacturonate, propionate, salicylate, stearate, sulfate, subacetate, succinate, tannate, tartrate, teoclate, tosylate, triethiodide, undecanoate, valerate, and the like (see, for example, Berge, S. M., et al, "Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977, 66, 1-19). 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.

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.

In addition to salt forms, 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 formula (I). A prodrug is a pharmacologically active or inactive compound that is modified chemically through in vivo physiological action, such as hydrolysis, metabolism and the like, into a compound of this invention following administration of the prodrug to a patient. Additionally, prodrugs can be converted to the compounds of the present invention by chemical or biochemical methods in an ex vivo environment. For example, prodrugs can be slowly converted to the compounds of the present invention when placed in a transdermal patch reservoir with a suitable enzyme. The suitability and techniques involved in making and using prodrugs are well known by those skilled in the art. For a general discussion of prodrugs involving esters see Svensson and Tunek Drug Metabolism Reviews 16.5 (1988) and Bundgaard Design of Prodrugs, Elsevier (1985). Examples of a masked carboxylate anion include a variety of esters, such as alkyl (for example, methyl, ethyl), cycloalkyl (for example, cyclohexyl), aralkyl (for example, benzyl, p-methoxybenzyl), and alkylcarbonyloxyalkyl (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)). Hydroxyl groups have been masked as esters and ethers. EP 0 039 051 (Sloan and Little, Apr. 1 1, 1981) discloses Mannich-base hydroxamic acid prodrugs, their preparation and use. Compounds and also the starting materials for their preparation according to the invention can be synthesized by methods and standard procedures known to those skilled in the art, i.e. as described in the literature (for example in the standard works, such as Houben-Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg-Thieme-Verlag, Stuttgart), to be precise under reaction conditions which are known to those skilled in the art and suitable for the said reactions. Use can also be made here of variants which are known per se, but are not mentioned here in greater detail.

If desired, the starting materials can also be formed in situ by not isolating them from the reaction mixture, but instead immediately converting them further into the compounds of the present invention. On the other hand, it is possible to carry out the reaction stepwise. It should be noted that the general procedures are shown as it relates to preparation of compounds having unspecified stereochemistry. However, such procedures are generally applicable to those compounds of a specific stereochemistry, e.g., where the stereochemistry at a sterogenic center about a group is (S) or (R). In addition, the compounds having one stereochemistry (e.g., (R)) can often be utilized to produce those having opposite stereochemistry (i.e., (S)) using well- known methods, for example, by inversion.

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.

Certain compounds of the present invention possess asymmetric carbon atoms (optical centers) or double bonds; the racemates, enantiomers, diastereomers, geometric isomers and individual isomers are all intended to be encompassed within the scope of the present invention. Accordingly, the compounds of this invention include mixtures of stereoisomers, especially mixtures of enantiomers, as well as purified stereoisomers, especially purified enantiomers, or stereoisomerically enriched mixtures, especially enantiomerically enriched mixtures. Also included within the scope of the invention are the individual isomers of the compounds represented by formulas (I) and (V) below as well as any wholly or partially equilibrated mixtures thereof. The present invention also covers the individual isomers of the compounds represented by the formulas below as mixtures with isomers thereof in which one or more chiral centers are inverted. Also, it is understood that all tautomers and mixtures of tautomers of the compounds of formulae formulas (I) and (V) are included within the scope of the compounds of formulae formulas (I) and (V) and preferably the formulae and subformulae corresponding thereto.

Racemates obtained can be resolved into the isomers mechanically or chemically by methods known per se. Diastereomers are preferably formed from the racemic mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids, such as -camphorsulfonic acid. Also advantageous is enantiomer resolution with the aid of a column filled with an optically active resolving agent (for example dinitrobenzoylphenylglycine); an example of a suitable eluent is a hexane/isopropanol/acetonitrile mixture.

The diastereomer resolution can also be carried out by standard purification processes, such as, for example, chromatography or fractional crystallization.

It is also possible to obtain optically active compounds of formulas (I) and (V) by the methods described above by using starting materials which are already optically active. 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. For example, the compounds may be radiolabeled with radioactive isotopes, such as for example tritium (3H), iodine-125 (¹²⁵I) or carbon-14 (¹⁴C). All isotopic variations of the compounds of the present invention, whether radioactive or not, are intended to be encompassed within the scope of the present invention.

General

The present invention provides compositions, compounds and uses of compounds for inhibiting Aurora kinase, in particular Aurora A kinase in a cell. The compositions which are useful as inhibitors will typically be those which contain an effective amount of an Aurora kinase inhibitory compound. In general, an effective amount of an aurora kinase inhibitory compound is a concentration of the compound that will produce a 50 percent decrease in an Aurora kinase activity assay as described in the examples below. Embodiments of the Invention

The present invention provides compounds of formula (I)

(I) wherein

R¹ is alkyl, in particular CpC₆ alkyl, e.g. C₁, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wo-propyl, butyl, wo-butyl, tert-butyl, pentyl, or hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-/_?o-propenyl, 2-ώø-propenyl, 1-butenyl, 2-butenyl, or 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; heterocycloalkyl, in particular piperidinyl, morpholinyl, 1,3-diazacyclohexane, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza- spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro- [5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l-aza-7,l l-dioxo-spiro[5,5] undecyl, 1,4- diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2- yl, tetrahydrothien-3-yl, or piperazinyl, more particular piperazinyl; an alicyclic system, in particular 1,2-dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,4-tetrahydropyridyl, 1,2-dihydropyrazyl, 1,2,3,4-tetrahydropyrazyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl; aryl, e.g. phenyl, napthyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,- thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4- triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. CrC₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, or phenyl butyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2- furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2-isoxazolyl) methyl,

(3-isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4-isoxazolyl), (3-(l,2,5-oxadiazolyl)) methyl, (4-(l,2,5-oxadiazolyl)) methyl, (3- (1,2,5-oxadiazolyl)) ethyl, (4-(l,2,5-oxadiazolyl)) ethyl, (4-(l,2,3-oxadiazolyl)) methyl, (5-(l,2,3-oxadiazolyl)) methyl, (4-(l,2,3-oxadiazolyl)) ethyl, (5-(l,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-ρyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2- imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3- pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4- (1,2,3-triazolyl) methyl, (4-(l,2,3-triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4- triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4- thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4-isothiazolyl) methyl, (5- isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l,2,3,-thiadiazolyl)) methyl, (5-(l,2,3,-thiadiazolyl)) methyl, (4-(l,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5- pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3- pyrazinyl) ethyl, (4-(l,2,3-triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-(l,2,3- triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l,2,4-triazinyl)) methyl, (5-(l,2,4- triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l,2,4-triazinyl)) ethyl, (5-(l,2,4- triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l-benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l-benzofuranyl)) ethyl,

(7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l-(2-benzofuranyl)) methyl, (4- (2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2-benzofuranyl)) ethyl, (4-(2- benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7- indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1- isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (β-(l-benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l- benzothienyl)) ethyl, (ό-(l-benzothienyl)) ethyl, (7-(l-benzothienyl)) methyl, (l-(2- benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2- benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2-benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4-(lH-indazolyl)) ethyl, (5-(1H- indazolyl)) ethyl, (ό-(lH-indazolyl)) ethyl, (7-(lH-indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5-benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5-benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4- benzoxazolyl) methyl, (5-benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7- benzoxazolyl) methyl, (2-benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4- indoxazinyl) methyl, (5-indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6- indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3 -(2,1 -benzoxazolyl)) methyl, (4-(2,l- benzoxazolyl)) methyl, (5-(2,l -benzoxazolyl)) methyl, (6-(2, 1 -benzoxazolyl)) methyl, (7-

(2, 1 -benzoxazolyl)) methyl, (3-(2,l -benzoxazolyl)) ethyl, (4-(2,l -benzoxazolyl)) ethyl, (5 -(2,1 -benzoxazolyl)) ethyl, (6-(2,l -benzoxazolyl)) ethyl, (7-(2,l -benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4-benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6- benzothiazolyl) methyl, (7-benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4- benzothiazolyl) ethyl, (5-benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7- benzothiazolyl) ethyl, (3-(l,2-benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l ,2-benzisothiazolyl)) methyl, (7-(l ,2- benzisothiazolyl)) methyl, (3-(l,2-benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2- benzisothiazolyl)) ethyl, (3-(2,l-benzisothiazolyl)) methyl, (4-(2,l-benzisothiazolyl)) methyl, (5-(2,l -benzisothiazolyl)) methyl, (6-(2,l -benzisothiazolyl)) methyl, (7-(2,l- benzisothiazolyl)) methyl, (3-(2,l -benzisothiazolyl)) ethyl, (4-(2,l -benzisothiazolyl)) ethyl, (5-(2,l -benzisothiazolyl)) ethyl, (6-(2,l -benzisothiazolyl)) ethyl, (7-(2,l- benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4- benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2-quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8- quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5- quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1-isoquinolinyl) methyl, (3- isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5-isoquinolinyl) methyl, (6- isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8-isoquinolinyl) methyl, (1- isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8-isoquinolinyl) ethyl, (l-(2,3- benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-(2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3-benzodiazinyl)) ethyl, (5-(2,3- benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7-(2,3-benzodiazinyl)) ethyl, (8- (2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3-quinoxalinyl) methyl, (5- quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2-quinazolinyl) methyl, (4- quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4-quinazolinyl) ethyl, (5- quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l,2,3- benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3-benzotriazinyl)) methyl, (4-( 1,2,3 -benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3- benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3-benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4- benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-(l,2,4-benzotriazinyl)) methyl, (3-(l,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4- benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-(l,2,4-benzotriazinyl)) ethyl; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, ϊso- propyl, butyl, zso-butyl, tert-buty\, pentyl, or hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-iso- propenyl, 2-zsø-propenyl, 1-butenyl, 2-butenyl, or 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, /so-propoxy, butoxy, iso- butoxy, tert-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular C)-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -C0-R^c, -OOC-R⁰; - COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyi'azolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5- thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5- triazinyl, 1-benzo furanyl, 2-benzo furanyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1- benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl; aralkyl; or heteroaralkyl; optionally substituted, wherein

R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted;

R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl; or two or more of substituents of R¹ are taken together to form a cycloalkyl, heterocycloalkyl, an alicyclic system, aryl or heteroaryl; optionally substituted; optionally the alkyl moiety of R¹, including the alkyl moiety of the aralkyl and the heteroaralkyl moiety, respectively is interrupted 1, 2, 3, 4 or more times by O, N, and/or S;

R², R³, and R⁴ are independent of each other selected from H; halogen, in particular F, Cl, Br or I; OH; CN; NO₂; NR'R"; -00C-R⁶; -COO-R⁶; alkyl, e.g. C₁, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wo-propyl, butyl, iso-butyl, ter/-butyl, pentyl, or hexyl; alkoxy, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein

R' and R" are independent of each other hydrogen, alkyl, alkenyl, alkynyl or together form a heteroaryl; optionally substituted; R⁶ is alkyl, in particular CpC₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wo-propyl, butyl, wσ-butyl, før/-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1- propenyl, 2-propenyl, 1-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3- butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or Ce alkynyl; aryl or heteroaryl; optionally substituted;

R⁶ is H, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wo-propyl, butyl, wσ-butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1- propenyl, 2-propenyl, 1-wø-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3- butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; aryl or heteroaryl; optionally substituted; is H; NR⁷R⁸; alkyl, in particular C_rC₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wo-propyl, butyl, wo-butyl, ter/-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl,

1 -propenyl, 2-propenyl, 1-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl, in particular cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl; heterocycloalkyl, in particular piperidinyl, morpholinyl, 1,3-diazacyclohexane, 1,8 diaza- spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza- spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro- [5,4] decyl, 1 ,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l-aza-7,l l-dioxo-spiro[5,5] undecyl, l ,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, piperazinyl; an alicyclic system, in particular

1 ,2-dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,4-tetrahydropyridyl, 1,2- dihydropyrazyl, 1,2,3,4-tetrahydropyrazyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and cycloheptenyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,- thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4- triazinyl, 1,3,5-triazinyl, 1 -benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2, 1 -benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl, more particular pyridinyl; aralkyl, e.g. Ci- C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl; or heteroaralkyl, preferably Ci- C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, (2-furanyl) methyl, (3- furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl. (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2- isoxazolyl) methyl, (3-isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4-isoxazolyl), (3-(l,2,5-oxadiazolyl)) methyl, (4-(l,2,5- oxadiazolyl)) methyl, (3-(l ,2,5-oxadiazolyl)) ethyl, (4-(l,2,5-oxadiazolyl)) ethyl, (4-

(1,2,3-oxadiazolyl)) methyl, (5-( 1,2,3 -oxadiazolyl)) methyl, (4-(l,2,3-oxadiazolyl)) ethyl, (5-(l,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4- imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4- pyrazolyl) ethyl, (4-(l,2,3-triazolyl) methyl, (4-(l ,2,3-triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2- thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4- isothiazolyl) methyl, (5-isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l,2,3,-thiadiazolyl)) methyl, (5-(l ,2,3,-thiadiazolyl)) methyl,

(4-(l,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3- (1,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4- pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2- pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4-(l,2,3-triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-(l ,2,3-triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l,2,4-triazinyl)) methyl, (5-(l ,2,4-triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l,2,4-triazinyl)) ethyl, (5- (1,2,4-triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5- triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l- benzofurany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l- benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l- benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l-(2- benzofuranyl)) methyl, (4-(2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2- benzofuranyl)) ethyl, (4-(2-benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7- indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5- isoindolyl) methyl, (l-isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l- benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (6-(l- benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l- benzothienyl)) ethyl, (4-(l-benzothienyl)) ethyl, (6-(l-benzothienyl)) ethyl, (7-(l- benzothienyl)) methyl, (l-(2-benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2- benzothienyl)) methyl, (l-(2-benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2- benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4- (lH-indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (6-(lH-indazolyl)) ethyl, (7-(1H- indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5- benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5- benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5- benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2- benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4-indoxazinyl) methyl, (5- indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6-indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l-benzoxazolyl)) methyl, (4-(2,l-benzoxazolyl)) methyl, (5-(2,l- benzoxazolyl)) methyl, (6-(2, 1 -benzoxazolyl)) methyl, (7-(2,l-benzoxazolyl)) methyl, (3- (2,1-benzoxazolyl)) ethyl, (4-(2,l -benzoxazolyl)) ethyl, (5-(2,l -benzoxazolyl)) ethyl, (6- (2,1 -benzoxazolyl)) ethyl, (7-(2,l -benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4- benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7- benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5- benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7-benzothiazolyl) ethyl, (3-(l,2- benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l ,2-benzisothiazolyl)) methyl, (3 -(1,2- benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3-(2,l- benzisothiazolyl)) methyl, (4-(2,l-benzisothiazolyl)) methyl, (5-(2,l-benzisothiazolyl)) methyl, (6-(2, 1 -benzisothiazolyl)) methyl, (7-(2,l-benzisothiazolyl)) methyl, (3-(2,l- benzisothiazolyl)) ethyl, (4-(2,l-benzisothiazolyl)) ethyl, (5-(2,l-benzisothiazolyl)) ethyl, (6-(2,l-benzisothiazolyl)) ethyl, (7-(2,l-benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2- quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8-quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl,

(4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1- isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5- isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8- isoquinolinyl) methyl, (l-isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8- isoquinolinyl) ethyl, (l-(2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5- (2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3- benzodiazinyl)) ethyl, (5-(2,3-benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7- (2,3-benzodiazinyl)) ethyl, (8-(2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3- quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2- quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4- quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl,

(8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3- benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3-benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3- benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4-benzotriazinyl)) methyl, (7-(l ,2,4-benzotriazinyl)) methyl, (8-(l,2,4- benzotriazinyl)) methyl, (3-(l,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4-benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-(l,2,4- benzotriazinyl)) ethyl; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; hydroxyl; NR^dR^e; and R¹⁰; wherein

R⁷ and R⁸ are independently selected from the group consisting of H; alkyl, in particular CpC₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, jso-propyl, butyl, iso-butyl, /erf-butyl, pentyl, hexyl; cycloalkyl, heterocycloalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN: NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /so-propyl, butyl, /so-butyl, /erf-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2- propenyl,

2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, wo-propoxy, butoxy, iso-butoxy, /er/-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R⁰, -0OC-R⁰; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1 ,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3- triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4- benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Cj-C₆ heteroaralkyl, e.g. Cj, C₂,

C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted, wherein

R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g.

C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Cj-C₆ alkyl, e.g. C₁, C₂, C₃, C₄, C₅, or C₆ alkyl; and R⁸ are taken together to form a heterocycloalkyl, an alicyclic system or heteroaryl moiety; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propyl, butyl, wo-butyl, fer/-butyl, pentyl, hexyl; alkenyl, in particular

C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2- propenyl, 1-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, iso-propoxy, butoxy, iso-butoxy, tert-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R^C, -OOC-R^C; -COO-R^C; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3- triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1 -benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1 ,2,3-benzotriazinyl, or 1,2,4- benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted, wherein R^a and R^b are independent of each other hydrogen, alkyl, in particular CpC₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g.

