Imidazole derivatives and use thereof as antifibrotic agents

Abstract

According to some estimate, 45% of all deaths is attributed to organ fibrosis in the developed world. Independently from the primary disease, the pathophysiology of the fibrosis shows a highly overlapping mechanism in the different organs. The main effector cells of fibrosis are the activated fibroblasts, characterized by increased proliferation rate and excessive production of extracellular matrix. Chronic activation of myofibroblasts leads to the excessive deposition of the extracellular matrix replacing the healthy tissue leading to the impairment and finally to the loss of organ function. The unmet medical need makes it necessary to develop new drugs to hinder organ fibrosis. We aimed to develop novel antifibrotic compounds targeting PDGFRs, including PDGFR-A and -B, an element of the core pathway responsible for the activation of the fibroblasts, the main effector cells of organ fibrosis. The effect of the developed compounds was first tested using in vitro biochemical assay investigating the kinase activity of PDGFR-A and -B. The inhibitory effect of the compounds on the PDGF-B induced proliferation of myofibroblasts originated from lung and kidney were investigated in vitro. One of the most promising compounds was further investigated in vivo, as well.

Description

[0001] IMIDAZOLE DERIVATIVES AND USE THEREOF AS ANTIFIBROTIC AGENTS FIELD OF THE INVENTION The present invention relates to new compounds of the general formula (I), as well as their isomers, pharmaceutically accepted salts and solvates, to the pharmaceutical compositions containing them and to the therapeutic application thereof. Further subjects of the invention are the methods of preparation of the compounds of the general formula (I) and the new intermediates of these processes. TECHNICAL BACKGROUND According to some estimate 45% of all deaths is attributed to organ fibrosis in the developed world. Independently from the primary disease, the pathophysiology of the fibrosis shows a highly overlapping mechanism in the different organs. The main effector cells of fibrosis are the myofibroblasts, characterized by increased proliferation rate and excessive production of extracellular matrix. Chronic activation of myofibroblasts leads to the excessive deposition of the extracellular matrix replacing the healthy tissue leading to the impairment and finally to the loss of organ function. The unmet medical need makes it necessary to develop new drugs to hinder organ fibrosis. Receptor tyrosine kinases (e.g. platelet-derived growth factor (PDGF) receptor) and non-receptor tyrosine kinases (e.g. c-Abl, c-Kit, Src kinases) have been identified as potential targets for anti-fibrotic therapies. Inhibitors of these kinases might be useful for the treatment of idiopathic pulmonary fibrosis, renal-, liver- or dermal fibrosis. Gleevec (Imatinib) has been tested for potential use in slowing down pulmonary fibrosis. This drug can suppress platelet-derived growth factor (PDGF) by inhibiting its receptor (PDGFR-β). Pirfenidone reduces renal fibrosis and lung fibrosis through downregulation of the production of profibrotic growth factors (e.g. PDGF) and procollagenes. Based on the above, we can expect that compounds exerting downregulation of the production of profibrotic growth factors (e.g. PDGF) or inhibiting the activation of their receptors are suitable – among others – to treat diseases like pulmonary-, renal-, liver- or dermal fibrosis. US patent US5958959A discloses composition comprising compounds which can inhibit platelet derived growth factor receptor (PDGF-R) activity and thereby treating patients suffering from cell proliferative disorders like cancer or fibrotic disorders. We aimed to prepare novel compounds suitable for drug development, exerting strong inhibition of PDGFR- α and β receptors. Similar compounds are disclosed in WO 2020172609 A1, WO 2018183122 A1 and in Zeidan et al, Eur. J. Med. Chem., 168(15), 315-329 (2019). The compounds and general formulas mentioned in those documents are not part of the compound claims of the present application. BRIEF DESCRIPTION OF THE INVENTION We have found that the compounds of the general formula (I) and their salts, isomers, and solvates exert significant inhibition of PDGFR-α and -β. Accordingly, an object of the present disclosure is therefore 1. a compound of general formula (I), wherein Ar is phenyl, or 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms independently selected from N and S, such as pyrrole, tiophene, imidazole, pyrazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, thiazine; wherein each of the phenyl and the heteroaromatic ring is optionally substituted with 1 or 2 substituents independently selected from C1-4 alkyl, halogen, -OH, -NH2, -NHC1-4 alkyl, C1-4 alkoxy; R1is H, halogen, C1-2 alkyl, or C1-2 alkoxy; R2is H, halogen, or C1-2 alkyl; X1is NH or CO X2is NH or CO, with the proviso that X1and X2are not the same; Y is a bond or (CH2)n; where n is 1 or 2; or Y is NH, provided that X2is CO; or Y is NHCO, provided that X2is NH; Z is phenyl, or a 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, or a 7-10-membered aromatic bicyclic moiety containing 1-3 heteroatoms, independently selected from N, O and S, preferably N, or 3-, 4-, 5- or 6-membered cycloalkyl group, or a 5- or 6-membered saturated heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N, O and S, where any of these rings or cyclic groups is optionally substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, benzyloxy, halogen, trihalogenoC1-2 alkyl, -NO2, -CN, -OH, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, di(C1-2 alkyl)aminoC1-4 alkyl, di(C1-2 alkyl)aminoC1-4 alkenylcarbonyl, phenyl, -NHphenyl, C1-4 alkoxycarbonyl group, C1-4 alkylcarbonyl group, C2-4 alkenylcarbonyl group, 5- or 6-membered saturated heterocyclic ring containing 1-3 heteroatoms independently selected from N, O and S, 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, heterocyclylaminosulfonyl group, heteroarylaminosulfonyl group, arylcarbonylamino group, heteroarylcarbonylamino group, 3-, 4-, 5- or 6-membered cycloalkyl group, heterocyclylalkyl group, heteroarylalkyl group, -NH-C(O)-NH-phenyl, N(C1-4 alkyl)-C(O)-C1-2alkyl-heterocyclyl, where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, halogen, -OH, hydroxyalkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, -NO2, -CN, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, C1-4 alkoxycarbonyl group. 2. Compound according to point 1, wherein Ar is a 5-membered heteroaromatic ring comprising 1 or 2 heteroatoms independently selected from N and S; preferably N wherein each of the heteroaromatic ring is optionally substituted with a substituent selected from C1-2 alkyl, halogen, -OH, -NH2, -NHC1-2 alkyl, C1-2 alkoxy, preferably, methyl, methoxy, and halogen. 3. Compound according to point 1 or 2, wherein Ar is a 5-membered heteroaromatic ring comprising 2 nitrogen atoms, such as imidazolyl or pyrazolyl, optionally substituted with methyl, preferably imidazole-4-yl, 1-methylimidazol-4-yl, 1-methylimidazol-5-yl, more preferably 1-methylimidazol-5-yl. 4. Compound according to any of the previous points, wherein R1is H, methyl, methoxy, fluoro or chloro, preferably hydrogen, methyl, fluoro or chloro, more preferably methyl; R2is H, fluoro or methyl, preferably H. 5. Compound according to any of the previous points, wherein Y is a bond, or Y is (CH2)n, provided that X2is NH, or Y is NH, provided that X2is CO; preferably Y is a bond. 6. Compound according to any of the previous points, wherein Z is phenyl, or a 5- or 6-membered heteroaromatic ring containing 1-2 heteroatoms independently selected from N, O and S, or a 8-10-membered aromatic bicyclic moiety containing 1-2 heteroatoms, independently selected from N, O and S, preferably N, or 3-, 4-, 5- or 6-membered cycloalkyl group, or a 6-membered saturated heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N, O and S, preferably N, where any of these rings or cyclic groups is optionally substituted 1-3 substituents independently selected from C1-2 alkyl, t-butyl, C1-2 alkoxy, benzyloxy, halogen, trihalogenomethyl, -NO2, -CN, -OH, -NH2, - NHC1-2 alkyl, -N(C1-2 alkyl)2, di(C1-2 alkyl)aminoC1-3 alkyl, di(C1-2 alkyl)aminoC2-3 alkenylcarbonyl, -NHphenyl, C1-4 alkoxycarbonyl group, C1-2 alkylcarbonyl group, C2-4 alkenylcarbonyl group, 5- or 6-membered saturated heterocyclic ring containing 1-2 heteroatoms independently selected from N and O such as pyrrolidine, pyrazolidine, tetrahydrofuran, piperidine, piperazine, tetrahydropyran and morpholine; 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N and S, preferably N, heterocyclylaminosulfonyl group where the heterocyclyl moiety is a 5- or 6-membered group containing 1 or 2 heteroatoms independently selected from N, O and S, heteroarylaminosulfonyl group where the heteroaryl moiety is a 5- or 6- membered group containing 1 to 3 heteroatoms independently selected from N and S, arylcarbonylamino group, 5-membered heteroarylcarbonylamino group, heterocyclylalkyl group where the heterocyclyl moiety is a 6-membered group containing 1 or 2 heteroatoms independently selected from N and O, heteroarylalkyl group where the heteroaryl moiety is a 8-10-membered aromatic bicyclic moiety containing 1-2 N, and -NH-C(O)-NH-phenyl, N(C1-2 alkyl)-C(O)-C1-2alkyl-heterocyclyl where the heterocyclyl moiety is a 5- or 6-membered group containing 1 or 2 heteroatoms independently selected from N and O , where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with 1-3 substituents independently selected from C1- 2 alkyl, C1-2 alkoxy, halogen, -OH, hydroxyC1-2alkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, - NO2, -CN, -NH2, -NHC1-2 alkyl, -N(C1-2 alkyl)2, C1-4 alkoxycarbonyl group. 7. Compound according to any of the previous points, wherein Z is phenyl, pyrrolyl, thiophenyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzopyrazolyl, pyrazolo[1,5-a]pyridinyl, indolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, and tetrahydropyranyl, preferably phenyl where any of these rings or cyclic groups is optionally substituted 1-3 substituents independently selected from methyl, ethyl, methoxy, ethoxy, benzyloxy, halogen, trifluoromethyl, -NO2, -CN, -OH, -NH2, - NHC1-2 alkyl, -N(C1-2 alkyl)2, di(C1-2 alkyl)aminoC1-2 alkyl, di(C1-2 alkyl)aminoC2-3 alkenylcarbonyl, -NHphenyl, C1-4 alkoxycarbonyl group, C1-4 alkylcarbonyl group, C2-4 alkenylcarbonyl group, imidazolyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolidinyl, pyrazolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl; heterocyclylaminosulfonyl group where the heterocyclyl moiety is thiazolidinyl, heteroarylaminosulfonyl group where the heteroaryl moiety is thiazolyl or thiadiazolyl, heterocyclylmethyl group where the heterocyclyl moiety is tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, heteroarylmethyl group where the heteroaryl moiety is a 8-10-membered aromatic bicyclic moiety containing 1-2 N such as benzopyrazole, benzothiazole and benzimidazole, and -NH-C(O)-NH-phenyl, N(methyl)-C(O)-methyl-heterocyclyl where the heterocyclyl moiety is tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with 1-3 substituents independently selected from C1- 2 alkyl, C1-2 alkoxy, halogen, -OH, hydroxyC1-2alkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, - NO2, -CN, -NH2, -NHC1-2 alkyl, -N(C1-2 alkyl)2, C1-4 alkoxycarbonyl group. 8. Compound according to any of the previous points, wherein Z is phenyl, thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrazinyl, benzimidazolyl, benzopyrazolyl, pyrazolo[1,5-a]pyridinyl, indolyl, cyclohexyl, and tetrahydropyranyl, preferably phenyl; wherein the substituents of Z is as defined in any of the previous points. 9. Compound according to any of points 1-8, wherein Z is selected from

[0002]

