Title of Invention	SUBSTITUTED P-DIAMINOBENZENE DERIVATIVES
Abstract	The present invention relates to a substituted p-diaminobenzene derivative of the general formula I wherein the substituents are as described in the description.

Full Text

Substituted p-diaminobenzene derivatives Field of the invention The present invention relates to novel substituted p-diaminobenzene derivatives being openers of the KCNQ family potassium ion channels. The compounds are useful for the prevention, treatment and inhibition of disorders and diseases being responsive to opening of the KCNQ family potassium ion channels, one such disease is epilepsy. Background of the invention Ion channels are cellular proteins that regulate the flow of ions, including potassium, calcium, chloride and sodium into and out of cells. Such channels are present in all animal and human cells and affect a variety of processes including neuronal transmission, muscle contraction, and cellular secretion. Humans have over 70 genes encoding potassium channel subunits (jentsch Nature Reviews Neuroscience 2000,1,21-30) with a great diversity with regard to both structure and function. Neuronal potassium channels, which are found in the brain, are primarily responsible for maintaining a negative resting membrane potential, as well as controlling membrane repolarisation following an action potential. One subset of potassium channel genes is the KCNQ family. Mutations in four out of five KCNQ genes have been shown to underlie diseases including cardiac arrhythmias, deafness and epilepsy (Jentsch Nature Reviews Neuroscience 2000,1, 21-30). The KCNQ4 gene is thought to encode the molecular correlate of potassium channels found in outer hair cells of the cochlea and in Type I hair cells of the vestibular apparatus, in which mutations can lead to a form of inherited dea&ess. KCNQ1 (KvLQTl) is co-assembled with the product of the KCNE1 (minimal K(+> channel protein) gene in the heart to form a cardiac-delayed rectifier-like K(+) current. Mutations in this channel can cause one form of inherited long QT syndrome type 1 (LQT1), as well as being associated with a form of dea&ess (Robbins Pharmacol Ther 2001,90,1-19). The genes KCNQ2 and KCNQ3 were discovered in 1988 and appear to be mutated in an inherited fonn of epilepsy known as benign familial neonatal convulsions (Rogawski Trends in Neurosciences 2000,23,393-398). The proteins encoded by the KCNQ2 and KCNQ3 genes are localised in the pyramidal neurons of the human cortex and hippocampus, regions of the brain associated with seizure generation and propagation (Cooper et al. Proceedings National Academy of Science USA 2000,97, 4914-4919). KCNQ2 and KCNQ3 are two potassium channel subunits that form "{M-currents" when expressed in vitro. The M-current is a non-inactivating potassium current found in many neuronal cell types. In each cell type, it is dominant in controlling membrane excitability by being the only sustained current in the range of action potential initiation (Marrion Annual Review Physiology 1997,59,483-504). Modulation of the M-current has dramatic effects on neuronal excitability, for example activation of the current will reduce neuronal excitability. Openers of these KCNQ channels, or activators of the M-current, will reduce excessive neuronal activity and may thus be of use in the treatment, prevention or inhibition of seizures and other diseases and disorders characterised by excessive neuronal activity, such as neuronal hyperexcitability including convulsive disorders, epilepsy and neuropathic pain. Retigabine (D-23129; N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester) and analogues thereof are disclosed in EP554543. Retigabine is an anticonvulsive compound with a broad spectrum and potent anticonvulsant properties, both in vitro and in vivo. It is active after oral and intraperitoneal administration in rats and mice in a range of anticonvulsant tests including: electrically induced seizures, seizures induced chemically by pentylenetetrazole, picrotoxin and N-methyl-D-aspartate (NMDA) and in a genetic animal model, the DBA/2 mouse (Rostock et al. Epilepsy Research 1996,23,211-223). In addition, retigabine is active in the amygdala kindling model of complex partial seizures, further indicating that this compound has potential for anti-convulsive therapy. In clinical trials, retigabine has recently shown effectiveness in reducing the incidence of seizures in epileptic patients (Bialer et al. Epilepsy Research 2002,51,31-71). Retigabine has been shown to activate a K(+) current in neuronal cells and the pharmacology of tins induced current displays concordance with the published pharmacology of the M-channel, which recently was correlated to the KCNQ2/3 K(+) channel heteromultimer. This suggests that activation of KCNQ2/3 channels may be responsible for some of the anticonvulsant activity of this agent (Wickenden et al. Molecular Pharmacology 2000, 58, 591-600) - and that other agents working by the same mechanism may have similar uses. KCNQ 2 and 3 channels have also been reported to be upregulated in models of neuropathic pain (Wickenden et al. Society for Neuroscience Abstracts 2002,454.7), and potassium channel modulators have been hypothesised to be active in both neuropathic pain and epilepsy (Schroder et al Neuropharmacology 2001,40, 888-898). Retigabine has also been shown to be beneficial in animal models of neuropathic pain (Blackburn-Munro and Jensen European Journal of Pharmacology 2003,460,109-116), and it is thus suggested that openers of KCNQ channels will be of use in treating pain disorders including neuropathic pain. The localisation of KCNQ channel mRNA is reported in brain and other central nervous system areas associated with pain (Goldstein et al. Society for Neuroscience Abstracts 2003,53.8). In addition to a role in neuropathic pain, the expression of mRNA for KCNQ 2-5 in the trigeminal and dorsal root ganglia and in the trigeminal nucleus caudalis implies that openers of these channels may also affect the sensory processing of migraine pain (Goldstein et al. Society for Neuroscience Abstracts 2003, 53.8). Recent reports demonstrate that mRNA for KCNQ 3 and 5, in addition to that for KCNQ2, are expressed in astrocytes and glial cells. Thus KCNQ 2,3 and 5 channels may help modulate synaptic activity in the CNS and contribute to the neuroprotective effects of KCNQ channel openers (Noda et al, Society for Neuroscience Abstracts 2003, 53.9). Retigabine and other KCNQ modulators may thus exhibit protection against the neurodegenerative aspects of epilepsy, as retigabine has been shown to prevent limbic neurodegeneration and the expression of markers of apoptosis following kainic acid-induced status epilepticus in the rat (Ebert et al. Epilepsia 2002,43 Suppl 5, 86-95). This may have relevance for preventing the progression of epilepsy in patients, i.e. be anti-epileptogenic. Retigabine has also been shown to delay the progression of hippocampal kindling in the rat, a further model of epilepsy development (Tober et al. European Journal Of Pharmacology 1996, 303,163-169). It is thus suggested that these properties of retigabine and other KCNQ modulators may prevent neuronal damage induced by excessive neuronal activation, and may be of use in the treatment of neurodegenerative diseases, and be disease modifying (or antiepileptogenic) in patients with epilepsy. Given that anticonvulsant compounds such as benzodiazepines and chlormethiazole are used clincially in the treatment of the ethanol withdrawal syndrome and that other anticonvulsant compounds e.g. gabapentin, are very effective in animal models of this syndrome (Watson et al. Neuropharmacology 1997,36,1369-1375), other anticonvulsant compounds such as KCNQ openers are thus expected to be effective in this condition. mRNA for KCNQ 2 and 3 subunits are found in brain regions associated with anxiety and emotional behaviours such as bipolar disorder e.g. hippocampus and amygdala (Saganich et al. Journal of Neuroscience 2001, 21,4609-4624), and retigabine is reportedly active in some animal models of anxiety-like behaviour (Hartz et al. Journal of Psychopharmacology 2003,17 suppl 3, A28,B16), and other clinically used anticonvulsant compounds are used in the treatment of bipolar disorder. WO 200196540 discloses the use of modulators of the M-current formed by expression of KCNQ2 and KCNQ3 genes for insomnia, while WO 2001092526 discloses that modulators of KCNQ5 can be utilized for the treatment of sleep disorders. WO01/022953 describes the use of retigabine for prophylaxis and treatment of neuropathic pain such as allodynia, hyperalgesic pain, phantom pain, neuropathic pain related to diabetic neuropathy and neuropathic pain related to migraine. WO02/049628 describes the use of retigabine for the prevention, treatment, inhibition and amelioration of anxiety disorders such as anxiety, generalized anxiety disorder, panic anxiety, obsessive compulsive disorder, social phobia, performance anxiety, post-traumatic stress disorder, acute stress reaction, adjustment disorders, hypochondriacal disorders, separation anxiety disorder, agoraphobia and specific phobias. WO97/15300 describes the use of retigabine for the treatment of neurodegenerative disorders such as Alzheimer's disease; Huntington's chorea; sclerosis such as multiple sclerosis and amyotrophic lateral sclerosis; Creutzfeld-Jakob disease; Parkinson's disease; encephalopathies induced by AIDS or infection by rubella viruses, herpes viruses, borreha and unknown pathogens; trauma-induced neurodegenerations; neuronal hyperexcitation states such as in medicament withdrawal or intoxication; and neurodegenerative diseases of the peripheral nervous system such as polyneuropathies and polyneuritides. Hence, there is a great desire for novel compounds, which are potent openers of the KCNQ family potassium channels. Also desired are novel compounds with improved properties relative to known compounds, which are openers of the KCNQ family potassium channels, such as retigabine. Improvement of one or more of the following parameters is desired: half-life, clearance, selectivity, interactions with other medications, bioavailability, potency, formulability, chemical stability, metabolic stability, membrane permeability, solubility and therapeutic index. The improvement of such parameters may lead to improvements such as: © an improved dosing regime by reducing the number of required doses a day, o ease of administration to patients on multiple medications, • reduced side effects, • enlarged therapeutic index, • improved tolerability or • improved compliance. Summary of the invention One object of the present invention is to provide novel compounds, which are potent openers of the KCNQ family potassium channels. The compounds of the invention are substituted aniline derivatives of the general , formula I or salts thereof wherein Y, U, X, Z, s, q, R1, R2 and R3 are as defined below. The invention further relates to a pharmaceutical composition comprising one or more compounds