C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂,

C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted;

R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. C,, C₂, C₃, C₄, C₅, or C₆ alkyl; or two or more of substituents of R⁷ and/or R⁸ are taken together to form a cycloalkyl, heterocycloalkyl, an alicyclic system, aryl or heteroaryl; optionally substituted; R¹⁰ is -R"-R¹²;

R¹ ' is a bond, -OOC-, -COO-, CO, O, or S, preferably S;

R¹² is alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /sø-propyl, butyl, wø-butyl, tert-buty\, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1- propenyl, 2-propenyl, 1-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3- butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl; heterocycloalkyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1 ,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1- benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl,

1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1 ,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. CpC₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Cj-C₆ hetero aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted;

R^d and R^e are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄,

C₅, or C₆ alkenyl, or alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or two or more of substituents of R⁵ are taken together to form a cycloalkyl, heterocycloalkyl, an alicyclic system, aryl or heteroaryl; optionally substituted; optionally the alkyl moiety of R⁵, including the alkyl moiety of the aralkyl and the heteroaralkyl moiety, respectively, is interrupted 1, 2, 3, 4 or more times by O, N, and/or S;

X and Y are independently selected from O and S, preferably at least one of X and Y is O and more preferably both X and Y are O; and p is 0, 1, or 2, preferably 1; and pharmaceutically acceptable salts thereof. Preferred salts comprise Na⁺. K⁺, and Ca²⁺ salts.

The compounds of the general formula (I) according to the present invention may be prepared according to the following scheme I:

wherein R¹, R², R³, R⁴, R⁵, X, Y and p are as defined above, or have the particularly preferred meanings as defined below, Lie is a conventional leaving group such as halogen, sulfonyl or the like. The above process comprise reacting a compound of the genera formula (1) with a -C(=Y)-R⁵ group in an organic solvent to obtain a compound of the general formula (2). The -C(=Y)-R⁵ group-providing agent used in the above reaction may include 1,1- carbonyldiimidazole, 1 , 1 -carbonylthiodiimidazole, phosgene, thiophosgene, carbonyldiphenoxide and phenylchloro formate, and it may be used in an amount of 1-1.5 equivalent, preferably 1-1.1 equivalent to the starting compound (1).

The reaction may be carried out in a conventional organic solvent such as, for example, tetrahydrofuran, dichloromethane, acetonitrile, chloroform and dimethylformamide. The reaction is preferably carried out in the presence of a coupling agent such as a conventional inorganic or an organic base.

Such conventional inorganic or organic bases used in the reaction may include sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, pyridine and DBU.

The reaction may be carried out at a temperature between 3⁰C and boiling point of the solvent used, preferably at 50⁰C-IOO⁰C and for 5-48 hours, preferably for 10-24 hours.

In the above reaction process, if any acid material is formed, a basic material may be added as a scavenger in order to eliminate the acid material from the reaction phase. Such basic material may be alkali metal hydroxide, alkali earth metal hydroxide, alkali metal oxide, alkali earth metal oxide, alkali metal carbonate, alkali earth metal carbonate, alkali metal hydrogen carbonate, alkali earth metal hydrogen carbonate such as for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, magnesium oxide, calcium oxide, potassium carbonate, sodium carbonate, calcium carbonate, magnesium carbonate, magnesium bicarbonate, sodium bicarbonate, calcium bicarbonate or the like, and organic amines.

R³ and R⁴ or any substituent of R¹, R², R³, R⁴ and/or R⁵, which would undergo unwanted reactions when carrying out a synthesis according to scheme I may be protected by a conventional protecting group, which is not cleaved during the reaction according to schema I but is cleavable under known conditions. The skilled person is aware of a large variety of protection groups, which can be employed in organic synthesis. Protecting groups are reviewed in, for example, Wuts, P.G.M. and Greene, T. W., Protective Groups in Organic Chemistry, 3^rd Ed., 1999; Wily & Sons Inc. and in Kocienski, P. J., Protecting groups. 2^nd Ed., 2000, Thieme Medical Publishing. Protecting groups are organized in these reference books according to the functionalities that are protected as well as according to the conditions which remove the respective protecting groups selectively. Particularly preferred protective groups, which can be used are:

(i) protective group removed at acidic conditions, preferably at a pH between 4 and 6, which is selected from the group consisting of Boc or Trityl protecting groups;

(ii) a protecting group removed by a nucleophile, which is selected from the group consisting of Fmoc or Dde protecting groups; (iii) a protecting group removed by hydrogenolysis consisting of the allyl type, the tert-butyl type, the benzyl type or Dmab (4,4-dimethyl-2,6-dicyclohexylidene)-3-methylbutyl]- amino} benzyl ester ;

(iv) a protecting group removed by radiation, which is selected from the group consisting of nitroveratryloxy carbonyl, nitrobenzyloxy carbonyl, dimethyl dimethoxybenzyloxy carbonyl, 5-bromo-7-nitroindolinyl, o-hydroxy-α-methyl cinnamoyl, and 2-oxymethylene anthraquinone. In a preferred embodiment of the compounds according to the present invention R¹ is selected from the group consisting of 1,2,5,6-tetrahydropyridinyl, piperidinyl, l-oxo-3- azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza- spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, 1,4- diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuranyl, tetrahydrothienyl, piperazinyl; furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1 ,2,3-triazinyl, 1,2,4-triazinyl, 1 ,3,5-triazinyl, 1-benzo furanyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, and 1 ,2,4-benzotriazinyl, in particular piperazinyl; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wo-propyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-wo-propenyl, 2-z.yø-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, iso-propoxy, butoxy, iso-butoxy, tert-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Cp C₆ alkyl, e.g. methoxy methyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R⁰, -OOC-R⁰; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1 ,3,5-triazinyl, 1 -benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, 1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl; or heteroaralkyl; optionally substituted; wherein

R^a and R^b are independent of each other hydrogen, alkyl, in particular Cj-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci,

C₂, C₃, C₄, C₅, or C₆ alkyl. In a preferred embodiment of the compound according to formula (I) R⁷ and R⁸ are taken together to form a 1,2,5,6-tetrahydropyridinyl, piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro- [5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct-2-yl, piperazinyl; isoxazolyl; 1 ,2,5-oxadiazolyl; 1,2,3-oxadiazolyl; pyrrolyl, imidazolyl, pyrazolyl, 1 ,2,3-triazolyl, thiazolyl; isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl; pyrazinyl; 1,2,3-triazinyl; 1,2,4-triazinyl; 1 ,3,5-triazinyl; 1-benzofuranyl; 2- benzofuranyl; indolyl; isoindolyl; 1 H-indazolyl; benzimidazolyl; indoxazinyl; 2,1- benzisoxazolyl; benzothiazolyl; 1,2-benzisothiazolyl; 2, 1-benziso thiazolyl; benzotriazolyl; quinolinyl; isoquinolinyl; 2,3-benzodiazinyl; quinoxalinyl; quinazolinyl; quinolinyl; 1,2,3- benzotriazinyl; or 1,2,4-benzotriazinyl moiety; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^dR^e; alkyl, in particular C,-C₆ alkyl, e.g. C|, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propyϊ, butyl, wo-butyl, /e/7-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably C)-C₆ alkanoyl, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, zso-propoxy, butoxy, /so-butoxy, ter/-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular CpC₆ alkoxy-Cp C₆ alkyl, e.g. methoxy methyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxy propyl, ethoxypropyl, or propoxypropyl; -CO-R^f, -OOC-R^f; -COO-R^f; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl; or heteroaralkyl; optionally substituted, wherein R^d and R^e are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, or alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, R^f is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci,

C₂, C₃, C₄, C₅, or C₆ alkyl. In a particular preferred embodiment of the present invention the compound has a structure according to formula (II)

(H) wherein R¹, R², R³, R⁴, p, X, and Y have the preferred and particular preferred meanings indicated above

R¹⁰ is halogen, e.g. F, Cl, Br, or I; OH; CN; NO₂; NR'R"; -Rⁿ-R¹²; and wherein

R', and R" are independent of each other hydrogen, alkyl, in particular C)-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wø-propyl, butyl,

/sø-butyl, tert-buty\, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃,

C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1 -wo-propenyl, 2- wø-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted;

R¹ ' is a bond, -OOC-, -COO-, CO, O, or S, preferably S; and

R¹² is alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /so-propyl, butyl, wσ-butyl, terf-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1- propenyl, 2-propenyl, 1-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3- butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl; heterocycloalkyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1 ,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2.5-thiadiazolyI, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1- benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, 1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted; m is an integer from 0 to 4, e.g. 0, 1 , 2, 3, 4, preferably 0, 1 or 2; and one or two of A, B, D, E, and G are indepently nitrogen atoms, while all other are carbon atoms, preferably one of A, B or D is a nitrogen atom and all other are carbon atoms.

In a preferred embodiment of the present invention the compound according to formula (I) or (II) has structure selected from one of the following:

(R^k)o (R^k)_c (R^k)_c (R^k)_c

R9— R9— z <y ^"N^'

(R^k)₀ (R^k)o (R^k)o (R^k)o (R^k)c

R9

wherein

R ,9 is alkyl, in particular Cj-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl in particular Ci-C₆ alkyl, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /jo-propyl, butyl, iso-butyl, terf-butyl, pentyl, or hexyl; cycloalkyl, in particular C₃ to C₇ cycloalkyl, heterocycloalkyl, in particular piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza- spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro- [5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l ,4-diazabicyclo[2.2.2]oct-2- yl, tetrahydrofuranyl, tetrahydrothienyl, or piperazinyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2- benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3- benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. C_rC₆ aralkyl, preferably CpC₆ aralkyl, e.g. Cj, C₂, C₃, C₄, C₅, or Ce aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3- furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2- oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2-isoxazolyl) methyl, (3- isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3 -isoxazolyl), ethyl

(4-isoxazolyl), (3-(l ,2,5-oxadiazolyl)) methyl, (4-( 1,2,5-oxadiazolyl)) methyl, (3-(l ,2,5- oxadiazolyl)) ethyl, (4-(l,2,5-oxadiazolyl)) ethyl, (4-(l,2,3-oxadiazolyl)) methyl, (5- ( 1,2,3-oxadiazolyl)) methyl, (4-( 1,2,3-oxadiazolyl)) ethyl, (5 -(1,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2- imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3- pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4- (1 ,2,3-triazolyl) methyl, (4-(l,2,3-triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4- triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4- thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4-isothiazolyl) methyl, (5- isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-( 1,2,3,-thiadiazolyl)) methyl, (5-( 1,2,3,-thiadiazolyl)) methyl, (4-(l,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5- pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3- pyrazinyl) ethyl, (4-(l,2,3-triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-(l,2,3- triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l,2,4-triazinyl)) methyl, (5-(l,2,4- triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l,2,4-triazinyl)) ethyl, (5-(l,2,4- triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l-benzofiiranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l-benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l-benzofuranyl)) ethyl,

(7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l-(2-benzofuranyl)) methyl, (4- (2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2-benzofuranyl)) ethyl, (4-(2- benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7- indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1- isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (ό-(l-benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l- benzothienyl)) ethyl, (ό-(l-benzothienyl)) ethyl, (7-(l-benzothienyl)) methyl, (l-(2- benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2- benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2-benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4-(lH-indazolyl)) ethyl, (5-(1H- indazolyl)) ethyl, (6-(lH-indazolyl)) ethyl, (7-(lH-indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5-benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5-benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4- benzoxazolyl) methyl, (5-benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7- benzoxazolyl) methyl, (2-benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4- indoxazinyl) methyl, (5-indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6- indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l-benzoxazolyl)) methyl, (4-(2,l- benzoxazolyl)) methyl, (5-(2,l-benzoxazolyl)) methyl, (6-(2,l-benzoxazolyl)) methyl, (7- (2,1-benzoxazolyl)) methyl, (3-(2,l-benzoxazolyl)) ethyl, (4-(2,l-benzoxazolyl)) ethyl, (5-(2,l-benzoxazolyl)) ethyl, (6-(2,l-benzoxazolyl)) ethyl, (7-(2,l-benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4-benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6- benzothiazolyl) methyl, (7-benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4- benzothiazolyl) ethyl, (5-benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7- benzothiazolyl) ethyl, (3-(l,2-benzisothiazolyl)) methyl, (4-(l ,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l ,2-benzisothiazolyl)) methyl, (7-(l,2- benzisothiazolyl)) methyl, (3-(l,2-benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l ,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2- benzisothiazolyl)) ethyl, (3-(2,l-benzisothiazolyl)) methyl, (4-(2,l-benzisothiazolyl)) methyl, (5-(2, 1 -benzisothiazolyl)) methyl, (6-(2,l -benzisothiazolyl)) methyl, (7-(2,l- benzisothiazolyl)) methyl, (3-(2,l -benzisothiazolyl)) ethyl, (4-(2, 1 -benzisothiazolyl)) ethyl, (5-(2,l -benzisothiazolyl)) ethyl, (6-(2,l -benzisothiazolyl)) ethyl, (7-(2,l- benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4- benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2-quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8- quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5- quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1-isoquinolinyl) methyl, (3- isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5-isoquinolinyl) methyl, (6- isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8-isoquinolinyl) methyl, (1- isoquinolinyl) ethyl, (3 -isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8-isoquinolinyl) ethyl, (l-(2,3- benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-(2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3-benzodiazinyl)) ethyl, (5-(2,3- benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7-(2,3-benzodiazinyl)) ethyl, (8- (2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3-quinoxalinyl) methyl, (5- quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2-quinazolinyl) methyl, (4- quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8 -quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4-quinazolinyl) ethyl, (5- quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l ,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l,2,3- benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3-benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3- benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3-benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4- benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-(l,2,4-benzotriazinyl)) methyl, (3-(l,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4- benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-(l,2,4-benzotriazinyl)) ethyl; optionally substituted; is in each instance selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular C,-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, zso-propyl, butyl, /so-butyl, /er/-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-z^'sø-propenyl, 2-/so-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, iso-propoxy, butoxy, wo-butoxy, /er/-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R^C, -OOC-R^C; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1 ,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1- benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl; or heteroaralkyl; optionally substituted; wherein

R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. C₁, C₂, C₃, C₄, C₅, or C₆ alkyl; 5. Z is CR'" or N; wherein

R" ' is hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-pτopy\, butyl, wo-butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, 0 preferably ethenyl, 1-propenyl, 2-propenyl, l-wo-propenyl, 2-z.yø-propenyl, 1- butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄,

C₅, or C₆ alkynyl; optionally substituted; o is between 0 and 4, i.e. 0, 1, 2, 3, or 4, for six membered rings and between 0 and 3, i.e. 0,

1 , 2, or 3 for five membered rings; and 5 * is the attachment point between the compound according to formula (I) or (II) and R¹.

In a particular preferred embodiment of the present invention the compound has a structure according to formula (III)

0 (III) wherein

R², R³, R⁴ X, Y and p have the meaning and preferred meanings as outlined above;

R⁹ is alkyl, in particular Cj-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl in particular CpC₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propyl, 5 butyl, Λsø-butyl,

pentyl, or hexyl; cycloalkyl, in particular C₃ to C₇ cycloalkyl, heterocycloalkyl, in particular piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza- spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro- [5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct-2- yl, tetrahydrofuranyl, tetrahydrothienyl, or piperazinyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1 -benzofuranyl, 2- benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzo thiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3- benzodiazinyl, quinoxalinyl, quinazolinyl, 1 ,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably C)-C₆ aralkyl, e.g. C₁, C₂, C₃, C₄, C₅, or Ce aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3- furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2- oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2-isoxazolyl) methyl, (3- isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3 -isoxazolyl), ethyl (4-isoxazolyl), (3 -(1 ,2,5-oxadiazolyl)) methyl, (4-(l ,2,5-oxadiazotyl)) methyl, (3-(l,2,5- oxadiazolyl)) ethyl, (4-(l,2,5-oxadiazolyl)) ethyl, (4-(l,2,3-oxadiazolyl)) methyl, (5- (1,2,3-oxadiazolyl)) methyl, (4-( 1,2,3-oxadiazolyl)) ethyl, (5-(l,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3 -pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3 -pyrrolyl) ethyl, (2- imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3- pyrazolyl) methyl, (4-pyrazolyl) methyl, (3 -pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4- (1,2,3-triazolyl) methyl, (4-(l,2,3-triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4- triazolyl) ethyl, (2-thienyl) methyl, (3 -thienyl) methyl, (2 -thienyl) ethyl, (3 -thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4- thiazolyl) ethyl, (5-thiazolyl) ethyl, (3 -isothiazolyl) methyl, (4-isothiazolyl) methyl, (5- isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l,2,3,-thiadiazolyl)) methyl, (5-(l,2,3,-thiadiazolyl)) methyl, (4-( 1,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2 -pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5 -pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5- pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3- pyrazinyl) ethyl, (4-(l,2,3-triazinyl) methyl, (5-( 1,2,3-triazinyl)) methyl, (4-(l,2,3- triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l,2₅4-triazinyl)) methyl, (5-(l,2,4- triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l,2,4-triazinyl)) ethyl, (5-(l,2,4- triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzoftiranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzoftirany I)) methyl, (ό-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l-benzofiiranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l-benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofiiranyl)) ethyl, (l-(2-benzofuranyl)) methyl, (4- (2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2-benzofuranyl)) ethyl, (4-(2- benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7- indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1 - isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (6-( 1-benzothienyl)) methyl, (7-( 1-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l- benzothienyl)) ethyl, (6-( 1 -benzothienyl)) ethyl, (7-( 1-benzothienyl)) methyl, (l-(2- benzothienyl)) methyl, (4-(2 -benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2- benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2-benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4-(lH-indazolyl)) ethyl, (5-(1H- indazolyl)) ethyl, (ό-(lH-indazolyl)) ethyl, (7-(lH-indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5-benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5-benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4- benzoxazolyl) methyl, (5-benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7- benzoxazolyl) methyl, (2-benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4- indoxazinyl) methyl, (5-indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6- indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3 -(2,1 -benzoxazolyl)) methyl, (4-(2,l- benzoxazolyl)) methyl, (5-(2,l -benzoxazolyl)) methyl, (6-(2,l -benzoxazolyl)) methyl, (7-