[0003] . 10. Compound according to any of the previous points selected from 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.1); 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-4-carboxamide (Ex.2); N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-4-carboxamide (Ex.3); 1-Methyl-N-{3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.4); 4-Chloro-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex.5); N-{2-chloro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.6); N-[2-chloro-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.7); N-{5-[(4-methoxybenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.8); N-{5-[(4-chlorobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.9); 1-Methyl-N-[2-methyl-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1H-imidazole-5-carboxamide (Ex.10); 1-Methyl-N-(2-methyl-5-{[(2-methyl-3-thienyl)carbonyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.11); N-(5-{[(3,4-dichlorophenyl)carbamoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.12); N,N'-(4-methyl-1,3-phenylene)bis(1-methyl-1H-imidazole-5-carboxamide) (Ex.13); N-{2-fluoro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.14); 1-Methyl-N-{4-methyl-3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.15); N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-4-[(3,4,5- trimethoxyphenyl)amino]pyridine-2-carboxamide (Ex.16); N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (Ex.17); N-{4-fluoro-2-methoxy-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.18); 4-Hydroxy-2-(methylamino)-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)pyrimidine-5- carboxamide (Ex.19); 4-Ethoxy-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex. 20); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxybenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.21); 1-Methyl-N-(2-methyl-5-{[4-(trifluoromethyl)benzoyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.22); N-(5-{[3,5-bis(trifluoromethyl)benzoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.23); 1-[2-(Dimethylamino)pyrimidin-4-yl]-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-1H- imidazole-4-carboxamide (Ex.24); 4-Methoxy-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex. 25); N-{5-[(4-cyanobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.26); N-[5-({[3-(benzyloxy)cyclobutyl]carbonyl}amino)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex. 27); N-{5-[(4-chlorophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.28); 1-Methyl-N-(2-methyl-5-{[2-methyl-5-({[3-(trifluoromethyl)phenyl]- carbamoyl}amino)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.29); N-{5-[(3,4-dimethoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.30); N-{5-[(2,4-dichloro-5-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex. 31); N-{5-[(2-fluoro-4-methoxy-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.32); N-{5-[(4-methoxy-2-morpholin-4-yl-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5- carboxamide (Ex.33); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.34); N-{5-[(5-tert-butylisoxazol-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.35); N-{5-[(4-chlorobenzyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.36); N-{5-[(4-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.37); N-{5-[(5-methoxypyridin-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.38); 1-Methyl-N-{2-methyl-5-[(4-methylphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.39); N-(5-{[4-(4-bromo-1H-imidazol-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.40); Tert-butyl 4-[(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}-benzoyl)amino]piperidine-1- carboxylate (Ex.41); 1-Methyl-N-(2-methyl-5-{[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.42); 1-Methyl-N-[2-methyl-5-(piperidin-4-ylcarbamoyl)phenyl]-1H-imidazole-5-carboxamide (Ex.43); N-{5-[(3,4-dimethoxybenzyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.44); N-[5-(cyclohexylcarbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.45); N-(5-{[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex. 46); N-[5-({3-cyano-1-[3-(dimethylamino)propyl]-4,5-dimethyl-1H-pyrrol-2-yl}carbamoyl)-2-methylphenyl]-1- methyl-1H-imidazole-5-carboxamide (Ex.47); N-[5-({4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl}carbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5- carboxamide (Ex.48); N-{5-[(4-acetylphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.49); N-(5-{[4-(4-hydroxypiperidin-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.50); N-{5-[(3,5-dimethylisoxazol-4-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.51); N-[5-({4-[(2E)-3-(dimethylamino)prop-2-enoyl]phenyl}carbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5- carboxamide (Ex.52); 1-Methyl-N-(2-methyl-5-{[4-(1H-pyrazol-3-yl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.53); 1-Methyl-N-[2-methyl-5-({4-[4-(methylsulfonyl)piperazin-1-yl]phenyl}carbamoyl)phenyl]-1H-imidazole-5- carboxamide (Ex.54); N-(5-{[3-(1H-benzimidazol-1-ylmethyl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.55); 1-Methyl-N-[2-methyl-5-({4-[(1,3-thiazol-2-ylamino)sulfonyl]phenyl}-carbamoyl)phenyl]-1H-imidazole-5- carboxamide (Ex.56); 1-Methyl-N-{2-methyl-5-[(4-{[(5-methyl-1,3,4-thiadiazol-2-yl)amino]sulfonyl}phenyl)carbamoyl]phenyl}-1H- imidazole-5-carboxamide (Ex.57); N-[5-(cyclopropylcarbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.58); 1-Methyl-N-(2-methyl-5-{[3-(morpholin-4-ylmethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.59); 1-Methyl-N-(2-methyl-5-{[4-(piperidin-1-ylmethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex. 60); 1-Methyl-N-[2-methyl-5-({4-[methyl(piperidin-1-ylacetyl)amino]phenyl}-carbamoyl)phenyl]-1H-imidazole-5- carboxamide (Ex.61); 1-Methyl-N-(2-methyl-5-{[2-(4-methylbenzoyl)hydrazino]carbonyl}phenyl)-1H-imidazole-5-carboxamide (Ex. 62); N-[5-({2-[(4-chloropyridin-2-yl)carbonyl]hydrazino}carbonyl)-2-methylphenyl]-1-methyl-1H-imidazole-5- carboxamide (Ex.63). 11. Compound according to any of the previous points selected from 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.1); 1-Methyl-N-{3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.4); 4-Chloro-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex.5); N-{2-chloro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.6); N-{5-[(4-chlorobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.9); 1-Methyl-N-[2-methyl-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1H-imidazole-5-carboxamide (Ex.10); 1-Methyl-N-(2-methyl-5-{[(2-methyl-3-thienyl)carbonyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.11); N-(5-{[(3,4-dichlorophenyl)carbamoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.12); N-{2-fluoro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.14); N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (Ex.17); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxybenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.21); 1-Methyl-N-(2-methyl-5-{[4-(trifluoromethyl)benzoyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.22); N-(5-{[3,5-bis(trifluoromethyl)benzoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.23); 4-Methoxy-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex. 25); N-{5-[(4-cyanobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.26); N-{5-[(4-chlorophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.28); 1-Methyl-N-(2-methyl-5-{[2-methyl-5-({[3-(trifluoromethyl)phenyl]- carbamoyl}amino)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.29); N-{5-[(3,4-dimethoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.30); N-{5-[(2,4-dichloro-5-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex. 31); N-{5-[(2-fluoro-4-methoxy-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.32); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.34); N-{5-[(5-tert-butylisoxazol-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.35); N-{5-[(4-chlorobenzyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.36); N-{5-[(4-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.37); N-{5-[(5-methoxypyridin-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.38); 1-Methyl-N-{2-methyl-5-[(4-methylphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.39); N-(5-{[4-(4-bromo-1H-imidazol-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.40); 1-Methyl-N-(2-methyl-5-{[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.42); N-[5-(cyclohexylcarbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.45); N-{5-[(4-acetylphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.49); 1-Methyl-N-(2-methyl-5-{[4-(1H-pyrazol-3-yl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.53); N-(5-{[3-(1H-benzimidazol-1-ylmethyl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.55). 12. Compound according to any of the previous points which is 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.1). 13. Method for the production of a compound of general formula (I) as defined in any of point 1-12, comprising reacting the acid of general formula (II) with the amine of the general formula (III) in the presence of an activating agent, in an inert solvent, preferably the activating agent is 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide (EDC) and the inert solvent is pyridine, dichloromethane, tetrahydrofuran, dioxane, or N,N-dimethylformamide . 14. Method for the production of a compound of general formula (I) as defined in any of point 1-12, wherein X1is NH, X2is CO and Y is a bond, comprising reacting the amine of the general formula (IV) with the compound of the general formula (V) – where Q is chloro atom or hydroxyl group, if Q represents chloro atom, in an inert solvent in the presence of a base or in pyridine, preferably the inert solvent is dichoromethane, chloroform, or ethyl acetate and the base is triethylamine, if Q represents hydroxyl group, in the presence of an activating agent, in an inert solvent, preferably the inert solvent is pyridine, dichloromethane, tetrahydrofuran, dioxane, or N,N-dimethyl- formamide and the activating agent is 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide (EDC) 15. Method for the production of a compound of general formula (I) as defined in any of point 1-12, wherein X1is CO, and X2is NH, comprising reacting the acid of the general formula (VI) with the amine of the general formula (VII) in the presence of an activating agent, in an inert solvent, preferably the activating agent is 1-ethyl-3-(3’- dimethylaminopropyl)carbodiimide (EDC) and the inert solvent is pyridine, dichloromethane, tetrahydrofuran, dioxane, or N,N-dimethylformamide 16. Method for the production of a compound of general formula (I) as defined in any of point 1-12, wherein X1is CO, X2is NH, and Y is NHCO, comprising reacting the hydrazide of the general formula (VIII) with compound of the general formula (V) – where Q is chloro atom or hydroxyl group, if Q represents chloro atom, in an inert solvent in the presence of a base or in pyridine, preferably the inert solvent is dichoromethane, chloroform, or ethyl acetate and the base is triethylamine, if Q represents hydroxyl group, in the presence of an activating agent, in an inert solvent, preferably the inert solvent is pyridine, dichloromethane, tetrahydrofuran, dioxane, or N,N-dimethyl- formamide and the activating agent is 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide (EDC) . Another object of the present invention is 17. compound according to any of the previous points for use as a medicine. Preferably, the compound according to any of points 1 to 12 is for use in therapy or as a prophylactic. 18. Compound according to any of points 1 to 12 for use in treating or preventing a platelet-derived growth factor receptor (PDGFR) mediated disease or disorder. Preferably, the platelet-derived growth factor receptor (PDGFR) is PDGFR-alpha (PDGFR-A) and / or PDGFR-beta (PDGFR-B) homo or hetero(di)mer. Preferably, the PDGFR is PDGFR-alpha (PDGFR-A) homodimer. Preferably, the PDGFR is PDGFR-beta (PDGFR-B) homodimer. Preferably, the PDGFR is PDGFR-alpha (PDGFR-A) and PDGFR-beta (PDGFR-B) heterodimer. 19. Compound according to any of points 1 to 12 for use in treating or preventing a cell proliferative disease. Preferably the cell proliferative disease is selected from fibrosis comprising progressive fibrosis, a fibroproliferative disease, in particular a fibroproliferative disease involving progressive fibrosis, tumours, cancers and neoplasms. 20. The compound according to any of points 1 to 12 or a compound for use according to point 19 for use in treating or preventing diseases or disorders or conditions associated with or characterized by fibrosis, or a fibroproliferative disorder. 21. The compound for use according to point 20, wherein the disease associated with or characterized by fibrosis is selected from renal disease, lung disease, pancreatic disease, intestinal disease, hepatic disease, eye disease, metabolic disease, autoimmune disease, skin disease, disease of the urogenital tract, disease associated with pathological pregnancy, cardiovascular disease, skeletal muscle disease or central nervous system disease. Preferably, the disease associated with or characterized by fibrosis is any of the diseases described in the Detailed description of the invention. 22. The compound according to any of points 1 to 12 or a compound for use according to any of points 19 to 21, wherein the disease is lung fibrosis or renal fibrosis or dermal fibrosis, or a fibroproliferative disease of the lung, the kidney or the skin, in particular psoriasis. 23. Compound according to any of points 1 to 12 or a compound for use according to point 19, for use in treating or preventing a PDGFR and / or c-Kit-mediated disease or disorder. Preferably wherein the PDGFR and / or c-Kit mediated disease or disorder is a cancer or a tumour. Preferably wherein the c-Kit mediated disease or disorder is gastrointestinal cancer. 24. Compound according to any of points 1 to 12 for use in treating or preventing a cancer or a tumour. Preferably, the cancer or tumour is associated with PDGFR and / or c-Kit. Preferably wherein the cancer is gastrointestinal cancer. 25. Compound according to any of points 1 to 12 for use in treating or preventing an inflammatory disease or disorder. Preferably wherein the inflammatory disease or disorder is chronic inflammation. Preferably wherein the disease is psoriasis. 26. Compound for use according to any of points 17 to 25, in combination with an additional therapeutic agent or active agent or medicament. Preferably, the additional therapeutic agent or active agent or medicament is an antifibrotic agent, such as nintedanib and / or pirfenidone. Preferably, the additional therapeutic agent or active agent or medicament is a PDGFR inhibitor, such as avapritinib, dasatinib and / or imatinib. The invention also relates to a combination of a compound of the invention, preferably as defined in any of points 1 to 12, and an additional therapeutic agent for use in a condition or disease as defined in any of points 18 to 25. 27. Pharmaceutical composition comprising a compound according to any of points 1 to 12 or a compound for use according to any of points 17 to 25, and a pharmaceutically acceptable carrier or excipient. 28. Pharmaceutical composition comprising a compound according to any of points 1 to 12 or a compound for use according to any of points 17 to 25, and an additional therapeutic agent or active agent or medicament, and a pharmaceutically acceptable carrier or excipient. Preferably, the additional therapeutic agent or active agent or medicament is an antifibrotic agent, such as nintedanib and / or pirfenidone. Preferably, the additional therapeutic agent or active agent or medicament is a PDGFR inhibitor, such as avapritinib, dasatinib and / or imatinib. 29. A method for treating or preventing a cell proliferative disease, said method comprising administering a compound according to any of points 1 to 12 or a pharmaceutical composition according to point 27 or point 28 to a subject. Preferably, the cell proliferative disease is selected from fibrosis comprising progressive fibrosis, a fibroproliferative disease, in particular a fibroproliferative disease involving progressive fibrosis, tumours, cancers and neoplasms. 30. The method according to claim 29, wherein said method is a method for treating or preventing a disease or disorder or condition associated with or characterized by fibrosis in a subject in need thereof, said method comprising administering a compound according to any of points 1 to 12 or a pharmaceutical composition according to point 27 or point 28 to the subject. 31. The method according to claim 29, wherein said method is a method for treating or preventing a cancer or tumour in a subject in need thereof, said method comprising administering a compound according to any of points 1 to 12 or a pharmaceutical composition according to point 27 or point 28 to the subject. 32. A method for treating or preventing an inflammatory disease or disorder in a subject in need thereof, said method comprising administering a compound according to any of points 1 to 12 or a pharmaceutical composition according to point 27 or point 28 to the subject. In points 29 to 32, preferably the compound is administered in an effective amount, preferably in a therapeutically effective amount. In points 29 to 32, preferably the compound or pharmaceutical composition is administered intraperitoneally, orally, or topically. BRIEF DESCRIPTION OF THE FIGURES Figure 1. IC50 values of VCC380920 on selected protein kinases. IC50 values were determined by in vitro biochemical assays on fibrosis and cancer specific kinases. Figure 2. Characterisation of primary lung fibroblasts. Lung fibroblast culture isolated from fibrotic tissue of mice was characterised by immunofluorescence staining of α-SMA (green) and PDGFR-B (red). Nuclei (blue) were counterstained by DAPI. Images were captured using 100x objective. Figure 3. Screening of VCC compounds on lung fibroblasts. The in vitro antiproliferative effects of compounds were determined by score system based on MTT assay results of PDGF-B treated cells. Representative MTT assay results of compounds with best score values can be seen in this figure. Violins indicate the distribution of data in the given group (n=5).*p<0.05 ˝PDGF-B˝ vs. ˝control˝ at 0 μM VCC…;#p<0.05 vs. ˝PDGF-B + 0 μM VCC…˝ (two-way ANOVA). Figure 4. Effect of compound VCC380920 on lung fibroblasts. Cells were stimulated by treatment with recombinant PDGF-B in the presence or absence of VCC380920, then proliferation was measured by MTT assay (b, violins) in parallel with LDH assay (c, dots) to detect the possible cytotoxic effect of treatments. Violins indicate the distribution of data in the given group (n=5). *p<0.05 ˝PDGF-B˝ vs. ˝control˝ at 0 μM VCC380920; #p<0.05 vs. ˝PDGF-B + 0 μM VCC380920˝ (two-way ANOVA). Figure 5. Effect of compound VCC380920 on lung fibroblasts. mRNA expression of Mki67 (d) and Pcna (e) cell proliferation marker was determined by real-time RT-PCR in comparison with Rn18s as internal control. Violins indicate the distribution of data in the given group (n=5).*p<0.05 ˝PDGF-B˝ vs. ˝control˝ at 0 μM VCC380920;#p<0.05 vs. ˝PDGF-B + 0 μM VCC380920˝ (two-way ANOVA). Figure 6. Screening of VCC compounds on renal fibroblasts. The in vitro antiproliferative effects of compounds were determined by score system based on MTT assay results of PDGF-B treated cells. Representative MTT assay results of compounds with best score values can be seen in this figure. Violins indicate the distribution of data in the given group (n=5).*p<0.05 ˝PDGF-B˝ vs. ˝control˝ at 0 μM VCC…;#p<0.05 vs. ˝PDGF-B + 0 μM VCC…˝ (two-way ANOVA). Figure 7. Effect of compound VCC380920 on renal fibroblasts. NRK-49F cells were stimulated by treatment with recombinant PDGF-B in the presence or absence of VCC380920. Proliferation was measured by MTT assay (a, violins) in parallel with LDH assay (b, dots) to detect the possible cytotoxic effect of treatments. (n=5).*p<0.05 ˝PDGF-B˝ vs. ˝control˝ at 0 μM VCC380920;#p<0.05 vs. ˝PDGF-B + 0 μM VCC380920˝ (two-way ANOVA). Figure 8. Effect of compound VCC380920 on renal fibroblasts. NRK-49F cells were stimulated by treatment with recombinant TGF-β (c) in the presence or absence of VCC380920. Collagen deposition was measured by SiriusRed assay (c). Violins indicate the distribution of data in the given group (n=5).*p<0.05 ˝TGF-β˝ vs. ˝control˝ at 0 μM VCC380920;#p<0.05 vs. ˝TGF-β + 0 μM VCC380920˝ (two-way ANOVA). Figure 9. Effect of compound VCC380920 on body weight of healthy mice and in the experimental model of bleomycin induced lung fibrosis (BILF). To detect the effect of the chronic administration of VCC380920, the body weight of the mice was monitored daily. Dots and error bars indicate the distribution of daily data in the given group (n=6-8). Control mice were treated with vehicle only. Figure 10. Effect of compound VCC380920 on lung weight in the experimental model of bleomycin induced lung fibrosis (BILF). Lung weight of mice was determined on 21st day. Violins indicate the distribution of data in the given group (n=6-8). Control mice were treated with vehicle only.*p<0.05 control vs. BILF;#p<0.05 BILF vs. BILF + VCC380920 (Mann-Whitney U-test). Figure 11. Effect of compound VCC380920 on survival in the experimental model of bleomycin induced lung fibrosis (BILF). To detect the effect of the chronic administration of VCC380920 the survival of mice was monitored daily. Dots indicate the survival rate in the given group (n=6-8). Control mice were treated with vehicle only. Figure 12. Effect of compound VCC380920 on fibrotic protein levels in the experimental model of bleomycin induced lung fibrosis (BILF). Protein amount of collagen type I (COL1A1) and fibronectin (FN1) was determined by Western blot analysis in comparison with GAPDH as internal control. Violins indicate the distribution of data in the given group (n=6-8). Control mice were treated with vehicle only.*p<0.05 control vs. BILF;#p<0.05 BILF vs. BILF + VCC380920 (Mann-Whitney U-test). Figure 13. Effect of VCC380920 on fibrotic mRNA expression in the experimental model of bleomycin induced lung fibrosis (BILF). The mRNA expression of Col1a1, Fn1 extracellular matrix components markers was determined by real-time RT-PCR in comparison with Rn18s as internal control. Violins indicate the distribution of data in the given group (n=6-8). Control mice were treated with vehicle only.*p<0.05 control vs. BILF;#p<0.05 BILF vs. BILF + VCC380920 (Mann-Whitney U-test). Figure 14. Effect of compound VCC380920 on UUO induced renal fibrosis. Main fibrosis markers were determined in the kidney tissue of control and VCC380920 treated mice following UUO. The extension of red areas in picro-SiriusRed (and the blue areas in Masson’s trichrome stained sections represent the deposition of collagen- rich extracellular matrix in renal tissue. Violins indicate the distribution of data in the given group (n=6-7). Control mice were treated with vehicle only. *p<0.05 control vs. UUO; #p<0.05 UUO vs. UUO + C380920 (Mann-Whitney U-test). Figure 15. Effect of compound VCC380920 on fibrotic mRNA expression in the experimental model of UUO induced renal fibrosis. The mRNA expression of Acta2 fibroblast marker, Fn1, Col1a1, Col3a1 extracellular matrix components and Kim1, Ngal kidney injury markers was determined by real-time RT-PCR in comparison with Rn18s as internal control. Violins indicate the distribution of data in the given group (n=6-7). Control mice were treated with vehicle only.*p<0.05 control vs. UUO;#p<0.05 UUO vs. UUO + VCC380920 (Mann-Whitney U-test). Figure 16. Effect of VCC380920 on fibrotic protein levels in the experimental model of UUO induced renal fibrosis. Protein amount of α-SMA and fibronectin was determined by Western blot analysis in comparison with GAPDH as internal control. Violins indicate the distribution of data in the given group (n=6-7). Control mice were treated with vehicle only.*p<0.05 control vs. UUO;#p<0.05 UUO vs. UUO + VCC380920 (Mann-Whitney U-test). Figure 17. Effect of compound VCC380920 on skin lesions in the experimental model of IMQ induced psoriasis. Effect of VCC380920 was investigated after intraperitoneal (ip) or topical (top) administration of the compound. Lesions, indicated by skin redness was graphically analyzed, determining the intensity peaks of red pixels. Violins indicate the distribution of data in the given group (n=6-7). Control mice were treated with vehicle only.*p<0.05 control vs. IMQ;#p<0.05 IMQ vs. IMQ + ip / top VCC380920 (Mann-Whitney U-test). Figure 18. Effect of compound VCC380920 on skin thickness in the experimental model of IMQ induced psoriasis. Effect of VCC380920 was investigated after intraperitoneal (ip) or topical (top) administration of the compound. Skin thickening was examined in the back (IMQ treated area) of mice and also in the abdomen (untreated area) as control. Violins indicate the distribution of data in the given group (n=6-7). Control mice were treated with vehicle only. White * symbols indicate intensified re-hairiness in pigmentated skin regions.*p<0.05 control vs. IMQ;#p<0.05 IMQ vs. IMQ + ip / top VCC380920 (Mann-Whitney U-test). Figure 19. Effect of compound VCC380920 on spleen weight in the experimental model of IMQ induced psoriasis. Effect of VCC380920 on spleen enlargement was investigated after intraperitoneal (ip) or topical (top) administration of the compound. Violins indicate the distribution of data in the given group (n=6-7). Control mice were treated with vehicle only. White * symbols indicate intensified re-hairiness in pigmentated skin regions.*p<0.05 control vs. IMQ;#p<0.05 IMQ vs. IMQ + ip / top VCC380920 (Mann-Whitney U-test). DETAILED DESCRIPTION OF THE INVENTION Abbreviations PDGF platelet-derived growth factor PDGFR platelet-derived growth factor receptor PDGFR-A platelet-derived growth factor receptor alpha (also abbreviated as PDGFR-alpha or PDGFR-α) PDGFR-B platelet-derived growth factor receptor beta (also abbreviated as PDGFR-beta or PDGFR-β) Definitions As used herein, the term “halo” or “halogen” means fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine. As used herein, the term “alkyl” alone or in combinations means a straight or branched-chain saturated hydrocarbon group containing from 1 to 6, preferably 1 to 5 carbon atom(s) (i.e. “C1-6” or “C1-5” alkyl groups), such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl and pentyl. In an embodiment, this phrase can relate to alkyl groups containing from 1 to 4, or 1 to 3, or 1 to 2 carbon atom(s) (i.e. “C1-4” or “C1-3” or “C1-2” alkyl groups), where the methyl or ethyl is a preferred embodiment. As used herein, the term “alkenyl” alone or in combinations means a straight or branched-chain hydrocarbon group containing from 2 to 6 carbon atom(s) or 2 to 5 carbon atom(s), one or more carbon-carbon double bonds, and no triple bonds (i.e. “C2-6” or “C2-5” alkenyl groups). In an embodiment, this phrase can relate to alkenyl groups containing from 2 to 4, or 2 to 3 (i.e. “C2-4” or “C2-3” alkenyl groups). Examples are ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, butadienyl, pentenyl, pentadienyl, hexenyl, and the like. As used herein, the term “alkynyl” alone or in combinations means a straight or branched-chain hydrocarbon group containing from 2 to 6 carbon atom(s) or 2 to 5 carbon atom(s), one or more carbon-carbon triple bonds, and optionally one or more double bonds (i.e. “C2-6” or “C2-5” alkynyl groups). In an embodiment, this phrase can relate to alkynyl groups containing from 2 to 4, or 2 to 3 (i.e. “C2-4” or “C2-3” alkynyl groups). Examples are ethynyl, 1- propynyl, 2-propynyl, 1-butynyl, 2-butynyl, pentynyl, hexynyl, and the like. As used herein, the term "alkoxy" means an alkyl-O- group in which the alkyl group is as previously described. Non-limiting examples of suitable alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy and n-butoxy, preferably methoxy. The bond to the parent moiety is through the oxygen (if to a carbon atom, ether oxygen). As used herein, the term “haloalkyl” means an alkyl group as defined above where one or more of the hydrogen atoms are substituted with halogen atoms. The term “amino” means an optionally substituted -NH2group. In an embodiment, amino is substituted with one or two alkyl, preferably methyl or ethyl. The term “hydroxyl” means an -OH group. The term "cycloalkyl" as used herein is a non-aromatic carbon-based alkyl ring composed of at least three carbon atoms. The cycloalkyl group is preferably saturated. In special cases, this phrase can relate to carbocyclyl groups containing from 3 to 8, or 3 to 6 (i.e. “C3-8” or “C3-6” cycloalkyl groups). Non-limiting examples are cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, Preferred carbocyclic groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. As used herein the term "heterocyclyl" or “heterocyclic ring” alone or in combinations means a saturated or partially unsaturated non-aromatic ring system having 4 to 9 ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3-10 membered heterocyclyl"). In special cases, this phrase can relate to heterocyclyl groups having 3-8 ring forming atoms ("3-8 membered heterocyclyl") or 4-6 ring forming atoms ("4-6 membered heterocyclyl"). In heterocyclyl groups that contain one or more nitrogen atoms, the point of attachment can be a carbon or nitrogen atom, as valency permits. Non-limiting examples are azirdinyl, oxiranyl, thiorenyl, azetidinyl, oxetanyl, thietanyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, pyrrolidinyl, dihydropyrrolyl, pyrrolyl-2,5-dione, dioxolanyl, oxasulfuranyl, disulfuranyl, oxazolidin-2-one, triazolinyl, oxadiazolinyl, thiadiazolinyl, piperidinyl, tetrahydropyranyl, dihydropyridinyl, thianyl, piperazinyl, morpholinyl, dithianyl, dioxanyl, triazinanyl, azepanyl, oxepanyl, thiepanyl, azocanyl, oxecanyl, thiocanyl, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and the like. Preferably the ring(s) of the heterocyclic moiety is / are 5 to 6 membered ring(s). The term “heteroaryl” or “heteroaromatic ring” means a group derived from a monocyclic or bicyclic aromatic ring system (condensed double ring systems) with 1 to 3 ring forming heteroatom(s) selected from the group of N, O and S and 3 to 9 ring forming carbon atoms ("5-10 membered heteroaryl"). In special cases, this phrase can relate to heteroaryl groups having 5-8 ring forming atoms ("5-8 membered heteroaryl") or 5-6 ring forming atoms ("5-6 membered heteroaryl"). "Heteroaryl" includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclic or heterocyclic groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system. "Heteroaryl" also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused (aryl / heteroaryl) ring system. Non-limiting examples are pyrrolyl, furanyl, thiophenyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl tetrazinyl, azepinyl, oxepinyl, thiepinyl, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl. In heteroaryl groups that contain one or more heteroatoms, the point of attachment can be a carbon or heteroatom, as valency permits. Exemplary heteroaryl groups are imidazole, pyrrole, pyrazole, oxazole, isoxazole, thiazole, isothiazole, furan, thiophene, pyridine, thiazole, pyridazine, pyrimidine, pyrazine, thiazine. The term “aminosulfonyl group” denotes an H2N-S(O)2- moiety. "Cell proliferative disorders" refer to disorders wherein unwanted cell proliferation of one or more subset of cells in a multicellular organism occurs resulting in harm (e.g., discomfort or decreased life expectancy) to the multicellular organism. Cell proliferative disorders can occur in different types of animals and in humans. Cell proliferative disorders include cancers, proliferative disorders, and fibrotic disorders, in particular fibroproliferative disorders. “Progressive fibrosis” in short is characterized by a process when ECM remodeling is shifted towards accumulation of ECM producing cells, like fibroblasts or myofibroblasts, and / or towards non-physiological, e.g. excessive deposition of ECM components leading to impairment or destruction of tissue architecture and / or to gradual decline of organ function, which is a kind of non-physiological ECM production / deposition. Progressive fibrosis may lead to the formation of permanent scar tissue, may cause tissue or organ failure and might lead to death. In “progressive fibrosis” ECM components and ECM producing cells, in particular fibrillar ECM components like type I and III collagen and fibronectin, as well as the cells producing them continue to accumulate even beyond the homeostatic / regenerative phase of ECM remodeling. The process in which an excessive amount of ECM replaces normal parenchyma or the ECM which is typical to the tissue affected by progressive fibrosis may also be considered “progressive fibrosis”. This process is characterized by overproliferation of ECM producing cells, e.g. fibroblasts, and excessive, unregulated or dysregulated deposition of ECM components and / or abnormal repair processes in different tissues upon injury. Collagen accumulation can be measured by Sirius Red assay. “Fibroproliferative disorder” is a disorder which is characterized by inter alia the presence of progressive fibrosis, in particular wherein at least partially ECM remodeling is shifted towards accumulation of ECM producing cells, like fibroblasts, and / or towards excessive deposition of ECM components leading to impairment or destruction of tissue architecture and / or to gradual decline of organ function. A “neoplasm” is a type of abnormal and excessive growth of tissue. (The process that occurs to form or produce a neoplasm is called “neoplasia”.) The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumour. Tumour cells often metastasize to various organs. “Inflammation” as defined herein as a process which is a biological response of an animal body, preferably a vertebrate or a mammalian body, in particular the immune system thereof, to a stimulus or stimuli recognized as harmful by the body in particular the immune system, typically involving injured or impaired cell(s), wherein inflammatory cells (macrophages, dendritic cells, granulocytes, lymphocytes, fibroblasts, endothelial and epithelial cells), and mediators, in particular cytokines, chemoattractants, complement, growth and angiogenic factors are produced in a level higher than in the same body without inflammation. “Deposition of ECM” is understood herein as a process leading to an increase in the amount of ECM components in a space among / between (i.e. outside) the cells of a tissue. A “physiological” or “regulated” or “normally regulated” deposition of ECM occurs when deposition of ECM components serves to restore tissue architecture and / or tissue function itself. The physiological deposition of ECM components is regulated or maintained under control to avoid non-physiological ECM deposition or production. Preferably, in in vivo setting the regulatory processes of the surrounding healthy tissue in question counter-acting deposition are capable of reversing, or at least arresting such deposition. A “non-physiological” or “dysregulated” deposition of ECM occurs when deposition of ECM components leads to impairment, i.e. destruction of tissue architecture and / or tissue function itself. The unregulated or abnormally regulated deposition of ECM components is a particular hallmark of non-physiological ECM deposition or production. Preferably, deposition of ECM components is considered as “non-physiological” (in case of fibrosis excessive) when there are no signs that regulatory processes of the surrounding healthy tissue in question counteracting deposition are capable of reversing, or at least arresting such deposition. A “subject” as used herein is an individual of an animal species, preferably a vertebrate, more preferably a mammalian or avian species, in particular a mammalian species, highly preferably the individual is a primate, a hominid or a human. The term “mammal’ is known in the art and relates to an animal species of which the female feeds her young on milk from her own body, and exemplary mammals include humans, primates, livestock animals (including bovines, porcines, goats, sheep, horses etc.), companion animals (e.g., canines, felines, etc.) and rodents (e.g., mice and rats) all or any of which is contemplated herein. A “patient” is a subject who is or intended to be under medical or veterinarian observation, supervision, diagnosis or treatment. A “treatment” refers to any process, action, application, therapy, or the like, wherein the subject or patient is under aid, in particular medical or veterinarian aid with the object of improving the subject’s or patient’s condition, either directly or indirectly. Improving the subject’s condition may include improving an aesthetic condition (cosmetic treatment) and / or may include, in particular, restoring or maintaining normal function of an organ or tissue, preferably at least partly restoring or maintaining health (medical or veterinarian treatment). Treatment typically refers to the administration of an effective amount of a compound or composition described herein. Treatment may relate to or include medical or veterinarian treatment and cosmetic treatment, in particular medical or veterinarian treatment. “Preventing” or “prevention” of the development of a disease or condition refers to at least the reduction of likelihood of the risk of or susceptibility to acquiring a disease or disorder, or preferably causing at least one of the clinical symptoms of the disease or disorder not to develop in a patient that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease. The terms “effective amount” or “therapeutically effective amount” are intended to qualify the amount of a therapeutic agent required to relieve to some extent one or more of the symptoms of a condition, disease or disorder, including but not limited to: 1) reducing the number of fibroblasts or myofibroblasts ; 2) reducing the synthesis of the ECM components, and / or increasing the degradation of the ECM component; 3) reducing the size of the fibrous tissue; 4) improving to at least some extent the physiological function of the tissue due to any of 1) to 3); 5) reducing the size of a tumour tissue; 6) inhibits the formation of tumour cell metastases; 7) inhibits immune cell proliferation or activation, including production of cytokines, growth factors or antibodies. The compounds of the invention have pharmaceutical (medicinal), nutritional, and cosmetic uses as well. The IC50values for inhibition of PDGFR-β receptor of the compounds of the general formula (I) are usually smaller than 1000 nM, the favourable compounds exhibit IC50 values smaller than 100 nM. For demonstration herebelow we give IC50values of three of our compounds of the general formula (I): 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide IC5090 nM N-{2-chloro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide IC5090 nM 1-Methyl-N-(2-methyl-5-{[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide IC5070 nM Schemes 1, 2, 3 and 4 demonstrate the processes for the preparation of the compounds of the general formula (I). According to the first process the acid of the general formula (II) is reacted with the amine of the general formula (III) – where in the formula X1, X2, Y, Z, R1and R2have the same meanings as defined above – in the presence of an activating agent. The activating agent may be the 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide (EDC). The reaction is carried out in an inert solvent (e.g. pyridine, dichloromethane, tetrahydrofuran, dioxane, N,N-dimethylformamide) at ambient temperature or at the reflux temperature of the reaction mixture. (Scheme 1, Method A). Method A Sc eme RAr: H, Me R1: H, Me, Cl, F, MeO R2: H, Me, F X1: NH X2: CO Y: (CH2)n n= 0, NH In another process the amine of the general formula (IV) – where in the formula RAr, R1and R2have the same meanings as defined above – is reacted with the compound of the general formula (V) – where Z have the same meanings as defined above and Q is chloro atom or hydroxyl group. The reaction is carried out in the case of acid chlorides of the general formula (V) – where Q represents chloro atom – in an inert solvent (e.g. dichoromethane, chloroform, ethyl acetate) in the presence of a base (e.g. triethylamine) or in pyridine. The reaction is carried out in the case of acids of the general formula (V) – where Q represents hydroxyl group – in the presence of an activating agent (e.g. 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide (EDC)), in an inert solvent (e.g. pyridine, dichloromethane, tetrahydrofuran, dioxane, N,N-dimethyl-formamide) at ambient temperature or at the reflux temperature of the reaction mixture. (Scheme 2, Method B). Method B Ia Scheme 2 RAr: Me R1: H, F, Me R2: H, Me Q: OH, ClIn another procedure the acid of the general formula (VI) – where in the formula RAr, R1, R2have the same meanings as defined above – is reacted with the amine of the general formula (VII) – where in the formula Y and Z have the same meanings as defined above – in the presence of an activating agent (e.g. 1-ethyl-3-(3’- dimethylaminopropyl)carbodiimide (EDC)), in an inert solvent (e.g. pyridine, dichloromethane, tetrahydrofuran, dioxane, N,N-dimethyl-formamide) at ambient temperature or at the reflux temperature of the reaction mixture. The functional groups of the compound of the general formula (I) may be transformed into other functional groups (e.g. substituent of the Ar group into another substituent). (Scheme 3, Method C). Method C Ib Scheme 3 RAr: Me R1: Me R2: H Y: (CH2)n, n= 0, 1, 2 In another process the hydrazide of the general formula (VIII) – where in the formula RAr, R1, R2have the same meanings as defined above – is reacted with compound of the general formula (V) – where in the formula Z have the same meanings as defined above and Q is chloro atom or hydroxyl group. The reaction is carried out in the case of acid chlorides of the general formula (V) – where Q represents chloro atom – in an inert solvent (e.g. dichoromethane, chloroform, ethyl acetate) in the presence of a base (e.g. triethylamine) or in pyridine. The reaction is carried out in the case of acids of the general formula (V) – where Q represents hydroxyl group – in the presence of an activating agent (e.g. 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide (EDC)), in an inert solvent (e.g. pyridine, dichloromethane, tetrahydrofuran, dioxane, N,N-dimethyl-formamide) at ambient temperature or at the reflux temperature of the reaction mixture. (Scheme 4, Method D). Method D Scheme 4 RAr: Me R1: Me R Q2:: O H H, ClThe compounds of the general formula (III) – where X1, X2Y, Z, R1and R2have the same meanings as defined above – can be prepared by the sequence of reactions shown in Scheme 5. Compounds of the general formula (IX) – where R1and R2have the same meanings as defined above are commercially available – can be acylated by acid chlorides (V) – where Q stands for chloro atom – in pyridine or by acids (V) –where Q stands for hydroxyl group –by the use of EDC in pyridine at room temperature. Ureas of the general formula (XI) – where X1and Y stand for NH, X2stands for CO – are prepared from compounds (IX) and isocyanates of the general formula (X) – where Z have the same meanings as defined above - in dichloromethane. Reduction of the nitro group in compound of the general formula (XI) – where X1, X2, Y, Z, R1and R2have the same meanings as defined above – can be performed using several methods (e.g. by iron in water and hydrochloric acid, or by sodium dithionite in water, or by tin(II)chloride dihydrate in ethyl acetate). (Scheme 5)