of formula I and the use thereof. Detailed description of the invention Accordingly, the present invention relates to substituted p-diaminobenzene derivatives of the general formula I In yet another embodiment, the invention relates to compounds of formula I, wherein s is 1 and U is S02NR11. In such compounds, the sulphur atom of SO2NR11 is attached to the benzene ring of formula I whereas the nitrogen atom is attached to R2. In yet another embodiment, the invention relates to compounds of formula I, wherein s is 1 and U is CO-O. In such compounds, the carbonyl group of CO-0 is attached to the benzene ring of formula I whereas the oxygen atom is attached to R2. In yet another embodiment, the invention relates to compounds of formula I, wherein s is 1 and U is CO-NR11. In such compounds, the carbonyl group of CO-NR11 is attached to the benzene ring of formula I whereas the nitrogen atom is attached to R2. In yet another embodiment, the invention relates to compounds of formula I, wherein Rn is a hydrogen atom. In yet another embodiment, the invention relates to compounds of formula I, wherein X is CO. In yet another embodiment, the invention relates to compounds of formula I, wherein X is SO2, with the proviso that q is 0 when X is SO2. In yet another embodiment, the invention relates to compounds of formula I, wherein q is 0. In yet another embodiment, the invention relates to compounds of formula I, wherein q is 1. In yet another embodiment, the invention relates to compounds of formula I, wherein q is 1 and Z is 0. ) In yet another embodiment, the invention relates to compounds of formula I, wherein q is 1 and Z is S. In yet another embodiment, the invention relates to compounds of formula I, wherein Xis CO,q is land Z is O. In yet another embodiment, the invention relates to compounds of formula I, wherein X is CO, q is l and Z is S. In yet another embodiment, the invention relates to compounds of formula I, wherein X is CO and q is 0. In yet another embodiment, the invention relates to compounds of formula I, wherein X is SO2 and q is 0. In another embodiment, the invention relates to compounds of formula I, wherein R1 is selected from the group consisting of acyl, hydroxy-C1-6-alk(en/yn)yl, hydroxy-C3-8-cycloalk(en)yl, hydroxy-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl, halo-CW alk(en/yn)yl, halo-C3-8-cycloalk(en)yl, halo-C3.8-cycloalk(en)yl-C1-6-alk(en/yn)yl, cyano-C1-6-alk(en/yn)yl, cyano-C3-8-cycloalk(en)yl and cyano-C3.8-cycloalk(en)yl-C1-6-alk(en/yn)yl. One embodiment of the invention relates to compounds of the general formula I, wherein R1 is selected from the group consisting of hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl and C3-8-Cycloalk(en)yl-C1-6-alk(en/yn)yl. A preferred embodiment of the invention relates to compounds of the general formula I, wherein R1 is selected from the group consisting of hydrogen and C1-6-alk(en/yn)yl In yet another embodiment, the invention relates to compounds of formula I, wherein R1 is C1-6-alk(en/yn)yl, typically Ci-3-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R1 is a hydrogen atom. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is selected from the group consisting of hydrogen, acyl, hydroxy-Ci^-aUc(en/yn)yl, In a preferred embodiment, the invention relates to compounds of formula I, wherein R2 is selected from the group consisting of C«-a]k(en/yn)yl, C3-8-cycloalk(en)yl, Ax-C1-6-alk(en/yn)yl, halogen and cyano; provided that when R2 is halogen or cyano then s is 0. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is a hydrogen atom. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is not a hydrogen atom. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is C1-6-alk(en/yn)yl, C1-3-alk(en/yn)yl.' In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is C3-8-cycloalk(en)yl, typically C3-6-cycloalk(en)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is Ar. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is not Ar. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is Ar~C1-6-alk(en/yn)yl, typically Ar-C1-3-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is a halogen atom, typically a chloro atom, a bromo atom or an iodo atom. In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is halo-C1-6-alk(en/yn)yl, typically halo-C1-3-alk(en/yn)yl In yet another embodiment, the invention relates to compounds of formula I, wherein R2 is not halo-C1-6-alk(en/yn)yl, typically halo-C1-3-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is Ar . In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is heterocycloalk(en)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is not heterocycloalk(en)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is heterocycloalk(en)yl-C1-6-allc(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is not heterocycloalk(en)yl-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is Ar-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is C1-6-alk(en/yn)yloxy-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is not C1-6-alk(en/yn)yloxy-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is Ar-oxy-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is Ar-C1-6-alk(en/yn)yloxy-C1-6-alk(en/yn)yl, In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is C1-6-alk(en/yn)yloxy-carbonyl-C1-6-alk(en/yn)yL In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is halo-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is halo-C1-6-alk(en/yn)yl-Ar. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is not halo-C1-6-alk(en/yn)yl-Ar. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is NR12R12 In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is not NR12R12. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is optionally substituted NR12R12-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is different from optionally substituted NR12R12'-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is optionally substituted NR,12R12-C3.8-cycloallc(en)yL In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is different from optionally substituted NR12R12,-C3-8-cycloalk(en)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein R3 is optionally substituted NR12R12,-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl. In a preferred embodiment, the invention relates to compounds of formula I, wherein R3 is Ar and q is 0. In a preferred embodiment, the invention relates to compounds of formula I, wherein R3 is not Ar when q is 0. In another embodiment, the invention relates to compounds of formula I, wherein Y is of formulae XXIV, XXV, XXVH, XXXXI or XXXXIL In another embodiment, the invention relates to compounds of formula I, wherein Y is of formula XXIV, In yet another embodiment, the invention relates to compounds of formula I, wherein Y is of formula XXV. In yet another embodiment, the invention relates to compounds of formula I, wherein Y is of formula XXVH. In yet another embodiment, the invention relates to compounds of formula I, wherein Y is of formula XXXXI. In yet another embodiment, the invention relates to compounds of formula I, wherein Y is of formula XXXXIL In yet another embodiment, the invention relates to compounds of formula I, wherein W is an oxygen atom. In yet another embodiment, the invention relates to compounds of formula I, wherein W is a sulphur atom. In yet another embodiment, the invention relates to compounds of formula I, wherein V is a nitrogen atom. In yet another embodiment, the invention relates to compounds of formula I, wherein one R5 is a halogen atom. In yet another embodiment, the invention relates to compounds of formula I, wherein one R5 is halo-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein no R5 is halo-Ci*6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein one R5 is halo-C3-8-cycloalk(en)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein no R5 is halo-C3-8-Cycloalk(en)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein one R5 is halo-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein no R5 is halo-C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl. In yet another embodiment, the invention relates to compounds of formula I, wherein one R5 is NR7R7. In yet another embodiment, the invention relates to compounds of formula I, wherein no R5 is NR7R7 In yet another embodiment, the invention relates to compounds of formula I, wherein one R5 is S-R8. In yet another embodiment, the invention relates to compounds of formula I, wherein one R5 is S02R8. In an embodiment, the invention relates to compounds of the general formula XXXI, wherein the nitrogen atom is attached to position 2 of the heteroaromatic group via the methylene group. In another embodiment, the invention relates to compounds of the general formula XXXI, wherein the nitrogen atom is attached to position 3 of the heteroaromatic group via the methylene group. In yet another embodiment, the invention relates to compounds of the general formula XXXI, wherein a is 0,1 or 2. In yet another embodiment, the invention relates to compounds of the general formula XXXI, wherein a is 0. In yet another embodiment, the invention relates to compounds of the general formula XXXI being substituted by one substituent R5. In yet another embodiment, the invention relates to compounds of the general formula XXXI being substituted by two independently selected R5 substituents. R11 , R12 and R12' are as defined under formula I. Any of the embodiments related to formula I are also embodiments of formula XXXII. In one embodiment, the invention relates to compounds of the general formula XXXII, wherein the nitrogen atom is attached to position 2 of the heteroaromatic group via the methylene group. In another embodiment, the invention relates to compounds of the general formula XXXII, wherein the nitrogen atom is attached to position 3 of the heteroaromatic group via the methylene group. In yet another embodiment, the invention relates to compounds of the general formula XXXII, wherein b is 0,1,2 or 3, typically 0,1 or 2. In yet another embodiment, the invention relates to compounds of the general formula XXXII, wherein c is 0 or 1, typically 0. In yet another embodiment, the invention relates to compounds of the general formula XXXII, wherein both b and c are 0. In yet another embodiment, the invention relates to compounds of the general formula XXXH being substituted by one substituent R5, in an aspect thereof b is 0 and c is 1 and in another aspect thereof b is 1 and c is 0. In yet another embodiment, the invention relates to compounds of the general formula XXXII being substituted by two independently selected R5 substituents, in an aspect thereof b is 1 and c is 1 and in another aspect thereof b is 2 and c is 0. In yet another embodiment, the invention relates to compounds of the general formula XXXII being substituted by threee independently selected R5 substituents, in an aspect thereof b is 2 and c is 1 and in another aspect thereof b is 3 and c is 0. Yet another aspect of the invention relates to compounds of the general formula XXXIII or salts thereof: In an embodiment, the invention relates to compounds of the general formula XXXIII, wherein the nitrogen atom is attached to position 4 of the heteroaromatic group via the methylene group. In another embodiment, the invention relates to compounds of the general formula XXXIII, wherein the nitrogen atom is attached to position 5 of the heteroaromatic group via the methylene group. In an embodiment, the invention relates to compounds of the general formula XXXIII, wherein the nitrogen atom is attached to position 6 of the heteroaromatic group via the methylene group. In another embodiment, the invention relates to compounds of the general formula XXXIII, wherein the nitrogen atom is attached to position 7 of the heteroaromatic group via the methylene group. In yet another embodiment, the invention relates to compounds of the general formula XXXIII, wherein d is 0,1 or 2, typically 0 or 1. In yet another embodiment, the invention relates to compounds of the general formula XXXIII, wherein e is 0,1 or 2. In yet another embodiment, the invention relates to compounds of the general formula XXXIXI, wherein both d and e are 0. In yet another embodiment, the invention relates to compounds of the general formula XXXIII being substituted by one substituent R5, in a particular aspect thereof d is 0 and e is 1 and in another particular aspect thereof d is 1 and e is 0. In yet another embodiment, the invention relates to compounds of the general formula XXXIII being substituted by two independently selected R5 substituents, in a particular aspect thereof d is 0 and e is 2, in another particular aspect thereof d is 1 and e is 1 and in yet another aspect thereof d is 2 and e is 0. In yet another embodiment, the invention relates to compounds of the general formula XXXIII being substituted by three independently selected R5 substituents, in an aspect thereof d is 1 and e is 2, in another aspect thereof d is 2 and e is 1 and in yet another aspect thereof d is 3 and e is 0. In another embodiment, the invention relates to compounds of the general formula XXXIII, wherein V is a carbon atom to which the nitrogen atom is attached via the methylene group. In an embodiment, the invention relates to compounds of the general formula XXXXIII, wherein the nitrogen atom is attached to the carbon atom, which is indicated with "1", via the methylene group. In an embodiment, the invention relates to compounds of the general formula XXXXHI, wherein the nitrogen atom is attached to the carbon atom, which is indicated with "2", via the methylene group. In another embodiment, the invention relates to compounds of the general formula XXXXIII, wherein the nitrogen atom is attached to the carbon atom, which is indicated with "3", via the methylene group. In another embodiment, the invention relates to compounds of the general formula XXXXIII, wherein the nitrogen atom is attached to the carbon atom, which is indicated with "4", via the methylene group. In yet another embodiment, the invention relates to compounds of the general formula XXXXIII, wherein dd is 0,1 or 2, typically 0 or 1. In one aspect of the invention dd is 0. In another aspect of the invention dd is 0. Yet another aspect of the invention relates to compounds of the general formula XXXXIV or salts thereof: wherein aa, s, q, T, U, X, Z, R\ R2, R3 and R5 are as defined under formula I. Any of the embodiments related to formula I are also embodiments of formula XXXXIV. In an embodiment, the invention relates to compounds of the general formula XXXXIV, wherein T is a nitrogen atom to which the nitrogen atom is attached via the methylene group. In an embodiment, the invention relates to compounds of the general formula XXXXIV, wherein the nitrogen atom is attached to the carbon atom, which is indicated with "1", via the methylene group. In an embodiment, the invention relates to compounds of the general formula XXXXIV, wherein the nitrogen atom is attached to the carbon atom, which is indicated with "2", via the methylene group. In another embodiment, the invention relates to compounds of the general formula XXXXIV, wherein the nitrogen atom is attached to the carbon atom, which is indicated with "3", via the methylene group. In yet another embodiment, the invention relates to compounds of the general formula XXXI, wherein aa is 0,1 or 2. In one embodiment aa is 0. In another embodiment, the general formula XXXXIV are substituted by one substituent R5. In yet another embodiment, the compounds of the general formula XXXI are substituted by two independently selected R5 substituents. XXXI or a salt thereof; or two compounds of formula XXXI or salts thereof; or three compounds of formula XXXI or salts thereof. According to one embodiment, the invention relates to a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers or diluents and a compound of formula XXXII wherein b, c, s, q, U, W, X, Z, R1, R2, R3 and R5 are as defined above, accordingly any of b, c, s, q, U, W, X, Z, R1, R2, R3, R5, R6, R6, R7, R7', R8, R9, R9', R10, R10', R11, R12 and R12'are as defined under formula XXXH. Pharmaceutical compositions of the invention may thus comprise one or more compounds of formula XXXII or salts thereof, such as one compound of formula XXXII or a salt thereof; or two compounds of formula XXXII or salts thereof; or three compounds of formula XXXII or salts thereof. According to one embodiment, the invention relates to a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers or diluents and a compound of formula XXXIII wherein d, e, s, q, U, W, X, Z, R1, R2, R3 and Rs are as defined above, accordingly any of d, e, g, q, U, W, X, Z, R1, R2, R3, R5, R6, R6', R7, Rr, R8, R9, R9\ R10, R10', R11, R12 and R12'are as defined under formula XXXIII. Pharmaceutical compositions of the invention may thus comprise one or more compounds of formula XXXIII or salts thereof such as one compound of formula XXXIII or a salt thereof; or two compounds of formula XXXIII or salts thereof; or three compounds of formula XXXIII or salts thereof. The invention thus provides a pharmaceutical composition for oral or parenteral administration, said pharmaceutical composition comprising at least one compound of fonnula I or XXIX or XXX or XXXI or XXXII or XXXIII or a salt thereof in a therapeutically effective amount together with one or more pharmaceuically acceptable carriers or diluents. In one aspect, the compounds of the invention may be administered as the only therapeutically effective compound. In another aspect the compounds of the invention may be administered as a part of a combination therapy, i.e. the compounds of the invention may be administered in combination with other therapeutically effective compounds having e.g. anticonvulsive properties. The effects of such other compounds having anti-convulsive properties may include but not be limited to activities on: . ion channels such as sodium, potassium, or calcium channels . the excitatory amino acid systems e.g. blockade or modulation of NMDA receptors the inhibitory neurotransmitter systems e.g. enhancement of GABA release, or blockade of GABA-uptake or membrane stabilisation effects. Current anti-convulsive medications include, but are not limited to, tiagabine, carbamazepine, sodium valproate, lamotrigine, gabapentin, pregabalin, ethosuximide, levetiracetam, phenytoin, topiramate, zonisamide as well as members of the benzodiazepine and barbiturate class. In one aspect, the compounds of the invention have been found to have effect on potassium channels of the KCNQ family, in particular the KCNQ2 subunit. In one embodiment, the invention relates to the use of one or more compounds according to the invention in a method of treatment. The disorder or condition to be prevented, treated or inhibited is responsive to an increased ion flow in a potassium channel such as the KCNQ family potassium ion channels. Such disorder or condition is preferably a disorder or condition of the central nervous system. The compounds of the invention are considered useful for increasing ion flow in a voltage-dependent potassium channel in a mammal such as a human. The compounds of the invention are considered useful for the prevention, treatment or inhibition of a disorder or condition being responsive to an increased ion flow in a potassium channel such as the KCNQ family potassium ion channels. Such disorder or condition is preferably a disorder or condition of the central nervous system. The compounds of the invention are thus considered useful for preventing, treating or inhibiting disorders or diseases such as seizure disorders, neuropathic and migraine pain disorders, anxiety disorders and neurodegenerative disorders. Accordingly, the compounds of the invention are considered useful for the prevention, treatment or inhibition of disorders or conditions such as convulsions, epilepsy, anxiety disorders, neuropathic pain and neurodegenerative disorders. According to one particular embodiment, the compounds of the invention are thus considered to be useful for preventing, treating or inhibiting seizure disorders such as convulsions, epilepsy and status epilepticus. In one embodiment, the compounds of the invention are considered useful in the prevention, treatment and inhibition of convulsions. In another embodiment, the compounds of the invention are considered useful in the prevention, treatment and inhibition of epilepsy, epileptic syndromes and epileptic seizures. In yet another embodiment, the compounds of the invention are considered useful in the prevention, treatment and inhibition of anxiety disorders such as anxiety and conditions and diseases related to panic attack, agoraphobia, panic disorder with agoraphobia, panic disorder without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia and other specific phobias, obsessive-compulsive disorder, posttraumatic stress disorder, acute stress disorders, generalized anxiety disorder, anxiety disorder due to general medical condition, substance-induced anxiety disorder, separation anxiety disorder, adjustment disorders, performance anxiety, hypochondriacal disorders, anxiety disorder due to general medical condition and substance-induced anxiety disorder and anxiety disorder not otherwise specified. In yet another embodiment, the compounds of the invention are considered useful in the prevention, treatment and inhibition of neuropathic pain and migraine pain disorders such as allodynia, hyperalgesic pain, phantom pain, neuropathic pain related to diabetic neuropathy and neupathic pain related to migraine. In yet another embodiment, t the compounds of the invention are considered useful in the prevention, treatment and inhibition of neurodegenerative disorders such as Alzheimer's disease; Huntington's chorea; multiple sclerosis; amyotrophic lateral sclerosis; Creutzfeld-Jakob disease; Parkinson's disease; encephalopathies induced by AIDS or infection by rubella viruses, herpes viruses, borrelia and unknown pathogens; trauma-induced neurodegenerations; neuronal hyperexcitation states such as in medicament withdrawal or