(2,1 -benzoxazolyl)) methyl, (3-(2,l -benzoxazolyl)) ethyl, (4-(2,l -benzoxazolyl)) ethyl, (5-(2,l -benzoxazolyl)) ethyl, (6-(2,l -benzoxazolyl)) ethyl, (7-(2,l -benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4-benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6- benzothiazolyl) methyl, (7-benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4- benzothiazolyl) ethyl, (5-benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7- benzothiazolyl) ethyl, (3-(l,2-benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7 -(1,2- benzisothiazolyl)) methyl, (3-(l,2-benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2- benzisothiazolyl)) ethyl, (3-(2,l-benzisothiazolyl)) methyl, (4-(2,l-benzisothiazolyl)) methyl, (5-(2,l-benzisothiazolyl)) methyl, (6-(2,l-benzisothiazolyl)) methyl, (7-(2,l- benzisothiazolyl)) methyl, (3-(2,l-benzisothiazolyl)) ethyl, (4-(2,l-benzisothiazolyl)) ethyl, (5-(2,l-benzisothiazolyl)) ethyl, (6-(2,l-benzisothiazolyl)) ethyl, (7-(2,l- benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4- benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2-quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8- quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5- quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1-isoquinolinyl) methyl, (3- isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5-isoquinolinyl) methyl, (6- isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8-isoquinolinyl) methyl, (1 - isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8-isoquinolinyl) ethyl, (l-(2,3- benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-(2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3-benzodiazinyl)) ethyl, (5-(2,3- benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7-(2,3-benzodiazinyl)) ethyl, (8- (2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3-quinoxalinyl) methyl, (5- quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2-quinazolinyl) methyl, (4- quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4-quinazolinyl) ethyl, (5- quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l,2,3- benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3-benzotriazinyl)) methyl, (4-( 1,2,3 -benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3- benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-( 1,2,3 -benzotriazinyl)) ethyl, (3-(l ,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4- benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-(l,2,4-benzotriazinyl)) methyl, (3-(l,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4- benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-(l,2,4-benzotriazinyl)) ethyl; optionally substituted;

R¹⁰ is H; halogen, e.g. F, Cl, Br, or I; OH; CN; NO₂; NR'R"; -R¹ '-R¹²; and wherein

R', and R" are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /so-propyl, butyl, wø-butyl, tert-buty\, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, Cs, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1-iso-propenyl, 2- /so-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted;

R¹ ' is a bond, -OOC-, -COO-, CO, O, or S, preferably S; and

R¹² is alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propyl, butyl, iso-buty\, tert-buty\, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1- propenyl, 2-propenyl, 1 -/so-propenyl, 2-/so-propenyl, 1-butenyl, 2-butenyl, 3- butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl; heterocycloalkyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1- benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Cj-C₆ aralkyl, preferably CpC₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably CpC₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted;

Z is CR'" or N; wherein

R'" is hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, zso-propyl, butyl, /5o-butyl, fer/-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1-wo-propenyl, 2-Λϊo-propenyl, 1- butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; optionally substituted.

In a particularly preferred embodiment of the present invention the compound has a structure according to formula (IV)

(IV). In some preferred embodiments the compound according to formula (IV) can additionally comprise one or more substituents, preferably 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propyl, butyl, iso- butyl, ter/-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2- butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, /so-propoxy, butoxy, wo-butoxy, /er/-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; - C0-R^c, -OOC-R^C; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5- thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1- benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3- benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Q-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted; wherein R^a and R are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂,

C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and

R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl.

In a further aspect the present invention relates to a compound according to formula (V)

(V) wherein

R¹³ is in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /_vo-propyl, butyl, wσ-butyl, tert-butyl, pentyl, hexyl, in particular methyl; alkenyl, in particular Cj-Ce alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1 - propenyl, 2-propenyl, l-«ø-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, in particular ethenyl; alkynyl, in particular C₂-C_O alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1 ,2,5-oxadiazolyl, 1 ,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1 ,3,5-triazinyl, 1- benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, IH- indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2, 1 -benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl; optionally substituted preferably with one or more 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wσ-propyl, butyl, wo-butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C2, C3, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1- /so-propenyl, 2-fsσ-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C3, C₄, C₅, or C₆ alkynyl; cycloalkyl, in particular C₃-C₇ cycloalkyl, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl; alkanoyl, preferably Cj-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Q- C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, /so-propoxy, butoxy, /sσ-butoxy, rerf-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R^C, -OOC-R⁰; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl,

1 ,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1-benzo furanyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, IH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1- benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. C_r

C₆ aralkyl, preferably CpC₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl; or heteroaralkyl, preferably Q- C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4- oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5- oxazolyl) ethyl, (2-isoxazolyl) methyl, (3 -isoxazolyl) methyl, (4-isoxazolyl) methyl, (2- isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4-isoxazolyl), (3-(l ,2,5-oxadiazolyl)) methyl, (4-(l,2,5-oxadiazolyl)) methyl, (3-(l,2,5-oxadiazolyl)) ethyl, (4-(l, 2,5- oxadiazolyl)) ethyl, (4-( 1,2,3-oxadiazolyl)) methyl, (5-(l,2,3-oxadiazolyl)) methyl, (4- (1 ,2,3-oxadiazolyl)) ethyl, (5-(l,2,3-oxadiazolyl)) ethyl, (2-ρyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4-(l,2,3-triazolyl) methyl, (4-(l,2,3- triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4-isothiazolyJ) methyl, (5-isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l,2,3,-thiadiazolyl)) methyl, (5- (1 ,2,3,-thiadiazolyl)) methyl, (4-(l ,2,3,-thiadiazolyl)) ethyl, (5-(l ,2,3,-thiadiazolyl)) ethyl,

(3-(l,2,5-thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4-(!,2,3-triazinyl) methyl, (5-(l,2,3- triazinyl)) methyl, (4-(l,2,3-triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l ,2,4- triazinyl)) methyl, (5-(l,2,4-triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-( 1,2,4- triazinyl)) ethyl, (5-(l,2,4-triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l-benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l -benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l -(2-benzofuranyl)) methyl, (4-(2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l -(2-benzofuranyl)) ethyl, (4-(2-benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6- indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1-isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (ό-(l-benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l-benzothienyl)) ethyl, (ό-(l-benzothienyl)) ethyl, (7-(l-benzothienyl)) methyl, (l-(2-benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2-benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2- benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4-

(lH-indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (ό-(lH-indazolyl)) ethyl, (7-(1H- indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5- benzitnidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5- benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5- benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2- benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4-indoxazinyl) methyl, (5- indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6-indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l-benzoxazolyl)) methyl, (4-(2,l-benzoxazolyl)) methyl, (5-(2,l- benzoxazolyl)) methyl, (6-(2,l-benzoxazolyl)) methyl, (7-(2,l-benzoxazolyl)) methyl, (3- (2,1-benzoxazolyl)) ethyl, (4-(2,l-benzoxazolyl)) ethyl, (5-(2,l-benzoxazolyl)) ethyl, (6- (2,1 -benzoxazolyl)) ethyl, (7-(2,l-benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4- benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7- benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5- benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7-benzothiazolyl) ethyl, (3 -(1,2- benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l,2-benzisothiazolyl)) methyl, (3 -(1,2- benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl,

(6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3-(2,l- benzisothiazolyl)) methyl, (4-(2,l -benzisothiazolyl)) methyl, (5-(2,l -benzisothiazolyl)) methyl, (6-(2,l -benzisothiazolyl)) methyl, (7-(2,l -benzisothiazolyl)) methyl, (3-(2,l- benzisothiazolyl)) ethyl, (4-(2,l -benzisothiazolyl)) ethyl, (5 -(2,1 -benzisothiazolyl)) ethyl, (6-(2,l -benzisothiazolyl)) ethyl, (7-(2,l -benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2- quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8-quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1- isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5- isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8- isoquinolinyl) methyl, (1 -isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8- isoquinolinyl) ethyl, (l-(2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5- (2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (1 -(2,3-benzodiazinyl)) ethyl, (4-(2,3- benzodiazinyl)) ethyl, (5-(2,3-benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7- (2,3-benzodiazinyl)) ethyl, (8-(2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3- quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2- quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4- quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l ,2,3-benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3- benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3-benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3- benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l ,2,4-benzotriazinyl)) methyl, (7-(l ,2,4-benzotriazinyl)) methyl, (8-(l ,2,4- benzotriazinyl)) methyl, (3-(l ,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4-benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-(l,2,4- benzotriazinyl)) ethyl; optionally substituted, wherein R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄,

C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and

R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. C], C₂, C₃, C₄, C₅, or C₆ alkyl; optionally substituted; is NR¹⁵R¹⁶, alkyl, in particular Q-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propy\, butyl, /sø-butyl, tert-buty\, pentyl, hexyl, in particular methyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1 -wo-propenyl, 2-/5O-propenyl, 1-butenyl, 2-butenyl, 3- butenyl, in particular ethenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; in particular C₃ to C₇ cycloalkyl, heterocycloalkyl, in particular piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza- spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuranyl, tetrahydrothienyl, or piperazinyl; an alicyclic system, in particular 1,2-dihydropyridinyl, 1,2,5,6- tetrahydropyridinyl, 1,2,3,4-tetrahydropyridyl, 1 ,2-dihydropyrazyl, 1,2,3,4- tetrahydropyrazyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1 ,2,5-oxadiazolyl, 1 ,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5- triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1- benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2- isoxazolyl) methyl, (3-isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4-isoxazolyl), (3-(l,2,5-oxadiazolyl)) methyl, (4-(l,2,5- oxadiazolyl)) methyl, (3-(l,2,5-oxadiazolyl)) ethyl, (4-(l ,2,5-oxadiazolyl)) ethyl, (4- (1,2,3-oxadiazolyl)) methyl, (5-(l,2,3-oxadiazolyl)) methyl, (4-(l,2,3-oxadiazolyl)) ethyl,

(5-(l,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4- imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4- pyrazolyl) ethyl, (4-(l,2,3-triazolyl) methyl, (4-( 1,2,3-triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl,

(3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2- thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4- isothiazolyl) methyl, (5-isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-( 1,2,3,-thiadiazolyl)) methyl, (5-( 1,2,3,-thiadiazolyl)) methyl, (4-( 1,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-

(1,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4- pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2- pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4-( 1,2,3-triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-( 1,2,3-triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3 -(1,2,4-triazinyl)) methyl, (5-( 1 ,2,4-triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-( 1,2,4-triazinyl)) ethyl, (5- ( 1,2,4-triazinyl)) ethyl, (6-( 1,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5- triazinyl) ethyl, (2-( 1-benzofuranyl)) methyl, (3 -(1-benzofuranyl)) methyl, (4-(l- benzofurany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l- benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l- benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l-(2- benzofuranyl)) methyl, (4-(2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2- benzoftiranyl)) ethyl, (4-(2-benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7- indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5- isoindolyl) methyl, (1-isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l- benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (6-(l- benzothienyl)) methyl, (7-(l -benzothienyl)) methyl, (2-(l -benzothienyl)) ethyl, (3-(l- benzothienyl)) ethyl, (4-(l -benzothienyl)) ethyl, (6-(l -benzothienyl)) ethyl, (7-(l- benzothienyl)) methyl, (l-(2-benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2- benzothienyl)) methyl, (l-(2-benzothienyl)) ethyl, (4-(2 -benzothienyl)) ethyl, (5-(2- benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4- (lH-indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (β-(lH-indazolyl)) ethyl, (7 -(I H- indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5- benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5- benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5- benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2- benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4-indoxazinyl) methyl, (5- indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6-indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l-benzoxazolyl)) methyl, (4-(2,l-benzoxazolyl)) methyl, (5-(2,l- benzoxazolyl)) methyl, (6-(2,l-benzoxazolyl)) methyl, (7-(2,l-benzoxazolyl)) methyl, (3- (2, 1 -benzoxazolyl)) ethyl, (4-(2,l-benzoxazolyl)) ethyl, (5-(2,l-benzoxazolyl)) ethyl, (6- (2, 1 -benzoxazolyl)) ethyl, (7-(2,l -benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4- benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7- benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5- benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7 -benzothiazolyl) ethyl, (3-(l,2- benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l,2-benzisothiazolyl)) methyl, (3-(l,2- benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3-(2,l- benzisothiazolyl)) methyl, (4-(2,l-benzisothiazolyl)) methyl, (5-(2,l-benzisothiazolyl)) methyl, (6-(2,l-benzisothiazolyl)) methyl, (7-(2,l-benzisothiazolyl)) methyl, (3-(2,l- benzisothiazolyl)) ethyl, (4-(2,l-benzisothiazolyl)) ethyl, (5-(2,l-benzisothiazolyl)) ethyl,

(6-(2,l-benzisothiazolyl)) ethyl, (7-(2,l -benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2- quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8-quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1- isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5- isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8- isoquinolinyl) methyl, (1-isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8- isoquinolinyl) ethyl, (l-(2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-

(2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3- benzodiazinyl)) ethyl, (5-(2,3-benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7- (2,3-benzodiazinyl)) ethyl, (8-(2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3- quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2- quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4- quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3- benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3-benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3- benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4-benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-( 1,2,4- benzotriazinyl)) methyl, (3-(l,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4-benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-( 1,2,4- benzotriazinyl)) ethyl; optionally substituted; R¹⁵ and R¹⁶ are independently selected from the group consisting of H; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propy\, butyl, wø-butyl, tert-buty\, pentyl, hexyl, in particular methyl; cycloalkyl, in particular C₃ to C₇ cycloalkyl; heterocycloalkyl, in particular piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl,

1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl,

1.7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl,

3.8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct- 2-yl, tetrahydrofuranyl, tetrahydrothienyl, or piperazinyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5- thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1 -benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl,

2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1- benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. CpC₆ aralkyl, preferably Q-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl, phenyl ethenyl, napthyl methyl, napthyl ethyl, napthyl propyl, or napthyl butyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2-isoxazolyl) methyl, (3-isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4- isoxazolyl), (3 -(1,2,5-oxadiazolyl)) methyl, (4-( 1,2,5-oxadiazolyl)) methyl, (3- ( 1,2,5-oxadiazolyl)) ethyl, (4-( 1,2,5-oxadiazolyl)) ethyl, (4-(l,2,3-oxadiazolyl)) methyl, (5-(l,2,3-oxadiazolyl)) methyl, (4-(l,2,3-oxadiazolyl)) ethyl, (5-(l,2,3- oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3- pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4-( 1,2,3-triazolyl) methyl, (4-(l,2,3- triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4- thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4-isothiazolyl) methyl, (5-isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5- isothiazolyl) ethyl, (4-(l ,2,3,-thiadiazolyl)) methyl, (5-(1 ,2,3,-thiadiazolyl)) methyl, (4-(l,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5- thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2- pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4-(l,2,3- triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-(l,2,3-triazinyl)) ethyl, (5-(l,2,3- triazinyl)) ethyl, (3-(l,2,4-triazinyl)) methyl, (5-(l,2,4-triazinyl)) methyl, (6- (1,2,4-triazinyl)) methyl, (3-(l,2,4-triazinyl)) ethyl, (5-(l,2,4-triazinyl)) ethyl, (6-

(1,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l- benzofuranyl)) methyl, (3-(l-benzoflιranyl)) methyl, (4-(l-benzoftirany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l- benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofυranyl)) ethyl, (6- ( 1 -benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl,

(l-(2-benzofuranyl)) methyl, (4-(2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2-benzofiiranyl)) ethyl, (4-(2-benzofuranyl)) ethyl, (5-(2- benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3- indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7- indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1- isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (6-(l- benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l-benzothienyl)) ethyl, (ό-(l-benzothienyl)) ethyl,