[0004] III Y: (CH2)n, n= 0, NHThe intermediate of the general formula (IV) – where in the formula RAr, R1and R2have the same meanings as defined above – can be synthesized in two steps as shown in Scheme 6. Compound of the general formula (XII) – where R1and R2have the same meanings as defined above – is acylated by the acid of the general formula (II) – where RArhave the same meanings as defined above – in the presence of an activating agent (e.g. EDC) in pyridine at ambient temperature. Reduction of the nitro group in compounds of the general formula (XIII) can be realized by tin(II)chloride dihydrate in ethyl acetate or by hydrogen transfer reaction using 10% Pd / C catalyst and ammonium formate in methanol – dichloromethane solvent mixture at ambient temperature or at reflux temperature. (Scheme , IV The two steps process for the synthesis of the acid intermediate of the general formula (VI) – where in the formula RAr, R1, R2have the same meanings as defined above – is shown in Scheme 7. Amide formation reaction between the acid of the general formula (II) and the amine of the general formula (XIV) – where R1and R2have the same meanings as defined above – is performed in the presence of EDC in a suitable solvent (e.g. in pyridine). The ester group of the compound of the general formula (XV) – where RAr, R1and R2have the same meanings as defined above – is hydrolyzed by sodium hydroxide in methanol – water solvent mixture at temperatures between 25 °C and 90 °C. (Scheme 7) The hydrazide intermediate of the general formula (VIII) – where in the formula RAr, R1and R2have the same meanings as defined above – is prepared from the ester of the general formula (XV) – where in the formula RAr, R1and R2have the same meanings as defined above- by hydrazine hydrate in ethanol at reflux temperature of the reaction mixture. (Scheme 8) VIII Scheme 8The compounds of the general formula (I), as well as their pharmaceutically acceptable derivatives can be used for the treatment of diseases where human PDGF receptors play a role, and for the treatment of which PDGF receptor inhibitors are needed. In the course of the therapy the compounds according to the invention are used in the form of pharmaceutical compositions. The pharmaceutical compositions contain the compounds of the general formula (I) or their pharmaceutically acceptable derivatives, together with pharmaceutically acceptable carriers and excipients. In the present project the inventors aimed to develop novel antiproliferative / antifibrotic compounds targeting PDGFR-α and -β, the receptor of PDGF-A, -B, -C, and -D, a core factor responsible for the activation of the myofibroblasts the main effector cells of organ fibrosis. The effect of the compounds, derived from computer-aided drug design, were first tested using in vitro biochemical assay investigating the kinase activity of PDGFR-α and -β (Figure 1, Table 7, Table 8) (see Example 64). The inhibitory effect of the compounds on the PDGF-B induced proliferation of myofibroblasts originated from lung and kidney were investigated in vitro (Figure 2, Figures 4-5, Figures 7-8) (see Example 65). To identify the best compounds, the present inventors developed an integrated mathematical scoring system that takes into account the drug-induced inhibition of myofibroblasts proliferation and in vitro toxicity, as well (Figure 3, Figure 6). One of the most promising compounds was further investigated in vivo (see Example 66). First, the antifibrotic effect of VCC380920 was investigated in a mouse model of bleomycin induced lung fibrosis. Indeed, VCC380920 treatment improved the survival of mice with lung fibrosis. Moreover, VCC380920 significantly inhibited the protein level of collagen type I and fibronectin in the lung tissue of bleomycin treated mice (Figures 9-12). In addition to its positive effects, VCC380920 showed no adverse or toxic effect - based on their behaviour or body weight change - nor in the control or bleomycin treated animals (Figures 9). The antifibrotic effect of VCC380920 has been proven in additional in vivo experiments, as well (see Example 66). Indeed, VCC380920 reduced the SiriusRed and also the Masson’s trichrome positive renal area and inhibited the protein amount of α-SMA and fibronectin and the mRNA expression of Ngal, Fn1, Col1a1 and Col3a1 in the kidney of mice underwent UUO (Figure 14-16). VCC380920 reduced skin lesions and thickening, and decreased spleen enlargement, characteristic for systematic inflammation in imiquimod induced psoriasis model (Figures 17-19). The compounds according to the invention (in particular compound VCC380920) are novel antifibrotic compounds targeting PDGFR-α and -β. The compounds according to the invention (in particular compound VCC380920) are predicted to have optimal physico-chemical properties to reach good oral bioavailability. The compounds according to the invention (in particular compound VCC380920) have in vitro PDGFR-α and -β inhibitory effect in biochemical assay (see Example 64). The compounds according to the invention (in particular compound VCC380920) dramatically reduce the PDGF-B induced proliferation of lung and kidney myofibroblasts (to the level of control cells). In vivo VCC380920 treatment improved the survival of mice with bleomycin induced lung fibrosis. VCC380920 has antifibrotic effect in vivo as it is inhibited the protein level of collagen type I and fibronectin in the lung of bleomycin treated mice. (See Example 66.) Antifibrotic effect of compound VCC380920 has been proven in additional in vivo experiments; it reduced the SiriusRed and Masson’s trichrome positive renal area of mice underwent UUO. VCC380920 inhibited the amount of αSMA and fibronectin (FN) and the mRNA expression of Ngal, Fn1, Col1a1 and Col3a1 in the kidney of mice underwent UUO (see Example 66). Compound VCC380920 reduced skin lesions and skin thickening and decreased the spleen enlargement characteristic for systemic inflammation in imiquimod induced psoriasis model (see Example 66). In summary, the present inventors successfully developed a new lead molecule that significantly inhibits the PDGF-B induced activation of fibroblasts in vitro and the bleomycin or UUO induced lung and kidney fibrosis in vivo. The lead molecule also inhibits skin lesions and thickening and decreased spleen enlargement in imiquimod induced mice model of psoriasis. Cell proliferation and migration in various disorders Fibroblasts are characterized by their intense proliferation, migration, and increased production of ECM during activation, which provided a particular example for inter-relation of these three processes. Moreover, fibrosis and chronic inflammation go hand in hand. Cytokines, growth factors, etc. produced during the inflammatory response activate fibroblasts i.e. increase their proliferation, migration and the production of the ECM. Different PDGF isoforms, including PDGF-BB and also other factors such as TGFβ or EGF play a significant role in the activation of fibroblasts, such as their proliferation, migration, and the production of the ECM. These growth factors and the fibroblasts also play a role in the development of different tumours and metastasis of them. The pathophysiological roles of cancer-associated fibroblasts (CAFs) in the heterogeneous tumour microenvironment have attracted increasing interest. CAFs play crucial roles in tumour progression and the response to chemotherapy. Several cytokines and chemokines are involved in the activation of CAFs, and some of these form a feedback loop between cancer cells and CAFs. In addition, the physical force between tumour cells and CAFs promotes cooperative invasion or co-migration of both types of cells [Yoshida, 2020]. Diseases Examples of renal diseases associated with or characterized by fibrosis include diabetic nephropathy, hypertensive nephropathy, glomerular diseases including proliferative glomerulonephritis (mesangial proliferative, membranoproliferative, focal proliferative, diffuse proliferative, crescenic), glomerulonepritis associated with lupus nephritis, bacterial endocarditis, vasculitis, chronic hepatitis, infections (e.g. hantavirus), non-inflammatory glomerular diseases (minimal change nephritis, focal glomerular sclerosis, membranous nephropathy, fibrillary glomerular disease), glomerular disease associated with Hodgkin's disease, antibiotic, drug (aspirin, ibuprofen, acetaminophen, tacrolimus, cyclosporine, contrast agents, chemotherapy, or heroin toxicity), HIV infection; hereditary nephritis (Alport syndrome), vascular diseases including renal artery stenosis, sickle cell disease, hemolytic uremic syndrome, atypic hemolytic uremic syndrome; tubulointerstitial diseases including pyelonephritis, analgesic nephritis, allergic interstitial nephritis, granulomatous interstitial nephritis, autoimmune interstitial nephritis, non-inflammatory diseases like reflux nephropathy, obstructive uropathies (anatomical abnormalities e.g. posterior urethra valve, or stones, or malignancy or prostatism) myeloma kidney, diseases in the transplant like chronic rejection, drug toxicity, recurrent disease, transplant glomerulopathy. Examples of lung diseases associated with or characterized by fibrosis include bronchitis, asthma, idiopathic pulmonary fibrosis, usual interstitial pneumonia, gas or ionizing radiation induced lung fibrosis, nitrofurantoin, tobacco smoke-induced lung fibrosis, emphysema, chronic obstructive pulmonary disease, tuberculosis, rheumatoid arthritis induced lung fibrosis, systemic lupus erythematosus induced lung fibrosis, sarcoidosis, Wegener’s granulomatosis, nonspecific interstitial pneumonitis, Hamman-Rich Syndrome, diffuse fibrosing alveolitis, inhalation of environmental and occupational pollutants (fume silica, asbestos, nitrogen, and sulfur gases, fumes, vapors of detergents, cleaners, hydrochloric acid, herbicide, hairspray), drug-induced pulmonary fibrosis (bleomycin, amiodarone, busulfan, methotrexate, apomorhpine, nitrofuratoin, phenytoin) and radiotherapy, Torque teno virus, pneumoconiosis, etc. Examples of pancreatic diseases associated with or characterized by fibrosis include alcoholic chronic pancreatitis, hereditary pancreatitis, autoimmune pancreatitis, obstructive chronic pancreatitis, tropical calcific pancreatitis, fibrocalculous pancreatic diabetes, chronic non-alcoholic pancreatitis, chronic atrophic pancreatitis, Groove pancreatitis. Examples of intestinal diseases associated with or characterized by fibrosis include ulcerative colitis, Crohn's disease, Collagenous colitis, microscopic colitis, diversion colitis, necrotizing enterocolitis, chemical colitis, ischemic enterocolitis, Helicobacter pylori-induced gastritis, chronic gastritis, oesophageal subepithelial fibrosis, Barrett's esophagus, gastroesophageal reflux disease, oral submucous fibrosis, oesophageal atresia. Examples of hepatic diseases associated with or characterized by fibrosis include nonalcoholic steatohepatitis, autoimmune hepatitis, viral hepatitis (hepatitis A, hepatitis B, hepatitis C, hepatitis D), alcoholic hepatitis, toxic and drug-induced hepatitis, non-alcoholic fatty liver disease, liver cirrhosis, fascioliasis, schistosomiasis, liver fluke induced fibrosis, primary sclerosing cholangitis, Budd-Chiari syndrome, biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, serotonergic agonist drugs: weight loss drugs (fenfluramine, chlorphentermine, aminorex), anti-migraine drugs (ergotamine, methysergide), antiparkinsonian drugs (pergolide, cabergoline), recreational drugs (MDA, MDMA, DOI, mCPP). Examples of eye diseases associated with or characterized by fibrosis include diabetic retinopathy, fibrosis of the cornea, neovascular glaucoma, retinopathy of prematurity, age-related macular degeneration, premacular fibrosis, herpetic keratitis, pingueculae, capsular fibrosis, fibrosis of the posterior lens capsule, fibrovascular scarring of the retina, gliosis in the retina, complication of surgery to treat retinal detachment, viral infection of the cornea, retinal injury due to hypoxia or inflammatory changes, trachoma, congenital fibrosis syndrome, levator muscle fibrosis, congenital fibrosis of the ocular muscles, congenital fibrosis of the extraocular muscles, proliferative retinopathy, macularfibrosis, talc retinopathy, subretinal fibrosis, syndrome, sub-conjunctival fibrosis. Examples of metabolic diseases associated with or characterized by fibrosis include type 2 diabetic complications atherosclerosis, arteriosclerosis, diabetic foot, metabolic syndrome, hyperlipidaemia, haemochromatosis, Wilson disease, alfa-1-antitrypsin deficiency, galactosaemia, glycogen storage disease I-IV, VI, IX, XI, urate nephropathy, hyperlipoproteinaemia I.-V., familiar hypercholesterineaemia, mucopolysaccharidosis type I-VII., mucolipidosis III-IV, Fabry disease (angiokeratoma corporis diffusum), pseudoxanthoma elasticum. Examples of autoimmune diseases associated with or characterized by fibrosis include Type 1 diabetic complications, rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease), systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, CREST-syndrome, polymyositis, dermatomyositis, primary biliary cirrhosis, primary sclerotising cholangitis, vasculitis: giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa, Wegener's granulomatosis, thromboangitis obliternas, sarcoidosis, Goodpasture syndrome, mixed connective tissue disease, Churg-Strauss-syndrome. Examples of skin diseases associated with or characterized by fibrosis include keloid and scars associated with trauma, operations, piercing, acne, chicken pox, infections, cutting, haematoma, spontaneusly, granuloma, tick- granuloma, solaris atrophia, burn injury, pseudocicatrix stellata (Batman purpura), ulcus associated with anthrax, gonorrhoea, ulcus molle, tularaemia, decubitus, diabetic foot ulcer, diabetes skin, necrobiosis lipoidica diabeticorum, varicosits cruris, thrombophlebitis, infections: fascitis necrotisans, ecthyma simplex, ecthyma gangrenosum, phlegmone abscessus, furunculus, carbunculus, anthrax, granuloma venereum, tularaemia, tbc (lupus vulgaris, scrofuloderma), lepra, Lyme-borreliosis, Tibola (Tick-Bone-Lymphadenopathy), syphilis, actinomycosis, every mycotic infection secundary infection scar tissue, HSV, VZV, erythema multiforme, dermatitis herpetiformis, scars associated with prurigo (infection, allergy, irritation, paraneopl.gravidarum, diabetes) acne: ecthyma simplex, acne inversa, acne vulg, rosacea, rinophima. Examples of diseases of the urogenital tract associated with or characterized by fibrosis include menstrual disorders: endometriosis, PCOS, adrenal diseases (CAH, Cushing, virilizing sy, acne, seborrhea), Asherman's syndrome (- iatrogen), endometritis, IUD), infections: perinephritis, paranephritis, pyelonephritis, pyelitis and pyelonephritis chronica, pyelonephros, chronic uretritis (gonorrhoea, E. coli, Proteus, HSV), retroperitoneal fibroma, cystitis chronica, cystitis after radiotherapy, ulcus simplex (Hunner), Trichomonases, tuberculosis (renis, vesicae urinariae, epididymitis, prostata), actinomycosisulcus, pelveopeitonitis, vulvovaginitis cand., herpes genitalis, genitalis HPV, chronic cervicitis, endometritis, salpingitis, abscessus, tuboovarii, syphilis, gonorrhoea, chlamidya, trichomonas, HPV, ulcus molle, HIV, tuberculosis. Examples of fibroproliferative diseases associated with pathological pregnancy associated with or characterized by fibrosis include pruritus gravidarum, bullosus pemphigoid, impetigo herpetiformis, caesarian section (or other operation) rupture corporis uteri, ulcer puerperalis, endometritis, myometritis puerperalis, adnexitis puerperalis, pelveoperitonitis puerperalis, parametritis puerperalis, thrombophlebitis, mastitis puerperalis; in men: penis, prostata, orchis: cavernitisi, induratio penis plastica, prostatitis, abscessus, orchitis, chronic epididymitis; obstructive uropathies associated with anatomical abnormalities posterior urethra valve, subvesical obstruction, vesicouretheral reflux nenhrolithiasis, inflammation, arthritis urica, hyperparathyreosis, hypercalcaemia, oxalosis, cystinuria, xantinuria. Examples of cardiovascular diseases associated with or characterized by fibrosis include dilated and hypertrophic cardiomyopathies, myocardial infarction, valvular diseases, arrhythmia, cardiac hypertrophy, hypertension induced cardiac fibrosis, Marfan syndrome, left ventricular fibrosis, myocardial necrosis and apoptosis induced cardiac fibrosis, vascular fibrosis, arteriosclerosis, atherosclerosis, venosclerosis. Examples of skeletal muscle system diseases associated with or characterized by fibrosis include myelofibrosis, muscle fibrosis. Examples of central nervous system diseases associated with or characterized by fibrosis include stroke and tissue injury induced glial fibrosis, Parkinson’s diseases, amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, dermatitis seborhoica, (Cushing-syndrome), operations, side effects of surgery (sec. infection, sponge, splintering). EXAMPLES Chemical Examples Conditions for HPLC analysis of the compounds: Instrument: Waters Acquity SQD LC-MS Waters 996 PDA Detector Waters Aliance 2795 Separation module Method E: Waters XBridge C18 column (5cm x 4.6mm, 3.5um), gradient 0-95% B over 7.00 min (0.00 min 5 % B, 0.50 min 5 % B, 5.50 min 95 % B, 6.00 min 95 % B, 6.50 min 5 % B, 7.00 min 5 % B), Solvent A: MilliQ water, 0,1 % HCOOH, Solvent B: AcCN, flow = 2.0 ml / min. Separation module was Waters Alliance 2795. Sample injection: 2-5^l from 5 mM solution. UV spectra were recorded using a Waters 996 DAD UV detector. Mass spectra were obtained using Waters SQD MS detector (Ionization: ES+ / ES-, Source block temp: 150 C, Desolvation temp: 250 °C, Desolvation Gas:650 L / h, Cone Gas: 80 L / h, Capillary: 3000 V, Cone: 30 V, Extractor: 6 V, Rf Lens: 0.1 V, Scan: 80 to 1000 m / z in 1 sec., Inter-scan delay: 0.1 s). The NMR spectra were recorded on a Bruker Avance 300 spectrometer operating at 7.04 Tesla magnetic field. Chemical shifts (δ) are given in ppm (parts per million unit). Example 1 Preparation of the compounds of the general formula (I) 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ia), Method A (Scheme 1) a) 4-Methyl-N-(4-methyl-3-nitrophenyl)benzamide (XI-1) To the solution made of 4-methyl-3-nitroaniline (3.04 g, 0.02 mol) and pyridine (20 ml) p-toluoyl chloride (3.71 g, 0.024 mol) is added dropwise at 0 °C. The mixture is stirred at 0 °C for 1 hour, then at room temperature for 3 hours. The solvent is evaporated in vacuum, the residue is treated with water (25 ml) and 5% NaHCO3 (15 ml), the yellow crystalline product is filtered off. Yield: 5.33 g (98 %). LCMS: [M+H]+271.1, Rt: 4.11 b) N-(3-amino-4-methylphenyl)-4-methylbenzamide (III-1) A mixture of 4-methyl-N-(4-methyl-3-nitrophenyl)benzamide (XI-1) (1.621 g, 0.006 mol), sodium dithionite (2.612 g 0.015 mol) and water (20 ml) is stirred at 90 °C for 8 hours. After 4 hours another portion of sodium dithionite (2.612 g, 0.015 mol) is added to the reaction mixture. After standing at room temperature overnight water (25 ml) is added and pH is adjusted to 8 by 10 % NaHCO3 solution. Beige solid is filtered and washed with water. Yield: 0.517 g (36 %). LCMS: [M+H]+241.1 1H-NMR (300 MHz, DMSO-d6): 2.02 (s, 3H), 2.37 (s, 3H), 4.80 (s, 2H, NH2), 6.81 (d, 1H, J=8.2 Hz), 6.85 (d, 1H, J=8.2 Hz), 7.12 (s, 1H), 7.30 (d, 2H, J=7.7 Hz), 7.83 (d, 2H, J=7.7 Hz), 9.79 (s, 1H, CONH). c) 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ia), A mixture of 1-methyl-1H-imidazole-5-carboxylic acid (0.267 g, 0.00212 mol), N-(3-amino-4- methylphenyl)-4-methylbenzamide (III-1) (0.510 g, 0.00212 mol), 1-ethyl-3-(3’- dimethylaminopropyl)carbodiimide hydrochloride (EDC) (0.406 g, 0.00212 mol) and pyridine (25 ml) is stirred at ambient temperature for 4 days. The solvent is evaporated in vacuum, the residue is treated with water (50 ml), beige crystalline product is filtered, washed with water. the crude product is purified by column chromatography on silicagel using EtOAc / MeOH 90 / 10 solvent mixture as eluent.0.509 g (68.9 %) white crystals are obtained. LCMS: [M+H]+349.3. 1H-NMR (300 MHz, DMSO-d6): 2.20 (s, 3H), 2.38 (s, 3H), 3.85 (s, 3H, NCH3), 7.22 (d, 1H, J=8.3 Hz), 7.33 (d, 2H, J=8.0 Hz), 7.58 (dd, 1H, J=8.3 Hz, J=1.9 Hz), 7.80 (s, 1H, imidazole), 7.82 (s, 2H, imidazole + phenyl- C(6)H), 7.88 (d, 2H, J=8.0 Hz), 9.68 (s, 1H, imidazole-CONH), 10.14 (s, 1H, CONH). Example 2 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-4-carboxamide (Ia), Method A (Scheme 1) VCC437598 A mixture of 1-methyl-1H-imidazole-4-carboxylic acid (0.126 g, 0.001 mol), N-(3-amino-4-methylphenyl)- 4-methylbenzamide (III-1) (0.240 g, 0.001 mol), 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide hydrochloride (0.192 g, 0.001 mol) and pyridine (10 ml) is stirred at ambient temperature for 24 hours. The solvent is evaporated in vacuum, water (15 ml) is added and the crystalline product is filtered, washed with water (10 ml), acetonitrile (5 ml), and diisopropyl ether (10 ml).0.205 g (58.9 %) white crystals are obtained. LCMS: [M+H]+349.3. 1H-NMR (300 MHz, DMSO-d6): 2.24 (s, 3H), 2.39 (s, 3H), 3.74 (s, 3H, NCH3), 7.19 (d, 1H, J=8.2 Hz), 7.32 (d, 2H, J=7.9 Hz), 7.54 (dd, 1H, J=8.2 Hz, J=1.7 Hz), 7.76 (s, 1H, imidazole), 7.80 (s, 1H, imidazole), 7.88 (d, 2H, J=7.9 Hz), 8.25 (s, 1H), 9.25 (s, 1H, imidazole-CONH), 10.13 (s, 1H, CONH). Example 3 N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-4-carboxamide (Ia), Method A (Scheme 1) A mixture of 1H-imidazole-4-carboxylic acid (0.112 g, 0.001 mol), N-(3-amino-4-methylphenyl)-4- methylbenzamide (III-1) (0.240 g, 0.001 mol), 1-ethyl-3-(3’-dimethylaminopropyl)carbodiimide hydrochloride (0.192 g, 0.001 mol) and pyridine (10 ml) is stirred at ambient temperature for 4 days. The solvent is evaporated in vacuum, water (15 ml) is added and the crystalline product is filtered, washed with water (10 ml), dried and chromatographed on silicagel using EtOAc / MeOH 100 / 10 solvent mixture as eluent. 0.123 g (36.8 %) off-white crystals are isolated. LCMS: [M+H]+335.2 1H-NMR (300 MHz, DMSO-d6): 2.25 (s, 3H), 2.39 (s, 3H), 7.20 (d, 1H, J=8.2 Hz), 7.32 (d, 2H, J=7.9 Hz), 7.54 (d, 1H, J=8.2 Hz), 7.79 (s, 1H, imidazole), 7.82 (s, 1H, imidazole), 7.88 (d, 2H, J=7.9 Hz), 8.24 (s, 1H), 9.32 (s, 1H, imidazole-CONH), 10.14 (s, 1H, CONH), 12.70 (br s, 1H, NH). Example 4 1-Methyl-N-{3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ia), Method B (Scheme 2)