intoxication; and neurodegenerative diseases of the peripheral nervous system such as polyneuropathies and polyneuritides. In yet another embodiment, the compounds of the invention are considered useful in the prevention, treatment and inhibition of neurodegenerative disorders such as Alzheimer's disease; Huntington's chorea; multiple sclerosis; amyotrophic lateral sclerosis; Creutzfeld-Jakob disease; Parkinson's disease; encephalopathies induced by AIDS or infection by rubella viruses, herpes viruses, borrelia and unknown pathogens; and trauma-induced neurodegenerations. In yet another embodiment, the compounds of the invention are considered useful in the prevention, treatment and inhibition of neuronal hyperexcitation states such as in medicament withdrawal or intoxication. The invention provides compounds showing effect in one or more of the following tests: • "Relative efflux through the KCNQ2 channel" Which is a measure of the potency of the compound at the target channel • 'Maximum electroshock" Which is a measure of seizures induced by non-specific CNS stimulation by electrical means © "Pilocarpine induced seizures" Seizures induced by pilocarpine are often difficult to treat with many existing antiseizure medications and so reflect a model of "drug resistant seizures" • "Electrical seizure-threshold tests" and "Chemical seizure-threshold tests" These models measure the threshold at which seizures are initiated, thus being models that detect whether compounds could delay seizure initiation. o "Amygdala kindling" Which is used as a measure of disease progression, as in normal animals the seizures in this model get more severe as the animal receives further stimulations. According to one particular aspect of the invention, the compounds are KCNQ2 active with an EC50 of less than 15000nM such as less than 10000 nM as measured by the test "Relative efflux through the KCNQ2 channel" which is described below. According to one particular aspect of the invention, the compounds are KCNQ2 active with an EC50 of less than 2000nM such as less than 1500nM as measured by the test "Relative efflux through the KCNQ2 channel" which is described below. According to another particular aspect of the invention, the compounds are KCNQ2 active with an EC50 of less than 200riM such as less than 150nM as measured by the test "Relative efflux through the KCNQ2 channel" which is described below. According to another particular aspect of the invention, the compounds have an ED50 of less than 15 mg/kg in the test "Maximum electroshock" which is described below. According to yet another particular aspect of the invention, the compounds have an ED50 of less than 5 mg/kg in the test "Maximum electroshock" which is described below. According to one particular aspect of the invention, the compounds have an ED50 of less than 5 mg/kg in the "Electrical seizure -threshold test" and "Chemical seizure -threshold test" which is described below. Some compounds have few or clinically insignificant side effects. Some of the compounds are thus tested in models of the unwanted sedative, hypothermic and ataxic actions of the compounds. Some of the compounds have a large therapeutic index between anticonvulsant efficacy and side-effects such as impairment of locomotor activity or ataxic effects as measured by performance on a rotating rod. This means that the compounds will expectedly be well tolerated in patients permitting high doses to be used before side effects are seen. Thereby compliance with the therapy will expectedly be good and administration of high doses may be permitted making the treatment more efficacious in patients who would otherwise have side effects with other medications. Definitions The term heteroatom refers to a nitrogen, oxygen or sulphur atom. Halogen means fluoro, chloro, bromo or iodo. The expressions C1-6-alk(en/yn)yl and C1-6-alk(an/en/yn)yl mean a C1-6-alkyl, C2-6-alkenyl or a C2-6-alkynyl group. The term C1-6-alkyl refers to a branched or un-branched alkyl group having from one to six carbon atoms inclusive, including but not limited to methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2~methyl-2-propyl and 2-methyl-l-propyl. Similarly, C2-6-alkenyl and C2-6-alkynyl, respectively, designate such groups having from two to six carbon atoms, including one double bond and one triple bond respectively, including but not limited to ethenyl, propenyl, butenyl, ethynyl, propynyl and butynyl. The expressionC1-3-alk(en/yn)yl means aC1-3-alkyl, C2-3-alkenyl or a C2-3-alkynyl group. The term C1-3-alkyl refers to a branched or un-branched alkyl group having from one to three carbon atoms inclusive, including but not limited to methyl, ethyl, 1-propyl and 2-propyl. Similarly, C2-3-alkenyl and C2-3-alkynyl, respectively, designate such groups having from two to three carbon atoms, including one double bond and one triple bond respectively, including but not limited to ethenyl, propenyl, ethynyl and propynyl. The expressions C3-8-cycloalk(en)yl and C3-8-cycloalk(an/en)yl mean a C3-8-cycloallcyl- or cycloalkenyl group. The term C3-8-cycloalkyl designates a monocyclic or bicyclic carbocycle having three to eight C-atoms, including but not limited to cyclopropyl, cyclopentyl, cyclohexyl, etc. The expressions C3-6-cycloalk(en)yl and C3-6-cycloalk(an/en)yl mean a C3-6-cycloalkyl- or cycloalkenyl group. The term C3-6-cycloalkyl designates a monocyclic or bicyclic carbocycle having three to six C-atoms, including but not limited to cyclopropyl, cyclopentyl, cyclohexyl, etc. The term C3-8-cycloalkenyl designates a monocyclic or bicyclic carbocycle having three to eight C-atoms and including one double bond. The term heterocycloalk(en)yl designates monocyclic or bicyclic ring systems wherein the ring is formed by 5 to 8 atoms being selected from the group consisting of carbonatoms and heteroatoms; with the proviso that one or two of the ring forming atoms are independently selected heteroatoms. The term heterocycloalk(en)yl may thus designate a monocyclic or bicyclic ring system wherein the ring is formed by 5 to 8 atoms selected from 3-7 carbonatoms and 1 or 2 heteroatoms selected from N, S, or 0. Examples of such ring systems are morpholine, pyrrolidine, piperidine and piperazine. The term halo-C1-6-alk(en/yn)yl designates C1-6-alk(en/yn)yl being substituted with one or more halogen atoms, including but not limited to trifluoromethyl. Similarly, halo-C3-8-cycloalk(en)yl designates C3.8-cycloalk(en)yl being substituted with one or more halogen atoms andhalo-heterocycloalk(en)yl designates heterocycloalk(en)yl being substituted with one or more halogen atoms. The term NRi0R10'-C1-6-alk(en/yn)yl designates C1-6-alk(en/yn)yl being substituted with NR10R10'; NR12R12-C1-6-alk(en/yn)yl designates C1-6-alk(en/yn)yl being substituted with NR12R12'; and NR7Rr-C1-6"alk(en/yn)yl designates C1-6~alk(en/yn)yl being substituted withNR7R7\ 2-amino-4-methyl»pentane is an example of such group, the example is not intended to be construed as limiting. The term NR10R10'-C3-8-cycloalk(en)yl designates C3.8-cycloalk(en)yl being substituted with NR10R10,;NR12Rir"C3.8-cycloalk(en)yl designates C3.8-cycloalk(en)yl being substituted with NR12R12'; and NR7R7'-C3-8-cycloalk(en)yl designates C3-8-cycloalk(en)yl being substituted with NR7R7\ 1-amino-cyclopropane is an example of such group, the example is not intended to be construed as limiting. The term NR10R10'-C3.8-cycloalk(en)yl-C1-6-alk(en/yn)yl designates C3.8-cycloalk(en)yl-C1-6-alk(en/yn)yl being substituted with NR10R10'; NRnR12,-C3.8-cycloalk(en)yl-Ci,6-alk(en/yn)yl designates C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl being substituted with NR12R12'; andNR7R7'-C3.8-cycloalk(en)yl-C1-6«alk(en/yn)yl designates C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl being substituted withNR7R7'. When any of NR12R12,-C1-6-alk(en/yn)yl, NR12R12,-C3.8-cycloaUc(en)yl, NR12R12'-C3. 8-cycloallc(en)yl-C1-6-alk(en/yn)yl is optionally substituted, then any of Q-6-aflc(en/yn)yl, C3-8-cycloalk(en)yl, C3.8-cycloalk(en)yl-C1-6-alk(en/yn)yl is optionally substituted with one or more substituents independently being C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl or Ar. As used herein, the term acyl refers to formyl, C1-6-a]k(en/yn)ylcarbonyl, C3.8-cycloalk(en)ylcarbonyl, Ar-carbonyl, Ar-C1-6-alk(en/yn)ylcarbonyl or a C3-8-cycloalk(en)yl-C1-6-alk(en/yn)yl-carbonyl group, wherein C1-6-alk(en/yn)yl, C3-8-cycloalk(en)yl and Ar are as defined above. When two substituents together with a nitrogen atom form a 5-8 membered saturated or unsaturated ring which optionally contains one further heteroatom, then a monocyclic ring system is formed by 5 to 8 atoms, one or two of said atoms are heteroatoms selected from N, S, or O. Examples of such ring systems are pyrrolidine, piperidine, piperazine, morpholine, pyrrole, oxazolidine, thiazolidine, imidazolidine, azetidine, beta-lactame, tetrazole and pyrazole. When two adjacent substituents together with an aromatic group to which they are attached form a 5-8 membered ring, which optionally contains one or two heteroatoms, then a ring is formed by 5-8 atoms selected from 3-8 carbonatoms and 0-2 heteroatoms selected from N, S, or 0 and. Such two adjacent substituents may together form: The term Ar refers to optionally substituted aromatic systems of 5-10 carbon atoms, wherein 0,1,2,3 or 4 carbon atoms may be replaced by heteroatoms independently selected from N, S, or 0 . Examples of such Ar groups are optionally substituted phenyl, optionally substituted naphtyl, optionally substituted quinoline, optionally substituted indol, optionally substituted pyridine, optionally substituted pyrimidine, optionally substituted thiophene, optionally substituted furan, optionally substituted thiazole and optionally substituted oxazole. Such optionally substituted Ar groups may be substituted with one or more substituents independently being hydroxy, substituents may together with the aromatic group form a 5-8 membered ring, which optionally contains one or two heteroatoms and which may be saturated or unsaturated. The salts of the invention are preferably pharmaceuically acceptable salts. Such salts include pharmaceuically acceptable acid addition salts, pharmaceuically acceptable metal salts, ammonium and alkylated ammonium salts. The pharmaceuically acceptable salts of the invention are preferably acid addition salts. The acid addition salts of the invention are preferably pharmaceuically acceptable salts of the compounds of the invention formed with non-toxic acids. Acid addition salts include salts of inorganic acids as well as organic acids. Representative examples of suitable inorganic acids include hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfamic, phosphoric and nitric acids and the like. Such acid addition salts can be formed by methods known to the person skilled in the art. Further examples of pharmaceuically acceptable inorganic or organic acid addition salts include the pharmaceuically acceptable salts listed in J. Pharm. Sci. 1917, 66,2, which is