(7-(l-benzothienyl)) methyl, (l-(2-benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2-benzothienyl)) ethyl, (4-(2- benzothienyl)) ethyl, (5-(2-benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(1H- indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (β-(lH-indazolyl)) methyl, (7-(1H- indazolyl)) methyl, (1-indazolyl) ethyl, (4-(lH-indazolyl)) ethyl, (5-(1H- indazolyl)) ethyl, (6-(lH-indazolyl)) ethyl, (7-(lH-indazolyl)) ethyl, (2- benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5-benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5-benzimidazolyl) ethyl, (2- benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5-benzoxazolyl) methyl, (6- benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2-benzoxazolyl) ethyl, (4- benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7- benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4-indoxazinyl) methyl, (5- indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3- indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6-indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l-benzoxazolyl)) methyl, (4-(2,l- benzoxazolyl)) methyl, (5-(2,l-benzoxazolyl)) methyl, (6-(2,l-benzoxazolyl)) methyl, (7-(2, 1 -benzoxazolyl)) methyl, (3-(2,l-benzoxazolyl)) ethyl, (4-(2,l- benzoxazolyl)) ethyl, (5-(2,l -benzoxazolyl)) ethyl, (6-(2,l -benzoxazolyl)) ethyl, (7-(2,l -benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4-benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7-benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5-benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7-benzothiazolyl) ethyl, (3 -(1,2- benzisothiazolyl)) methyl, (4-( 1 ,2-benzisothiazolyl)) methyl, (5-(l ,2- benzisothiazolyl)) methyl, (6-( 1 ,2-benzisothiazolyl)) methyl, (7-(l,2- benzisothiazolyl)) methyl, (3-(l,2-benzisothiazolyl)) ethyl, (4-0,2- benzisothiazolyl)) ethyl, (5-(l ,2-benzisothiazolyl)) ethyl, (6-0,2- benzisothiazolyl)) ethyl, (7-(l ,2-benzisothiazolyl)) ethyl, (3-(2,l- benzisothiazolyl)) methyl, (4-(2, 1 -benzisothiazolyl)) methyl, (5-(2,l- benzisothiazolyl)) methyl, (6-(2, 1 -benzisothiazolyl)) methyl, (7-(2,l- benzisothiazolyl)) methyl, (3 -(2, 1 -benzisothiazolyl)) ethyl, (4-(2,l- benzisothiazolyl)) ethyl, (5-(2, 1 -benzisothiazolyl)) ethyl, (6-(2,l- benzisothiazolyl)) ethyl, (7-(2,l -benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2-quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5- quinolinyl) methyl, (7-quinolinyl) methyl, (8-quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7- quinolinyl) ethyl, (8-quinolinyl) ethyl, (1-isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5-isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8-isoquinolinyl) methyl, (1-isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6- isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8-isoquinolinyl) ethyl, (l-(2,3- benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-(2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3- benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3-benzodiazinyl)) ethyl, (5-(2,3-benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7-(2,3- benzodiazinyl)) ethyl, (8-(2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3- quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2- quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6- quinoxalinyl) ethyl, (2-quinazolinyl) methyl, (4-quinazolinyl) methyl, (5- quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8- quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4-quinazolinyl) ethyl, (5- quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8- quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l ,2,3-benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l ,2,3-benzotriazinyl)) methyl, (8- (1,2,3-benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-( 1 ,2,3- benzotriazinyl)) ethyl, (6-(l,2,3-benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3-benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5-(l,2,4- benzotriazinyl)) methyl, (6-(l,2,4-benzotriazinyl)) methyl, (7-(l ,2,4- benzotriazinyl)) methyl, (8-(l,2,4-benzotriazinyl)) methyl, (3-(l ,2,4- benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4-benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-(l,2,4-benzotriazinyl)) ethyl; in particular R¹⁵ and R¹⁶ are both aryl, more preferably both phenyl or R¹⁵ is heteroaryl, preferably thiazolyl and R¹⁶ is aralkyl, preferably phenyl methyl; optionally substituted; nd R¹⁶ are taken together to form a heterocycloalkyl, in particular piperidinyl, 1- oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro- [4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza- spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza- spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza- spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuranyl, tetrahydrothienyl, or piperazinyl; an alicyclic system, in particular 1 ,2-dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,4- tetrahydropyridyl, 1,2-dihydropyrazyl, 1,2,3,4-tetrahydropyrazyl; or heteroaryl moiety, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2- benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; optionally substituted;

X' and Y' are independently O or S, preferably at least one of X' and Y' is O and more preferably both X' and Y' are O; and pharmaceutically acceptable salts thereof. Preferred salts comprise Na⁺, K⁺, and Ca²⁺ salts.

The compounds of the general formula (V) according to the present invention may be prepared according to the following scheme II:

wherein R¹³, R¹⁴, X', and Y' are as defined above, or have the particularly preferred meanings as defined below, Lie is a conventional leaving group such as halogen, sulfonyl or the like. The above process comprise reacting a compound of the genera formula (3) with a

-C(=Y')-R¹⁴ group in an organic solvent to obtain a compound of the general formula (4). The

-C(=Y')-R¹⁴ group-providing agent used in the above reaction may include 1,1 - carbonyldiimidazole, 1,1-carbonylthiodiimidazole, phosgene, thiophosgene, carbonyldiphenoxide and phenylchloroformate, and it may be used in an amount of 1-1.5 equivalent, preferably 1-1.1 equivalent to the starting compound (3).

The reaction may be carried out in a conventional organic solvent such as, for example, tetrahydrofuran, dichloromethane, acetonitrile, chloroform and dimethylformamide.

The reaction is preferably carried out in the presence of a coupling agent such as a conventional inorganic or an organic base. Such conventional inorganic or organic bases used in the reaction may include sodium hydride, potassium hydride, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, triethylamine, pyridine and DBU.

The reaction may be carried out at a temperature between 3°C and boiling point of the solvent used, preferably at 50⁰C-IOO⁰C and for 5-48 hours, preferably for 10-24 hours. In the above reaction process, if any acid material is formed, a basic material may be added as a scavenger in order to eliminate the acid material from the reaction phase. Such basic material may be alkali metal hydroxide, alkali earth metal hydroxide, alkali metal oxide, alkali earth metal oxide, alkali metal carbonate, alkali earth metal carbonate, alkali metal hydrogen carbonate, alkali earth metal hydrogen carbonate such as for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, magnesium oxide, calcium oxide, potassium carbonate, sodium carbonate, calcium carbonate, magnesium carbonate, magnesium bicarbonate, sodium bicarbonate, calcium bicarbonate or the like, and organic amines.

Any substituent of R¹³, or R¹⁴, which would undergo unwanted reactions when carrying out a synthesis according to scheme II may be protected by a conventional protecting group, which is not cleaved during the reaction according to schema II but is cleavable under known conditions. Suitable protecting groups are taught above with respect to scheme I.

In a preferred embodiment of the compound with a structure (V) R is selected from the group consisting of Cj to C₄ alkyl, in particular methyl, ethyl, propyl, iso-pτopy\, butyl, /sø-butyl, (ert-butyl, pentyl, hexyl, ethenyl, 1-propenyl, 2-propenyl, l-/5o-propenyl, 2-wo-propenyl, 1- butenyl, 2-butenyl, and 3-butenyl; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wo-propyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C2-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, \-iso- propenyl, 2-iso-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl, in particular C₃-C₇ cycloalkyl, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or Cβ alkynoyl, preferably propynoyl; alkoxy, in particular C]-C₆ alkoxy, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, wo-propoxy, butoxy, wo-butoxy, tert-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R⁰, -OOC-R^C; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1 ,2,5- oxadiazolyl, 1 ,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3- triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzo furanyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, 1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1- benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably CpC₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted; wherein

R^a and R are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and

R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl; optionally substituted.

In the context of this preferred embodiment of the compound with a structure according to formula (V) it is further preferred that both X' and Y' are O and/or that R¹⁴ is NR¹⁵R¹⁶. In a preferred embodiment R¹³ is alkyl, alkenyl or alkynyl R¹³ is substituted with

(i) aryl, wherein aryl is selected from phenyl and napthyl; optionally substituted; (ii) cycloalkyl, wherein cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, spiro[3,3]heptyl, spiro[3,4]octyl, spiro[4,3]octyl, spiro[3,5]nonyl, spiro[5,3]nonyl, spiro[3,6]decyl, spiro[6,3]decyl, spiro[4,5]decyl, spiro[5,4]decyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, and adamantyl; optionally substituted;

(iii) heterocycloalkyl, wherein heterocycloalkyl is selected from the group consisting of 1 ,2,5,6-tetrahydropyridinyl, 1,4,5,6-tetrahydropyridyl, piperidinyl, morpholinyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl,

1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l-aza-7,11- dioxo-spiro[5,5] undecyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1 -piperazinyl, and 2- piperazinyl; optionally substituted; and

(iv) alicyclic system, wherein alicyclic system is selected from the group consisting of 1,2- dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,4-tetrahydropyridyl, 1,2- dihydropyrazyl, 1,2,3,4-tetrahydropyrazyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and cycloheptenyl; or

(v) heteroaryl, wherein heteroaryl is selected from the group consisting of furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1- benzo furanyl, 2-benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, IH- indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, and 1 ,2,4-benzotriazinyl; optionally substituted.

Preferred substituents of (i) to (v) are selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^gR^h; alkyl, in particular C₁-C₆ alkyl, e.g. C,, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, zso-propyl, butyl, iso-butyl, /erf-butyl, pentyl, hexyl, trifluoromethyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or Ce alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Cj, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, iso-propoxy, butoxy, iso-butoxy, tert- butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-C)-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R^J, -OOC-R*; -COO-R*; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1 ,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1-benzo furanyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, 1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Cj-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted; wherein R⁸ and R^h are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, or alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, R* is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl. In a preferred embodiment wherein R¹³ is aryl or heteroaryl, in particular phenyl, naphthalenyl or anthracenyl; furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,- thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1 ,3,5-triazinyl, 1-benzo furanyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4- benzotriazinyl, most preferably phenyl; R¹³ is substituted with 1, 2, 3, 4, or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR⁸R*¹; alkyl, in particular CpC₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso- propyl, butyl, wø-butyl, tert-buty\, pentyl, hexyl, trifluoromethyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, \-iso- propenyl, 2-/.yø-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, /so-propoxy, butoxy, wo-butoxy, tert-bntoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Cj-C₆ alkoxy-C|-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R*, -OOC-R^J; -COO-R¹; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1 ,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,- thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4- benzotriazinyl; aralkyl, e.g. CpC₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅. or C₆ heteroaralkyl; optionally substituted, e.g. preferbyl with 1, 2, 3, or more halogen residues to form, e.g. CF₃; wherein

R^g and R^h are independent of each other hydrogen, alkyl, in particular C]-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, or alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, R^J is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci,

C₂, C₃, C₄, C₅, or C₆ alkyl.

In a particular preferred embodiment of the compound according to formula (V), wherein R¹³ is phenyl or a six-membered heterocycle it is preferred that R¹³ is substituted with 1, 2, or 3 substitutents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH, and CF₃.

In a preferred embodiment of the compound according to formula (V) R¹⁵ and R¹⁶ together form a 1 ,2-dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,4,5,6-tetrahydropyridyl, piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-

[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-

[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l ,4-diazabicyclo[2.2.2]oct-2-yl, piperazinyl; isoxazolyl, 1 ,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5- thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1- benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, lH-indazolyl, benzimidazolyl, indoxazinyl,

2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl moiety, in particular a 1,2,5,6-tetrahydropyridinyl; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /so-propyl, butyl, iso-butyl, ter/-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, l-propenyl, 2-propenyl, 1-iso-propenyl, 2-zso-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl, in particular C₃-C₇ cycloalkyl, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, wo-propoxy, butoxy, /sσ-butoxy, før/-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular CpC₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; - CO-R⁰, -OOC-R^C; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl, preferably phenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,- thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1 ,3,5-triazinyl, 1 -benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, 1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4- benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. d, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2- isoxazolyl) methyl, (3 -isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3- isoxazolyl), ethyl (4-isoxazolyl), (3-(l,2,5-oxadiazolyl)) methyl, (4-(l,2,5-oxadiazolyl)) methyl, (3-(l ,2,5-oxadiazolyl)) ethyl, (4-( 1,2,5-oxadiazolyl)) ethyl, (4-(l,2,3-oxadiazolyl)) methyl, (5- (1 ,2,3-oxadiazolyl)) methyl, (4-(l ,2,3-oxadiazolyl)) ethyl, (5-(l,2,3-oxadiazolyl)) ethyl, (2- pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4-(l,2,3-triazolyl) methyl, (4- (1 ,2,3-triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3 -isothiazolyl) methyl, (4-isothiazolyl) methyl, (5 -isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l,2,3,-thiadiazolyl)) methyl, (5-(l,2,3,-thiadiazolyl)) methyl, (4- (1,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-(l,2,5- thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2- pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4- (1 ,2,3-triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-(l,2,3-triazinyl)) ethyl, (5-(l,2,3- triazinyl)) ethyl, (3-(l,2,4-triazinyl)) methyl, (5-(l,2,4-triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l ,2,4-triazinyl)) ethyl, (5-(l,2,4-triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5- triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l-benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l- benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l-(2- benzofuranyl)) methyl, (4-(2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2- benzofuranyl)) ethyl, (4-(2-benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1- isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l- benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (6-(l -benzothienyl)) methyl, (7-(l- benzothienyl)) methyl, (2-(l -benzothienyl)) ethyl, (3 -(I -benzothienyl)) ethyl, (4-(l- benzothienyl)) ethyl, (6-(l -benzothienyl)) ethyl, (7-(l -benzothienyl)) methyl, (l-(2- benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2- benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2-benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (6-(lH-indazolyl)) methyl, (7-(1H- indazolyl)) methyl, (1-indazolyl) ethyl, (4-(lH-indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (6- (lH-indazolyl)) ethyl, (7-(lH-indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5-benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5- benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5-benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2-benzoxazolyl) ethyl, (4- benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3- indoxazinyl) methyl, (4-indoxazinyl) methyl, (5-indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6- indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l-benzoxazolyl)) methyl, (4-(2,l-benzoxazolyl)) methyl, (5-(2,l-benzoxazolyl)) methyl, (6-(2,l-benzoxazolyl)) methyl, (7-(2,l-benzoxazolyl)) methyl, (3-(2,l-benzoxazolyl)) ethyl, (4-(2,l-benzoxazolyl)) ethyl, (5-(2,l-benzoxazolyl)) ethyl, (6-(2,l-benzoxazolyl)) ethyl, (7-(2,l-benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4- benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7-benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5-benzothiazolyl) ethyl, (6- benzothiazolyl) ethyl, (7-benzothiazolyl) ethyl, (3-(l,2-benzisothiazolyl)) methyl, (4-(l,2- benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l,2-benzisothiazolyl)) methyl, (3-(l,2-benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l ,2-benzisothiazolyl)) ethyl, (6-(l ,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3-(2,l-benzisothiazolyl)) methyl, (4-(2,l-benzisothiazolyl)) methyl, (5-(2,l- benzisothiazolyl)) methyl, (6-(2,l-benzisothiazolyl)) methyl, (7-(2,l-benzisothiazolyl)) methyl, (3-(2,l -benzisothiazolyl)) ethyl, (4-(2,l-benzisothiazolyl)) ethyl, (5-(2,l-benzisothiazolyl)) ethyl, (6-(2, 1 -benzisothiazolyl)) ethyl, (7-(2,l-benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5- benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2-quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8- quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1-isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5-isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7- isoquinolinyl) methyl, (8-isoquinolinyl) methyl, (1-isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8-isoquinolinyl) ethyl, (l-(2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-(2,3- benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3- benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3-benzodiazinyl)) ethyl, (5-(2,3- benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7-(2,3-benzodiazinyl)) ethyl, (8-(2,3- benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3-quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2-quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2- quinazolinyl) ethyl, (4-quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7- quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3- benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8- (1 ,2,3-benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l ,2,3-benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3-benzotriazinyl)) ethyl, (3-(l ,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4-benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-(l,2,4-benzotriazinyl)) methyl, (3-(l,2,4- benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4-benzotriazinyl)) ethyl, (7-( 1,2,4- benzotriazinyl)) ethyl, or (8-(l,2,4-benzotriazinyl)) ethyl; optionally substituted, wherein R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. C|, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl or together form a heteroaryl; optionally substituted; and R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular C]-C₆ alkyl, e.g. Ci,

C₂, C₃, C₄, C₅, or C₆ alkyl; optionally substituted. In a particular preferred embodiment of the compound according to formula (V) the compound has a structure according to formula (VI)

(VI) wherein R¹³ is selected from the group consisting of Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso-propy\, butyl, iso-buty\, tert-butyl, pentyl, hexyl, in particular methyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1 -wo-propenyl, 2-wø-propenyl, 1-butenyl, 2- butenyl, 3-butenyl, in particular ethenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1 ,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5- triazinyl, 1-benzo furanyl, 2-benzo furanyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1- benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl; optionally substituted preferably with one or more 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /so-propyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1- /jO-propenyl, 2-/5o-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl, in particular C₃-C₇ cycloalkyl, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl; alkanoyl, preferably CpC₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci- C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy,