[0005] a) 1-Methyl-N-(3-nitrophenyl)-1H-imidazole-5-carboxamide (XIII-1), A mixture of 1-methyl-1H-imidazole-5-carboxylic acid (2.522 g, 0.02 mol), 3-nitroaniline (3.039 g, 0.022 mol), ethyl-3-(3’-dimethylaminopropyl)carbodiimide hydrochloride (4.217 g, 0.022 mol) and pyridine (100 ml) is stirred at room temperature for 3 days. The solvent is evaporated in vacuum, water (75 ml) is added to the residue, white crystals are formed, filtered and washed with water (2x20 ml). Yield: 4.668 g (94.7 %). Recrystallization from methanol affords analytical sample. LCMS: [M+H]+247.0 b) N-(3-aminophenyl)-1-methyl-1H-imidazole-5-carboxamide (IV-1), A mixture of iron powder (6.137 g, 0.110 mol), water (150 ml) and 36 % HCl (5 ml) is heated at 80 °C under vigorous stirring for 5 minutes, then 1-methyl-N-(3-nitrophenyl)-1H-imidazole-5-carboxamide (XIII-1) (3.865 g, 0.0157 mol) in tetrahydrofuran (30 ml) is added to the suspension. Stirring is continued at 100 °C for 1 hour. After cooling to room temperature the suspension is filtered, the filtrate is evaporated in vacuum. The residue is treated with water (20 ml), beige crystals formed, filtered and washed with water (10 ml). Yield: 2.76 g (81.1%). LCMS: [M+H]+217.1 c) 1-Methyl-N-{3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ia), N-(3-aminophenyl)-1-methyl-1H-imidazole-5-carboxamide (IV-1) (0.648 g ,0.003 mol) is dissolved in pyridine (10 ml) and cooled in ice bath. p-Toluoyl chloride (0.557 g, 0.0036 mol) is added to the solution and stirred at 0 °C for 1 hour and at room temperature for 2 hours. The solvent is evaporated in vacuum, water (15 ml) is added to the residue, crystalline product is filtered, washed with water (10ml). The crude product is purified by column chromatography on silicagel using EtOAc / MeOH 100 / 10 solvent mixture as eluent. Yield: 0.51 g (crystallized with diisopropyl ether), 50.8%. LCMS: [M+H]+335.2 1H-NMR (300 MHz, DMSO-d6): 2.39 (s, 3H), 3.87 (s, 3H, N-CH3), 7.29 (dd, 1H, J=7.8 Hz, J=7.8 Hz), 7.33 (d, 2H, J=7.9 Hz), 7.41 (d, 1H, J=7.8 Hz), 7.47 (d, 1H, J=7.8 Hz), 7.83 (s, 2H, imidazole), 7.89 (d, 2H, J=7.9 Hz), 8.27 (s, 1H), 10.05 (s, 1H, imidazole-CONH), 10.13 (s, 1H, CONH). Example 5 4-Chloro-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ia), Method B (Scheme 2) a) 1-Methyl-N-(2-methyl-5-nitrophenyl)-1H-imidazole-5-carboxamide (XIII-2), A mixture of 1-methyl-1H-imidazole-5-carboxylic acid (1.26 g, 0.01 mol), 2-methyl-5-nitroaniline (1.67 g, 0.011 mol), ethyl-3-(3’-dimethylaminopropyl)carbodiimide hydrochloride (2.11 g, 0.011 mol) and pyridine (50 ml) is stirred at room temperature for 40 hours. The solvent is evaporated in vacuum, water (50 ml) is added to the residue, yellow crystals are formed, filtered and washed with water (20 ml). Yield: 2.519 g (96.8%). Recrystallization from methanol affords analytical sample. LCMS: [M+H]+261.0 1H-NMR (300 MHz, DMSO-d6): 2.38 (s, 3H, C-CH3), 3,86 (s, 3H, N-CH3), 7.56 (d, 1H, J=8.4 Hz), 7.84 (s, 1H, imidazole), 7.86 (s, 1H, imidazole), 8.02 (dd, 1H, J=8.4 Hz, J=2.0 Hz), 8.30 (d, 1H, J=2.0 Hz), 9.89 (s, 1H, CONH). b) N-(5-amino-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (IV-2), To the mixture of 1-methyl-N-(2-methyl-5-nitrophenyl)-1H-imidazole-5-carboxamide (XIII-2) (1.426 g, 0.00548 mol) and dichloromethane (50 ml) 10 % Pd / C catalyst (0.25 g) is added. Argon is introduced for 10 minutes, followed by ammonium formate (2.765 g, 0.04384 mol) and methanol (50 ml). The reaction mixture is stirred at reflux temperature for 2 hours. After filtration the solvent is evaporated in vacuum, the residue is treated with water (15 ml), white crystals filtered, washed with water (10ml). Yield: 0.991 g (78.5 %). LCMS: [M+H]+231.1 1H-NMR (300 MHz, DMSO-d6): 2.04 (s, 3H, C-CH3), 3.83 (s, 3H, N-CH3), 4.89 (s, 2H, NH2), 6.38 (dd, 1H, J=8.1 Hz, J=2.1 Hz), 6.57 (d, 1H, J=2.1 Hz), 6.87 (d, 1H, J=8.1 Hz), 7.73 (s, 1H, imidazole), 7.78 (s, 1H, imidazole), 9.40 (s, 1H, CONH). c) 4-Chloro-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}-phenyl)pyridine-2-carboxamide (Ia), RAr= Me, R1= Me, R2= H, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-Cl-2-pyridyl A mixture of N-(5-amino-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (IV-2) (0.207 g, 0.0009 mol), 4-chloropicolinic acid (0.142 g, 0.0009 mol), ethyl-3-(3’-dimethylaminopropyl)carbodiimide hydrochloride (0.173 g, 0.0009 mol) and pyridine (10 ml) is stirred at room temperature for 4 days. The solvent is evaporated in vacuum, water (25 ml) is added to the residue, yellow crystals are formed, filtered and washed with water (2x15 ml). The crude product (0.270 g) is purified by column chromatography on silicagel using CHCl3 / MeOH 100 / 5 solvent mixture as eluent. Yield: 0.22 g (66.1 %) white crystals. LCMS: [M+H]+370.2 1H-NMR (300 MHz, DMSO-d6): 2.20 (s, 3H), 3.85 (s, 3H, N-CH3), 7.25 (d, 1H, J=8.2 Hz), 7.64 (dd, 1H, J=8.2 Hz, J=1.9 Hz), 7.80 (s, 1H, imidazole), 7.82 (s, 1H, imidazole), 7.83 (dd, 1H, J=5.2 Hz, J=1.7 Hz), 7.96 (d, 1H, J=1.9 Hz), 8.14 (d, 1H, J=1.7 Hz), 8.72 (d, 1H, J=5.2 Hz), 9.72 (s, 1H, imidazole-CONH), 10.65 (s, 1H, CONH). The compounds (Ia) of Example 6, Example 8, Example 9, Example 11, Example 13 have been prepared according to Method A (Scheme 1) as described in Example 1 and their data are demonstrated in Table 1 (see below Example 24). Example 7 N-[2-chloro-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1-methyl-1H-imidazole-5- carboxamide (Ia), RAr= Me, R1= Cl, R2= H, X1= NH, X2= CO, Y = NH, Z = 4-CF3-phenyl VCC461798 Method A (Scheme 1) a) 1-(4-Chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]urea (XI-3), R1= Cl, R2= H, X1= NH, X2= CO, Y = NH, Z = 4-CF3-phenyl To the solution made of 4-chloro-3-nitroaniline (0.863 g, 0.005 mol) and dichloromethane (40 ml) 3’- (trifluoromethyl)phenyl isocyanate (0.936 g, 0.005 mol) in dichloromethane (10 ml) is added dropwise. The solution is stirred at ambient temperature for 5 hours, the solvent is evaporated in vacuum. The residue is treated with diisopropyl ether (10 ml) and filtered. Yield: 0.647 g (36 %) beige crystalline powder. LCMS: [M+H]+360.0 b) 1-(3-Amino-4-chlorophenyl)-3-[3-(trifluoromethyl)phenyl]urea (III-3), R1= Cl, R2= H, X1= NH, X2= CO, Y = NH, Z = 4-CF3-phenyl A mixture of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]urea (XI-3) (1.079 g, 0.003 mol), sodium dithionite (2.611 g, 0.015 mol) and water (15 ml) is stirred at 90 °C for 5 hours. After cooling to room temperature pH is adjusted to 8 by 10% NaHCO3 solution, the product is filtered, washed with water (2 x 10 ml). Yield: 0.322 g (32.5%) off-white crystalline powder. LCMS: [M+H]+330.0 c) N-[2-chloro-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1-methyl-1H-imidazole-5- carboxamide (Ia), RAr= Me, R1= Cl, R2= H, X1= NH, X2= CO, Y = NH, Z = 4-CF3-phenyl A mixture of 1-methyl-1H-imidazole-5-carboxylic acid (0.126 g, 0.001 mol), 1-(3-amino-4-chlorophenyl)- 3-[3-(trifluoromethyl)phenyl]urea (III-3) (0.329 g, 0.001 mol), ethyl-3-(3’-dimethylaminopropyl)carbodiimide hydrochloride (0.192 g, 0.001 mol) and pyridine (10 ml) is stirred at ambient temperature for 4 days. After evaporation of the solvent in vacuum the residue is treated with water (15 ml). Beige solid is formed, filtered, washed with water (2 x 10 ml). The crude product is purified by column chromatography on silicagel using CHCl3 / MeOH 100 / 5 solvent mixture as eluent. Yield: 0.070 g (16 %) white crystals (ether). LCMS: [M+H]+438.2 1H-NMR (300 MHz, DMSO-d6): 3.85 (s, 3H, N-Me) 7.32 (d, 1H, J=7.9 Hz), 7.36 (dd, 1H, J=8.7 Hz, J=2.4 Hz), 7.44 (d, 1H, J=8.7 Hz), 7.51 (t, 1H, J=7.9 Hz), 7.58 (d, 1H, J=7.9 Hz), 7.80 (d, 1H, J=2.4 Hz), 7.83 (s, 1H, imidazole), 7.84 (s, 1H, imidazole), 8.01 (s, 1H), 9.05 (s, 1H, NHCONH), 9.08 (s, 1H, NHCONH), 9.77 (s, 1H, imidazole- CONH). The compounds (Ia) of Example 10 and Example 12 have been prepared according to Method A (Scheme 1) as described in Example 7 and their data are demonstrated in Table 1 (see below Example 24). The compounds (Ia) of Example 14 and Example 15 have been prepared according to Method B (Scheme 2) as described in Example 4 and their data are demonstrated in Table 1 (see below Example 24). Example 16 N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-4-[(3,4,5- trimethoxyphenyl)amino]pyridine-2-carboxamide (Ia), RAr= Me, R1= Me, R2= H, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-[(3,4,5-trimethoxyphenyl)amino]-2-pyridyl Method A (Scheme 1) a) 4-[(3,4,5-trimethoxyphenyl)amino]pyridine-2-carboxylic acid (V) A mixture of 4-chloropicolinic acid (0.315 g, 0.002 mol), 3,4,5-trimethoxyaniline (0.366 g, 0.002 mol), pyridine hydrochloride (0.231 g, 0.002 mol) and 1-methyl-2-pyrrolidine (6 ml) is stirred at 135 °C for 3 hours. After cooling and dilution with water (20 ml) white crystals are separated, filtered, washed with water. Yield: 0.415 g (68%). LCMS: [M+H]+ 305.2, Rt: 0.38, 1.94. 1H-NMR (300 MHz, DMSO-d6): 3.68 (s, 3H,), 3.78 (s, 6H,), 6.62 (s, 2H), 7.03 (dd, 1H, J=6.6 Hz, J=2.4 Hz), 7.42 (d, 1H, J=2.4 Hz), 8.03 (d, 1H, J=6.6 Hz), 10.03 (s, 1H, NH). b) N-(4-methyl-3-nitrophenyl)-4-[(3,4,5-trimethoxyphenyl)amino]pyridine-2-carboxamide (XI-10), R1= Me, R2= H, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-[(3,4,5-trimethoxyphenyl)amino]-2-pyridyl A mixture of 4-[(3,4,5-trimethoxyphenyl)amino]pyridine-2-carboxylic acid (V) (1.217 g, 0.004 mol), 4- methyl-3-nitroaniline (0.609 g, 0.004 mol), EDC.HCl (0.767 g, 0.004 mol) and pyridine (20 ml) is stirred for 4 days. After evaporation in vacuum, the residue is treated with water (25 ml), yellow crystals are filtered and washed with water (3 x 10 ml). Yield: 0.952 g (54.3%, after recrystallization from methanol). LCMS: [M+H]+439.1 1H-NMR (300 MHz, DMSO-d6): 2.49 (s, 3H), 3.67 (s, 3H), 3.78 (s, 6H), 6.54 (s, 2H), 7.11 (dd, 1H, J=5.6 Hz, J=2.3 Hz), 7.47 (d, 1H, J=8.4 Hz), 7.68 (d, 1H, J=2.3 Hz), 8.09 (dd, 1H, J=8.4 Hz, J=2.0 Hz), 8.31 (d, 1H, J=5.6 Hz), 8.72 (d, 1H, J=2.0 Hz), 9.08 (s, 1H, NH), 10.93 (s, 1H, CONH). c) N-(3-amino-4-methylphenyl)-4-[(3,4,5-trimethoxyphenyl)amino]pyridine-2-carboxamide (III-10) R1= Me, R2= H, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-[(3,4,5-trimethoxyphenyl)amino]-2-pyridyl N-(4-methyl-3-nitrophenyl)-4-[(3,4,5-trimethoxyphenyl)amino]pyridine-2-carboxamide (XI-10), (0.845 g, 0.00192 mol) is reduced by tin(II)chloride dihydrate (2.6 g, 0.01152 mol) in ethyl acetate (30 ml) at reflux temperature for 2 hours. After cooling water (20 ml) is added, pH is adjusted to 9 by 10% NaOH solution, filtered through Celite. The organic phase is separated, dried over anhydrous sodium sulfate, evaporated, crystallized with ether. Yield: 0.518 g (66%) beige crystalline powder. LCMS: [M+H]+409.1 1H-NMR (300 MHz, DMSO-d6): 2.02 (s, 3H), 3.66 (s, 3H), 3.78 (s, 6H), 4.85 (br s, 2H, NH2), 6.53 (s, 2H), 6.84 (d, 1H, J=9.4 Hz), 6.87 (d, 1H, J=9.4 Hz), 7.07 (dd, 1H, J=5.7 Hz, J=2.4 Hz), 7.20 (s, 1H), 7.66 (d, 1H, J=2.4 Hz), 8.26 (d, 1H, J=5.7 Hz), 9.05 (s, 1H, NH), 10.06 (s, 1H, CONH). d) N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-4-[(3,4,5- trimethoxyphenyl)amino]pyridine-2-carboxamide (Ia) RAr= Me, R1= Me, R2= H, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-[(3,4,5-trimethoxyphenyl)amino]-2-pyridyl A mixture of 1-methyl-1H-imidazole-5-carboxylic acid (0.126 g, 0.001 mol), N-(3-amino-4-methylphenyl)- 4-[(3,4,5-trimethoxyphenyl)amino]pyridine-2-carboxamide (III-10) (0.408 g, 0.001 mol), EDC.HCl (0.192 g, 0.001 mol) and pyridine (15 ml) is stirred at ambient temperature for 4 days. After evaporation of the solvent in vacuum water (10 ml) is added, pale yellow precipitate is filtered, washed with water (2 x 10 ml). Yield: 0.218 g (42.3% off-white crystals after recrystallization from methanol). LCMS: [M+H]+517.1 1H-NMR (300 MHz, DMSO-d6): 2.19 (s, 3H, C-CH3), 3.66 (s, 3H, OCH3), 3.78 (s, 6H, 2xOCH3), 3.85 (s, 3H, NCH3), 6.53 (s, 2H), 7.09 (dd, 1H, J=5.7 Hz, J=2.4 Hz), 7.23 (d, 1H, J=8.4 Hz), 7.60 (dd, 1H, J=8.4 Hz, J=2.0 Hz), 7.67 (d, 1H, J=2.4 Hz), 7.80 (s, 1H, imidazole), 7.82 (s, 1H, imidazole), 7.97 (d, 1H, J=2.0 Hz), 8.29 (d, 1H, J=5.7 Hz), 9.05 (s, 1H, NH), 9.71 (s, 1H, imidazole-CONH), 10.48 (s, 1H, CONH). Example 18 N-{4-fluoro-2-methoxy-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ia), RAr= Me, R1= MeO, R2= F, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-Me-phenyl Method A (Scheme 1) HZ) a) 2-Fluoro-4-methoxy-5-nitroaniline (IX), R1= MeO, R2= F To a solution of 2-fluoro-4-methoxyaniline (1.411 g, 0.01 mol) in conc. sulfuric acid (7 ml) at 0 °C potassium nitrate (1.011 g, 0.01 mol) is added and stirred for 2 hours. The mixture is poured into ice-cold solution of NaOH (10 g) in water (50 ml) under vigorous stirring (pH = 1-2), then pH is adjusted to 8 by addition of 10% NaHCO3 solution. The precipitate is filtered, washed by water (2 x 10 ml). Yield: 1.547 g (83%) light brown crystalline powder. LCMS: [M+H]+187.0 1H-NMR (300 MHz, DMSO-d6): 3.81 (s, 3H, O-CH3), 5.24 (s, 2H, NH2), 7.18 (d, 1H, JH-F=12.9 Hz), 7.37 (d, 1H, JH-F=9.1 Hz). b) N-(2-fluoro-4-methoxy-5-nitrophenyl)-4-methylbenzamide (XI-11), R1= MeO, R2= F, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-Me-phenyl To the solution of 2-fluoro-4-methoxy-5-nitroaniline (IX) (0.745 g, 0.004 mol) in pyridine (10 ml) p-toluoyl chloride (0.742 g, 0.0048 mol) is added at 0 °C. The mixture is stirred at 0 °C for 1 hour, then at room temperature for 3 hours. The solvent is evaporated in vacuum, the residue is treated with water (20 ml), pH is adjusted to 7 by 5% NaHCO3. The precipitate is filtered, washed with water (10 ml) and acetonitrile (2 x 4 ml). Yield: 0.934 g (76%) beige crystalline powder. LCMS: [M+H]+305.0 1H-NMR (300 MHz, DMSO-d6): 2.39 (s, 3H, C-CH3), 3.96 (s, 3H, O-CH3), 7.35 (d, 2H, J=8.0 Hz), 7.46 (d, 1H, JH-F=12.2 Hz), 7.88 (d, 2H, J=8.0 Hz), 8.22 (d, 1H, JH-F=7.9 Hz), 10.15 (s, 1H, CONH). c) N-(5-amino-2-fluoro-4-methoxyphenyl)-4-methylbenzamide (III-11), R1= MeO, R2= F, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-Me-phenyl N-(2-fluoro-4-methoxy-5-nitrophenyl)-4-methylbenzamide (XI-11) (0.883 g, 0.0029 mol), is reduced by tin(II)chloride dihydrate (3.926 g, 0.0174 mol) in ethyl acetate (40 ml) at reflux temperature for 6 hours. After cooling water (20 ml) is added, pH is adjusted to 9 by 10% NaOH solution, filtered through Celite. The organic phase is separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuum. The crude product is purified by column chromatography on silicagel using CHCl3 / MeOH 100 / 5 solvent mixture as eluent. Yield: 0.198 g (25%, beige crystalline powder, crystallized with diisopropyl ether. LCMS: [M+H]+275.1 1H-NMR (300 MHz, DMSO-d6): 2.38 (s, 3H, C-CH3), 3.78 (s, 3H, O-CH3), 4.61 (s, 2H, NH2), 6.75 (d, 1H, JH-F=8.0 Hz), 6.80 (d, 1H, JH-F=12.0 Hz), 7.31 (d, 2H, J=8.0 Hz), 7.85 (d, 2H, J=8.0 Hz), 9.65 (s, 1H, CONH). d) N-{4-fluoro-2-methoxy-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ia), RAr= Me, R1= MeO, R2= F, X1= NH, X2= CO, Y = (CH2)n, n = 0, Z = 4-Me-phenyl A mixture of 1-methyl-1H-imidazole-5-carboxylic acid (0.087 g, 0.69 mmol), N-(5-amino-2-fluoro-4- methoxyphenyl)-4-methylbenzamide (III-11) (0,189 g, 0.69 mmol), EDC.HCl (0.132 g, 0.69 mmol) and pyridine (10 ml) is stirred at room temperature for 20 hours. The solvent is evaporated in vacuum, the residue is treated with water (15 ml), filtered, washed with water (10 ml) and acetonitrile (10 ml). Crude product is purified by column chromatography on silicagel using CHCl3 / MeOH 100 / 5 solvent mixture as eluent. Yield: 0.075 g (25%, beige powder from acetonitrile). LCMS: [M+H]+383.1 1H-NMR (300 MHz, DMSO-d6): 2.39 (s, 3H, C-CH3), 3.83 (s, 3H, O-CH3), 3.85 (s, 3H, N-CH3), 7.12 (d, 1H, JH-F=12.1 Hz), 7.33 (d, 2H, J=8.0 Hz), 7.73 (d, 1H, JH-F=8.4 Hz), 7.80 (s, 1H, imidazole), 7.81 (s, 1H, imidazole), 7.88 (d, 2H, J=8.0 Hz), 9.34 (s, 1H, imidazole-CONH), 9.92 (s, 1H, CONH). The compounds (Ia) of Example 17, Example 19, Example 20, Example 21, Example 22, Example 23 have been prepared according to Method B (Scheme 2) as described in Example 5 and their data are demonstrated in Table 1 (see below Example 24). Example 24 1-[2-(Dimethylamino)pyrimidin-4-yl]-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5- yl)carbonyl]amino}phenyl)-1H-imidazole-4-carboxamide (Ia), RAr= Me, R1= Me, R2= H, X1= NH, X2=CO, Y = (CH2)n, n = 0, Z = 1-[2-(dimethylamino)pyrimidin-4-yl]-1H-imidazol-4-yl Method B (Scheme 2) a) Methyl 1-[2-methylsulfanyl)pyrimidin-4-yl]-1H-imidazole-4-carboxylate Methyl 1H-imidazole-4-carboxylate (1.26 g, 0.01 mol) is mixed with DMF (20 ml) at 0 °C under argon atmosphere. Sodium hydride (60%, 0.48 g, 0.012 mol) is added and stirred for 30 minutes. 