incorporated herein by reference. Representative examples of suitable organic acids include formic, acetic, trichloroacetic, trifluoroacetic, propionic, benzoic, cinnamic, citric, fumaric, glycolic, lactic, maleic, malic, malonic, mandelic, oxalic, picric, pyruvic, salicylic, succinic, ethanesulfonic, tartaric, ascorbic, pamoic, gluconic, citraconic, aspartic, stearic, palmitic, EDTA, glycolic, p-aminobenzoic, glutamic, bis-methylenesalicylic, methanesulfonic, ethanedisulfonic, itaconic, benzenesulfonic, p-toluenesulfonic acids, theophylline acetic acids, as well as the 8-halotheophyllines, for example 8-bromotheophylline and the like. Further examples of pharmaceutical acceptable inorganic or organic acid addition salts include the pharmaceutically acceptable salts listed in J. Pharm. Sci. 1977,66,2, which is incorporated herein by reference. Examples of metal salts include lithium, sodium, potassium, magnesium salts and the like. Examples of ammonium and alkylated ammonium salts include ammonium, methyl-, dimethyl-, trimethyl-, ethyl-, hydroxyethyl-, diethyl-, n-butyl-, sec-butyl-, tert-butyl-, tetramethylammonium salts and the like. Also intended as pharmaceutically acceptable acid addition salts are the hydrates, which the present compounds are able to form. The compounds of the present invention may have one or more asymmetric centres and it is intended that any optical isomers, as separated, pure or partially purified optical isomers or racemic mixtures thereof are included within the scope of the invention. Furthermore, when a double bond or a fully or partially saturated ring system is present in the molecule geometric isomers may be formed. It is intended that any geometric isomers, as separated, pure or partially purified geometric isomers or mixtures thereof are included within the scope of the invention. Likewise, molecules having a bond with restricted rotation may form geometric isomers. These are also intended to be included within the scope of the present invention. Furthermore, some of the compounds of the present invention may exist in different tautomeric forms and it is intended that any tautomeric forms that the compounds are able to form are included within the scope of the present invention. The compounds of this invention may exist in unsolvated as well as in solvated forms with solvents such as water, ethanol and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of this invention. Some of the compounds of the present invention contain chiral centres and such compounds exist in the form of isomers (i.e. enantiomers). The invention includes all such isomers and any mixtures thereof including racemic mixtures. Racemic forms can be resolved into the optical antipodes by known methods, for example, by separation of diastereomeric salts thereof with an optically active acid, and liberating the optically active amine compound by treatment with a base. Another method for resolving racemates into the optical antipodes is based upon chromatography on an optically active matrix. Racemic compounds of the present invention can also be resolved into their optical antipodes, e.g. by fractional crystallization of d- or 1- (tartrates, mandelates or camphorsulphonate) salts. The compounds of the present invention may also be resolved by the formation of diastereomeric derivatives. Additional methods for the resolution of optical isomers, known to those skilled in the art, may be used. Such methods include those discussed by J. Jaques, A. Collet and S. Wilen in "Enantiomers, Racemates, and Resolutions", John Wiley and Sons, New York (1981). Optically active compounds can also be prepared from optically active starting materials. The invention also encompasses prodrugs of the present compounds, which on administration undergo chemical conversion by metabolic processes before becoming pharmacologically active substances. In general, such prodrugs will be functional derivatives of the compounds of the general formulas I, XXIX, XXX, XXXI, XXXII or XXXIII, which are readily convertible in vivo into the required compound of the formulas I, XXIX, XXX, XXXI, XXXII or XXXIII. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985. The invention also encompasses active metabolites of the present compounds. Whenever mentioned in relation to the compounds of the formulas I, XXIX, XXX, XXXI, XXXII or XXXIII, the terms epilepsy and epilepsies embrace any of the epilepsies, epileptic syndromes and epileptic seizures referred to in International League Against Epilepsy: Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1981 22: 489-501 and in International League Against Epilepsy: Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989 30(4): 389-399. Whenever mentioned in relation to the compounds of the formulas I, XXIX, XXX, XXXI, XXXII or XXXIII, the term anxiety disorders embraces conditions and diseases related to panic attack, agoraphobia, panic disorder with agoraphobia, panic disorder without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, posttraumatic stress disorder, acute stress disorders, generalized anxiety disorder, anxiety disorder due to general medical condition, substance-induced anxiety disorder, separation anxiety disorder, adjustment disorders and anxiety disorder not otherwise specified as defined by American Psychiatric Association Diagnostic and statistical manual of mental disorders, 4ed 1994:110-113,393-444 and 623-627. Pharmaceutical compositions The compounds of this invention are generally utilized as the free base or as a pharmaceutically acceptable salt thereof. Representative examples are mentioned above. If desired, the pharmaceutical composition of the invention may comprise the compound of formula I in combination with further pharmacologically active substances such as those described in the foregoing. The compounds of the invention may be administered alone or in combination with pharmaceutically acceptable carriers or excipients, in either single or multiple doses. The pharmaceutical compositions according to the invention may be formulated with pharmaceutically acceptable carriers or diluents as well as any other known adjuvants and excipients in accordance with conventional techniques such as those disclosed in Remington: The Science and Practice of Pharmacy, 19 Edition, Gennaro, Ed., Mack Publishing Co., Easton, PA, 1995. The pharmaceutical compositions may be specifically formulated for administration by any suitable route such as the oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), transdermal, intracisternal, intraperitoneal, vaginal and parenteral (including subcutaneous, intramuscular, intrathecal, intravenous and intradermal) route, the oral route being preferred. It will be appreciated that the preferred route will depend on the general condition and age of the subject to be treated, the nature of the condition to be treated and the active ingredient chosen. Pharmaceutical compositions for oral administration include solid dosage forms such as capsules, tablets, dragees, pills, lozenges, powders and granules. Where appropriate, they can be prepared with coatings such as enteric coatings or they can be formulated so as to provide controlled release of the active ingredient such as sustained or prolonged release according to methods well known in the art. Liquid dosage forms for oral administration include solutions, emulsions, suspensions, syrups and elixirs. Pharmaceutical compositions for parenteral administration include sterile aqueous and nonaqueous injectable solutions, dispersions, suspensions or emulsions as well as sterile powders to be reconstituted in sterile injectable solutions or dispersions prior to use. Depot injectable formulations are also contemplated as being within the scope of the present invention. Other suitable administration forms include suppositories, sprays, ointments, cremes, gels, inhalants, dermal patches, implants etc. The pharmaceutical compositions of this invention or those which are manufactured in accordance with this invention may be administered by any suitable route, for example orally in the form of tablets, capsules, powders, syrups, etc., or parenterally in the form of solutions for injection. For preparing such compositions, methods well known in the art may be used, and any pharmaceuically acceptable carriers, diluents, excipients or other additives normally used in the art may be used. A typical oral dosage is in the range of from about 0.001 to about 100 mg/kg body weight per day, preferably from about 0.01 to about 50 mg/kg body weight per day, and more preferred from about 0.05 to about 10 mg/kg body weigjit per day administered in one or more dosages such as 1 to 3 dosages. The exact dosage will depend upon the frequency and mode of administration, the sex, age, weight and general condition of the subject treated, the nature and severity of the condition treated and any concomitant diseases to be treated and other factors evident to those skilled in the art. The formulations may conveniently be presented in unit dosage form by methods known to those skilled in the art. A typical unit dosage form for oral administration one or more times per day such as 1 to 3 times per day may contain from 0.05 to about 1000 mg, preferably from about 0.1 to about 500 mg, and more preferred from about 0.5 mg to about 200 mg. For parenteral routes such as intravenous, intrathecal, intramuscular and similar administration, typically doses are in the order of about half the dose employed for oral administration. The compounds of this invention are generally utilized as the free substance or as a pharmaceutically acceptable salt thereof. One example is a base addition salt of a compound having the utility of a free acid. When a compound of the invention contains a free acid such salts may be prepared in a conventional maimer by treating a solution or suspension of a free acid of the compound of the invention with a chemical equivalent of a pharmaceutically acceptable base. Representative examples are mentioned above. For parenteral administration, solutions of the novel compounds of the invention in sterile aqueous solution, aqueous propylene glycol, aqueous vitamin E or sesame or peanut oil may be employed. Such aqueous solutions should be suitably buffered if necessary and the liquid diluent first rendered isotonic with sufficient saline or glucose. The aqueous solutions are particularly suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. The sterile aqueous media employed are all readily available by standard techniques known to those skilled in the art. Solutions for injections may be prepared by dissolving the active ingredient and possible additives in apart of the solvent for injection, preferably sterile water, adjusting the solution to a desired volume, sterilising the solution and filling it in suitable ampules or vials. Any suitable additive conventionally used in the art may be added, such as tonicity agents, preservatives, antioxidants, etc. Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solution and various organic solvents. Examples of solid carriers are lactose, terra alba, sucrose, cyclodextrin, talc, agar, pectin, acacia, stearic acid and lower alkyl ethers of cellulose corn starch, potato starch, talcum, magnesium stearate, gelatine, lactose, gums, and the like. Any other adjuvants or additives usually used for such purposes such as colourings, flavourings, preservatives etc. may be used provided that they are compatible with the active ingredients. Examples of liquid carriers are syrup, peanut oil, olive oil, phospho lipids, fatty acids, fatty acid amines, polyoxyethylene and water. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The pharmaceutical compositions formed by combining the novel compounds of the invention and the pharmaceutical acceptable carriers are then readily administered in a variety of dosage forms suitable for the disclosed routes of administration. The formulations may conveniently be presented in unit dosage form by methods known in the art of pharmacy. Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules or tablets, each containing a predetermined amount of the active ingredient, and which may include one or more suitable excipients. Furthermore, the orally available formulations may be in the form of a powder or granules, a solution or suspension in an aqueous or non-aqueous liquid, or an oil-in-water or water-in-oil liquid emulsion. If a solid carrier is used for oral administration, the preparation may be tablette, placed in a hard gelatine capsule in powder or pellet form or it can be in the form of a troche or lozenge. The amount of solid carrier will vary widely but will usually be from about 25 mg to about 1 g. If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gelatine capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution. If desired, the pharmaceutical composition of the invention may comprise the compound of the formulae I, XXIX, XXX, XXXI, XXXII or XXXIII in combination with further pharmacologically active substances such as those described in the foregoing. Typical examples of recipes for the formulation of the invention are as follows: 1) Tablets containing 5.0 mg of a compound of the invention calculated as the free base: Compound of formula I, XXIX, XXX, XXXI, XXXH or XXXm 5.0 mg Lactose 60 mg Maize starch 30 mg Hydroxypropylcellulose 2,4 mg Microcrystalline cellulose 19.2 mg Croscarmellose Sodium Type A 2.4 mg Magnesium stearate 0.84 mg 2) Tablets containing 0.5 mg of a compound of the invention calculated as the free base: Compound of formula I, XXK, XXX, XXXI, XXXII or XXXIII 0.5 mg Lactose 46.9 mg Maize starch 23.5 mg Povidone 1.8 mg Microcrystalline cellulose 14.4 mg Croscarmellose Sodium Type A 1.8 mg Magnesium stearate 0.63 mg 3) Syrup containing per millilitre: Compound of formula I, XXIX, XXX, XXXI, XXXII or XXXIII 25 mg Sorbitol 500 mg Hydroxypropylcellulose 15 mg Glycerol 50 mg Methyl-paraben 1 mg Propyl-paraben 0.1 mg Ethanol 0.005 mL Flavour 0.05 mg Saccharin sodium 0.5 mg Water ad 1 mL 4) Solution for injection containing per millilitre: Compound of formula I, XXIX, XXX, XXXI, XXXII or XXXIII 0.5 mg Sorbitol 5.1 mg Acetic Acid 0.05 mg Saccharin sodium 0.5 mg Water ad 1 mL The compounds of the invention of the general formula I, wherein a, b, c, d, e, f, g, h, s, q, U, W, X, Z, R1 R2, R3, R5, R6, R6', R7, R7', R8, R9, R9' R10, R10', R11, R12 and R12' are defined under formula I may be prepared by the methods as described below and as represented in the scheme. Substituted 4-nitroanilines of the general formula IX or XI are commercially available, described in the literature or prepared according to methods known to chemists skilled in the art In particular, compounds of the general formula IX or XI with s being 0 and R2 being substituted aryl or substituted heteroaryl as defined above such as furanyl, thienyl, phenyl, pyridinyl can be prepared from corresponding compounds with R being I or Br by means of cross-coupling reactions known to chemists skilled in the art, such as Suzuki coupling, Stille coupling, or other transition metal catalyzed cross-coupling reactions [D.W. Knight "Coupling Reactions Between sp2 Carbon Centers" in Comprehensive Organic Synthesis, v. 3, pp. 481-520, Pergamon Press 1991]. Alternatively, 4-nitroanilines with the general formula IX or XI can be prepared from the corresponding 2-substituted aniline in the protected or unprotected form by nitration known to chemists skilled in the art [R. Behnisch " Aromatische Nitro-Verbindungen" in Methoden der Organische Chemie/(Houben-Weyl) p. 255, v. E16d, Thieme: 1992], In particular, this method can be applied for compounds with the general formula IX or XI where U is S, SO2, or SO2NR11. Also, compounds of the general formula IX or XI where U is S can be converted into compounds of the general formula IX or XI where U is SO2 by oxidation according to methods known to the chemist skilled in the art, for example by oxidation with 3-chloroperoxybenzoic acid or NaI04 in the presence of RUCI3 as a catalyst. Compounds of the general formula XI are also prepared from compounds of general formula IX by the reaction with suitable electrophilic reagents forming an R3-(Z)q-X group, such as, but not limited to, alkyl, aryl, or heteroaryl chloroformiates or carbamoyl chlorides, carbonic acid anhydrides, acid fluorides, acid chlorides, acid bromides, acid iodides, activated esters, activated carbonic acids with activating reagents such as carbodiimides, sulfonyl chlorides, or isocyanates in suitable solvents, such as acetonitrile, tetrahydrofuran, 1,2-dichloroethane, or methylene chloride, at a suitable temperature, such as room temperature or reflux, achieved by conventional heating or under microwave irradiation, with or without addition of bases, such magnesium oxide, potassium carbonate, sodium hydride, trialkylamines, sodium- or potassium alcoholates, sodium or potassium carbonate, sodium or potassium bicarbonate, or pyridine, reactions well known to the chemist skilled in the art. Additionally, for further variation of R2, compounds of the general formula XI, wherein R2 is methyl, U is oxygen, and s is 1, can be demethylated by methods known to chemists skilled in the art, such as treatment with boron tribromide in a suitable solvent, such as dichloromethane, at a suitable temperature, such as 0 °C or room temperature. The resulting phenols can then be transformed into compounds of the general formula XI, wherein U is oxygen, and s is 1, by methods known to chemists skilled in the art. Such methods include: (a) the reaction with electrophiles, such as alkyl chlorides, alkyl bromides, alkyl iodides, benzyl chlorides, benzyl bromides, benzyl iodides, carbonic acid chlorides, carbonic acid bromides, or carbonic acid anhydrides in the presence of suitable bases, such as potassium carbonate, in a suitable solvent, such ' as tetrahydrofuran, N,N-dimethylformamide, or 1,2-dichloroethane, at suitable temperatures, such as room temperature or reflux temperature; (b) the reaction with alkyl, benzylic, or heteroarylalkyl alkohols under conditions known as the Mitsunobu reaction (O. Mitsunobu Synthesis 1981,1). The nitro group in compounds of the general formula XI can be reduced with suitable reducing agents such as zinc or iron powder in the presence of acid such as acetic acid or aqueous hydrochloric acid, or hydrogen gas or ammonium formiate in the presence of suitable hydrogenation catalyst such as palladium on activated carbon in suitable solvents such as methanol, ethanol, or tetrahydrofuran, at suitable temperatures or under ultrasonic irradiation, to obtain anilines with the general formula XII. Alternatively, tin (II) chloride or sodium dithionite can be used as reducing agents under conditions well known to the chemist skilled in the art. Obtained anilines with the general formula XII are subjected to reductive alkylation i reactions, known to chemists skilled in the art, with aldehydes of the general formula YCHO where Y is defined as above in suitable solvents such as methanol, ethanol, xylene, tetrahydrofuran, acetonitrile, or mixtures thereof, at suitable temperatures with the formation of intermediate imines which can be reduced in situ or can be separated by evaporation of the solvent or crystallisation. They are reduced to the compounds of the invention of the general formula I, where R1 is hydrogen, with reducing agents, such as sodium borohydrate or sodium cyanoborohydrate, in a suitable solvent, such as ethanol, methanol or acetonitrile with or without addition of catalytic amounts of acid, such as acetic acid, at suitable temperatures. Optionally, for variation of R1, the obtained compounds of the general formula I where R1 is hydrogen can be further derivatized by the second reductive alkylation procedure using suitable aldehydes and reducing agents such as sodium cyanoborohydrate, as described above. This procedure can be performed in situ after the first reductive alkylation with aldehydes of the general formula YCHO. Alternatively, R1 can be introduced by the electrophilic substitution reaction with the appropriate electrophiles of the general formula Ra-LG, where LG is a suitable leaving group such as iodide, bromide, or sulphonate under conditions known to the chemist skilled in the art. For the further variation of R3, Z and X, the compounds of the invention with the general formula I can be obtained by an alternative route: Compounds with the general formula XIII may be prepared by protection of the aniline nitrogen in the substituted 4-nitro anilines with the general formula IX with an appropriate protecting group (PG1) [Protective Groups in Organic Synthesis, 3rd Edition T. W. Greene, P. G. M. Wuts, Wiley Interscience 1999], such as a trifloroacetyl group known to chemists skilled in the art as TFA group, by reaction with the reagent forming the protective group such as trifluoroacetic acid anhydride in a suitable solvent, such as 1,2-dichloroethane at appropriate temperatures. Anilines with the general formula XIV are obtained by reduction of the nitro group according to methods known to chemists skilled in the art, as described above. Then they are subjected to the reductive alkylation reactions as described above, with the aldehydes of the general formula YCHO to furnish compounds with the general formula XV. Compounds with the general formula XV are subjected to the second reductive alkylation step, as described above, to furnish compounds with the general formula XVI, where PG1 is TFA. Then the TFA group can be removed by methods known to chemists skilled in the art, such as hydrolysis with aqueous potassium carbonate in an appropriate solvent, such as methanol, at a suitable temperature, furnishing compounds of the general formula XVII. The compounds of the invention with the general formula I where R1 is not hydrogen are obtained from anilines with the general formula XVII by the reaction with suitable electrophilic reagents forming a R3-(Z)q-X group such as alkyl, aryl or heteroaryl chloroformates or carbamoyl chlorides, acid chlorides, acid