/so-propoxy, butoxy, iso-butoxy, fer/-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R⁰, -OOC-R⁰; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5- oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1- benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. C)- C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl; or heteroaralkyl, preferably Ci- C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4- oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5- oxazolyl) ethyl, (2-isoxazolyl) methyl, (3 -isoxazolyl) methyl, (4-isoxazolyl) methyl, (2- isoxazolyl) ethyl, ethyl (3 -isoxazolyl), ethyl (4-isoxazolyl), (3-(l,2,5-oxadiazolyl)) methyl, (4-(l,2,5-oxadiazolyl)) methyl, (3-(l,2,5-oxadiazolyl)) ethyl, (4-( 1,2,5- oxadiazolyl)) ethyl, (4-( 1,2,3-oxadiazolyl)) methyl, (5-(l,2,3-oxadiazolyl)) methyl, (4- (1,2,3-oxadiazolyl)) ethyl, (5-( 1,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4-(l,2,3-triazolyl) methyl, (4-(l,2,3- triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4-isothiazolyl) methyl, (5-isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l,2,3,-thiadiazolyl)) methyl, (5- (1,2,3,-thiadiazolyl)) methyl, (4-(l,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4-(l,2,3-triazinyl) methyl, (5-(l,2,3- triazinyl)) methyl, (4-(l ,2,3-triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l ,2,4- triazinyl)) methyl, (5-(l ,2,4-triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l,2,4- triazinyl)) ethyl, (5-(l ,2,4-triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l -benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-( 1 -benzofuranyl)) ethyl, (3 -(I -benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l -benzofuranyl)) ethyl, (7-(l -benzofuranyl)) methyl, (4-(l -benzofuranyl)) ethyl, (l-(2-benzofuranyl)) methyl, (4-(2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2-benzofuranyl)) ethyl, (4-(2-benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6- indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1-isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (ό-(l-benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l-benzothienyl)) ethyl, (ό-(l-benzothienyl)) ethyl, (7-(l-benzothienyl)) methyl, (l-(2-benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2-benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2- benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4- (lH-indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (ό-(lH-indazolyl)) ethyl, (7-(1H- indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5- benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5- benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5- benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2- benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4-indoxazinyl) methyl, (5- indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6-indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l-benzoxazolyl)) methyl, (4-(2,l-benzoxazolyl)) methyl, (5-(2,l- benzoxazolyl)) methyl, (6-(2,l-benzoxazolyl)) methyl, (7-(2,l-benzoxazolyl)) methyl, (3- (2,1 -benzoxazolyl)) ethyl, (4-(2,l-benzoxazolyl)) ethyl, (5-(2,l-benzoxazolyl)) ethyl, (6-

(2,1 -benzoxazolyl)) ethyl, (7-(2,l-benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4- benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7- benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5- benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7-benzothiazolyl) ethyl, (3-(l,2- benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l,2-benzisothiazolyl)) methyl, (3-(l,2- benzisothiazolyl)) ethyl, (4-(l ,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3-(2,l- benzisothiazolyl)) methyl, (4-(2,l -benzisothiazolyl)) methyl, (5-(2,l -benzisothiazolyl)) methyl, (6-(2,l -benzisothiazolyl)) methyl, (7-(2,l -benzisothiazolyl)) methyl, (3-(2,l- benzisothiazolyl)) ethyl, (4-(2,l -benzisothiazolyl)) ethyl, (5-(2,l -benzisothiazolyl)) ethyl, (6-(2,l -benzisothiazolyl)) ethyl, (7-(2,l -benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2- quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8-quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl,

(4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1- isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5- isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8- isoquinolinyl) methyl, (1-isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8- isoquinolinyl) ethyl, (l-(2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5- (2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3- benzodiazinyl)) ethyl, (5-(2,3-benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7- (2,3-benzodiazinyl)) ethyl, (8-(2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3- quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2- quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4- quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3- benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3-benzotriazinyl)) ethyl, (7-(l ,2,3-benzotriazinyl)) ethyl, (8-(l,2,3- benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4-benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-( 1,2,4- benzotriazinyl)) methyl, (3-(l,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4-benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-(l,2,4- benzotriazinyl)) ethyl; optionally substituted, wherein

R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl; optionally substituted; is selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wø-propyl, butyl, wo-butyl, ter/-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl,

2-propenyl, 1-zso-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; cycloalkyl, in particular C₃-C₇ cycloalkyl, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Cj-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, wo-propoxy, butoxy, wo-butoxy, tert-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Cj-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R⁰, -OOC-R^C; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl, preferably phenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1 ,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1 -benzofuranyl, 2- benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzo thiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3- benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl; or heteroaralkyl, preferably C]-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2- furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl,

(5-oxazolyl) ethyl, (2-isoxazolyl) methyl, (3 -isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4-isoxazolyl), (3-( 1,2,5-oxadiazolyl)) methyl, (4-(l,2,5-oxadiazolyl)) methyl, (3-(l,2,5-oxadiazolyl)) ethyl, (4-(l,2,5- oxadiazolyl)) ethyl, (4-( 1,2,3-oxadiazolyl)) methyl, (5-( 1,2,3-oxadiazolyl)) methyl, (4- (1,2,3-oxadiazolyl)) ethyl, (5-( 1,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4-( 1,2,3 -triazolyl) methyl, (4-(l ,2,3- triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3 -isothiazolyl) methyl, (4-isothiazolyl) methyl, (5-isothiazolyl) methyl, (3 -isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-( 1 ,2,3,-thiadiazolyl)) methyl, (5- ( 1 ,2,3,-thiadiazolyl)) methyl, (4-( 1,2,3,-thiadiazolyl)) ethyl, (5 -(1,2,3,-thiadiazolyl)) ethyl, (3-( 1,2,5-thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2 -pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4-( 1,2,3-triazinyl) methyl, (5-(l,2,3- triazinyl)) methyl, (4-(l,2,3-triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l,2,4- triazinyl)) methyl, (5-(l,2,4-triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3 -(1,2,4- triazinyl)) ethyl, (5-(l,2,4-triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l-benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l-benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l-(2-benzofuranyl)) methyl, (4-(2-benzofiιranyl)) methyl, (5-(2-benzofϊιranyl)) methyl, (l-(2-benzofliranyl)) ethyl, (4-(2-benzofϊiranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6- indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1-isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l -benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (6-( 1 -benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l -benzothienyl)) ethyl, (4-(l -benzothienyl)) ethyl, (6-(l -benzothienyl)) ethyl, (7-(l -benzothienyl)) methyl, (l-(2-benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2-benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2- benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4-

(lH-indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (ό-(lH-indazolyl)) ethyl, (7-(1H- indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5- benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5- benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5- benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2- benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4-indoxazinyl) methyl, (5- indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6-indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3 -(2,1 -benzoxazolyl)) methyl, (4-(2,l -benzoxazolyl)) methyl, (5-(2,l- benzoxazolyl)) methyl, (6-(2,l -benzoxazolyl)) methyl, (7-(2, 1 -benzoxazolyl)) methyl, (3- (2,1 -benzoxazolyl)) ethyl, (4-(2,l -benzoxazolyl)) ethyl, (5-(2,l -benzoxazolyl)) ethyl, (6- (2,1 -benzoxazolyl)) ethyl, (7-(2,l -benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4- benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7- benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5- benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7-benzothiazolyl) ethyl, (3 -(1,2- benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l,2-benzisothiazolyl)) methyl, (3-(l,2- benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl,

(6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3-(2,l- benzisothiazolyl)) methyl, (4-(2,l -benzisothiazolyl)) methyl, (5-(2,l -benzisothiazolyl)) methyl, (6-(2,l -benzisothiazolyl)) methyl, (7-(2,l -benzisothiazolyl)) methyl, (3-(2,l- benzisothiazolyl)) ethyl, (4-(2, 1 -benzisothiazolyl)) ethyl, (5-(2,l -benzisothiazolyl)) ethyl, (6-(2,l -benzisothiazolyl)) ethyl, (7-(2,l -benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2- quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8-quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1- isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5- isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8- isoquinolinyl) methyl, (1 -isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8- isoqυinolinyl) ethyl, (l-(2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5- (2,3-benzodiazinyl)) methyl, (6-(2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (1 -(2,3-benzodiazinyl)) ethyl, (4-(2,3- benzodiazinyl)) ethyl, (5-(2,3-benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7- (2,3-benzodiazinyl)) ethyl, (8-(2,3-benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3- quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2- quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4- quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3-benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8-(l,2,3- benzotriazinyl)) methyl, (4-(l,2,3-benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l ,2,3-benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3- benzotriazinyl)) ethyl, (3-(l ,2,4-benzotriazinyl)) methyl, (5-(l,2,4-benzotriazinyl)) methyl, (6-(l,2,4-benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-(l,2,4- benzotriazinyl)) methyl, (3-(l,2,4-benzotriazinyl)) ethyl, (5-(l,2,4-benzotriazinyl)) ethyl, (6-(l,2,4-benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8-( 1,2,4- benzotriazinyl)) ethyl; each of R^k may optionally be substituted, wherein R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄,

C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl or together form a heteroaryl; optionally substituted; and R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl; optionally substituted. n is an integer from 0 to 4, e.g. 0, 1 , 2, 3, or 4, preferably 0, 1 or 2;

X' and Y' are independently O or S, preferably at least one of X' and Y' is O and more preferably both X' and Y' are O; the dashed line may be a bond, preferably is a bond; and pharmaceutically acceptable salts thereof. Preferred salts comprise Na⁺, K⁺, and Ca²⁺ salts. In a particular preferred embodiment of the compound according to formula (V) the compound has a structure according to formula (VII)

(VII). In a preferred embodiments the compound according to formula (VII) can additionally comprise one or more substituents, preferably 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular CpC₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, wø-propyl, butyl, iso- butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-wo-propenyl, 2-z.yø-propenyl, 1-butenyl, 2- butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, Gj, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, iso-pτopoxy, butoxy, /sø-butoxy, tert-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; - CO-R^C, -OOC-R^C; -COO-R^C; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2.3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5- thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1- benzofuranyl, 2-benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3- benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted; wherein

R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂,

C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular Ci-C₆ alkyl, e.g. Ci,

C₂, C₃, C₄, C₅, or C₆ alkyl.