4-Chloro-2- (methylsulfanyl)pyrimidine (1.77 g, 0.011 mol) is added to the mixture and stirred at 120 °C for 3 hours. The suspension is cooled, diluted with water (100 ml), filtered, washed with water (2 x 20 ml). Yield: 1.955 g (78.2%) beige powder. LCMS: [M+H]+251.0 1H-NMR (300 MHz, DMSO-d6): 2.60 (s, 3H, S-CH3), 3.82 (s, 3H, O-CH3), 7.75 (d, 1H, J=5.5 Hz), 8.69 (s, 1H, imidazole), 8.76 (s, 1H, imidazole), 8.78 (d, 1H, J=5.5 Hz). b) Methyl 1-[2-methylsulfonyl)pyrimidin-4-yl]-1H-imidazole-4-carboxylate To the stirred solution of methyl 1-[2-methylsulfanyl)pyrimidin-4-yl]-1H-imidazole-4-carboxylate (0.928 g, 3.7 mmol) in dichloromethane (120 ml) at 0 °C 3-chloroperoxybenzoic acid (70%, 2.28 g, 9.25 mmol) is added in portions in 10 minutes. Stirring is continued at room temperature for 5 hours. The colorless solution is extracted with 10% NaHCO3(1 x 100ml, 1 x 40 ml), dried over anhydrous sodium sulfate and evaporated in vacuum. White solid is treated with diisopropyl ether (10 ml) and filtered. Yield: 0.815 g (78.3%). Analytical sample is obtained by recrystallization from methanol. LCMS: [M+H]+283.1 1H-NMR (300 MHz, DMSO-d6): 3.53 (s, 3H, SO2-CH3), 3.84 (s, 3H, O-CH3), 8.36 (d, 1H, J=5.6 Hz), 8.85 (d, 1H, J=0.8 Hz, imidazole), 8.90 (d, 1H, J=0.8 Hz, imidazole), 9.24 (d, 1H, J=5.6 Hz). c) Methyl 1-[2-(dimethylamino)pyrimidin-4-yl]-1H-imidazole-4-carboxylate A mixture of methyl 1-[2-methylsulfonyl)pyrimidin-4-yl]-1H-imidazole-4-carboxylate (1.975 g, 0.007 mol), dimethylamine in THF (2 mol / l, 14 ml, 4 eq) and THF (14 ml) is stirred at ambient temperature for 4 hours. Precipitate is filtered, washed with water (15 ml). Yield: 1.054 g (60.9%) white crystals. LCMS: [M+H]+248.1 1H-NMR (300 MHz, DMSO-d6): 3.18 (s, 6H, N(CH3)2), 3.81 (s, 3H, O-CH3), 7.12 (d, 1H, J=5.4 Hz), 8.49 (d, 1H, J=5.4 Hz), 8.64 (d, 1H, J=0.8 Hz, imidazole), 8.73 (d, 1H, J=0.8 Hz, imidazole). d) 1-[2-(Dimethylamino)pyrimidin-4-yl]-1H-imidazole-4-carboxylic acid (V) Methyl 1-[2-(dimethylamino)pyrimidin-4-yl]-1H-imidazole-4-carboxylate (0.967 g, 3.91 mmol) is hydrolyzed by lithium hydroxide monohydrate (0.328 g, 7.82 mmol) in water / THF 1 / 1 solvent mixture (20 ml) at room temperature with stirring for 3 hours. After evaporation in vacuum the residue is treated with water (10 ml), pH adjusted to 3 by 1M HCl, precipitate is filtered, washed with water (5 ml). Yield: 0.67 g (73%) white crystals. LCMS: [M+H]+234.1 1H-NMR (300 MHz, DMSO-d6): 3.18 (s, 6H, N(CH3)2), 7.10 (d, 1H, J=5.3 Hz), 8.48 (d, 1H, J=5.3 Hz), 8.55 (s, 1H, imidazole), 8.69 (s, 1H, imidazole), 12.65 (br s, 1H, COOH). e) 1-[2-(Dimethylamino)pyrimidin-4-yl]-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5- yl)carbonyl]amino}phenyl)-1H-imidazole-4-carboxamide (Ia), RAr= Me, R1= Me, R2= H, X1= NH, X2=CO, Y = (CH2)n, n = 0, Z = 1-[2-(dimethylamino)pyrimidin-4-yl]-1H-imidazol-4-yl A mixture of N-(5-amino-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (IV-2) (0.161 g, 0.7 mmol), 1-[2-(dimethylamino)pyrimidin-4-yl]-1H-imidazole-4-carboxylic acid (V) (0.163 g, 0.7 mmol), EDC.HCl (0.134 g, 0.7 mmol) and pyridine (20 ml) is stirred at ambient temperature for 20 hours. After evaporation of the solvent in vacuum the residue is treated with water (20 ml), filtered, washed with water (2 x 10 ml) and acetonitrile (2 x 10 ml). Yield: 0.24 g (77%) off-white crystals. LCMS: [M+H]+446.2 1H-NMR (300 MHz, DMSO-d6): 2.18 (s, 3H, C-CH3), 3.20 (s, 6H, N(CH3)2), 3.85 (s, 3H, N-CH3), 7.15 (d, 1H, J=5.4 Hz), 7.21 (d, 1H, J=8.3 Hz), 7.61 (dd, 1H, J=8.3 Hz, J=2.1 Hz), 7.80 (s, 1H, imidazole), 7.82 (s, 1H, imidazole), 7.88 (d, 1H, J=2.1 Hz), 8.50 (d, 1H, J=5.4 Hz), 8.60 (s, 1H, pyrimidyl-imidazole), 8.78 (s, 1H, pyrimidyl- imidazole), 9.72 (s, 1H, CONH), 10.00 (s, 1H, CONH). The compounds (Ia) of Example 25, Example 26, and Example 27 have been prepared according to Method B (Scheme 2) as described in Example 5 and their data are demonstrated in Table 1. Table 1. Diamides and Ureas Example 28 N-{5-[(4-chlorophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = 4-Cl-phenyl Method C (Scheme 3) a) Methyl 4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoate (XV), RAr= Me, R1= Me, R2= H (Scheme 7) A mixture of 1-methyl-1H-imidazole-5-carboxylic acid (1.892 g, 0.015 mol), methyl 3-amino-4- methylbenzoate (XIV) (2.478 g, 0.015 mol), EDC.HCl (2.876 g, 0.015 mol) and pyridine (75 ml) is stirred at room temperature for 48 hours. The solvent is evaporated in vacuum, water (50 ml) is added to the residue, the precipitate is filtered, washed with water (2 x 20 ml). Crude product dried, treated with ether (40 ml), filtered, washed with ether (20 ml). Yield: 3.413 g (83.2%) off-white crystalline powder. LCMS: [M+H]+274.0 1H-NMR (300 MHz, DMSO-d6): 2.31 (s, 3H, C-CH3), 3.85 (s, 6H, O-CH3 + N-CH3), 7.42 (d, 1H, J=7.9 Hz), 7.74 (dd, 1H, J=7.9 Hz, J=1.3 Hz), 7.81 (s, 1H, imidazole), 7.83 (s, 1H, imidazole), 7.95 (d, 1H, J=1.3 Hz), 9.77 (s, 1H, CONH). b) 4-Methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoic acid (VI), RAr= Me, R1= Me, R2= H (Scheme 7) Methyl 4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoate (XV) (3.279 g, 0.012 mol) is hydrolyzed by sodium hydroxide (0.96 g, 0.024 mol) in water / MeOH 1 / 1 solvent mixture (30 ml) at 90 °C with stirring for 1 hour. After evaporation in vacuum the residue is treated with water (25 ml), pH adjusted to 3 by 3M HCl, precipitate is filtered, washed with water (2 x 10 ml). Yield: 2.752 g (88.4%) white crystals. LCMS: [M+H]+260.0 1H-NMR (300 MHz, DMSO-d6): 2.30 (s, 3H, C-CH3), 3.85 (s, 3H, N-CH3), 7.39 (d, 1H, J=7.9 Hz), 7.72 (dd, 1H, J=7.9 Hz, J=1.3 Hz), 7.81 (s, 1H, imidazole), 7.83 (s, 1H, imidazole), 7.91 (d, 1H, J=1.3 Hz), 9.77 (s, 1H, CONH), 12.87 (br s, 1H, COOH). c) N-{5-[(4-chlorophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ib) RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = 4-Cl-phenyl A mixture of 4-Methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoic acid (VI) (0.259 g, 1 mmol), 4-chloroaniline (0.13 g, 1.02 mmol), EDC.HCl (0.196 g, 1.02 mol) and pyridine is stirred at ambient temperature for 20 hours. After evaporation in vacuum, the residue is treated with water (10 ml), crystals are filtered, washed with water (2 x 10 ml). Crude product is stirred with methanol (5 ml), filtered, washed with ether (3 ml). Yield: 0.205 g (55.7%) white crystals. LCMS: [M+H]+369.1 1H-NMR (300 MHz, DMSO-d6): 2.31 (s, 3H, C-CH3), 3.85 (s, 3H, N-CH3), 7.41 (d, 2H, J=8.6 Hz), 7.44 (d, 1H, J=7.7 Hz), 7.80 (d, 1H, J=7.7 Hz), 7.83 (d, 2H, J=8.6 Hz), 7.83 (s, 1H, imidazole), 7.84 (s, 1H, imidazole), 7.93 (s, 1H), 9.83 (s, 1H, imidazole-CONH), 10.31 (s, 1H, CONH). The compounds (Ib) of Example 29, Example 30, Example 31, and Example 32 have been prepared according to Method C (Scheme 3) as described in Example 28 and their data are demonstrated in Table 2 (see below Example 63). Example 33 N-{5-[(4-methoxy-2-morpholin-4-yl-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5- carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = 4-methoxy-2-morpholin-4-yl-5-nitrophenyl Method C (Scheme 3) a) 4-Methoxy-2-morpholin-4-yl-5-nitroaniline (VII-2) 2-Fluoro-4-methoxy-5-nitroaniline (Example 18a) (0.372 g, 0.002 mol) is reacted with morpholine (0.523 g, 0.006 mol) at 120 °C for 2 hours. After cooling to room temperature the mixture is stirred with water (20 ml) for 30 minutes. The precipitate is filtered, washed with water (2 x 10 ml). Yield: 0.41 g (81%) light brown powder. LCMS: [M+H]+254.0 b) N-{5-[(4-methoxy-2-morpholin-4-yl-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole- 5-carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = 4-methoxy-2-morpholin-4-yl-5- nitrophenyl A mixture of 4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoic acid (Example 28b) (VI), (0.207 g, 0.8 mmol), 4-methoxy-2-morpholin-4-yl-5-nitroaniline (VII-2) (0.203 g, 0.8 mmol), EDC.HCl (0.153 g, 0.8 mmol) and pyridine (10 ml) is stirred at ambient temperature for 3 days. After evaporation in vacuum, the residue is treated with water (10 ml), crystals are filtered, washed with water (2 x 10 ml). Crude product is purified by column chromatography on silicagel using CHCl3 / MeOH 100 / 5 solvent mixture as eluent. Yield: 0.104 g (26%, beige crystalline powder, washed with ether). LCMS: [M+H]+495.4 1H-NMR (300 MHz, DMSO-d6): 2.32 (s, 3H, C-CH3), 3.11 (dd, 4H, J=4.4 Hz, J=4.0 Hz), 3.75 (dd, 4H, J=4.6 Hz, J=3.8 Hz), 3.86 (s, 3H, N-CH3), 3.97 (s, 3H, O-CH3), 6.91 (s, 1H), 7.45 (d, 1H, J=8.0 Hz), 7.78 (dd, 1H, J=8.0 Hz, J=1.3 Hz), 7.83 (s, 1H, imidazole), 7.84 (s, 1H, imidazole), 7.98 (d, 1H, J=1.0 Hz), 8.30 (s, 1H), 9.65 (s, 1H, CONH), 9.79 (s, 1H, imidazole-CONH). The compounds (Ib) of Example 34, Example 35, Example 36, Example 37, Example 38 and Example 39 have been prepared according to Method C (Scheme 3) as described in Example 28 and their data are demonstrated in Table 2 (see below Example 63). Example 40 N-(5-{[4-(4-bromo-1H-imidazol-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = 4-(4-bromo-1H-imidazol-1-yl)phenyl Method C (Scheme 3) a) (4-Bromo-1H-imidazol-1-yl)-4-nitrobenzene A mixture of 4-bromo-1H-imidazole (1.47 g, 0.01 mol), 1-fluoro-4-nitrobenzene (1.41 g, 0.01 mol), potassium carbonate (4.15 g, 0.03 mol) and acetonitrile (100 ml) is stirred at reflux temperature for 5 hours. After evaporation in vacuum the residue is treated with water (30 ml), crystals are filtered, washed with water (2 x 10 ml). Yield: 2.388 g (89%) beige crystalline powder. 1H-NMR (300 MHz, DMSO-d6): 7.98 (d, 2H, J=9.1 Hz), 8.17 (d, 1H, J=1.5 Hz), 8.37 (d, 2H, J=9.1 Hz), 8.50 (d, 1H, J=1.5 Hz) b) 4-(4-Bromo-1H-imidazol-1-yl)aniline (VII-3), Y = (CH2)n, n = 0, Z = 4-(4-bromo-1H-imidazol-1-yl)phenyl (4-Bromo-1H-imidazol-1-yl)-4-nitrobenzene (2.388 g, 8.9 mmol), is reduced by tin(II)chloride dihydrate (12.05 g, 53.4 mmol) in ethyl acetate (120 ml) at reflux temperature for 2 hours. After cooling water (10 ml) is added, pH is adjusted to 9 by 10% NaOH solution, filtered through Celite. The organic phase is separated, dried over anhydrous sodium sulfate, filtered and evaporated in vacuum. Yield: 2.039 g (96.2%) yellow oil. LCMS: [M+H]+237.9 c) N-(5-{[4-(4-bromo-1H-imidazol-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = 4-(4-bromo-1H-imidazol-1-yl)phenyl A mixture of 4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoic acid (VI) (0.233 g, 0.9 mmol), 4-(4-Bromo-1H-imidazol-1-yl)aniline (VII-3) (0.214 g, 0.9 mmol), EDC.HCl (0.173 g, 0.9 mmol) and pyridine (10 ml) is stirred at ambient temperature for 2 hours. After evaporation in vacuum, the residue is treated with water (15 ml), crystals are filtered, washed with water (5 ml). Crude product is purified by column chromatography on silicagel using CHCl3 / MeOH 100 / 5 solvent mixture as eluent. Yield: 0.246 g (57%) pale yellow crystalline powder. LCMS: [M+H]+479.0 1H-NMR (300 MHz, DMSO-d6): 2.32 (s, 3H, C-CH3), 3.86 (s, 3H, N-CH3), 7.45 (d, 1H, J=8.3 Hz), 7.64 (d, 2H, J=9.0 Hz), 7.82 (dd, 1H, J=8.3 Hz, J=1.8 Hz), 7.83 (s, 1H, imidazole), 7.84 (s, 1H, imidazole), 7.91 (d, 1H, J=1.5 Hz), 7.93 (d, 2H, J=9.0 Hz), 7.96 (d, 1H, J=1.8 Hz), 8.22 (d, 1H, J=1.5 Hz), 9.84 (s, 1H, imidazole-CONH), 10.37 (s, 1H, CONH). The compounds (Ib) of Example 41 and Example 42 have been prepared according to Method C (Scheme 3) as described in Example 28 and their data are demonstrated in Table 2 (see below Example 63). Example 43 1-Methyl-N-[2-methyl-5-(piperidin-4-ylcarbamoyl)phenyl]-1H-imidazole-5-carboxamide hydrochloride (Ib) RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = piperidin-4-yl A mixture of tert-butyl 4-[(4-methyl-3-{[(1-methyl-1H-imidazol-5- yl)carbonyl]amino}benzoyl)amino]piperidine-1-carboxylate (Example 41) (0.156 g, 0.353 mmol) and HCl / dioxane (3.5 ml) is stirred at ambient temperature for 90 minutes. After evaporation in vacuum, the residue is treated with ether (10 ml), filtered, washed with ether (4 x 5 ml). Yield: 0.100 g (75%) ivory powder. LCMS: [M+H]+342.1 1H-NMR (300 MHz, DMSO-d6): 1.79 (d, 2H, J=11.2 Hz, C-CH2), 1.95 (d, 2H, J=12.0 Hz, C-CH2), 2.29 (s, 3H, C-CH3), 3.00 (br, 2H, N-CH2), 3.30 (d, 2H, J=12.2 Hz, N-CH2), 4.01 (s, 3H, N-CH3), 4.04 (br, 1H, CH- piperidine), 7.38 (d, 1H, J=7.9 Hz), 7.75 (dd, 1H, J=7.9 Hz, J=1.5 Hz), 7.83 (d, 1H, J=1.5 Hz), 8.46 (s, 1H, imidazole), 8.49 (d, 1H, J=7.8 Hz, CONH-piperidine), 8.93 (br s, 2H, NH2+), 9.04 (s, 1H, imidazole), 10.47 (s, 1H, imidazole-CONH). The compounds (Ib) of Example 44, Example 45, and Example 46 have been prepared according to Method C (Scheme 3) as described in Example 28 and their data are demonstrated in Table 2 (see below Example 63). Example 47 N-[5-({3-cyano-1-[3-(dimethylamino)propyl]-4,5-dimethyl-1H-pyrrol-2-yl}carbamoyl)-2-methylphenyl]-1- methyl-1H-imidazole-5-carboxamide (Ib) RAr= Me, R1= Me, R2= H, Y =(CH2)n, n = 0, Z = 3-cyano-1-[3- (dimethylamino)propyl]-4,5-dimethyl-1H-pyrrol-2-yl Method C (Scheme 3) a) 2-amino-1-[3-(dimethylamino)propyl]-4,5-dimethyl-1H-pyrrole-3-carbonitrile (VII-4) Y =(CH2)n, n = 0, Z = 3-cyano-1-[3-(dimethylamino)propyl]-4,5-dimethyl-1H-pyrrol-2-yl Into a 250 ml flask equipped with Marcusson-condenser and thermometer 3-hydroxy-2-butanone (7.049 g, 0.07 mol), 3-dimethylaminopropylamine (7.152 g, 0.07 mol), malononitrile (4.624 g, 0.07 mol), toluene (70 ml) and concentrated hydrochloric acid (0.05 ml) are added under stirring. The reaction mixture is heated to boiling until no more water is distilled-off. The reaction having been completed in 2 hours, treated with charcoal, filtered, evaporated in vacuum. The residue is treated with diisopropyl ether (30 ml), crystals are filtered off, washed with diisopropyl ether (3 x 10 ml). Yield: 11.32 g (73.4%) beige crystalline powder. LCMS: [M+H]+221.0 b) N-[5-({3-cyano-1-[3-(dimethylamino)propyl]-4,5-dimethyl-1H-pyrrol-2-yl}carbamoyl)-2-methylphenyl]- 1-methyl-1H-imidazole-5-carboxamide (Ib) RAr= Me, R1= Me, R2= H, Y =(CH2)n, n = 0, Z = 3-cyano-1-[3- (dimethylamino)propyl]-4,5-dimethyl-1H-pyrrol-2-yl A mixture of 4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoic acid (VI) (0.219 g, 0.844 mmol), 2-amino-1-[3-(dimethylamino)propyl]-4,5-dimethyl-1H-pyrrole-3-carbonitrile (VII-4) (0.186 g, 0.844 mmol), EDC.HCl (0.162 g, 0.844 mmol) and pyridine (10 ml) is stirred at ambient temperature for 48 hours. After evaporation in vacuum water (15 ml) is added, pH adjusted to 9 by the addition of 5% NaHCO3solution then extracted with ethyl acetate (3 x 20 ml), dried over anhydrous Na2SO4and evaporated in vacuum. Crude product is purified by column chromatography on silicagel using CHCl3 / MeOH(NH3) 100 / 5 solvent mixture as eluent. Yield: 0.105 g (27%) yellow crystalline powder. LCMS: [M+H]+462.2 1H-NMR (300 MHz, DMSO-d6): 1.70 (t, 2H, J=6.6 Hz), 2.03 (s, 3H, C-CH3), 2.04 (s, 6H, N(CH3)2), 2.10 (t, 2H, J=6.4 Hz), 2.15 (s, 3H, C-CH3), 2.32 (s, 3H, C-CH3), 3.79 (t, 2H, J=6.8 Hz), 3.85 (s, 3H, N-CH3), 7.47 (d, 1H, J=8.0 Hz), 7.76 (dd, 1H, J=8.0 Hz, J=1.0 Hz), 7.82 (s, 1H, imidazole), 7.84 (s, 1H, imidazole), 7.90 (d, 1H, J=1.0 Hz), 9.85 (s, 1H, imidazole-CONH), 10.50 (s, 1H, CONH). The compounds (Ib) of Example 48 – Example 51 have been prepared according to Method C (Scheme 3) as described in Example 28 and their data are demonstrated in Table 2 (see below Example 63). Example 52 N-[5-({4-[(2E)-3-(dimethylamino)prop-2-enoyl]phenyl}carbamoyl)-2-methylphenyl]-1-methyl-1H- imidazole-5-carboxamide (Ib) RAr= Me, R1= Me, R2= H, Y = (CH2)n, n = 0, Z = 4-[(2E)-3-(dimethylamino)prop- 2-enoyl)phenyl A mixture of N-{5-[(4-acetylphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Example 49) (0.795 g, 2.11 mmol) and N,N-dimethylformamide dimethylacetal (2.514 g, 2.11 mmol) is stirred at 140 °C for 90 minutes. After cooling upon addition of diisopropyl ether (50 ml) crystals are formed, filtered, washed with diisopropyl ether (20 ml), then with methanol (20 ml). Yield: 0.365 g (40%) yellow crystalline powder. LCMS: [M+H]+432.2 1H-NMR (300 MHz, DMSO-d6): 2.31 (s, 3H, C-CH3), 2.92 (br s, 3H) and 3.13 (br s, 3H, N(CH3)2), 3.86 (s, 3H, N-CH3), 5.85 (d, 1H, J=12.3 Hz), 7.44 (d, 1H, J=8.2 Hz), 7.69 (d, 1H, J=12.3 Hz), 7.82 (dd, 1H, J=8.2 Hz, J=1.6 Hz), 7.84 (s, 2H, imidazole), 7.86 (d, 2H, J=9.0 Hz), 7.92 (d, 2H, J=9.0 Hz), 7.96 (d, 1H, J=1.6 Hz), 9.84 (s, 1H, imidazole-CONH), 10.37 (s, 1H, CONH). Example 53 1-methyl-N-(2-methyl-5-{[4-(1H-pyrazol-3-yl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ib) RAr= Me, R1= Me, Y = (CH2)n, n = 0, Z = 4-(1H-pyrazol-3-yl)phenyl A mixture N-[5-({4-[(2E)-3-(dimethylamino)prop-2-enoyl]phenyl}carbamoyl)-2-methylphenyl]-1-methyl- 1H-imidazole-5-carboxamide (Example 52) (0.227 g, 0.526 mmol), hydrazine hydrate (0.038 ml) and ethanol (15 ml) is stirred at reflux temperature for 5 hours. Solvent is evaporated in vacuum, the residue is stirred with water (10 ml) for 1 hour, crystals are filtered, washed with water (10 ml), then with acetonitrile (6 ml) and with ether (6 ml). Yield: 0.145 g (69%) beige powder. LCMS: [M+H]+401.1 1H-NMR (300 MHz, DMSO-d6): 2.31 (s, 3H, C-CH3), 3.86 (s, 3H, N-CH3), 6.66 (s, 2H), 7.44 (d, 1H, J=8.1 Hz), 7.80 (m, 8H), 7.95 (s, 1H), 9.84 (s, 1H, imidazole-CONH), 10.26 (s, 1H, CONH), 12.81 (s) and 13.19 (s) (1H, pyrazole-NH, tautomeria). The compounds (Ib) of Example 54 – Example 61 have been prepared according to Method C (Scheme 3) as described in Example 28 and their data are demonstrated in Table 2 (see below Example 63). Example 62 1-Methyl-N-(2-methyl-5-{[2-(4-methylbenzoyl)hydrazino]carbonyl}phenyl)-1H-imidazole-5-carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = NHCO, Z = 4-Me-phenyl Method D (Scheme 4) a) N-[5-(hydrazinocarbonyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (VIII), R1= Me, R1 = Me, R2 = H To the solution of methyl 4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}benzoate (XV) (1.366 g, 0.005 mol) in ethanol (50 ml) hydrazine hydrate (0.025 mol) is added. The pale yellow solution is stirred at reflux temperature for 42 hours. After evaporation in vacuum the yellow oil residue crystallized upon stirring with water (15 ml) for 15 minutes. White crystals are filtered, washed with water (3 x 15 ml), dried, washed with ether (25 ml). Yield: 0.834 g (61%) white crystals. LCMS: [M+H]+274.0 1H-NMR (300 MHz, DMSO-d6): 2.26 (s, 3H, C-CH3), 3.85 (s, 3H, N-CH3), 4.47 (br s, 2H, NH2), 7.33 (d, 1H, J=7.8 Hz), 7.62 (dd, 1H, J=7.8 Hz, J=1.3 Hz), 7.80 (d, 1H), 7.80 (s, 1H, imidazole), 7.82 (s, 1H, imidazole), 9.71 (s, 1H, CONHNH2), 9.76 (s, 1H, CONH). b) 1-Methyl-N-(2-methyl-5-{[2-(4-methylbenzoyl)hydrazino]carbonyl}phenyl)-1H-imidazole-5-carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = NHCO, Z = 4-Me-phenyl To the solution of N-[5-(hydrazinocarbonyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (VIII) (0.218 g, 0.8 mmol) in pyridine (15 ml) p-toluoyl chloride (0.127 g, 0.82 mmol) is added. The colorless solution is stirred at ambient temperature for 20 hours, then evaporated in vacuum. White solid residue is stirred with water (15 ml) for 1 hour, filtered, washed with water (2 x 10 ml). Crude product is triturated with acetonitrile (10 ml), filtered, washed with ether (15 ml). Yield: 0.11 g (35%), off-white crystals. LCMS: [M+H]+392.0 1H-NMR (300 MHz, DMSO-d6): 2.30 (s, 3H, C-CH3), 2.38 (s, 3H, C-CH3), 3.86 (s, 3H, N-CH3), 7.32 (d, 2H, J=8.1 Hz), 7.42 (d, 1H, J=8.0 Hz), 7.75 (dd, 1H, J=8.0 Hz, J=1.7 Hz), 7.83 (d, 2H, J=8.1 Hz), 7.82 (s, 1H, imidazole), 7.84 (s, 1H, imidazole), 7.89 (d, 1H, J=1.7 Hz), 9.82 (s, 1H, CONH), 10.41 (s, 2H, CONHNHCO). Example 63 N-[5-({2-[(4-chloropyridin-2-yl)carbonyl]hydrazino}carbonyl)-2-methylphenyl]-1-methyl-1H-imidazole-5- carboxamide (Ib), RAr= Me, R1= Me, R2= H, Y = NHCO, Z = 4-chloropyridin-2yl Method D (Scheme 4) A mixture of N-[5-(hydrazinocarbonyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (VIII) (Example 62a) (0.273 g, 1 mmol), 4-chloropicolinic acid (0.157 g, 1 mmol), EDC.HCl (0.192 g, 1 mmol) and pyridine (10 ml) is stirred at ambient temperature for 42 hours. After evaporation in vacuum water (20 ml) is added, precipitate is filtered, washed with water (3 x 10 ml). Crude product is stirred with acetonitrile (10 ml) for 1 hour, filtered and washed with ether (10 ml). Yield: 0.312 g (75.7%) ivory crystals. LCMS: [M+H]+413.1 1H-NMR (300 MHz, DMSO-d6): 2.30 (s, 3H, C-CH3), 3.86 (s, 3H, N-CH3), 7.42 (d, 1H, J=8.0 Hz), 7.74 (dd, 1H, J=8.0 Hz, J=1.6 Hz), 7.82 (s, 1H, imidazole), 7.83 (s, 1H, imidazole), 7.83 (dd, 1H, J=5.2 Hz, J=2.0 Hz), 7.89 (d, 1H, J=1.6 Hz), 8.07 (d, 1H, J=2.0 Hz), 8.70 (d, 1H, J=5.2 Hz), 9.82 (s, 1H, CONH), 10.56 (s, 1H, CONHNHCO), 10.72 (s, 1H, CONHNHCO). Table 2. Reverse diamides and hydrazides The new intermediates of the general formula (XI) are prepared as described in Examples 1a) (Y = (CH2)n, n = 0) and 7a) (Y = NH), respectively. Formula XI Table 3