bromides, acid iodides, sulfonyl chlorides, isocyanates, carbonic acid anhydrides, activated carbonic acids with activating reagents such as carbodimides or others as known to chemists skilled in the art, in the suitable solvents, such as acetonitrile, tetrahydrofuran, 1,2-dichloroethane, or methylene chloride at a suitable temperature, such as room temperature or reflux, with or without addition of bases, such as magnesium oxide, potassium carbonate, trialkylamines, or pyridine, or other methods as descibed above. For the compounds of the invention with general formula I wherein R: is hydrogen, compounds with the general formula XV are subjected to the protection with appropriate protective group (PG2), known to chemists skilled in the art [Protective Groups in Organic Synthesis, 3rd Edition T. W. Greene, P. G. M. Wuts, Wiley Interscience 1999], to furnish compounds with the general formula XVTH. In particular, compounds of the general formula XVBI where PG2 is tert-butylcarbonyl group, known to chemists skilled in the art as Boc group, can be prepared with the appropriate reagent forming protective group such as terf-butyl carbonic acid anhydride in an appropriate solvent such as acetonitrile and at appropriate temperature such as +80°C, to furnish compounds of the general formula XVIII where PG2 is Boc. Then the TFA protective group (PG1) is removed, as described above, to furnish compounds with the general formula XIX, followed by derivatisation with appropriate electrophiles forming R3~(Z)q-X group to furnish compounds with the general formula XX, as described above. Alternatively, compounds of the general formula XIX can be prepared from 4-nitroanilines in three steps as follows: reductive alkylation of compounds of the general formula XXXIV as described above will furnish compounds of the general formula XXXV, which can then be protected e.g. using di-tert-butyldicarbonate and dimethylaminopyridine in a suitable solvent such as tetrahydrofuran, thus yielding compounds of the general formula XXXVI, which can then be reduced to compounds of the general formula XIX by an appropriate reducing agent such as Na2S2O4 as described above. Finally, the compounds of the invention with general formula I wherein R1 is hydrogen are obtained from the compounds with the general formula XX by means of deprotection of PG2 by the methods known to chemists skilled in the art.In particular, the Boc protective group can be cleaved by the methods known to chemists skilled in the art such as deprotection with an appropriate acid, for example trifluoroacetic acid, in the absence or presence of solvent such as methylene chloride or toluene at appropriate temperatures. Alternatively, compounds of the general formula I can be prepared by a route as follows: Compounds of the general formula XXI, wherein R2, U, and s are as defined above, are commercially available or prepared by methods known to the chemist skilled in the art. These include the reactions of 5-fluoro-2-nitrophenol under Mitsunobu-, alkylation- or acylation conditions as described above for the synthesis of compounds of the general formula XI from phenols. Nucleophilic aromatic substitution with amines of the type Y-CH2-NH-R1, a reaction well known to chemists skilled in the art, furnishes compounds with the general formula XXII. Alternatively, compounds with the general formula XXII can be prepared by reductive alkylation as described above of 4-nitroanilines of the general formula XXXIV. Compounds with the general formula XXIII may be prepared by the reduction of the nitro group, carried out under the conditions as described above for the synthesis of compounds of the general structures XII. The reaction of compounds with the the general formula XXIII with suitable electrophilic reagents forming an R3-(Z)q-X group, as described above for compounds of the general formula XI, furnishes the compounds of the invention with the general formula I. Alternatively, compounds of the general formula I with s being 0 and R2 being substituted aryl or substituted heteroaryl as defined above such as furanyl, thienyl, phenyl, pyridinyl can be prepared from the corresponding compounds with R2 being I or Br by means of cross-coupling reactions, as described above. Examples Analytical LC-MSdaia (LC-MS = LC/MS) were obtained on a PE Sciex API 150EX instrument equipped with an APPI (atmospheric pressure photo ionisation) ion source and Shimadzu LC-8A/SLC-10A LC system. Column: 30 X 4.6 mm Waters Symmmetry CI8 column with 3.5 μm particle size; Solventsystem: A = water/trifluoroacetic acid (100:0.05) and B = water/acetonitrile/trifluoroacetic acid (5:95:0.03); Method: Linear gradient elution with 90% A to 100% B in 4 minutes and with a flow rate of 2 mL/minute. LC/MS-TOF (time-of-flight) data were obtained on a micromass LCT 4-ways MUX equipped with a Waters 2488/Sedex 754 detector system. Column: 30 X 4.6 mm Waters Symmetry C18 column with 3.5 μm particle size; Solventsystem: A = water/trifluoroacetic acid (100:0.05) and B = water/acetonitrile/txifluoroacetic acid (5:95:0.03); Method: Linear gradient elution with 90% A to 100% B in 4 minutes and with a flow rate of 2 mL/minute.The values for the found molecular ions (m/z, wherein m is the molecular ion mass and z is the charge) are assigned to the molecular mass (M), composed of the most abundant isotopes, optionally plus or minus fragments. In the examples with [M+3]+ or [M+2]+ assignments, the reported m/z values correspond to the highest peak selected from several molecular ion peaks with different isotope composition and the molecular mass M is calculated based on the most abundant isotope distribution. Purity was determined by integration of the UV (254 nm) and ELSD trace. The retention times (RT) are expressed in minutes. Preparative LC-MS-purification was performed on the same PE Sciex API 150EX instrument. Column: 50 X 20 mm YMC ODS-A with 5 μm particle size; Method: Linear gradient elution with 80% A to 100% B in 7 minutes and with a flow rate of 22.7 mL/minute. Fraction collection was performed by split-flow MS detection. l HNMR spectra were recorded at 500.13 MHz or at 250.13 MHz, both on a Bruker Avance DRX500 or on a Bruker AC 250 instrument, respectively. Deuterated chloroform (99.8%D) or dimethyl sulfoxide (99.8%D) were used as solvents. TMS was used as internal reference standard. Chemical shift values are expressed in ppm-values. The following abbreviations are used for multiplicity of NMR signals: s = singlet, d = doublet, t = triplet, q = quartet, qui = quintet, h = heptet, dd = double doublet, dt = double triplet, dq = double quartet, tt = triplet of triplets, m = multiplet and br. s = broad singlet, br. d = broad doublet, br. t = broad triplet Preparation of intermediates Ar-(p-Fluorobenzyl)-methylamine was synthesised according to the procedure described by G, M. Singer and A. W. Andrews J. Med. Chem. 1983,26, 309. 2-Iodo-4-nitroaniline was prepared according to the procedure described by J. J. Pak, T. J. R. Weakley, and M. M Haley J. Amer. Chem. Soc. 1999,121, 8182. Preparation of intermediates of the general formula XI (2-Chloro-4-nitrophenyl)-carbamic acid ethyl ester. A suspension of MgO (2.0 g), 2-chloro-4-nitroaniline (3.768 g, 21.83 mmol) and ethyl chloroformate (5 mL) in acetonitrile (25 mL) was heated to reflux temperature for 4 hours followed by addition of more ethyl chloroformate (4 mL). The heating was continued until full conversion (20 hours) then the reaction mixture was filtered via a plug of S1O2 (5 g) with ethyl acetate as an eluent Evaporation in vacuo (50°C) gave 5.8 g (100% yield) of crude title compound which was used in the next step without further purification. LC/MS (m/z) 245 ([M+H]4); RT = 2.95, (UV, ELSD) 96%, 98.5%. !H NMR (DMSO-d6): 1.27 (t, 3H), 4.19 (q, 2H), 8.06 (d, 1H), 8.19 (dd, 1H)S 8.30 (d,1H), 9.49 (s, NH). The following compounds were prepared analogously using appropriate chloroformates: (2-ChlorO'4-nitrophenyl)-carbamic acid propyl ester. Propyl chloroformate and tetrahydrofuran were used instead. The title compound was crystallized by addition of diisopropyl ether to the crude product and separated by filtration. Yield 3.3 g (62%), colorless solid. !HNMR (DMSO-d6): 0.94 (t, 3H), 1.67 (in, 2H), 4.10 (t, 2H), 8.06 (d, 1H), 8.20 (dd, 1H), 8.31 (d, 1H), 9.52 (s, NH). (4-Nitrophenyl)-carbamic acid propyl ester. Reaction was performed at room temperature in acetone as a solvent. The product was used in the next step without purification. (4-Nitrophenyl)-carbamic acid ethyl ester. Reaction was performed at room temperature in acetone as a solvent The product was used in the next step without purification. (2-Methoxy-4-nitrophenyl)-carbamic acid methyl ester. Reaction was performed at room temperature in acetone as a solvent. The product was used in the next step without purification. (2-Methoxy-4-nitrophenyl)-carbamic acid isopropyl ester. Reaction was performed at room temperature in acetone as a solvent. The product was used in the next step without purification. (2-Methoxy-4-nitrophenyl)-carbamic acid propyl ester. Reaction was performed at room temperature in acetone as a solvent. The product was used in the next step without purification. (2-Methoxy-4-nitrophenyl)-carbamic acid 4-fluorophenyl ester. Reaction was performed at room temperature in acetone as a solvent The product was used in the next step without purification. (2-Methyl-4-nitrophenyl)-carbamic acid ethyl ester. The crude product was used in the next step without further purification. LC/MS (m/z) 207.9 ([M-16]4); RT = 2.69, (UV, ELSD) 75% 99.7%. (2-Methyl-4-nitrophenyl)-carbamic acid propyl ester. The crude product was used in the next step without further purification. LC/MS (m/z) 223.1 ([M-15]4); RT = 2.97, (UV, ELSD) 62%, 99.7%. (2-Bromo-4-nitrophenyl)-carbamic acid propyl ester. The crude product was purified by crystallisation from ethyl acetate - hexane. 'H NMR (DMSO-d6): 0.94 (t, 3H), 1.66 (m, 2H), 4.10 (t, 2H), 7.97 (d, 1H), 8.23 (dd, 1H), 8.44 (d, 1 H), 9.28 (br. s, NH). (2~Iodo-4-nitrophenyl)-carbamic acid propyl ester. The crude product was purified by crystallisation from ethyl acetate - hexane. Pale yellow needles. 1H NMR (DMSO-de): 0.94 (t, 3H), 1.66 (m, 2H), 4.09 (t, 2H), 7.79 (d, 1H), 8.24 (dd, 1H), 8.60 (d, 1H), 9.07 (br. s, NH). LC/MS (m/z) 335.0 ([M-0]4); RT = 3.40, (UV, ELSD) 99%, 100%. (4-Nitro-2-cyanophenyI)-carbamic acid propyl ester. Sodium hydride was used instead as a base prior to addition of propyl chloroformate at room temperature. The crude product contaminated with double acylation product was treated with saturated aqueous sodium bicarbonate (NaHCO3) in methanol for 16 hours and purified by flash chromatography. 