In a further preferred embodiment R¹⁵ is selected from the group consisting of heterocycloalkyl, in particular piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza- spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza- spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuranyl, tetrahydrothienyl, or piperazinyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,- thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1 ,3,5-triazinyl, 1 -benzo furanyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, 1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1,2,4- benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Cj-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl, phenyl ethenyl, napthyl methyl, napthyl ethyl, napthyl propyl, or napthyl butyl; or heteroaralkyl, preferably Cj- C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3- furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2-oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2-isoxazolyl) methyl, (3-isoxazolyl) methyl, (4-isoxazolyl) methyl, (2-isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4-isoxazolyl), (3-(l,2,5-oxadiazolyl)) methyl, (4-(l,2,5-oxadiazolyl)) methyl, (3-(l ,2,5- oxadiazolyl)) ethyl, (4-(l,2,5-oxadiazolyl)) ethyl, (4-(l,2,3-oxadiazolyl)) methyl, (5-(l,2,3- oxadiazolyl)) methyl, (4-(l,2,3-oxadiazolyl)) ethyl, (5-(l,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3-pyrrolyl) ethyl, (2-imidazolyl) methyl, (4- imidazolyl) methyl, (2-imidazolyl) ethyl, (4-imidazolyl) ethyl, (3-pyrazolyl) methyl, (4- pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4-(l ,2,3-triazolyl) methyl, (4-(l ,2,3- triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4-triazolyl) ethyl, (2-thienyl) methyl, (3- thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2-thiazolyl) methyl, (4-thiazolyl) methyl, (5- thiazolyl) methyl, (2-thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4-isothiazolyl) methyl, (5-isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l ,2,3,-thiadiazolyl)) methyl, (5-(l,2,3,-thiadiazolyl)) methyl, (4- (1 ,2,3,-thiadiazolyl)) ethyl, (5-(l,2,3,-thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-(l ,2,5- thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2- pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4- (1,2,3-triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-(l,2,3-triazinyl)) ethyl, (5-(l,2,3- triazinyl)) ethyl, (3-(l,2,4-triazinyl)) methyl, (5-(l ,2,4-triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l,2,4-triazinyl)) ethyl, (5-(l,2,4-triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5- triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l-benzofuranyl)) methyl, (3-(l-benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l-benzofuranyl)) methyl, (7-(l-benzofuranyl)) methyl, (2-(l-benzofuranyl)) ethyl, (3-(l-benzofuranyl)) ethyl, (4-(l-benzofuranyl)) ethyl, (6-(l- benzofuranyl)) ethyl, (7-(l-benzofuranyl)) methyl, (4-(l-benzofuranyl)) ethyl, (l-(2- benzofuranyl)) methyl, (4-(2-benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2- benzofuranyl)) ethyl, (4-(2-benzofuranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4-indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3-indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1-isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1- isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l- benzothienyl)) methyl, (4-(l-benzothienyl)) methyl, (6-(l -benzothienyl)) methyl, (7-(l- benzothienyl)) methyl, (2-(l-benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l- benzothienyl)) ethyl, (6-(l -benzothienyl)) ethyl, (7-(l -benzothienyl)) methyl, (l -(2- benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5-(2-benzothienyl)) methyl, (l-(2- benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2-benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(l H-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (ό-(lH-indazolyl)) methyl, (7-(1H- indazolyl)) methyl, (1-indazolyl) ethyl, (4-(lH-indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (6- (l H-indazolyl)) ethyl, (7-(lH-indazolyl)) ethyl, (2-benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5-benzimidazolyl) methyl, (2-benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5- benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5-benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7-benzoxazolyl) methyl, (2-benzoxazolyl) ethyl, (4- benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3- indoxazinyl) methyl, (4-indoxazinyl) methyl, (5-indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6- indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3 -(2,1 -benzoxazolyl)) methyl, (4-(2,l -benzoxazolyl)) methyl, (5-(2,l -benzoxazolyl)) methyl, (6-(2,l -benzoxazolyl)) methyl, (7-(2,l -benzoxazolyl)) methyl, (3-(2,l -benzoxazolyl)) ethyl, (4-(2,l -benzoxazolyl)) ethyl, (5-(2,l -benzoxazolyl)) ethyl, (6-(2, 1 -benzoxazolyl)) ethyl, (7-(2,l -benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4- benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7-benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4-benzothiazolyl) ethyl, (5-benzothiazolyl) ethyl, (6- benzothiazoiyl) ethyl, (7-benzothiazolyl) ethyl, (3-(l,2-benzisothiazolyl)) methyl, (4-(l,2- benzisothiazolyl)) methyl, (5-(l,2-benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l ,2-benzisothiazolyl)) methyl, (3-(l,2-benzisothiazolyl)) ethyl, (4-( 1 ,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3 -(2,1 -benzisothiazolyl)) methyl, (4-(2,l -benzisothiazolyl)) methyl, (5-(2,l- benzisothiazolyl)) methyl, (6-(2,l -benzisothiazolyl)) methyl, (7-(2,l -benzisothiazolyl)) methyl, (3-(2,l -benzisothiazolyl)) ethyl, (4-(2,l -benzisothiazolyl)) ethyl, (5-(2,l -benzisothiazolyl)) ethyl, (6-(2,l -benzisothiazolyl)) ethyl, (7-(2,l -benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5- benzotriazolyl) methyl, (4-benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2-quinolinyl) methyl, (3-quinolinyl) methyl, (4-quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8- quinolinyl) methyl, (2-quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-qυinolinyl) ethyl, (1-isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5-isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7- isoquinolinyl) methyl, (8-isoquinolinyl) methyl, (1-isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5-isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8-isoquinolinyl) ethyl, (l-(2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-(2,3- benzodiazinyl)) methyl, (6-(2,3-benzodiazinγl)) methyl, (7-(2.3-benzodiazinyl)) methyl, (8-(2,3- benzodiazinyl)) methyl, (l-(2,3-benzodiazinyl)) ethyl, (4-(2,3-benzodiazinyl)) ethyl, (5-(2,3- benzodiazinyl)) ethyl, (6-(2,3-benzodiazinyl)) ethyl, (7-(2,3-benzodiazinyl)) ethyl, (8-(2,3- benzodiazinyl)) ethyl, (2-quinoxalinyl) methyl, (3-quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2-quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2- quinazolinyl) ethyl, (4-quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7- quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4-(l,2,3-benzotriazinyl)) methyl, (5-(l,2,3- benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l,2,3-benzotriazinyl)) methyl, (8- (1 ,2,3-benzotriazinyl)) methyl, (4-( 1,2,3 -benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l ,2,3-benzotriazinyl)) ethyl, (7-(l,2,3-benzotriazinyl)) ethyl, (8-(l,2,3-benzotriazinyl)) ethyl, (3-(l ,2,4-benzotriazinyl)) methyl, (5-(l ,2,4-benzotriazinyl)) methyl, (6-(l ,2,4-benzotriazinyl)) methyl, (7-(l ,2,4-benzotriazinyl)) methyl, (8-(l,2,4-benzotriazinyl)) methyl, (3-(l,2,4- benzotriazinyl)) ethyl, (5-(l ,2,4-benzotriazinyl)) ethyl, (6-(l ,2,4-benzotriazinyl)) ethyl, (7-(l ,2,4- benzotriazinyl)) ethyl, or (8-(l,2,4-benzotriazinyl)) ethyl; and R¹⁶ is selected from the group consisting of H; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, /5O-propyl, butyl, iso-buty\, tør/-butyl, pentyl, hexyl, in particular methyl; cycloalkyl, in particular C₃ to C ₇ cycloalkyl; heterocycloalkyl, in particular piperidinyl, l-oxo-3- azacyclohexanyl, moφholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza- spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1 ,8 diaza-spiro-[5,4] decyl, 1 ,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, 1,4- diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuranyl, tetrahydrothienyl, or piperazinyl; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl, preferably phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl, phenyl ethenyl, napthyl methyl, napthyl ethyl, napthyl propyl, or napthyl butyl; or heteroaralkyl, preferably Cj-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl, preferably (2-furanyl) methyl, (3-furanyl) methyl, (2-furanyl) ethyl, (3-furanyl) ethyl, (2- oxazolyl) methyl, (4-oxazolyl) methyl, (5-oxazolyl) methyl, (2-oxazolyl) ethyl, (4-oxazolyl) ethyl, (5-oxazolyl) ethyl, (2-isoxazolyl) methyl, (3-isoxazolyl) methyl, (4-isoxazolyl) methyl, (2- isoxazolyl) ethyl, ethyl (3-isoxazolyl), ethyl (4-isoxazolyl), (3-(l,2,5-oxadiazolyl)) methyl, (4- (1 ,2,5-oxadiazolyl)) methyl, (3-(l,2,5-oxadiazolyl)) ethyl, (4-(l,2,5-oxadiazolyl)) ethyl, (4- (1 ,2,3-oxadiazolyl)) methyl, (5-(l,2,3-oxadiazolyl)) methyl, (4-(l,2,3-oxadiazolyl)) ethyl, (5- (1 ,2,3-oxadiazolyl)) ethyl, (2-pyrrolyl) methyl, (3-pyrrolyl) methyl, (2-pyrrolyl) ethyl, (3- pyrrolyl) ethyl, (2-imidazolyl) methyl, (4-imidazolyl) methyl, (2-imidazolyl) ethyl, (4- imidazolyl) ethyl, (3-pyrazolyl) methyl, (4-pyrazolyl) methyl, (3-pyrazolyl) ethyl, (4-pyrazolyl) ethyl, (4-(l ,2,3-triazolyl) methyl, (4-(l,2,3-triazolyl) ethyl, (3-(l,2,4-triazolyl) methyl, (3-(l,2,4- triazolyl) ethyl, (2-thienyl) methyl, (3-thienyl) methyl, (2-thienyl) ethyl, (3-thienyl) ethyl, (2- thiazolyl) methyl, (4-thiazolyl) methyl, (5-thiazolyl) methyl, (2-thiazolyl) ethyl, (4-thiazolyl) ethyl, (5-thiazolyl) ethyl, (3-isothiazolyl) methyl, (4-isothiazolyl) methyl, (5-isothiazolyl) methyl, (3-isothiazolyl) ethyl, (4-isothiazolyl) ethyl, (5-isothiazolyl) ethyl, (4-(l,2,3,- thiadiazolyl)) methyl, (5-(l,2,3,-thiadiazolyl)) methyl, (4-(l ,2,3,-thiadiazolyl)) ethyl, (5-(l ,2,3,- thiadiazolyl)) ethyl, (3-(l,2,5-thiadiazolyl)), (3-(l,2,5-thiadiazolyl)) ethyl, (2-pyridinyl) methyl, (3-pyridinyl) methyl, (4-pyridinyl) methyl, (2-pyridinyl) ethyl, (3-pyridinyl) ethyl, (4-pyridinyl) ethyl, (2-pyrimidinyl) methyl, (4-pyrimidinyl) methyl, (5-pyrimidinyl) methyl, (2-pyrimidinyl) ethyl, (4-pyrimidinyl) ethyl, (5-pyrimidinyl) ethyl, (2-pyrazinyl) methyl, (3-pyrazinyl) methyl, (2-pyrazinyl) ethyl, (3-pyrazinyl) ethyl, (4-(l,2,3-triazinyl) methyl, (5-(l,2,3-triazinyl)) methyl, (4-(l ,2,3-triazinyl)) ethyl, (5-(l,2,3-triazinyl)) ethyl, (3-(l,2,4-triazinyl)) methyl, (5-(l,2,4- triazinyl)) methyl, (6-(l,2,4-triazinyl)) methyl, (3-(l,2,4-triazinyl)) ethyl, (5-(l,2,4-triazinyl)) ethyl, (6-(l,2,4-triazinyl)) ethyl, (2-(l,3,5-triazinyl) methyl, (2-(l,3,5-triazinyl) ethyl, (2-(l- benzofuranyl)) methyl, (3-(l -benzofuranyl)) methyl, (4-(l-benzofurany I)) methyl, (6-(l- benzofuranyl)) methyl, (7-(l -benzofuranyl)) methyl, (2-(l -benzofuranyl)) ethyl, (3-(l- benzofuranyl)) ethyl, (4-(l -benzofuranyl)) ethyl, (6-(l -benzofuranyl)) ethyl, (7-(l- benzofuranyl)) methyl, (4-(l -benzofuranyl)) ethyl, (1 -(2 -benzofuranyl)) methyl, (4-(2- benzofuranyl)) methyl, (5-(2-benzofuranyl)) methyl, (l-(2-benzofuranyl)) ethyl, (4-(2- benzofυranyl)) ethyl, (5-(2-benzofuranyl)) ethyl, (2-indolyl) methyl, (3-indolyl) methyl, (4- indolyl) methyl, (5-indolyl) methyl, (6-indolyl) methyl, (7-indolyl) methyl, (2-indolyl) ethyl, (3- indolyl) ethyl, ethyl (4-indolyl), ethyl (5-indolyl), ethyl (6-indolyl), ethyl (7-indolyl), methyl (1- isoindolyl), (4-isoindolyl) methyl, (5-isoindolyl) methyl, (1-isoindolyl) ethyl, (4-isoindolyl) ethyl, (5-isoindolyl) ethyl, (2-(l-benzothienyl)) methyl, (3-(l-benzothienyl)) methyl, (4-(l- benzothienyl)) methyl, (ό-(l-benzothienyl)) methyl, (7-(l-benzothienyl)) methyl, (2-(l- benzothienyl)) ethyl, (3-(l-benzothienyl)) ethyl, (4-(l-benzothienyl)) ethyl, (ό-(l-benzothienyl)) ethyl, (7-(l-benzothienyl)) methyl, (l-(2-benzothienyl)) methyl, (4-(2-benzothienyl)) methyl, (5- (2-benzothienyl)) methyl, (l-(2-benzothienyl)) ethyl, (4-(2-benzothienyl)) ethyl, (5-(2- benzothienyl)) ethyl, (1-indazolyl) methyl, (4-(lH-indazolyl)) methyl, (5-(lH-indazolyl)) methyl, (6-(lH-indazolyl)) methyl, (7-(lH-indazolyl)) methyl, (1-indazolyl) ethyl, (4-(1H- indazolyl)) ethyl, (5-(lH-indazolyl)) ethyl, (6-(lH-indazolyl)) ethyl, (7-(lH-indazolyl)) ethyl, (2- benzimidazolyl) methyl, (4-benzimidazolyl) methyl, (5-benzimidazolyl) methyl, (2- benzimidazolyl) ethyl, (4-benzimidazolyl) ethyl, (5-benzimidazolyl) ethyl, (2-benzoxazolyl) methyl, (4-benzoxazolyl) methyl, (5-benzoxazolyl) methyl, (6-benzoxazolyl) methyl, (7- benzoxazolyl) methyl, (2-benzoxazolyl) ethyl, (4-benzoxazolyl) ethyl, (5-benzoxazolyl) ethyl, (6-benzoxazolyl) ethyl, (7-benzoxazolyl) ethyl, (3-indoxazinyl) methyl, (4-indoxazinyl) methyl, (5-indoxazinyl) methyl, (6-indoxazinyl) methyl, (7-indoxazinyl) methyl, (3-indoxazinyl) ethyl, (4-indoxazinyl) ethyl, (5-indoxazinyl) ethyl, (6-indoxazinyl) ethyl, (7-indoxazinyl) ethyl, (3-(2,l- benzoxazolyl)) methyl, (4-(2,l-benzoxazolyl)) methyl, (5-(2,l-benzoxazolyl)) methyl, (6-(2,l- benzoxazolyl)) methyl, (7-(2,l -benzoxazolyl)) methyl, (3-(2,l -benzoxazolyl)) ethyl, (4-(2,l- benzoxazolyl)) ethyl, (5-(2,l -benzoxazolyl)) ethyl, (6-(2,l -benzoxazolyl)) ethyl, (7-(2,l - benzoxazolyl)) ethyl, (2-benzothiazolyl) methyl, (4-benzothiazolyl) methyl, (5-benzothiazolyl) methyl, (6-benzothiazolyl) methyl, (7-benzothiazolyl) methyl, (2-benzothiazolyl) ethyl, (4- benzothiazolyl) ethyl, (5-benzothiazolyl) ethyl, (6-benzothiazolyl) ethyl, (7-benzothiazolyl) ethyl, (3-(l,2-benzisothiazolyl)) methyl, (4-(l,2-benzisothiazolyl)) methyl, (5-(l,2- benzisothiazolyl)) methyl, (6-(l,2-benzisothiazolyl)) methyl, (7-(l,2-benzisothiazolyl)) methyl, (3-(l ,2-benzisothiazolyl)) ethyl, (4-(l,2-benzisothiazolyl)) ethyl, (5-(l,2-benzisothiazolyl)) ethyl, (6-(l,2-benzisothiazolyl)) ethyl, (7-(l,2-benzisothiazolyl)) ethyl, (3-(2,l-benzisothiazolyl)) methyl, (4-(2,l-benzisothiazolyl)) methyl, (5-(2,l-benzisothiazolyl)) methyl, (6-(2,l- benzisothiazolyl)) methyl, (7-(2,l-benzisothiazolyl)) methyl, (3-(2,l-benzisothiazolyl)) ethyl, (4- (2, 1 -benzisothiazolyl)) ethyl, (5-(2,l-benzisothiazolyl)) ethyl, (6-(2,l-benzisothiazolyl)) ethyl, (7-(2,l-benzisothiazolyl)) ethyl, (4-benzotriazolyl) methyl, (5-benzotriazolyl) methyl, (4- benzotriazolyl) ethyl, (5-benzotriazolyl) ethyl, (2-quinolinyl) methyl, (3-quinolinyl) methyl, (4- quinolinyl) methyl, (5-quinolinyl) methyl, (7-quinolinyl) methyl, (8-quinolinyl) methyl, (2- quinolinyl) ethyl, (3-quinolinyl) ethyl, (4-quinolinyl) ethyl, (5-quinolinyl) ethyl, (7-quinolinyl) ethyl, (8-quinolinyl) ethyl, (1-isoquinolinyl) methyl, (3-isoquinolinyl) methyl, (4-isoquinolinyl) methyl, (5-isoquinolinyl) methyl, (6-isoquinolinyl) methyl, (7-isoquinolinyl) methyl, (8- isoquinolinyl) methyl, (1-isoquinolinyl) ethyl, (3-isoquinolinyl) ethyl, (4-isoquinolinyl) ethyl, (5- isoquinolinyl) ethyl, (6-isoquinolinyl) ethyl, (7-isoquinolinyl) ethyl, (8-isoquinolinyl) ethyl, (1 - (2,3-benzodiazinyl)) methyl, (4-(2,3-benzodiazinyl)) methyl, (5-(2,3-benzodiazinyl)) methyl, (6- (2,3-benzodiazinyl)) methyl, (7-(2,3-benzodiazinyl)) methyl, (8-(2,3-benzodiazinyl)) methyl, (1- (2,3-benzodiazinyl)) ethyl, (4-(2,3-benzodiazinyl)) ethyl, (5-(2,3-benzodiazinyl)) ethyl, (6-(2,3- benzodiazinyl)) ethyl, (7-(2,3-benzodiazinyl)) ethyl, (8-(2,3-benzodiazinyl)) ethyl, (2- quinoxalinyl) methyl, (3-quinoxalinyl) methyl, (5-quinoxalinyl) methyl, (6-quinoxalinyl) methyl, (2-quinoxalinyl) ethyl, (3-quinoxalinyl) ethyl, (5-quinoxalinyl) ethyl, (6-quinoxalinyl) ethyl, (2- quinazolinyl) methyl, (4-quinazolinyl) methyl, (5-quinazolinyl) methyl, (6-quinazolinyl) methyl, (7-quinazolinyl) methyl, (8-quinazolinyl) methyl, (2-quinazolinyl) ethyl, (4-quinazolinyl) ethyl, (5-quinazolinyl) ethyl, (6-quinazolinyl) ethyl, (7-quinazolinyl) ethyl, (8-quinazolinyl) ethyl, (4- (1 ,2,3-benzotriazinyl)) methyl, (5-(l ,2,3-benzotriazinyl)) methyl, (6-(l,2,3-benzotriazinyl)) methyl, (7-(l ,2,3-benzotriazinyl)) methyl, (8-(l,2,3-benzotriazinyl)) methyl, (4-(l,2,3- benzotriazinyl)) ethyl, (5-(l,2,3-benzotriazinyl)) ethyl, (6-(l,2,3-benzotriazinyl)) ethyl, (7-(l,2,3- benzotriazinyl)) ethyl, (8-(l ,2,3-benzotriazinyl)) ethyl, (3-(l,2,4-benzotriazinyl)) methyl, (5- (1 ,2,4-benzotriazinyl)) methyl, (6-(l,2,4-benzotriazinyl)) methyl, (7-(l,2,4-benzotriazinyl)) methyl, (8-( 1 ,2,4-benzotriazinyl)) methyl, (3-( 1,2,4-benzotriazinyl)) ethyl, (5 -(1,2,4- benzotriazinyl)) ethyl, (6-( 1 ,2,4-benzotriazinyl)) ethyl, (7-(l,2,4-benzotriazinyl)) ethyl, or (8- ( 1 ,2,4-benzotriazinyl)) ethyl; in particular R¹⁵ and R¹⁶ are both aryl, more preferably both phenyl or R¹⁵ is heteroaryl, preferably thiazolyl and R¹⁶ is aralkyl, preferably phenyl methyl; optionally substituted.

In a further preferred embodiment of the compound according to formula (V) R¹⁵ and R¹⁶ are independently selected from the group consisting of phenyl, napthyl, phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl, phenyl ethenyl, napthyl methyl, napthyl ethyl, napthyl propyl, napthyl butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1 -cyclohexenyl, 3-cyclohexenyl, cycloheptyl, spiro[3,3]heptyl, spiro[3,4]octyl, spiro[4,3]octyl, spiro[3,5]nonyl, spiro[5,3]nonyl, spiro[3,6]decyl, spiro[6,3]decyl, spiro[4,5]decyl, spiro[5,4]decyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, adamantyl, 1,2,5,6-tetrahydropyridinyl, 1,4,5,6-tetrahydropyridyl, piperidinyl, piperidinyl, piperidinyl, piperidinyl, moφholinyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro- [5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l-aza-7,l l-dioxo-spiro[5,5] undecyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1- piperazinyl, and 2-piperaziny, furanyl, thienyl, oxazolyl, isoxazolyl, 1 ,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,- thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1 ,3,5-triazinyl, 1 -benzo furanyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2- benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, and 1,2,4- benzotriazinyl, in a particular preferred embodiment both R¹⁵ and R¹⁶ are the same, preferably are both phenyl or in further preferred embodiment R¹⁵ is aryl or heteroaryl, preferably thiazolyl and R¹⁶ is aralkyl, preferably phenyl methyl; optionally substituted, preferably with 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. C_J , C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, zso-propyl, butyl, iso-bvtyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, l-wo-propenyl, 2-wo-propenyl, 1-butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular CpC₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, iso-propoxy, butoxy, iso-butoxy, tert-butoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-Ci- C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; -CO-R^C, -OOC-R^C; -COO-R⁰; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1 -benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3- benzotriazinyl, or 1,2,4-benzotriazinyl; aralkyl, e.g. Cj-C₆ aralkyl, preferably Ci-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted; wherein R^a and R^b are independent of each other hydrogen, alkyl, in particular C]-C₆ alkyl, e.g. Ci, C₂,

C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and R^c is hydrogen, alkyl, alkenyl, alkynyl, aryl or heteroaryl, in particular CpC₆ alkyl, e.g. Ci,

C₂, C₃, C₄, C₅, or C₆ alkyl; optionally substituted.

In a preferred embodiment of the present invention the compound according formula (V) has a structure according to formula (VIII) or (IX)

(VIII) or

(IX).

In some preferred embodiments the compound according to formula (VIII) or (IX) can additionally comprise one or more substituents, preferably 1, 2, 3, 4 or more substituents selected from the group consisting of halogen, e.g. F, Cl, Br or I; CN; NO₂; OH; NR^aR^b; alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, preferably methyl, ethyl, propyl, iso- propyl, butyl, wo-butyl, tert-butyl, pentyl, hexyl; alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, preferably ethenyl, 1-propenyl, 2-propenyl, 1-wo-propenyl, 2-wo-propenyl, 1 -butenyl, 2-butenyl, 3-butenyl; alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl; alkanoyl, preferably Ci-C₆ alkanoyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkanoyl; alkenoyl, in particular C₃-C₆ alkenoyl, e.g. C₃, C₄, C₅, or C₆ alkenoyl, preferably propenoyl; alkynoyl, in particular C₃-C₆ alkynoyl, e.g. C₃, C₄, C₅, or C₆ alkynoyl, preferably propynoyl; alkoxy, in particular Ci-C₆ alkoxy, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkoxy, preferably methoxy, ethoxy, propoxy, /50-propoxy, butoxy, /5O-butoxy, tert-bxitoxy, pentoxy, or hexoxy; alkoxyalkyl, in particular Ci-C₆ alkoxy-C|-C₆ alkyl, e.g. methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, methoxypropyl, ethoxypropyl, or propoxypropyl; - CO-R⁰, -OOC-R⁰; -COO-R^C; aryl, in particular phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5- thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1 ,3,5-triazinyl, 1- benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3- benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl; aralkyl, e.g. Ci-C₆ aralkyl, preferably C]-C₆ aralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ aralkyl; or heteroaralkyl, preferably Ci-C₆ heteroaralkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ heteroaralkyl; optionally substituted; wherein

R^a and R^b are independent of each other hydrogen, alkyl, in particular Ci-C₆ alkyl, e.g. Ci, C₂, C₃, C₄, C₅, or C₆ alkyl, alkenyl, in particular C₂-C₆ alkenyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkenyl, alkynyl, in particular C₂-C₆ alkynyl, e.g. C₂, C₃, C₄, C₅, or C₆ alkynyl, or together form a heteroaryl; optionally substituted; and

The compounds of the present invention show an Aurora kinase, preferably Aurora A kinase inhibiting activity, preferably they have an IC₅₀ of 500 μM or less, preferably of 50 μM or less, more preferably of 10 μM or less, and more preferably of 1 μM or less. This activity is preferably measured in a biological assay, for example, an in vitro Auroa kinase assay, for example, as set out below. The Aurora kinase inhibitors of the present invention preferably have an IC₅₀ in the range from about 0.001 μM to about 50 μM, more preferably in the range from about 0.001 μM to about 10 μM, or more preferably in the range from about 0.001 μM to about 1 μM. Preferably, the inhibitors of the present invention preferentially inhibit Aurora A kinase.