[0006] The new intermediates of the general formula (III) are prepared as described in Examples 1b) (Y = (CH2)n, n = 0) and 7b) (Y = NH), respectively. Formula III Table 4

[0007] The new intermediates of the general formula (XIII) are prepared as described in Examples 4a) (R1= R2= H) and 5a) (R1= Me, R2= H), respectively. Formula XIII Table 5 The new intermediates of the general formula (IV) are prepared as described in Examples 4b) (R1= R2= H) and 5b) (R1= Me, R2= H), respectively. Table 6 Biological Examples Different assays and examinations were carried out with the compounds according to the invention. The inventors carried out recombinant kinase inhibitor assays (see Example 64), in vitro experiments (see Example 65), and in vivo experiments (see Example 66), as well. Example 64: Recombinant kinase inhibitor assays Methods Enzyme activity assays (ProQinase) were performed in 384-well low volume black polystyrene non-binding surface microtiter plates, types 3676 (Corning, One Riverfront Plaza, NY, US) and 784900 (Greiner Bio-One, Kremsmünster, Austria). The tested inhibitor compounds were dissolved in 100% DMSO in 5 mM concentration and serial dilutions were prepared for determination of the IC50 values. 12 serially diluted concentrations of the compound were prepared, in total volume of 8 μl. Specific reaction conditions are described below. The kinase reactions were initiated by the addition of 2 µL of a given enzyme in 4X concentration and the reactions were progressing, i.e. the enzyme reactions were incubated in 8 µL final volume for 60 or 120 minutes at room temperature. The reactions were stopped by adding 8 µL of stop and detection mixture containing 20 mM HEPES pH 7.5 (Sigma-Aldrich / Merck), 40 mM EDTA (Sigma-Aldrich / Merck) and 0.02 V / V% Brij35 (Sigma- Aldrich / Merck), as well as 12.04 µg / mL ADP2Antibody (BellBlook Labs) and 3 nM ADP Alexa633 far-red fluorescent tracer (BellBrook Labs). Assay wells were incubated with the stop and detection mixture for 1 hour, followed by fluorescence polarization and fluorescence intensity measurements using a Tecan Infinite M1000Pro multimode microplate reader (Tecan Group, Männedorf, Switzerland). The kinase assays were performed using Transcreener®ADP2Assay with FP readout (BellBrook Labs, Madison, WI, US). PDGFR-A Assay buffer: 20 mM HEPES pH 7.5 + 1 mM DTT + 2 mM MgCl2 + 0.01 V / V% Brij35. The final PDGFR- A concentration was 30 nM. Poly Ala-Glu-Lys-Tyr (6:2:5:1) (Sigma-Aldrich) was used as substrate at a final concentration of 0.01 mg / ml. The final ATP concentration was 10.22 µM. Enzyme reactions were incubated for 120 minutes. PDGFR-B Assay buffer: 20 mM MOPS pH 7.5 (Sigma-Aldrich / Merck) + 1 mM DTT (Sigma-Aldrich / Merck) + 2 mM MgCl2(Sigma-Aldrich / Merck) + 0.01 V / V% Brij35 (Sigma-Aldrich / Merck). The final PDGFR-B (ProQinase / Reaction Biology Europe, Freiburg, Germany) concentration was 8 nM. Poly Ala-Glu-Lys-Tyr (6:2:5:1) (Sigma- Aldrich / Merck, Budapest, Hungary) was used as substrate at a final concentration of 0.01 mg / ml. The final ATP (Sigma-Aldrich / Merck) concentration was 10.22 µM. Enzyme reactions were incubated for 60 minutes. c-Kit Assay buffer: 20 mM HEPES pH 7.5 + 1 mM DTT + 3 mM MgCl2+ 3 mM MnCl2+ 0.01 V / V% Tween20. The final c-Kit concentration was 20 nM. Poly Glu-Tyr (4:1) (Sigma-Aldrich) was used as substrate at a final concentration of 0.05 mg / ml. The final ATP concentration was 15 µM. Lck Assay buffer: 20 mM HEPES pH 7.5 + 1 mM DTT + 3 mM MgCl2+ 3 mM MnCl2+ 0.01 V / V% Tween20. The final Lck concentration was 10 nM. Poly Glu-Tyr (4:1) (Sigma-Aldrich) was used as substrate at a final concentration of 0.4 mg / ml. The final ATP concentration was 2.61 µM. TGFB-R1 Assay buffer: 20 mM HEPES pH 7.5 + 1 mM DTT + 3 mM MgCl2 + 3 mM MnCl2 + 0.01 V / V% Tween20. The final TGFBR1 concentration was 6 nM. Casein (Sigma-Aldrich) was used as substrate at a final concentration of 0.01 mg / ml. The final ATP concentration was 13 µM. PAK2 Assay buffer: 20 mM HEPES pH 7.5 + 1 mM DTT + 2 mM MgCl2 + 0.01 V / V% Triton X-100. The final PAK2 concentration was 5 nM. TAMRA-KA10 (Genecust) was used as substrate at a final concentration of 400 nM. The final ATP concentration was 218 µM. c-Abl Assay buffer: 20 mM TRIS pH 8 + 1 mM DTT + 0.4 mM MgCl2 + 0.4 mM MnCl2 + 0.01 V / V% Tween20. The final c-Abl concentration was 6 nM. TAMRA-KA12 (Genecust) was used as substrate at a final concentration of 400 nM. The final ATP concentration was 0.6 µM. Akt1 Assay buffer: 20 mM MES pH 6 + 1 mM DTT + 10 mM MgCl2 + 2 mM MnCl2 + 0.01 V / V% Triton X-100. The final Akt1 concentration was 5 nM. TAMRA-PKAtide (Genecust) was used as substrate at a final concentration of 400 nM. The final ATP concentration was 40 µM. Results First the PDGFR-A and PDGFR-B inhibitory effects of VCC compounds were investigated by a single point screening method. Thirty-four compounds resulted higher than 50% inhibitory effect, presuming them as potential PDGFR-B kinase inhibitors (Table 7). These compounds were further investigated in a second experiment, determining their IC50 values on PDGFR-B (Table 7). Based on these results, kinase inhibitor profile of VCC380920, one of the most outstanding compounds was examined. VCC380920 showed high affinity to PDGFR- B and c-Kit kinases (Table 8 and Figure 1). Table 7. Single point PDGFR-B and PDGFR-A inhibition screening of compounds and PDGFR-B IC50of presumed inhibitor compounds. Kinase inhibitory effects of compounds were determined using in vitro biochemical recombinant protein kinase assay. In single point measurement, inhibitory activity was investigated at 1.25 μM compound concentration. At values above 50%, inhibitory activity of compounds was presumed effective.

[0008] Kinase inhibition profile of compound VCC380920 is shown in Table 8 and Figure 1. Table 8. IC50 values of VCC380920 on selected protein kinases. IC50 values were determined by in vitro biochemical assays on fibrosis specific kinases. Example 65: In vitro experiments Methods Cell Cultures Primary lung fibroblasts were isolated from fibrotic tissue of bleomycin treated C57BL / 6J mice. Primary lung fibroblasts were identified as based on their morphology and smooth muscle actin (α-SMA) immunopositivity. NRK-49F rat kidney interstitial fibroblast cell line was purchased from American Type Culture Collection (ATCC). Both cell types were cultured in Dulbecco’s modified Eagle’s medium (Life Technologies) supplemented with 10% fetal bovine serum (FBS) (Life Technologies) and 1% Antibiotic-Antimycotic Solution (Sigma-Aldrich) at 37°C and 5% CO2. Immunocytochemistry Primary lung fibroblasts were characterized by immunofluorescence staining of α smooth muscle actin (α- SMA) and platelet-derived growth factor receptor beta (PDGFR-B). Primary lung fibroblasts were seeded into chambers and cultured for 24 hours in 37 °C and 5% CO2. After repeated washing with PBS, slides were permeabilized with Cytofix / Cytoperm (BD Pharmingen) for 15 minutes at room temperature (RT), washed with Perm / Wash Buffer solution (BD Pharmingen), and incubated with primary antibody specific for α-SMA (sc-53015; mouse, 1:1000, Santa Cruz Biotechnology) or PDGFR-B (ab124332; rabbit, 1:100, Abcam) for 1 hour at RT. Slides were incubated with anti-mouse Alexa Fluor 488® conjugated secondary antibody (1:1000, A11001; Thermo Fisher Scientific) or anti-rabbit Alexa Fluor 568® conjugated secondary antibody (1:1000, A10042; Thermo Fisher Scientific) for 30 minutes at RT. Thereafter the slides were washed with Perm / Wash Buffer solution and coverslipped with ProLong™ Gold Antifade Mountant with DAPI (Thermo Fisher Scientific). Sections were analyzed with an Olympus IX81 fluorescent microscope system. For MTT and LDH assays, cells were seeded into 96-well plates at a density of 104cells / well (n=5 well / treatment group) and treated with PDGF-B (10 ng / ml, R&D Systems) in the presence or absence of the investigated compounds of the invention for 24 hours. For SiriusRed assay, cells were seeded into 96-well plates at a density of 1010cells / well (n=5 well / treatment group) and treated with TGF-β1 (1 nM, Life Technologies) in the presence or absence of the investigated compounds of the invention for 48 hours. MTT assay To detect cell proliferation, MTT assay was performed by using Cell Proliferation Kit I (Roche Diagnostics) according to the manufacturer’s recommendations. Absorbance was recorded at 570 nm and at 690 nm as background using a Hidex Chameleon Microplate Reader (Triathler, Plate Chameleion, 300SL Lablogic Systems, Inc., Brandon, FL, USA) using MikroWin 2000 software. LDH assay To detect viability and cytotoxic effect of VCC compounds, LDH assay was performed as previously described [Korzeniewski & Callewaert, 1983]. All reagents were purchased from Sigma-Aldrich. Absorbance was recorded at 570 nm and at 690 nm as background in a Hidex Chameleon Microplate Reader using MikroWin 2000 software. SiriusRed assay To determine the extent of collagen deposition, SiriusRed assay was performed, as previously described [Walsh et al., 1992]. All reagents were purchased from Sigma-Aldrich. Absorbance was determined at 544 nm and at 690 nm as background using Hidex Chameleon Microplate Reader using MikroWin 2000 software. Score In vitro antiproliferative effect of VCC compounds was calculated based on MTT assays. Partial score values were determined at specified concentration of VCC compounds by the degree of PDGF-B induced proliferation inhibition, compensated by its effect on the viability of untreated cells. Statistical analysis of MTT, LDH and SiriusRed assays Statistical evaluation was performed by GraphPad Prism 6.01 software. Multiple comparisons of row data derived from MTT, LDH, SiriusRed assays were performed using multiple t-test and ordinary two-way ANOVA with Dunnett correction. p≤0.05 was considered as statistically significant. Results are presented as a ratio of control group and illustrated as violin plot, indicating the data distribution in the given group, or as mean ± SD at dot plots. The Brief description of the figures contains the corresponding n values and the statistical tests. RNA isolation, cDNA synthesis, real-time RT-PCR Total RNA was isolated from cells by Geneaid Total RNA Mini Kit (Geneaid Biotech Ltd.). Equal RNA was reverse-transcribed using Maxima First Strand cDNA Synthesis Kit for RT-qPCR (Life Technologies) to generate first-stranded cDNA. The mRNA expressions were determined by real-time RT-PCR using LightCycler 480 SYBR Green I Master enzyme mix on a Light Cycler 480 system (Roche Diagnostics, Mannheim, Germany). Nucleotide sequences and species specificity of the applied primer pairs and the lengths of the resulted PCR products are shown in Table 9. Results were analyzed by Light-Cycler 480 software version 1.5.0.39 (Roche Diagnostics). Relative mRNA expression was determined by comparison with Rn18s as internal control using the ∆∆Ct method. Data were normalized and presented as the ratio of their control values. Table 9. Applied primer pairs and the length of the resulted PCR products. F means forward primer and R means reverse primer. Statistical analysis of mRNA expression Statistical evaluation was performed by GraphPad Prism 6.01 software. After testing normality with Kolmogorov-Smirnov test, row data of Western blot and real-time RT-PCR measurements were analyzed with Mann–Whitney U-test to determine differences between the corresponding groups. p≤0.05 was considered as statistically significant. Results are presented as a ratio of control group and illustrated as violin plot, indicating the data distribution in the given group, or as mean ± SD at dot plots. The Brief description of the figures contains the corresponding n values and the statistical tests. Results A) Primary lung fibroblasts Immunocytochemistry Characterization of primary lung fibroblasts by immunofluorescence staining of α smooth muscle actin (α- SMA) and platelet-derived growth factor receptor beta (PDGFR-B), are shown in Figure 2. MTT and LDH assays VCC380920 treatment decreased the PDGF-B induced proliferation of primary lung fibroblasts as revealed by MTT assay (Figure 4b). Based on results derived from LDH assay (Figure 4c), there was no detectable cytotoxic effect at the examined concentrations. RT-PCR Gene expression measurements showed that VCC380920 decreased the mRNA expression of Mki67 and Pcna cell proliferation markers in PDGF-B treated cells (Figure 5). Thus, the effect of compound VCC380920 on lung fibroblasts is shown in Figure 4 and Figure 5. B) Renal fibroblasts MTT and LDH assays VCC380920 decreased the PDGF-B induced proliferation of NRK-49F cells as revealed by MTT assay (Figure 7a). Based on the LDH assay (Figure 7b), there was no detectable cytotoxic effect at the examined concentrations. SiriusRed assay VCC380920 treatment decreased the TGF-β induced collagen deposition of NRK-49F cells as revealed by SiriusRed assay (Figure 8). Thus, the effect of compound VCC380920 on renal fibroblasts is shown in Figure 7 and Figure 8. C) Score (MTT-based screening method) of primary lung fibroblasts and renal fibroblasts The in vitro effect of compounds was investigated on various fibroblast cell lines. Proliferation and viability of cells was determined by MTT assay within a defined concentration range of VCC compounds. The in vitro effect of compounds was quantified by a sigmoid curve-based scoring method, wherein score values include antiproliferative efficiency on PDGF-B treated cells, compensated by cytotoxicity on untreated cells, if it was observable. This scoring system was validated in two ways. First, the antiproliferative effect of 35 compounds was subjectively categorised (effective – uncertain – not effective) by independent persons based on their graphs, derived from MTT assays. Score values of compounds belonging to these groups were well separated. ROC analysis of these data determined suitable threshold value to identify certainly effective compound with perfect specificity and sensitivity. Second, 14 randomly selected compounds were ordered by independent persons based on their MTT graphs. As the correlation between subjective and score value-based order was almost perfect, this scoring system is suitable not only for distinguish between effective and not effective compounds, but for ordering them based on their effectiveness. The score values of VCC compounds determined on lung and kidney fibroblast showed positive correlation, suggesting that their antiproliferative effect is mostly independent of the origin of the investigated cell. In case of lung fibroblasts, the in vitro efficiency of VCC compounds was determined by MTT assay on PDGF-B treated primary lung fibroblasts (Table 10, Figure 3). A significant part of the VCC compounds, that inhibited the activity of PDGFR-B in the previous biochemical assays (see example 64), hindered the PDGF-B induced proliferation of primary lung fibroblasts, as well. The in vitro antiproliferative effects of compounds according to the invention on lung fibroblasts is shown in Figure 3. In case of renal fibroblast, the in vitro efficiency of VCC compounds was determined by MTT assay on PDGF-B treated NRK-49F cells (Table 10, Figure 6). A significant part of the compounds, that inhibited the activity of PDGFR-B in the previous biochemical assays (see Example 64), hindered the PDGF-B induced proliferation of renal fibroblasts, as well. Thus, the in vitro antiproliferative effects of compounds according to the invention on renal fibroblasts is shown in Figure 6. Table 10. In vitro efficacy score of VCC compounds on primary lung fibroblasts and renal fibroblasts (NRK- 49F cells). Antiproliferative effect of compounds was investigated using MTT assay on PDGF-B treated primary lung fibroblasts and NRK-49F cells (renal fibroblasts). Example 66: In vivo experiments Methods Animals All animal procedures were approved. In the experiments 6-8 weeks old male C57BL / 6J mice were used. All animals were kept in plastic cages under 12-hour dark / light cycle at constant temperature (24 ± 0.2°C) with free access to standard rodent chow and drinking water. Bleomycin induced lung fibrosis (BILF) Lung fibrosis was induced by 50 mg / kg bleomycin in 100 µl saline injected ip. at day 0, 3, and 7, respectively (n=6-8 / group). Experiment was terminated 21 days after the initiation of BILF, lungs and spleens were surgically removed. To examine the effect of VCC380920, mice were daily treated with 50 mg / kg in 100 µl of DMSO ip. Control mice were treated with vehicle only. UUO induced renal fibrosis Renal fibrosis was induced by unilateral ureteral obstruction (UUO) of mice (n=6 / group). After general anaesthesia by the intraperitoneal (ip.) injection of a mixture of 100 mg / kg ketamine and 10 mg / kg xylazine, the left ureter was isolated by blunt dissection and completely ligated using fine suture material in the UUO group. The sham-operated (control) animals underwent identical surgical procedures without the occlusion of the left ureter. Experiment was terminated 7 days after the onset of UUO. To examine the effect of VCC380920, mice were daily treated with 50 mg / kg in 100 µl of dimethyl sulfoxide (DMSO) ip. Control mice were treated with vehicle only. IMQ induced psoriasis Psoriasis was induced by local imiquimod (IMQ) treatment of the mice (n=6 / group). The shaved back of each mice was treated with 62.5 mg Aldara Cream containing 5% IMQ for 5 days. To examine the effect of VCC380920, mice were daily treated with 50 mg / kg in 100 µl of DMSO ip, or topically with Aldara Cream containing 5% IMQ and 2% VCC380920. Histology Formalin-fixed paraffin-embedded kidney samples were cut into 4-μm sections and stained with picro- SiriusRed or Masson’s trichome staining. The sections were scanned, and on average 15 non-overlapping areas were randomly selected under 200x magnification from each kidney section. The analysis of the SiriusRed and Masson’s trichrome stained areas was performed with ImageJ (The National Institutes of Health). The results were expressed as a percentage of the positively stained area of SiriusRed (red) and Masson’s trichrome (blue) staining. Protein isolation and Western blot Tissue samples were homogenized in lysis buffer containing 50 mM HEPES, 150 mM NaCl, 1% Triton X- 100, 5 mM EDTA, 5 mM EGTA, 20 mM sodium pyrophosphate, 20 mM NaF, 0.2 mg / mL phenylmethylsulfonyl fluoride, 0.01 mg / mL leupeptin, and 0.01 mg / mL aprotinin (pH 7.4; each substance was obtained from Sigma- Aldrich). Protein concentration was determined in triplicates by a detergent-compatible protein assay (Bio-Rad, Hercules, CA). Denatured samples (20 μg protein / lane) were loaded and separated on 4-20% gradient SDS polyacrylamide gel and transferred to nitrocellulose membranes. To verify the transfer, membranes were stained with Ponceau S (Sigma Aldrich), then washed and blocked with 5% non-fat milk in TRIS-buffered saline (TBS) for 1 hour at RT. Thereafter the membranes were incubated overnight at 4°C with antibodies specific for α-SMA (sc- 53015; 1:10000, Santa Cruz), fibronectin (FN) (ab2413; 1:2000, Abcam), COL1A1 (sc-293182; 1:2000, Santa Cruz) or GAPDH (sc-47724; 1:2000, Santa Cruz). After repeated washing with TBS containing 0.05% Tween-20 and 1% non-fat milk, membranes were incubated with the corresponding HRP-conjugated secondary antibodies (1:2000 anti-rabbit or anti-mouse, Santa Cruz) for 1 hour at RT. Bands of interest were detected using enhanced chemiluminescence detection (Western Blotting Luminol Reagent, GE Healthcare, Waukesha, WI) and quantified by densitometry (VersaDoc, Quantity One Analysis software; Bio-Rad) as integrated optical density after subtraction of background. Relative protein levels were determined by comparison with GAPDH as internal control. Data were normalized and presented as the ratio of control values. RNA isolation, cDNA synthesis, real-time RT-PCR Total RNA was isolated from tissue samples by Geneaid Total RNA Mini Kit (Geneaid Biotech Ltd.). Equal RNA was reverse-transcribed using Maxima First Strand cDNA Synthesis Kit for RT-qPCR (Life Technologies) to generate first-stranded cDNA. The mRNA expressions were determined by real-time RT-PCR using LightCycler 480 SYBR Green I Master enzyme mix on a Light Cycler 480 system (Roche Diagnostics, Mannheim, Germany). Nucleotide sequences and species specificity of the applied primer pairs and the lengths of the resulted PCR products are shown in Table 11. Results were analyzed by Light-Cycler 480 software version 1.5.0.39 (Roche Diagnostics). Relative mRNA expression was determined by comparison with Rn18s as internal control using the ∆∆Ct method. Data were normalized and presented as the ratio of their control values. Table 11. Applied primer pairs and the length of the resulted PCR products. F means forward primer and R means reverse primer. Graphical analysis of skin lesions Skin symptoms of IMQ induced psoriasis, like skin lesions was investigated by graphical analysis. The mice were photographed with standard settings, then the skin redness was analysed based on the histogram of red pixels using ImageJ software. Mean intensity at the curve peaks were determined by Gaussian curve fitting on each histogram using GraphPad Prism 8.01 software (GraphPad Software Inc., La Jolla, CA, USA). Statistical analysis Statistical evaluation was performed by GraphPad Prism 6.01 software. After testing normality with Kolmogorov-Smirnov test, row data of Western blot and real-time RT-PCR measurements were analyzed with Mann–Whitney U-test to determine differences between the corresponding groups. p≤0.05 was considered as statistically significant. Results are presented as a ratio of control group and illustrated as violin plot, indicating the data distribution in the given group, or as mean ± SD at dot plots. The Brief description of the figures contains the corresponding n values and the statistical tests. Results Compound VCC380920 (Ex.1) as one of the most promising compounds was investigated in various in vivo experimental model of tissue fibrosis. In these experiments, mice were intraperitoneally treated with VCC380920 (50 mg / kg / day). This dose did not cause weight loss or behavioural signs suggesting toxic effects, even after 21 days treatment of the animals (see Figure 9, control groups). A) Bleomycin induced lung fibrosis (BILF) The in vivo effect of VCC380920 was investigated in bleomycin induced mice model of lung fibrosis (BILF). There was no detectable toxic effect of chronic administration of the compound nor in control or in bleomycin treated groups (Figures 9 and 11). The effect of compound VCC380920 on body weight in the experimental model of bleomycin induced lung fibrosis (BILF) is shown in Figure 9. As can be seen therein, control groups showed stable body wight during the whole experiment, while significant body weight loss was observed in BILF groups. Treatment with VCC380920 had no effect on body weight compared to the related vehicle-treated groups. The effect of compound VCC380920 on lung weight in the experimental model of bleomycin induced lung fibrosis (BILF) is shown in Figure 10. As can be seen therein, in BILF group an increment of the lung weight was observed, a sign of severe accumulation of scar tissue in the lung, and that was moderated by treatment with VCC380920. The effect of compound VCC380920 on survival in the experimental model of bleomycin induced lung fibrosis (BILF) is shown in Figure 11. As can be seen therein, significant mortality was observed in BILF group at the second phase of the experiment, which is sign of the chronic effect of bleomycin-induced lung injury. Treatment with VCC380920 improved the survival of the bleomycin-treated mice. Western blot VCC380920 treatment reduced the protein level of fibrotic markers, including collagen I and fibronectin (Figure 12). As can be seen therein, VCC380920 decreased the protein levels of collagen I and fibronectin extracellular matrix component markers in the experimental model of BILF RT-PCR The effect of compound VCC380920 on fibrotic mRNA in the experimental model of bleomycin induced lung fibrosis (BILF) is shown in Figure 13. As can be seen therein, VCC380920 decreased the mRNA expression of Col1a1 and Fn1 extracellular matrix component markers in the experimental model of BILF. B) UUO induced renal fibrosis The in vivo effect of VCC380920 was investigated in the mice model of unilateral ureteral obstruction (UUO) induced renal fibrosis. Treatment with VCC380920 resulted in decreased renal level of fibrotic markers, including fibrotic tissue area, protein and mRNA levels of α-SMA, fibronectin, collagens and Ngal injury marker (Figures 14- 16). Histology The effect of compound VCC380920 on UUO induced renal histological changes is shown in Figure 14. As can be seen therein, treatment with VCC380920 decreased fibrotic tissue area. Western blot The effect of compound VCC380920 on fibrotic protein levels in the experimental model of UUO induced renal fibrosis is shown in Figure 16. As can be seen therein, treatment with VCC380920 decreased protein amount of α-SMA and fibronectin. RT-PCR The effect of compound VCC380920 on fibrotic mRNA expression in the experimental model of UUO induced renal fibrosis is shown in Figure 15. As can be seen therein, treatment with VCC380920 decreased the mRNA expression levels of Acta2 fibroblast marker, decreased the mRNA expression levels of Fn1, Col1a1 and Col3a1 extracellular matrix components and decreased the mRNA expression levels of Kim1 and Ngal kidney injury markers. C) IMQ induced psoriasis The in vivo effect of VCC380920 was investigated in imiquimod (IMQ) induced mice model of psoriasis. Both local and ip VCC380920 treatment of IMQ treated mice decreased the extent of skin lesions (Figure 17) and skin thickening (Figure 18). VCC380920 also decreased the IMQ induced spleen enlargement, which is a characteristic of decreased systematic inflammation (Figure 19). REFERENCES Korzeniewski, C., & Callewaert, D. M. (1983). An enzyme-release assay for natural cytotoxicity. Journal of immunological methods, 64(3), 313–320. https: / / doi.org / 10.1016 / 0022-1759(83)90438-6 Walsh, B.J., Thornton, S.C., Penny, R., & Breit, S.N. (1992). Microplate reader-based quantitation of collagens. Analytical Biochemistry, 203(2), 187-190. https: / / doi.org / 10.1016 / 0003-2697(92)90301-M Yoshida, G.J. (2020). Regulation of heterogeneous cancer-associated fibroblasts: the molecular pathology of activated signalling pathways. Journal of Experimental & Clinical Cancer Research volume 39, Article number: 112

Claims

CLAIMS 1. Compound of general formula (I), or pharmaceutically acceptable salt thereofwherein Ar is phenyl, or 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms independently selected from N and S, such as pyrrole, tiophene, imidazole, pyrazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, thiazine; wherein each of the phenyl and the heteroaromatic ring is optionally substituted with 1 or 2 substituents independently selected from C1-4 alkyl, halogen, -OH, -NH2, -NHC1-4 alkyl, C1-4 alkoxy; R1is H, halogen, C1-2 alkyl, or C1-2 alkoxy; R2is H, halogen, or C1-2 alkyl; X1is NH or CO X2is NH or CO, with the proviso that X1and X2are not the same; Y is a bond or (CH2)n; where n is 1 or 2; or Y is NH, provided that X2is CO; or Y is NHCO, provided that X2is NH; Z is phenyl, or a 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, or a 7-10-membered aromatic bicyclic moiety containing 1-3 heteroatoms, independently selected from N, O and S, preferably N, or 3-, 4-, 5- or 6-membered cycloalkyl group, or a 5- or 6-membered saturated heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N, O and S, where any of these rings or cyclic groups is optionally substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, benzyloxy, halogen, trihalogenoC1-2 alkyl, -NO2, -CN, -OH, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, di(C1-2 alkyl)aminoC1-4 alkyl, di(C1-2 alkyl)aminoC1-4 alkenylcarbonyl, phenyl, -Nhphenyl, C1-4 alkoxycarbonyl group, C1-4 alkylcarbonyl group, C2-4 alkenylcarbonyl group, 5- or 6-membered saturated heterocyclic ring containing 1-3 heteroatoms independently selected from N, O and S, 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, heterocyclylaminosulfonyl group, heteroarylaminosulfonyl group, arylcarbonylamino group, heteroarylcarbonylamino group, 3-, 4-, 5- or 6-membered cycloalkyl group, heterocyclylalkyl group, heteroarylalkyl group, -NH-C(O)-NH-phenyl, N(C1-4 alkyl)-C(O)-C1-2alkyl-heterocyclyl, where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, halogen, -OH, hydroxyalkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, -NO2, -CN, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, C1-4 alkoxycarbonyl group with the proviso that- compounds are excluded where X2is -CO, Y is a bond and Z is phenyl substituted with at least one selected from the group consisting of Br, F, Cl, -OH, fluoroalkyl and fluoroalkoxy,: - compounds are excluded where X2is -CO, Y is a bond and Ar is phenyl substituted with at least one selected from the group consisting of Br, F, Cl, and -OH - compounds are excluded where X2is NH, Y is a bond and Z is phenyl or a 5- or 6-membered heteroaromatic ring which is substituted with 5-membered heteroaromatic ring - compounds are excluded where Ar is picoline.

2. Compound of general formula (I), or pharmaceutically acceptable salt thereof, wherein Ar is a 5-membered heteroaromatic ring comprising 1 or 2 heteroatoms independently selected from N and S; preferably N wherein each of the heteroaromatic ring is optionally substituted with a substituent selected from C1-2 alkyl, halogen, -OH, -NH2, -NHC1-2 alkyl, C1-2 alkoxy, preferably, methyl, methoxy, and halogen R1is H, halogen, C1-2 alkyl, or C1-2 alkoxy; R2is H, halogen, or C1-2 alkyl; X1is NH or CO X2is NH or CO, with the proviso that X1and X2are not the same; Y is a bond or (CH2)n; where n is 1 or 2; or Y is NH, provided that X2is CO; or Y is NHCO, provided that X2is NH; Z is phenyl, or a 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, or a 7-10-membered aromatic bicyclic moiety containing 1-3 heteroatoms, independently selected from N, O and S, preferably N, or 3-, 4-, 5- or 6-membered cycloalkyl group, or a 5- or 6-membered saturated heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N, O and S, where any of these rings or cyclic groups is optionally substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, benzyloxy, halogen, trihalogenoC1-2 alkyl, -NO2, -CN, -OH, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, di(C1-2 alkyl)aminoC1-4 alkyl, di(C1-2 alkyl)aminoC1-4 alkenylcarbonyl, phenyl, -Nhphenyl, C1-4 alkoxycarbonyl group, C1-4 alkylcarbonyl group, C2-4 alkenylcarbonyl group, 5- or 6-membered saturated heterocyclic ring containing 1-3 heteroatoms independently selected from N, O and S, 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, heterocyclylaminosulfonyl group, heteroarylaminosulfonyl group, arylcarbonylamino group, heteroarylcarbonylamino group, 3-, 4-, 5- or 6-membered cycloalkyl group, heterocyclylalkyl group, heteroarylalkyl group, -NH-C(O)-NH-phenyl, N(C1-4 alkyl)-C(O)-C1-2alkyl-heterocyclyl,where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, halogen, -OH, hydroxyalkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, -NO2, -CN, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, C1-4 alkoxycarbonyl group with the proviso that - compounds are excluded where X2is -CO, Y is a bond and Z is phenyl substituted with at least one selected from the group consisting of Br, F, Cl, -OH, fluoroalkyl and fluoroalkoxy,: - compounds are excluded where X2is NH, Y is a bond and Z is phenyl or a 5- or 6-membered heteroaromatic ring, which is substituted with 5-membered heteroaromatic ring.