A further aspect of the present invention is a pharmaceutical composition comprising an effective amount of at least one compound of the present invention and a pharmaceutically acceptable carrier or excipient. For preparing pharmaceutical compositions from the compounds of the present invention, pharmaceutically acceptable carriers can be either solid or liquid. Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules. A solid carrier can be one or more substances, which may also act as diluents, flavoring agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.

In powders, the carrier is a finely divided solid, which is in a mixture with the finely divided active component. In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired.

The powders and tablets preferably contain from 5% to 80%, more preferably from 20% to 70% of the active compound. Suitable carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. The term "preparation" is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. Similarly, cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid dosage forms suitable for oral administration.

For preparing suppositories, a low melting wax, such as a mixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and thereby to solidify.

Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water/propylene glycol solutions. Liquid forms are particularly preferred for topical applications to the eye. For parenteral injection, liquid preparations can be formulated in solution in aqueous polyethylene glycol solution.

Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizers, and thickening agents as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well-known suspending agents.

Also included are solid form preparations, which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

The pharmaceutical preparation is preferably in unit dosage form. In such form the preparation is subdivided into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.

In a further aspect the present invention concerns the use of compounds of the invention in the production of a medicament for treating, ameliorating or preventing diseases, conditions and/or disorders which benefit from reduced aurora kinase, in particular Aurora A kinase activity. A disease is considered to benefit from reduced aurora kinase, in particular Aurora A kinase activity, if a reduction of Aurora kinase activity of at least 10%, preferably of at least 20%, preferably of at least 30%, leads to an improvement of at least one clinical indicator of that disease. Examples of such indicators are proliferation rate, which is preferably reduced, cellular differentiation, which is preferably induced etc. The activity of Aurora kinases, in particular Aurora A kinase can be assayed by art know methods, including but not limited to those described below.

Since aurora kinases are known to have a central role in the cell cycle and in particular aurora A kinase shows an elevated expression in more than 50% of colorectal, ovarian and gastric cancers and in more than 95% of invasive adenocarcinomas in a preferred embodiment of the present invention the diseases, conditions and/or disorders, which can be prevented, ameliorated or treated with the compounds of the present invention are hyperproliferative diseases. It is further preferred that the hyperproliferative diseases are selected from the group consisting of precancerosis; dysplasia; metaplasia; carcinomas of the gastrointestinal or colorectal tract, liver, pancreas, kidney, bladder, prostate, endometrium, ovary, testes, melanoma, dysplastic oral mucosa, invasive oral cancers, small cell and non-small cell lung carcinomas, hormone-dependent breast cancers, hormone-independent breast cancers, transitional and squamous cell cancers, neurological malignancies including neuroblastoma, gliomas, astrocytomas, osteosarcomas, soft tissue sarcomas, hemangioamas, endocrinological tumors, hematologic neoplasias including leukemias, lymphomas, and other myeloproliferative and lymphoproliferative diseases, carcinomas in situ, hyperplastic lesions, adenomas, fibromas, histiocytosis, chronic inflammatory proliferative diseases, vascular proliferative diseases and virus-induced proliferative diseases, skin diseases characterized by hyperproliferation of keratinocytes and/or T cells. Particular preferred diseases treatable with the compounds of the present invention are colorectal, ovarian, prostatic and gastric cancers and adenocarcinomas, more preferably invasive adenocarcinomas. The precancerosis treatable with the compounds of the present invention are preferably selected from the group consisting of precancerosis of the skin, in particular actinic keratosis, cutaneaous horn, actinic cheilitis, tar keratosis, arsenic keratosis, x-ray keratosis, Bowen's disease, bowenoid papulosis, lentigo maligna, lichen sclerosus, and lichen rubber mucosae; precancerosis of the digestive tract, in particular erythroplakia, leukoplakia, Barrett's esophagus, Plummer-Vinson syndrome, crural ulcer, gastropathia hypertrophica gigantea, borderline carcinoma, neoplastic intestinal polyp, rectal polyp, porcelain gallbladder; gynecological precancerosis, in particular carcinoma ductale in situ (CDIS), cervical intraepithelial neoplasia (ClN), leukoplakia, endometrial hyperplasia (grade III), vulvar dystrophy, vulvar intraepithelial neoplasia (VIN), hydatidiform mole; urologic precancerosis, in particular bladder papillomatosis, Queyrat's erythroplasia, testicular intraepithelial neoplasia (TIN), leukoplakia; carcinoma in situ (CIS); precancerosis caused by chronic inflammation, in particular pyoderma, osteomyelitis, acne conglobata, lupus vulgaris, and fistula.

Dysplasia is frequently a forerunner of cancer, and is found mainly in the epithelia; it is the most disorderly form of non-neoplastic cell growth, involving a loss in individual cell uniformity and in the architectural orientation of cells. Dysplastic cells often have abnormally large, deeply stained nuclei, and exhibit pleomorphism. Dysplasia characteristically occurs where there exists chronic irritation or inflammation. Dysplastic disorders which can be treated with the compounds of the present invention include, but are not limited to, anhidrotic ectodermal dysplasia, anterofacial dysplasia, asphyxiating thoracic dysplasia, atriodigital dysplasia, bronchopulmonary dysplasia, cerebral dysplasia, cervical dysplasia, chondroectodermal dysplasia, cleidocranial dysplasia, congenital ectodermal dysplasia, craniodiaphysial dysplasia, craniocarpotarsal dysplasia, craniometaphysial dysplasia, dentin dysplasia, diaphysial dysplasia, ectodermal dysplasia, enamel dysplasia, encephalo-ophthalmic dysplasia, dysplasia epiphysialis heminelia, dysplasia epiphysialis multiplex, dysplasia epiphysalis punctata, epithelial dysplasia, faciodigitogenital dysplasia, familial fibrous dysplasia of jaws, familial white folded dysplasia, fibromuscular dysplasia, fibrous dysplasia of bone, florid osseous dysplasia, hereditary renal-retinal dysplasia hidrotic ectodermal dysplasia, hypohidrotic ectodermal dysplasia, lymphopenic thymic dysplasia, mammary dysplasia, mandibulofacial dysplasia, metaphysical dysplasia, Mondini dysplasia, monostotic fibrous dysplasia, mucoepithelial dysplasia, multiple epiphysial dysplasia, oculoauriculovertebral dysplasia, oculodentodigital dysplasia, oculovertebral dysplasia, odontogenic dysplasia, ophthalmomandibulomelic dysplasia, periapical cemental dysplasia, polyostotic fibrous dysplasia, pseudoachondroplastic spondyloepiphysial dysplasia, retinal dysplasia, septo-optic dysplasia, spondyloepiphysial dysplasia, and ventriculoradial dysplasia.

Metaplasia is a form of controlled cell growth in which one type of adult or fully differentiated cell substitutes for another type of adult cell. Metaplastic disorders, which are treatable are preferably selected from the group consisting of agnogenic myeloid metaplasia, apocrine metaplasia, atypical metaplasia, autoparenchymatous metaplasia, connective tissue metaplasia, epithelial metaplasia, intestinal metaplasia, metaplastic anemia, metaplastic ossification, metaplastic polyps, myeloid metaplasia, primary myeloid metaplasia, secondary myeloid metaplasia, squamous metaplasia, squamous metaplasia of amnion, symptomatic myeloid metaplasia and regenerative metaplasia.

Many skin diseases are characterized by hyperproliferation of keratinocytes and/or T cells. Examples of such diseases which are treatable with the compounds of the present invention comprise without limitations psoriasis in particular psoriasis vulgaris, psoriasis capitis, psoriasis guttata, psoriasis inversa; neurodermatitis; ichtyosises; alopecia areata; alopecia totalis; alopecia subtotalis; alopecia universalis; alopecia diffusa; atopic dermatitis; lupus erythematodes of the skin; dermatomyositis of the skin; atopic eczema; morphea; scleroderma; alopecia areata Ophiasis type; androgenic alopecia; allergic contact dermatitis; irritative contact dermatitis; contact dermatitis; pemphigus vulgaris; pemphigus foliaceus; pemphigus vegetans; scarring mucous membrane pemphigoid; bullous pemphigoid; mucous membrane pemphigoid; dermatitis; dermatitis herpetiformis Duhring; urticaria; necrobiosis lipoidica; erythema nodosum; prurigo simplex; prurigo nodularis; prurigo acuta; linear IgA dermatosis; polymorphic light dermatosis; erythema Solaris; exanthema of the skin; drug exanthema; purpura chronica progressiva; dihydrotic eczema; eczema; fixed drug exanthema; photoallergy skin reaction; and periorale dermatitis.

It is suspected that Aurora kinases are also involved in mediating activation of estrogen receptor controlled genes. Thus, in a further preferred embodiment the hyperproliferative disorders which are treatable by the Aurora kinase inhibitors of the present invention are those which benefit from a reduced estrogen receptor signalling. It is known that an increased activity of genes controlled by estrogen receptor is responsible or contributes to various hyperproliferative diseases. Thus preferred diseases, conditions and/or disorders which can be treated with the compounds of the present invention are selected from the group consisting of mammary tumors, endometrial tumors and tumors of the uterus. Similarly, someone of skill in the art is capable of assessing whether a given hyperproliferative disease involves increased estrogen receptor signalling by determining the expression level of an ER controlled gene, e.g. cathepsin D, lactoferrin, or IGF-I etc. The quantity of active component in a unit dose preparation administered in the use of the present invention may be varied or adjusted from about 1 mg to about 1000 mg per m², preferably about 5 mg to about 150 mg/m² according to the particular application and the potency of the active component. The pharmaceutical composition can, if desired, also contain other compatible therapeutic agents (e.g., cytotoxic or cytostatic compounds, including, but not limited to, pure or mixed anti-estrogens such as faslodex, tamoxifen or raloxifen; any inhibitors of topoisomerase I or II, such as camptothecin (topo I) or etoposide (topo II); any compound that acts through inhibiting aromatase activity, such as anastrozole or letrozole; any preparation that interferes with HER2 signalling such as herceptin; any compound that interchelates DNA, such as doxorubicin. Particularly preferred cytostatic or cytotoxic drugs, which can be combined with the compounds of the present invention are alkylating substances, anti-metabolites, antibiotics, epothilones, nuclear receptor agonists and antagonists, anti-androgenes, anti-estrogens, platinum compounds, hormones and antihormones, interferons and inhibitors of cell cycle-dependent protein kinases (CDKs), inhibitors of cyclooxygenases and/or lipoxygenases, biogeneic fatty acids and fatty acid derivatives, including prostanoids and leukotrienes, inhibitors of protein kinases, inhibitors of protein phosphatases, inhibitors of lipid kinases, platinum coordination complexes, ethyleneimenes, methylmelamines, trazines, vinca alkaloids, pyrimidine analogs, purine analogs, alkylsulfonates, folic acid analogs, anthracendiones, substituted urea, methylhydrazin derivatives, in particular acediasulfone, aclarubicine, ambazone, aminoglutethimide, L-asparaginase, azathioprine, bleomycin, busulfan, calcium folinate, carboplatin, carpecitabine, carmustine, celecoxib, chlorambucil, cis-platin, cladribine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin dapsone, daunorubicin, dibrompropamidine, diethylstilbestrole, docetaxel, doxorubicin, enediynes, epirubicin, epothilone B, epothilone D, estramucin phosphate, estrogen, ethinylestradiole, etoposide, flavopiridol, floxuridine, fludarabine, fluorouracil, fluoxymesterone, flutamide fosfestrol, furazolidone, gemcitabine, gonadotropin releasing hormone analog, hexamethylmelamine, hydroxycarbamide, hydroxymethylnitrofurantoin, hydroxyprogesteronecaproat, hydroxyurea, idarubicin, idoxuridine, ifosfamide, interferon α, irinotecan, leuprolide, lomustine, lurtotecan, mafenide sulfate olamide, mechlorethamine, medroxyprogesterone acetate, megastrolacetate, melphalan, mepacrine, mercaptopurine, methotrexate, metronidazole, mitomycin C, mitopodozide, mitotane, mitoxantrone, mithramycin, nalidixic acid, nifuratel, nifuroxazide, nifuralazine, nifurtimox, nimustine, ninorazole, nitrofurantoin, nitrogen mustards, oleomucin, oxolinic acid, pentamidine, pentostatin, phenazopyridine, phthalylsulfathiazole, pipobroman, prednimustine, prednisone, preussin, procarbazine, pyrimethamine, raltitrexed, rapamycin, rofecoxib, rosiglitazone, salazosulfapyridine, scriflavinium chloride, semustine streptozocine, sulfacarbamide, sulfacetamide. sulfachlopyridazine, sulfadiazine, sulfadicramide, sulfadimethoxine, sulfaethidole, sulfafurazole, sulfaguanidine, sulfaguanole, sulfamethizole, sulfamethoxazole, co-trimoxazole, sulfamethoxydiazine, sulfamethoxypyridazine, sulfamoxole, sulfanilamide, sulfaperin, sulfaphenazole, sulfathiazole, sulfϊsomidine, staurosporin, tamoxifen, taxol, teniposide, tertiposide, testolactone, testosteronpropionate, thioguanine, thiotepa, tinidazole, topotecan, triaziquone, treosulfan, trimethoprim, trofosfamide, UCN-Ol, vinblastine, vincristine, vindesine, vinblastine, vinorelbine, and zorubicin, or their respective derivatives or analogs thereof. Several of the above indicated drugs are now administered simultaneously for cancer therapy and, consequently, it is also envisioned that more than one cytostatic and/or cytotoxic drug is comprised in compositions of the present invention.

In therapeutic use as an inhibitor of aurora kinase activity, preferably aurora A kinase activity, the compounds employed in this use of the invention are administered at an initial dosage of about 0.05 mg/kg to about 20 mg/kg daily. A daily dose range of about 0.05 mg/kg to about 2 mg/kg is preferred, with a daily dose range of about 0.05 mg/kg to about 1 mg/kg being most preferred. The dosages, however, may be varied depending upon the requirements of the patient, the severity of the condition being treated, and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages, which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached. For convenience, the total daily dosage may be divided and administered in portions during the day, if desired.

BRIEF DESCRIPTION OF THE FIGURES

Fig. 1: Summarizes the results of various assays performed with particular preferred compounds of the present invention. Depicted are from left to right the IC_5O against Aurora A kinase, kinase activity of Aurora kinase A, B, C and FLT3, the cytotoxicity on HeLa, and the cytotoxicity on fibroblasts. Fig. 2: Depicts the effect of titration of ATP on the IC₅₀ values calculated in a dose response curve.

Fig. 3: Depicts evidence that preferred substances of the present invention inhibit Aurora kinase via the TPX2 binding site

EXPERIMENTAL SECTION

Assay for the identification of ATP non-competitive compounds

(2-allylsulfanyl-3-pyridyl)-[4-[4-[4-(3,5-dichloro-4-pyridyl)piperazin-l- yl]carbonylthiazol-2-yl]-l-piperidyl]-methanone (Compound according to formula IV), l-[4-[l- [[4-(p-tolyl)-3,6-dihydro-2H-pyridin-l-yl]carbonyl]-4-piperidyl]-l-piperidyl]-3-[3- (trifluoromethyl)phenyl]-prop-2-en-l-one (Compound according to formula VII), 4-[l-(2- cyclopentylacetyl)-4-piperidyl]-N-(3-hydroxyphenyl)-N-(o-tolyl)piperidine-l-carboxamide

(Compound according to formula VIII) and 4-[l-[3,5-bis(trifluoromethyl)benzoyl]-4-piperidyl]- N-[(2-hydroxyphenyl)methyl]-N-thiazol-2-yl-piperidine-l-carboxamide (Compound according to formula IX) were identified from a screen for inhibitors of Aurora A kinase using 20 μM ATP and kemptide peptide (amino acid sequence LRRASLG; SEQ ID NO:1) as substrate. The level of ATP consumption was monitored using couple luciferase (easylite-Kinase Luminescence Assay System PerkinElmer). Inhibitors of the kinase cause reduction of ATP turnover and increase in luminescence. Serial dilutions of the compounds were assayed using Z-lite (Invitrogen at 2, 20, 200, and 1000 μM to determine whether they were ATP competitive. This assay was screened against 53,000 compounds from a commercial library obtained under CDA. Dose response curves from active compounds were generated in a two fold 11 point serial dilution from a top concentration of 200 μM. The dose response curves were plotted in XLfit (IDBS, UK) and the IC_5O values reported in micromolar (μM).

To determine whether compounds were ATP competitive the IC₅₀ for the compound was determined at 3 different final ATP concentrations (20, 200, and 1000 μM) using Z'Lyte Kinase Assay Kit Ser/Thr Peptidel (PV3174) kit as described by the manufacturer. After resolution of the phosphorylation reaction the plates were read in an Envision HTS (PerkinElmer) and the dose response curves fitted as percent inhibitions in XLfit (IDBS, UK) and the IC₅₀ values reported in micromaolar (μM). When the calculated IC₅₀ value increased by greater than 5-fold per log 10 increase in ATP concentration the respective compound was deemed to be ATP competitive. Compounds that did not fulfill these criteria were deemed to be ATP noncompetitive. For the purpose of this invention only those compounds were further evaluated, which were ATP non-competitive inhibitors according to these criteria (see Fig. 2).

To determine whether the non-ATP competitive compounds were binding at the TPX2 binding site dose response curves were generated either in the absence or presence of recombinant TPX2 using a constant amount of ATP (20 μM) using EasyLite-Kinase

(PerkinElmer). The dose response curves calculated and fitted as percent inhibitions in XLfϊt

(IDBS, UK) and the ICs₀ values reported in micromolar (μM) (see Fig. 3).

Determination of aurora kinase activity

On the day, on which the assays were performed, 90 μl H₂O were added to each well of the master plate. To minimize precipitation, the H O was added to each well only a few minutes before the transfer of the compound solutions into the assay plates. The plate was shaken

-4 thoroughly, resulting in a "compound dilution plate" with a concentration of 5 x 10 M/10% DMSO. This plate was used for the transfer of 5 μl compound solution into the assay plates. The final volume of the assay was 50 μl. All compounds were tested at a final assay concentration of

5 x 10 M/1% DMSO in singlicate. The compound dilution plate was disposed at the end of the working day.

The following 4 protein kinases were used for determination of inhibitory profiles: i) Aurora-A ii) Aurora-B iii) Aurora-C iv) FLT3

All protein kinases were expressed in Sf9 insect cells as human recombinant GST-fusion proteins or His-tagged proteins by means of a baculovirus expression system. Kinases were purified by affinity chromatography using either GSH-agarose (Sigma) or Ni-NTH-agarose

(Qiagen). The purity of each kinase was checked by SDS-PAGE/silver staining and the identity of each kinase was verified by western blot analysis with kinase specific antibodies or by mass spectroscopy.

Protein Kinase Assay

A protein kinase assay ( PanQinase Activity Assay) was used for measuring the kinase

TM activity of the 4 protein kinases. All kinase assays were performed in 96-well FlashPlates from Perkin Elmer/NEN (Boston, MA, USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in 4 steps in the following order:

• 20 μl of assay buffer

• 5 μl of ATP solution (in H₃O) • 5 μl of test compound (in 10 % DMSO)

• 10 μl of substrate / 10 μl of enzyme solution (premixed)

The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl₂, 3 mM

MnCL, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG_,_Λnnn, 1 μM [γ- P]-ATP (approx. 5

5 x 10 cpm per well). For the 4 kinases the following amounts of enzyme and substrate were used per well:

# Kinase Kinase Kinase Substrate Substrate

Lot # ng/SOμl ng/50μl

1 Aurora-A SP004 50 tetra(LRRWSLG) 500

2 Aurora-B SP006 200 tetra(LRRWSLG) 250

3 Aurora-C SP007 200 tetra(LRRWSLG) 500

4 FLT3 SP006 100 Poly(Ala,Glu,Lys,Tyr)_{62 5 1} 125

The reaction cocktails were incubated at 30°C for 80 minutes. The reaction was stopped with 50 μl of 2% (v/v) H PO , plates were aspirated and washed two times with 200 μl of 0.9 %

33 (w/v) NaCl. Incorporation of P was determined with a microplate scintillation counter (Microbeta Trilux, Wallac). All assays were performed with a BeckmanCoulter/Sagian robotic system.

The median value of the counts in column 1 (n=8) of each assay plate was defined as

"low control". This value reflects unspecific binding of radioactivity to the plate in the absence of a protein kinase but in the presence of the substrate. The median value of the counts in column 2 of each assay plate (n=8) was taken as the "high control", i.e. full activity in the absence of any inhibitor. The difference between high and low control was taken as 100 % activity.

As part of the data evaluation the low control value from a particular plate was subtracted from the high control value as well as from all 80 "compound values" of the corresponding plate. The residual activity (in %) for each well of a particular plate was calculated by using the following formula:

Res. Activity (%) = 100 X [(cpm of compound - low control) / (high control - low control)] i.e. a low value is indicative of strong inhibition. Determination of cytotoxicity of preferred compounds of the invention

Compounds were analysed for their ability to inhibit growth of tumour cells (e.g. HeLa cells) and normal human cells (e.g. foreskin fibroblasts). Growth inhibition was tested from 50 μM to 97.7 nM in a 10 point two-fold serial dilution and cells incubated under standard mammalian tissue culture conditions for 72 hours in triplicate. Cell viability was measured by measuring ATP levels in viable cells using the ATPLite kit (PerkinElmer) as described in the user manual. Raw data was transformed to percentage inhibition of growth compared to a DMSO only control and values are expressed as IC_5O.

Claims

1. A compound of formula (I)

(I) wherein R¹ is alkyl, cycloalkyl, heterocylcoalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; R², R³, and R⁴ are independent of each other selected from H; halogen; hydroxy; CN; NO₂;

NR'R"; -OOC-R⁶; -COO-R^6'; alkyl, alkyloxy, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein

R' and R" are independent of each other hydrogen, alkyl, alkenyl, alkynyl or together form a heteroaryl;

R⁶ is alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted; R⁶ is H, alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted; R⁵ is H, NR⁷R⁸, alkyl, alkenyl, alkynyl, cycloalkyl, heterocylcoalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein R⁷ and R⁸ are independently selected from the group consisting of H, alkyl, cycloalkyl, heterocylcoalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; or R and R are taken together to form a heterocycloalkyl, an alicyclic system, or heteroaryl moiety; optionally substituted; X and Y are independently selected from O and S; and p is O, I, or 2 and pharmaceutically acceptable salts thereof.

2. Compound according to claim 1, wherein R is selected from the group consisting of 1 ,2,5,6-tetrahydropyridinyl, piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza- spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza- spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl,

3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuranyl, tetrahydrothienyl, piperazinyl; furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2, 1 -benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1- benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, and 1,2,4-benzotriazinyl; optionally substituted.

3. Compound according to claim 1 or 2, wherein R and R are taken together to form a 1,2- dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,4-tetrahydropyridyl, 1,2- dihydropyrazyl, 1,2,3,4-tetrahydropyrazyl, 1,2, piperidinyl, l-oxo-3-azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza- spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, 1,4- diazabicyclo[2.2.2]oct-2-yl, piperazinyl; isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl,

1 ,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5- triazinyl, 1 -benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, lH-indazolyl, benzimidazolyl, indoxazinyl, 2,1 -benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1- benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl moiety; optionally substituted.

4. Compound according to any of claims 1 to 3, wherein the compound has a structure according to formula (III)

(III) wherein

R², R³, and R⁴ are independent of each other selected from H; halogen; hydroxy; CN; NO₂;

NR'R"; -00C-R⁶; -COO-R^6'; alkyl, alkyloxy, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein

R⁶ is alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted;

R⁶ is H, alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted; R⁹ is alkyl, cycloalkyl, heterocylcoalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; R¹⁰ is H; halogen; hydroxy; CN; NO₂; NR'R"; -R^π-R¹²; and wherein

R', and R" independent of each other hydrogen, alkyl, alkenyl, alkynyl or together form a heteroaryl; optionally substituted; and

R¹ ' is a bond, -OOC-, -COO-, CO, O, or S;

R¹² is alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; Z is CR'" or N; wherein

R'" is hydrogen, alkyl, alkenyl, or alkynyl; optionally substituted.

Compound according to any of claims 1 to 4, wherein the compound has a structure according to formula (IV)

(IV).

Compound according to formula (V)

(V) wherein

R 13 is alkyl, alkenyl, alkynyl, aryl or heteroaryl; optionally substituted;

R ¹⁴ is NR¹⁵R¹⁶, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; wherein R¹⁵ and R¹⁶ are independently selected from the group consisting of H, alkyl, cycloalkyl, heterocylcoalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted; or R¹⁵ and R¹⁶ are taken together to form a heterocycloalkyl, an alicyclic system or heteroaryl moiety; optionally substituted; X' and Y' are independently O or S and pharmaceutically acceptable salts thereof.

7. Compound according to claim 6, wherein R¹³ is selected from the group consisting of methyl, ethyl, propyl, /so-propyl, butyl, /sø-butyl, tert-butyl, pentyl, hexyl, ethenyl, 1- propenyl, 2-propenyl, 1 -wo-propenyl, 2-/sø-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl.

8. Compound according to claims 6 or 7, wherein R¹³ is substituted with halogen, CN, NO₂, OH, alkoxy, cycloalkyl, heterocylcoalkyl, an alicyclic system, aryl, heteroaryl, aralkyl, or heteroaralkyl; optionally substituted.

9. Compound according to claim 8 wherein (i) aryl is selected from the group consisting of phenyl and napthyl; optionally substituted;

(ii) cycloalkyl is selected from the group consisiting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[3,3]heptyl, spiro[3,4]octyl,

5 spiro[4,3]octyl, spiro[3,5]nonyl, spiro[5,3]nonyl, spiro[3,6]decyl, spiro[6,3]decyl, spiro[4,5]decyl, spiro[5,4]decyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, and adamantyl; optionally substituted;

(ii) heterocycloalkyl is selected from the group consisting of 1,2,5,6-tetrahydropyridinyl,

1,4,5,6-tetrahydropyridyl, piperidinyl, morpholinyl, 1 ,8 diaza-spiro-[4,5] decyl, 1 ,7 C diaza-spiro-[4,5] decyl, 1 ,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1 ,8 diaza-spiro-[5,4] decyl, 1 ,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l-aza-7,l l-dioxo-spiro[5,5] undecyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, 5 tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, and 2-piperazinyl; optionally substituted; and

(iii) alicyclic system is selected from the group consisting of 1 -cyclohexenyl, 3- cyclohexenyl, 1,2-dihydropyridinyl, 1,2,5,6-tetrahydropyridinyl, 1,2,3,4- tetrahydropyridyl, 1 ,2-dihydropyrazyl, 1,2,3,4-tetrahydropyrazyl, cyclopropenyl, 0 cyclobutenyl, cyclopentenyl, cyclohexenyl, and cycloheptenyl;

(v) heteroaryl is selected from the group consisting of furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1 ,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl,

1,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1- 5 benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, IH- indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, and 1 ,2,4-benzotriazinyl; optionally substituted.

10. Compound according to claim 6, wherein R is selected from the group consisting of phenyl, naphthalenyl or anthracenyl; heteroaryl, in particular furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3- triazolyl, thiazolyl, isothiazolyl, 1,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1-benzofliranyl, 2- benzofuranyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2- benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3- benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, and 1 ,2,4-benzotriazinyl.

1 1. Compound according to any of claims 6 to 10, wherein R¹⁵ and R¹⁶ together form a 1,2,5,6-tetrahydropyridinyl, 1,4,5,6-tetrahydropyridyl, piperidinyl, l-oxo-3- azacyclohexanyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4,5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza- spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza-spiro- [5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l,4-diazabicyclo[2.2.2]oct-2-yl, piperazinyl; isoxazolyl, 1,2,5-oxadiazolyl, 1,2,3- oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1,2,3,- thiadiazolyl, 1 ,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4- triazinyl, 1,3,5-triazinyl, 1-benzofuranyl, 2-benzofuranyl, indolyl, isoindolyl, lH-indazolyl, benzimidazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1 - benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1,2,3-benzotriazinyl, or 1 ,2,4-benzotriazinyl moiety; optionally substituted.

12. Compound according to claim 11 having a structure accorroding to formula (VII)

(VII).

13. Compound according to any of claims 5 to 10, wherein R and R¹⁶ are independently selected from the group consisting of phenyl, napthyl, phenyl methyl, phenyl ethyl, phenyl propyl, phenyl butyl, phenyl ethenyl, napthyl methyl, napthyl ethyl, napthyl propyl, napthyl butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3- cyclohexenyl, cycloheptyl, spiro[3,3]heptyl, spiro[3,4]octyl, spiro[4,3]octyl, spiro[3,5]nonyl, spiro[5,3]nonyl, spiro[3,6]decyl, spiro[6,3]decyl, spiro[4,5]decyl, spiro[5,4]decyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, adamantyl, 1,2,5,6- tetrahydropyridinyl, 1,4,5,6-tetrahydropyridyl, piperidinyl, piperidinyl, piperidinyl, piperidinyl, morpholinyl, morpholinyl, 1,8 diaza-spiro-[4,5] decyl, 1,7 diaza-spiro-[4.5] decyl, 1,6 diaza-spiro-[4,5] decyl, 2,8 diaza-spiro[4,5] decyl, 2,7 diaza-spiro[4,5] decyl, 2,6 diaza-spiro[4,5] decyl, 1,8 diaza-spiro-[5,4] decyl, 1,7 diaza-spiro-[5,4] decyl, 2,8 diaza- spiro-[5,4] decyl, 2,7 diaza-spiro[5,4] decyl, 3,8 diaza-spiro[5,4] decyl, 3,7 diaza-spiro[5,4] decyl, l-aza-7,l l-dioxo-spiro[5,5] undecyl, l,4-diazabicyclo[2.2.2]oct-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1- piperazinyl, and 2-piperaziny, furanyl, thienyl, oxazolyl, isoxazolyl, 1,2,5-oxadiazolyl, 1 ,2,3-oxadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, thiazolyl, isothiazolyl, 1 ,2,3,-thiadiazolyl, 1,2,5-thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1 ,2,4-triazinyl, 1,3,5-triazinyl, 1-benzo furanyl, 2-benzo furanyl, indolyl, isoindolyl, benzothienyl, 2-benzothienyl, lH-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, 2,1-benzisoxazolyl, benzothiazolyl, 1 ,2-benzisothiazolyl, 2,1-benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, 2,3-benzodiazinyl, quinoxalinyl, quinazolinyl, 1 ,2,3-benzotriazinyl, and 1 ,2,4-benzotriazinyl; optionally substituted.

14. Compound according to any of claims 13, having a structure according to formula (VIII) or (IX)

(VIII), or

(IX).

15. Use of a compound of any of claims 1 to 14 for the production of a medicament for treating, ameliorating or preventing diseases, conditions and/or disorders which benefit from a reduced Aurora kinase activity.

16. Use of claim 15, wherein the diseases, conditions and/or disorders are hyperproliferative diseases.

17. Use of claim 16, wherein the hyperproliferative diseases are selected from the group consisting of precancerosis; dysplasia; metaplasia; carcinomas of the gastrointestinal or colorectal tract, liver, pancreas, kidney, bladder, prostate, endometrium, ovary, testes, melanoma, dysplastic oral mucosa, invasive oral cancers, small cell and non-small cell lung carcinomas, hormone-dependent breast cancers, hormone-independent breast cancers, transitional and squamous cell cancers, neurological malignancies including neuroblastoma, gliomas, astrocytomas, osteosarcomas, soft tissue sarcomas, hemangioamas, endocrinological tumors, hematologic neoplasias including leukemias, lymphomas, and other myeloproliferative and lymphoproliferative diseases, carcinomas in situ, hyperplastic lesions, adenomas, fibromas, histiocytosis, chronic inflammatory proliferative diseases, vascular proliferative diseases and virus-induced proliferative diseases, skin diseases characterized by hyperproliferation of keratinocytes and/or T cells.

18. Use of claim 16, wherein the hyperproliferative diseases are characterized by the hyperproliferation of T-cells and/or keratinocytes.

19. Use of claim 18, wherein the diseases are selected from the group consisting of psoriasis in particular psoriasis vulgaris, psoriasis capitis, psoriasis guttata, psoriasis inversa; neurodermatitis; ichtyosises; alopecia areata; alopecia totalis; alopecia subtotalis; alopecia universalis; alopecia diffusa; atopic dermatitis; lupus erythematodes of the skin; dermatomyositis of the skin; atopic eczema; morphea; scleroderma; alopecia areata

Ophiasis type; androgenic alopecia; allergic contact dermatitis; irritative contact dermatitis; contact dermatitis; pemphigus vulgaris; pemphigus foliaceus; pemphigus vegetans; scarring mucous membrane pemphigoid; bullous pemphigoid; mucous membrane pemphigoid; dermatitis; dermatitis herpetiformis Duhring; urticaria; necrobiosis lipoidica; erythema nodosum; prurigo simplex; prurigo nodularis; prurigo acuta; linear IgA dermatosis; polymorphic light dermatosis; erythema Solaris; exanthema of the skin; drug exanthema; purpura chronica progressiva; dihydrotic eczema; eczema; fixed drug exanthema; photoallergy skin reaction; and periorale dermatitis.

20. Use of claim 16, wherein the hyperproliferative disorders are those which benefit from a reduced estrogen receptor signalling.

21. Use of claim 20, wherein the diseases, conditions and/or disorders are selected from the group consisting of mammary tumors, endometrial tumors and tumors of the uterus.