3. Compound according to claim 1 or 2 or pharmaceutically acceptable salt thereof, wherein Ar is a 5-membered heteroaromatic ring comprising 2 nitrogen atoms, such as imidazolyl or pyrazolyl, optionally substituted with methyl, preferably imidazole-4-yl, 1-methylimidazol-4-yl, 1-methylimidazol-5-yl, more preferably 1-methylimidazol-5-yl.

4. Compound according to any of the previous claims or pharmaceutically acceptable salt thereof, wherein Ar is 1-methylimidazol-4-yl or 1-methylimidazol-5-ylR1is H, halogen, C1-2 alkyl, or C1-2 alkoxy; R2is H, halogen, or C1-2 alkyl; X1is NH or CO X2is NH or CO, with the proviso that X1and X2are not the same; Y is a bond or (CH2)n; where n is 1 or 2; or Y is NH, provided that X2is CO; or Y is NHCO, provided that X2is NH; Z is phenyl, or a 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, or a 7-10-membered aromatic bicyclic moiety containing 1-3 heteroatoms, independently selected from N, O and S, preferably N, or 3-, 4-, 5- or 6-membered cycloalkyl group, or a 5- or 6-membered saturated heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N, O and S, where any of these rings or cyclic groups is optionally substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, benzyloxy, halogen, trihalogenoC1-2 alkyl, -NO2, -CN, -OH, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, di(C1-2 alkyl)aminoC1-4 alkyl, di(C1-2 alkyl)aminoC1-4 alkenylcarbonyl, phenyl, -Nhphenyl, C1-4 alkoxycarbonyl group, C1-4 alkylcarbonyl group, C2-4 alkenylcarbonyl group, 5- or 6-membered saturated heterocyclic ring containing 1-3 heteroatoms independently selected from N, O and S, 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, heterocyclylaminosulfonyl group, heteroarylaminosulfonyl group, arylcarbonylamino group, heteroarylcarbonylamino group, 3-, 4-, 5- or 6-membered cycloalkyl group, heterocyclylalkyl group, heteroarylalkyl group, -NH-C(O)-NH-phenyl, N(C1-4 alkyl)-C(O)-C1-2alkyl-heterocyclyl, where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, halogen, -OH, hydroxyalkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, -NO2, -CN, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, C1-4 alkoxycarbonyl groupwith the proviso that - compounds are excluded where X2is NH, Y is a bond and Z is phenyl or a 5- or 6-membered heteroaromatic ring, which is substituted with 5-membered heteroaromatic ring.

5. Compound according to any of the previous claims or pharmaceutically acceptable salt thereof, wherein R1is H, methyl, methoxy, fluoro or chloro, preferably hydrogen, methyl, fluoro or chloro, more preferably methyl; R2is H, fluoro or methyl, preferably H.

6. Compound according to any of the previous claims, wherein Y is a bond, or Y is (CH2)n, provided that X2is NH, or Y is NH, provided that X2is CO; preferably Y is a bond.

7. Compound according to any of the previous claims or pharmaceutically acceptable salt thereof, wherein Z is phenyl, or a 5- or 6-membered heteroaromatic ring containing 1-2 heteroatoms independently selected from N, O and S, or a 8-10-membered aromatic bicyclic moiety containing 1-2 heteroatoms, independently selected from N, O and S, preferably N, or 3-, 4-, 5- or 6-membered cycloalkyl group, or a 6-membered saturated heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N, O and S, preferably N, where any of these rings or cyclic groups is optionally substituted 1-3 substituents independently selected from C1-2 alkyl, t-butyl, C1-2 alkoxy, benzyloxy, halogen, trihalogenomethyl, -NO2, -CN, -OH, -NH2, - NHC1-2 alkyl, -N(C1-2 alkyl)2, di(C1-2 alkyl)aminoC1-3 alkyl, di(C1-2 alkyl)aminoC2-3 alkenylcarbonyl, -Nhphenyl, C1-4 alkoxycarbonyl group, C1-2 alkylcarbonyl group, C2-4 alkenylcarbonyl group, 5- or 6-membered saturated heterocyclic ring containing 1-2 heteroatoms independently selected from N and O such as pyrrolidine, pyrazolidine, tetrahydrofuran, piperidine, piperazine, tetrahydropyran and morpholine; 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N and S, preferably N, heterocyclylaminosulfonyl group where the heterocyclyl moiety Is a 5- or 6-membered group containing 1 or 2 heteroatoms independently selected from N, O and S, heteroarylaminosulfonyl group where the heteroaryl moiety is a 5- or 6- membered group containing 1 to 3 heteroatoms independently selected from N and S, arylcarbonylamino group, 5-membered heteroarylcarbonylamino group, heterocyclylalkyl group where the heterocyclyl moiety is a 6-membered group containing 1 or 2 heteroatoms independently selected from N and O, heteroarylalkyl group where the heteroaryl moiety is a 8-10-membered aromatic bicyclic moiety containing 1-2 N, and -NH-C(O)-NH-phenyl, N(C1-2 alkyl)-C(O)-C1-2alkyl-heterocyclyl where the heterocyclyl moiety is a 5- or 6-membered group containing 1 or 2 heteroatoms independently selected from N and O, where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with 1-3 substituents independently selected from C1- 2 alkyl, C1-2 alkoxy, halogen, -OH, hydroxyC1-2alkyl, -S(O)2-C1-2 alkyl, trihalogenomethyl, - NO2, -CN, -NH2, -NHC1-2 alkyl, -N(C1-2 alkyl)2, C1-4 alkoxycarbonyl group.

8. Compound according to any of the previous claims or pharmaceutically acceptable salt thereof, whereinZ is phenyl, pyrrolyl, thiophenyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzimidazolyl, benzopyrazolyl, pyrazolo[1,5-a]pyridinyl, indolyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, and tetrahydropyranyl, preferably phenyl where any of these rings or cyclic groups is optionally substituted 1-3 substituents independently selected from methyl, ethyl, methoxy, ethoxy, benzyloxy, halogen, trifluoromethyl, -NO2, -CN, -OH, -NH2, - NHC1-2 alkyl, -N(C1-2 alkyl)2, di(C1-2 alkyl)aminoC1-2 alkyl, di(C1-2 alkyl)aminoC2-3 alkenylcarbonyl, -nHphenyl, C1-4 alkoxycarbonyl group, C1-4 alkylcarbonyl group, C2-4 alkenylcarbonyl group, imidazolyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolidinyl, pyrazolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl; heterocyclylaminosulfonyl group where the heterocyclyl moiety is thiazolidinyl, heteroarylaminosulfonyl group where the heteroaryl moiety is thiazolyl or thiadiazolyl, heterocyclylmethyl group where the heterocyclyl moiety is tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, heteroarylmethyl group where the heteroaryl moiety is a 8-10-membered aromatic bicyclic moiety containing 1-2 N such as benzopyrazole, benzothiazole and benzimidazole, and -NH-C(O)-NH-phenyl, N(methyl)-C(O)-methyl-heterocyclyl where the heterocyclyl moiety is tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with 1-3 substituents independently selected from C1- 2 alkyl, C1-2 alkoxy, halogen, -OH, hydroxyC1-2alkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, - NO2, -CN, -NH2, -NHC1-2 alkyl, -N(C1-2 alkyl)2, C1-4 alkoxycarbonyl group.

9. Compound according to any of the previous claims or pharmaceutically acceptable salt thereof, wherein Z is phenyl, thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrazinyl, benzimidazolyl, benzopyrazolyl, pyrazolo[1,5-a]pyridinyl, indolyl, cyclohexyl, and tetrahydropyranyl, preferably phenyl; wherein the substituents of Z is as defined in any of the previous points.

10. Compound according to any of claims 1-7 or pharmaceutically acceptable salt thereof, wherein Z is selected from.

11. Compound or pharmaceutically acceptable salt thereof selected from 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.1); 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-4-carboxamide (Ex.2); N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-4-carboxamide (Ex.3); 1-Methyl-N-{3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.4); 4-Chloro-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex.5); N-{2-chloro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.6); N-[2-chloro-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.7); N-{5-[(4-methoxybenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.8); N-{5-[(4-chlorobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.9); 1-Methyl-N-[2-methyl-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1H-imidazole-5-carboxamide (Ex.10); 1-Methyl-N-(2-methyl-5-{[(2-methyl-3-thienyl)carbonyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.11); N-(5-{[(3,4-dichlorophenyl)carbamoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.12); N,N'-(4-methyl-1,3-phenylene)bis(1-methyl-1H-imidazole-5-carboxamide) (Ex.13); N-{2-fluoro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.14); 1-Methyl-N-{4-methyl-3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.15); N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-4-[(3,4,5- trimethoxyphenyl)amino]pyridine-2-carboxamide (Ex.16); N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (Ex.17); N-{4-fluoro-2-methoxy-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.18); 4-Hydroxy-2-(methylamino)-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)pyrimidine-5- carboxamide (Ex.19); 4-Ethoxy-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex. 20); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxybenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.21); 1-Methyl-N-(2-methyl-5-{[4-(trifluoromethyl)benzoyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.22); N-(5-{[3,5-bis(trifluoromethyl)benzoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.23);1-[2-(Dimethylamino)pyrimidin-4-yl]-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-1H- imidazole-4-carboxamide (Ex.24); 4-Methoxy-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex. 25); N-{5-[(4-cyanobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.26); N-[5-({[3-(benzyloxy)cyclobutyl]carbonyl}amino)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex. 27); N-{5-[(4-chlorophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.28); 1-Methyl-N-(2-methyl-5-{[2-methyl-5-({[3-(trifluoromethyl)phenyl]- carbamoyl}amino)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.29); N-{5-[(3,4-dimethoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.30); N-{5-[(2,4-dichloro-5-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex. 31); N-{5-[(2-fluoro-4-methoxy-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.32); N-{5-[(4-methoxy-2-morpholin-4-yl-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5- carboxamide (Ex.33); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.34); N-{5-[(5-tert-butylisoxazol-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.35); N-{5-[(4-chlorobenzyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.36); N-{5-[(4-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.37); N-{5-[(5-methoxypyridin-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.38); 1-Methyl-N-{2-methyl-5-[(4-methylphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.39); N-(5-{[4-(4-bromo-1H-imidazol-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.40); Tert-butyl 4-[(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}-benzoyl)amino]piperidine-1- carboxylate (Ex.41); 1-Methyl-N-(2-methyl-5-{[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.42); 1-Methyl-N-[2-methyl-5-(piperidin-4-ylcarbamoyl)phenyl]-1H-imidazole-5-carboxamide (Ex.43); N-{5-[(3,4-dimethoxybenzyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.44); N-[5-(cyclohexylcarbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.45); N-(5-{[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex. 46); N-[5-({3-cyano-1-[3-(dimethylamino)propyl]-4,5-dimethyl-1H-pyrrol-2-yl}carbamoyl)-2-methylphenyl]-1- methyl-1H-imidazole-5-carboxamide (Ex.47); N-[5-({4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl}carbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5- carboxamide (Ex.48); N-{5-[(4-acetylphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.49); N-(5-{[4-(4-hydroxypiperidin-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.50); N-{5-[(3,5-dimethylisoxazol-4-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.51);N-[5-({4-[(2E)-3-(dimethylamino)prop-2-enoyl]phenyl}carbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5- carboxamide (Ex.52); 1-Methyl-N-(2-methyl-5-{[4-(1H-pyrazol-3-yl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.53); 1-Methyl-N-[2-methyl-5-({4-[4-(methylsulfonyl)piperazin-1-yl]phenyl}carbamoyl)phenyl]-1H-imidazole-5- carboxamide (Ex.54); N-(5-{[3-(1H-benzimidazol-1-ylmethyl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.55); 1-Methyl-N-[2-methyl-5-({4-[(1,3-thiazol-2-ylamino)sulfonyl]phenyl}-carbamoyl)phenyl]-1H-imidazole-5- carboxamide (Ex.56); 1-Methyl-N-{2-methyl-5-[(4-{[(5-methyl-1,3,4-thiadiazol-2-yl)amino]sulfonyl}phenyl)carbamoyl]phenyl}-1H- imidazole-5-carboxamide (Ex.57); N-[5-(cyclopropylcarbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.58); 1-Methyl-N-(2-methyl-5-{[3-(morpholin-4-ylmethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.59); 1-Methyl-N-(2-methyl-5-{[4-(piperidin-1-ylmethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex. 60); 1-Methyl-N-[2-methyl-5-({4-[methyl(piperidin-1-ylacetyl)amino]phenyl}-carbamoyl)phenyl]-1H-imidazole-5- carboxamide (Ex.61); 1-Methyl-N-(2-methyl-5-{[2-(4-methylbenzoyl)hydrazino]carbonyl}phenyl)-1H-imidazole-5-carboxamide (Ex. 62); N-[5-({2-[(4-chloropyridin-2-yl)carbonyl]hydrazino}carbonyl)-2-methylphenyl]-1-methyl-1H-imidazole-5- carboxamide (Ex.63).

12. Compound or pharmaceutically acceptable salt thereof according to claim 11 selected from 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.1); 1-Methyl-N-{3-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.4); 4-Chloro-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex.5); N-{2-chloro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.6); N-{5-[(4-chlorobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.9); 1-Methyl-N-[2-methyl-5-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]-1H-imidazole-5-carboxamide (Ex.10); 1-Methyl-N-(2-methyl-5-{[(2-methyl-3-thienyl)carbonyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.11); N-(5-{[(3,4-dichlorophenyl)carbamoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.12); N-{2-fluoro-5-[(4-methylbenzoyl)amino]phenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.14); N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (Ex.17); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxybenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.21); 1-Methyl-N-(2-methyl-5-{[4-(trifluoromethyl)benzoyl]amino}phenyl)-1H-imidazole-5-carboxamide (Ex.22); N-(5-{[3,5-bis(trifluoromethyl)benzoyl]amino}-2-methylphenyl)-1-methyl-1H-imidazole-5-carboxamide (Ex.23); 4-Methoxy-N-(4-methyl-3-{[(1-methyl-1H-imidazol-5-yl)carbonyl]amino}phenyl)-pyridine-2-carboxamide (Ex. 25);N-{5-[(4-cyanobenzoyl)amino]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.26); N-{5-[(4-chlorophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.28); 1-Methyl-N-(2-methyl-5-{[2-methyl-5-({[3-(trifluoromethyl)phenyl]- carbamoyl}amino)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.29); N-{5-[(3,4-dimethoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.30); N-{5-[(2,4-dichloro-5-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex. 31); N-{5-[(2-fluoro-4-methoxy-5-nitrophenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.32); 1-Methyl-N-{2-methyl-5-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.34); N-{5-[(5-tert-butylisoxazol-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.35); N-{5-[(4-chlorobenzyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.36); N-{5-[(4-methoxyphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.37); N-{5-[(5-methoxypyridin-3-yl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.38); 1-Methyl-N-{2-methyl-5-[(4-methylphenyl)carbamoyl]phenyl}-1H-imidazole-5-carboxamide (Ex.39); N-(5-{[4-(4-bromo-1H-imidazol-1-yl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.40); 1-Methyl-N-(2-methyl-5-{[3-(trifluoromethyl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.42); N-[5-(cyclohexylcarbamoyl)-2-methylphenyl]-1-methyl-1H-imidazole-5-carboxamide (Ex.45); N-{5-[(4-acetylphenyl)carbamoyl]-2-methylphenyl}-1-methyl-1H-imidazole-5-carboxamide (Ex.49); 1-Methyl-N-(2-methyl-5-{[4-(1H-pyrazol-3-yl)phenyl]carbamoyl}phenyl)-1H-imidazole-5-carboxamide (Ex.53); N-(5-{[3-(1H-benzimidazol-1-ylmethyl)phenyl]carbamoyl}-2-methylphenyl)-1-methyl-1H-imidazole-5- carboxamide (Ex.55).

13. Compound or pharmaceutically acceptable salt thereof according to any of claims 11-12 which is 1-Methyl-N-{2-methyl-5-[(4-methylbenzoyl)amino]phenyl}-1H-imidazole-5-carboxamide (Ex.1).

14. Compound of general formula (I), or pharmaceutically acceptable salt thereofwherein Ar is phenyl, or 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms independently selected from N and S, such as pyrrole, tiophene, imidazole, pyrazole, thiazole, pyridine, pyridazine, pyrimidine, pyrazine, thiazine; wherein each of the phenyl and the heteroaromatic ring is optionally substituted with 1 or 2 substituents independently selected from C1-4 alkyl, halogen, -OH, -NH2, -NHC1-4 alkyl, C1-4 alkoxy; R1is H, halogen, C1-2 alkyl, or C1-2 alkoxy; R2is H, halogen, or C1-2 alkyl;X1is NH or CO X2is NH or CO, with the proviso that X1and X2are not the same; Y is a bond or (CH2)n; where n is 1 or 2; or Y is NH, provided that X2is CO; or Y is NHCO, provided that X2is NH; Z is phenyl, or a 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, or a 7-10-membered aromatic bicyclic moiety containing 1-3 heteroatoms, independently selected from N, O and S, preferably N, or 3-, 4-, 5- or 6-membered cycloalkyl group, or a 5- or 6-membered saturated heterocyclic ring comprising 1 or 2 heteroatoms independently selected from N, O and S, where any of these rings or cyclic groups is optionally substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, benzyloxy, halogen, trihalogenoC1-2 alkyl, -NO2, -CN, -OH, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, di(C1-2 alkyl)aminoC1-4 alkyl, di(C1-2 alkyl)aminoC1-4 alkenylcarbonyl, phenyl, -Nhphenyl, C1-4 alkoxycarbonyl group, C1-4 alkylcarbonyl group, C2-4 alkenylcarbonyl group, 5- or 6-membered saturated heterocyclic ring containing 1-3 heteroatoms independently selected from N, O and S, 5- or 6-membered heteroaromatic ring containing 1-3 heteroatoms independently selected from N, O and S, heterocyclylaminosulfonyl group, heteroarylaminosulfonyl group, arylcarbonylamino group, heteroarylcarbonylamino group, 3-, 4-, 5- or 6-membered cycloalkyl group, heterocyclylalkyl group, heteroarylalkyl group, -NH-C(O)-NH-phenyl, N(C1-4 alkyl)-C(O)-C1-2alkyl-heterocyclyl, where the phenyl, saturated heterocyclic ring and heteroaromatic ring moiety of any of said substituents is optionally further substituted with one or more substituents independently selected from C1-4 alkyl, C1-4 alkoxy, halogen, -OH, hydroxyalkyl, - S(O)2-C1-2 alkyl, trihalogenomethyl, -NO2, -CN, -NH2, -NHC1-4 alkyl, -N(C1-4 alkyl)2, C1-4 alkoxycarbonyl group, or compound according to any of claims 1 to 13, for use as a medicine, preferably for use in therapy or as a prophylactic.

15. Compound as defined in claim 14 or compound according to any of claims 1 to 13 for use in treating or preventing a platelet-derived growth factor receptor (PDGFR) mediated disease or disorder, wherein preferably the platelet-derived growth factor receptor (PDGFR) is PDGFR-alpha (PDGFR-A) and / or PDGFR-beta (PDGFR-B) homodimer or heterodimer.

16. Compound as defined in claim 14 or compound according to any of claims 1 to 13 for use in treating or preventing a cell proliferative disease, wherein preferably the cell proliferative disease is selected from fibrosis comprising progressive fibrosis, a fibroproliferative disease, in particular a fibroproliferative disease involving progressive fibrosis, tumours, cancers and neoplasms.

17. Compound as defined in claim 14 or compound according to any of claims 1 to 13 or a compound for use according to claims 16, for use in treating or preventing diseases or disorders or conditions associated with or characterized by fibrosis, or a fibroproliferative disorder.

18. The compound for use according to claim 17, wherein the disease associated with or characterized by fibrosis is selected from renal disease, lung disease, pancreatic disease, intestinal disease, hepatic disease, eye disease, metabolic disease, autoimmune disease, skin disease, disease of the urogenital tract, disease associated with pathological pregnancy, cardiovascular disease, skeletal muscle disease or central nervous system disease; preferably, the disease associated with or characterized by fibrosis is any of the diseases described in the Detailed description of the invention.

19. Compound as defined in claim 14 or compound according to any of claims 1 to 13 or a compound for use according to any of claims 16 to 18, wherein the disease is lung fibrosis or renal fibrosis or dermal fibrosis, or a fibroproliferative disease of the lung, the kidney or the skin, in particular psoriasis.

20. Compound as defined in claim 14 or compound according to any of claims 1 to 13 or a compound for use according to claim 16, for use in treating or preventing a PDGFR and / or c-Kit-mediated disease or disorder; preferably wherein the PDGFR and / or c-Kit mediated disease or disorder is a cancer or a tumour, more preferably wherein the disease or disorder is gastrointestinal cancer.

21. Compound as defined in claim 14 or compound according to any of claims 1 to 13 for use in treating or preventing a cancer or a tumour; preferably, the cancer or tumour is associated with c-Kit, more preferably wherein the cancer is gastrointestinal cancer.

22. Compound as defined in claim 14 or compound according to any of claims 1 to 13 for use in treating or preventing an inflammatory disease or disorder, preferably wherein the inflammatory disease or disorder is chronic inflammation, preferably wherein the disease is psoriasis.

23. Compound for use according to any of claims 14 to 22, in combination with an additional therapeutic agent or active agent or medicament; preferably wherein the additional therapeutic agent or active agent or medicament is an antifibrotic agent, such as nintedanib and / or pirfenidone; and / or wherein the additional therapeutic agent or active agent or medicament is a PDGFR inhibitor, such as avapritinib, dasatinib and / or imatinib.

24. Pharmaceutical composition comprising a Compound as defined in claim 14 or compound according to any of claims 1 to 13 or a compound for use according to any of claims 14 to 22, and a pharmaceutically acceptable carrier or excipient.

25. Pharmaceutical composition comprising a Compound as defined in claim 14 or compound according to any of claims 1 to 13 or a compound for use according to any of claims 14 to 22, and an additional therapeutic agent or active agent or medicament, and a pharmaceutically acceptable carrier or excipient; preferably, wherein the additional therapeutic agent or active agent or medicament is an antifibrotic agent, such as nintedanib and / or pirfenidone; and / or preferably, wherein the additional therapeutic agent or active agent or medicament is a PDGFR inhibitor, such as avapritinib, dasatinib and / or imatinib.

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