1H NMR (CDC13): 1.01 (t, 3H), 1.76 (m, 2H), 4.22 (t, 2H), 7.47 (br. s, 1H, NH), 8.43 (dd, 1H), 8.47 (d, 1H), 8.57 (d, 1H). The following compounds were prepared analogously: (4-Nitro-2~cyanophenyl)-carbamic acid ethyl ester. ]H NMR (DMSO-d6): 1.28 (t, 3H), 4.21 (q, 2H), 7.88 (d, 1H), 8.47(dd, 1H), 8.68 (d, 1H), 10.34 (s, 1H, NH). LC/MS (m/z) 220.1 ([M+H]4), RT = 2.46, (UV, ELSD) 97%, 98%. (2-Trifluoromethyl-4-nitrophenyl)-carbamic acid propyl ester. lH NMR (CDCI3): 1.00 (t, 3H), 1.75 (m, 2H), 4.20 (t, 2H), 7.26 (br. s5 1H, NH), 8.41 (dd, 1H), 8.50 (d, 1H), 8.57 (d, 1H). (2-Trifluoromethyl-4-nitrophenyl)-carbamic acid ethyl ester. ]H NMR (CDCI3): 1.37 (t, 3H), 4.31 (q, 2H), 7.25 (br. s, 1H, NH), 8.41 (dd, 1H), 8.50 (d, 1H), 8.57 (d, 1H). N-(2-Methoxy-4-nitrophenyl)-butyramide. To a cold (ice/water bath) solution of 2-methoxy-4-nitroaniline (4.00 g, 23.8 mmol) in acetonitrile (40 mL) and triethylamine (5 mL) butyiyl chloride (2.66 g, 25 mmol) was added. After 30 minutes the obtained suspension was poured into saturated aqueous sodium bicarbonate (NaHCO3) (300 mL). After sonication for 10 minutes the title compound was separated by filtration as a yellow-brown solid, washed with water and dried in vacuo. Yield 5.34 g, 94%. LC/MS (m/z) 238.9 ([M+H]4); RT - 2.69, (UV, ELSD) 98%, 99%. !H NMR (DMSO-d6): 0.91 (t, 3H), 1.60 (m, 2H), 2.47 (t, 2H), 3.98 (s, 3H, OMe), 7.79 (s, 1H), 7.88 (dd, 1H), 8.39 (d, IK), 9.50 (s, 1H, NH). The following compound was prepared analagously using the appropriate acid chloride: N-(2-Methoxy-4-nitrophenyl)-3,4-dichlorobe}vzamide. LC/MS (m/z) 313.0 ([M+H-NO]+; RT = 3.72, (UV, ELSD) 99%, 100%. !H NMR (DMSO-de): 4.00 (s, 3H, OMe), 7.82 (d, 1H), 7.88 (d, 1H), 7.93 (m, 2H), 8.17 (d, 1H), 8.20 (s, 1H), 10.01 (s, 1H.NH). 3,3-Dimethyl-N-(2-methyl-4-nitrophenyl)-butyramide. To a solution of 2-methyl-4-nitroaniline (5 g, 32.9 mmol) in acetonitrile (75 mL) tert-butylacetyl chloride (5.3 g, 1.2 eq.) was added. The obtained mixtrure was distributed into 15 Smith Process Vials and sealed. Each vial was heated and stirred at 150°C under microwave irradiation for 10 minutes. The combined reaction mixture was evaporated in vacuo to give 9.27 g of solid (100%) which was used in the next step without further purification. LC/MS (m/z) 251.1 ([ M+H]4); RT = 3.01, (UV, ELSD) 89%, 99.6%. lH NMR (DMSO-de): 1.05 (s, 9H), 2.33 (s, 2H), 2.36 (s, 3H), 7.91 (d, 1H), 8.05 (dd, 1H), 8.12 (d, 1H), 9.41 (s, 1H, NH). The following compounds have been prepared analogously: 2,2-DimethyI-N-(2-methyl-4-nitrophenyl)-propionamide. LC/MS (m/z) 237.1 ([ M+H]4); RT = 2.72, (UV, ELSD) 96.7%, 98.6%. !H NMR (DMSO-de): 1.26 (s, 9H), 2.31 (s, 3H), 7.61 (d, 1H), 8.05 (dd, 1H), 8.14 (d, IS), 9.06 (s, 1H, NH). 2-(4-Fluorophenyl)~N-(2-methyl-4-nitrophenyl)-acetamide. LC/MS (m/z) 288.9 ([ M+H]"1"); RT = 2.90, (UV, ELSD) 99.6%, 99.4%. 1H NMR (DMSO-d6): 2.34 (s, 3H), 3.79 (s, 2H), 7.18 (t, 2H), 7.39 (dd, 2H), 7.91 (d, 1H), 8.06 (dd, 1H), 8.13 (d, 1H), 9.72 (s, 1H, NH). 2-(4~Ftuorophenyl)-N-(2-iodo-4-nitrophenyl)-acetatnide The product was washed with ice-cold acetonitrile. 1H NMR (DMSO-d6): 3.81 (s, 2H), 7.16-7.19 (m, 2H), 7.41-7.44 (m, 2H), 7.87 (d, 1H), 8.23 (dd, 1H), 8.62 (d, 1H), 9.66 (bs,1H). (2-Iodo-4-nitrophenyl)-carbamic acid ethyl ester. The product was purified by flash chromatography (silica, heptane/ethyl acetate). lH NMR (DMSO-d6): 1.27 (t, 3H), 4.18 (q, 2H), 7.80 (d, 1H), 8.24 (dd, 1H), 8.60 (d, 1H), 9.05 (s, 1H). (2-(Furan-2-yl)-4-nitrophenyl)-carbamic acid propyl ester. The mixture of (2-iodo-4-nitrophenyl)-cafbamic acid propyl ester (30 rug, 0.086 mmol), 0.9 M aqueous potassium carbonate (K2CO3) (0.285 mL, 0.257 mmol), palladium (II) acetate (5 mg) and 2-furanboronic acid (48 nag, 0.428 mmol) in acetone (2 mL) was heated to +125°C for 3 minutes in the sealed vial under microwave irradiation. The obtained reaction mixture was evaporated and the title compound was purified by flash chromatography on SiC>2 (5 g, gradient heptane - ethyl acetate). Yield 21 mg, 84%. ]H NMR (CDCfe): L00 (t, 3H), 1.75 (m, 2H), 4.18 (t, 2H), 6.62 (dd, 1H, form), 6.79 (d, 1H, furan), 7.64 (d, 1H, form), 8.16 (dd, 1H), 8.36 (br. ss 1H, NH), 8.39 (d, 1H), 8.48 (d, 1H). LC/MS (m/z) 261.0 (|M+H)+; RT = 1.57. The following compound was prepared analogously with the appropriated boronic acid: (2-Phenyl-4-nitrophenyl)-carbamic acid propyl ester. The compound was used in the next step without purification. (2-Methoxy-4-nitrophenyl)-carbamic acid ethyl ester 2-Methoxy-4-mtrophenylamine (5.0 g) was dissolved in dry dioxane (30 mL) and N,N-diisopropylethylamine (7.8 mL) was added at 0 °C. Ethyl chlorofonnate (4.25 mL) in dioxane (35 mL) was added dropwise, and the resulting mixture was allowed to warm to room temperature and stirred over night. Water (200 mL) was added and the mixture was extracted with ethyl acetate (3 x 150 mL). The combined organic phase was washed with water (2 x 200 mL) and brine (200 mL), dried over sodium sulfate, filtered, and evaporated in vacuo. The crude product was recrystallised from ethanol to yield the title compound as colourless solid (4.45 g, 62 %). 1H NMR (DMSO-d6): 1-26 (t, 3H), 3.94 (s, 3H), 4.18 (q, 2H), 7.78 (d, 1H), 7.90 (dd, 1H), 8.09 (d, 1H), 8.99 (s, 1H). (2-Hydroxy-4-nitrophenyl)-carbamic acid ethyl ester (2-Methoxy-4-nitrophenyl)-carbamic acid ethyl ester (2.15 g) was dispensed in 1,2-dichloroethane (20 mL) and cooled to 0 °C. Boron tribromide (2.0 mL) in 1,2-dichloroethane (10 mL) was added dropwise. The reaction mixture was stirred 10 minutes at 0 °C and 30 minutes at room temperature. The mixture was again cooled to 0 °C, and water (10 mL) was added carefully. The reaction mixture was neutralised with saturated aqueous sodium bicarbonate and aqueous hydrochloric acid (5M). The resulting mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic phase was washed with water (2 x 100 mL) and brine (100 mL), dried over magnesium sulfate, filtered, and evaporated in vacuo to yield the title compound as brownish solid (1.96 g, 97 %). !H NMR (DMSO-d6): 1.25 (t, 3H), 4.17 (q, 2H), 7.64 (d, 1H), 7.74 (dd, 1H), 8.01 (d, 1H), 8.69 (s, 1H), 10.96 (br. s, 1H). (2-Cyclopentyloxy-4-nitrophenyl)-carbamic acid ethyl ester Cyclopentanol (7.24 mL, 376 mM in dry tetrahydrofuran) was added to triphenylphosphine (1.44 g, polystyrene bound, 1.89 mMol / g) under argon, followed by the addition of a solution of (2-Hydroxy-4-nitrophenyl)-carbamic acid ethyl ester (25.6 mL, 62 mM in dry tetrahydrofuran) and a solution of diethylazodicarboxylate (7.24 mL, 376 mM in dry tetrahydrofuran). The reaction mixture was shaken at room temperature over night. The resin was filtered and washed with tetrahydrofuran (THF) (35 mL) and methanol (35 mL). The combined organic phase was evaporated in vacuo. The crude product was purified by flash chromatography (silica gel, heptane / ethyl acetate, gradient) to yield the title compound as slightly yellow solid (294 mg, 64 %). ]HNMR (DMSO-d6): 1.27 (t, 3H), 1.59 (m, 2H), 1.76 (m, 2H), 1.87 (m, 2H), 1.94 (m, 2H), 4.19 (q, 2H), 5.01 (h, 1H), 7.72 (d, 1H), 7.86 (dd, 1H), 8.11 (d, 1H), 8.82 (s, 1H). The following compounds were prepared in an analogous fashion: (4-Nitro-2~phenethyloxyphenyl)-carbamic acid ethyl ester 1H NMR (DMSO-d6): 1.28 (t, 3H), 3.15 (t, 2H), 4.19 (q, 2H), 4.38 (t, 2H), 7.23 (t, 1H), 7.32 (t, 2H), 7.36 (d, 2H), 7.80 (d, 1H), 7.88 (dd, 1H), 8.08 (d, 1H), 8.66 (s, 1H). (2-Benzylox))~4-nitrophenyl)-carbamic acid ethyl ester 1H NMR (DMSO-d6): 1.26 (t, 3H), 4.18 (q, 2H), 5.33 (s, 2H), 7.35 (t, 1H), 7.41 (t, 2H), 7.55 (d, 2H), 7.86 (d, 1H), 7.89 (dd, 1H), 8.06 (d, 1H), 8.95 (s,1H). (2-Isopropyloxy-4-nitrophenyl)'-carbamic acid ethyl ester ]H NMR (DMSO-d6): 1.27 (t, 3H), 1.33 (d, 6H), 4.19 (q, 2H)3 4.84 (h, 1H), 7.78 (d, 1H), 7.86 (dd, 1H), 8.12 (d, 1H), 8.77 (s, 1H). Preparation of intermediates of the general formula XII (4~Amino-2-methyloxyphenyl)-carbamic acid ethyl ester (2»Methoxy-4"nitrophenyl)-carbamic acid ethyl ester (2.20 g) was dissolved in ethanol (220 mL). Aqueous hydrochloric acid (26 mL, 6 M) and iron powder (4.74 g) were added, and the mixture was stirred at 65 °C for 15 minutes. After cooling to room temperature, the mixture was neutralised with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3 x 200 mL). The organic phase was washed with water (2 x 100 mL) and brine (100 mL), dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was dissolved in ethanol (100 mL), and the above procedure was repeated using aqueous hydrochloric acid (26 mL, 6 M) and iron powder (3.7 g)5 to yield the title compound as a dark oil (L80 g, 93 %). 'H NMR (DMSO-4): 1.19 (t, 3H), 3.67 (s, 3H), 4.01 (q, 2H), 4,97 (s, 2H), 6.08 (dd, 1H), 6.23 (d, 1H), 6.97 (br. s,1H), 7.92 (br. s, 1H). (4~Amino-2-iodophenyl)-carbarnic acid ethyl ester. 1H NMR (CDC13): 1.31 (t, 3H), 3.58 (br. s, 2H), 4.21 (q, 2H), 6.52 (br. s, 1H), 6.67 (dd, 1H), 7.12 (d, 1H), 7.60 (br. d, 1H). The following compound was prepared analogously: N-(4-Amino-24odophenyl)-2-(4-fluorophenyl)-acetamide. 1H NMR (DMSO-d6): 3.59 (br. s, 2H), 3.73 (s, 2H), 6.65 (dd, 1H), 7.05 (d, 1H), 7.09-7.12 (m, 3H), 7.34-7.37 (m, 2H), 7.82 (d, 1H). (4-Amino-2-chlorophenyl)-carbamic acid ethyl ester. To a cold (ice/water bath) vigorously stirred solution of crude (2-Chloro-4-ritrophenyl)-carbamic acid ethyl ester (5.8 g, 21.8 mmol) in tetrahydrofuran (THF) (100 mL) and acetic acid (12 mL) zinc powder (20 g) was added by small portions maintaining the temperature below 40°C. The mixture was allowed to warm slowly to room temperatue and after reaction completion (1 hour) it was filtered via a plug of S1O2 (20 g) with ethyl acetate as an eluent The obtained solution was evaporated in vacuo and the crude yellow solid residue (4.9 g) was purified by precipitation from tetrahydrofuran (THF)/heptane to give 3.00 g of the title compound as pale yellow solid, yield 56%. LC/MS (m/z) 214,216 (M4); RT = 1.18, (UV, ELSD) 86%, 97%. *H NMR (DMSO-d6): 1.18 (br. t, 3H), 4.02 (q, 2H), 5.29 (s, 2H, NH2), 6.45 (dd, 1H), 6.61 (d, 1H), 6.98 (br. d, 1H), 8.52 (br. s, NHCO). The following compounds were prepared analogously: (4-Amino-2-chlorophenyl)-carbamic acid propyl ester. Yield 84.6% (2.44 g, colorless solid). LC/MS (m/z) 228.1 (M*); RT = 1.53, (UV, ELSD) 97.3%, 99%. (4-Aminophenyl)~carbamic acid propyl ester. Purified by flash chromatography on Si02 (gradient heptane - ethyl acetate). Dark puiple crystalline solid, yield 3.066 g, 63.3%. LC/MS (m/z) 195 ([M+Hf); RT « 1.18, (UV, ELSD) 87%, 98.3%. (4-Aminophenyl)-carbamic acid ethyl ester. LC/MS (m/z) 180.8 ([M+H]*); RT = 0.48, (UV, ELSD) 71%, 97%. (4-Amino-2-methoxyphenyl)-carbamic acid methyl ester. LC/MS (m/z) 197.0 ([M+H); RT = 0.49, (UV, ELSD) 71%, 98%. (4-Amino-2-methoxyphenyl)-carbamic acid ethyl ester. LC/MS (m/z) 210.9 ([M+H]4); RT = 0.98, (UV, ELSD) 69%, 97%. (4-Amino-2-methoxyphenyl)-carbamic acid isopropyl ester. LC/MS (m/z) 224.0 (M*); RT = 1.33, (UV, ELSD) 63%, 99%. (4-Amino-2-methoxyphenyl)-carbamic acid propyl ester. LC/MS (m/z) 224.9 ([M+H]*); RT = 1.36, (UV, ELSD) 70%, 98%. (4-Amino-2-methoxyphenyl)-carbamic acid 4-fluorophenyl ester. LC/MS (m/z) 277.0 ([M+H]*); RT = 1.64, (UV, ELSD) 44%, 93%. (4-Amino~2-methylphenyl)-carbamic acid propyl ester. LC/MS (m/z) 208.1 (M*); RT = 1.16, (UV, ELSD) 95%, 100%. *H NMR (CDC13): 0.96 (t, 3H), 1.68 (m, 2H), 2.17 (s, 3H, Me), 3.59 (br. s, 2H, NH2), 4.09 (t, 2H), 6.14 (br. s, 1H, ArH), 6.51 (m, 2H), 7.32 (br. s, 1H, NH). (4-Amino-2-meihylphenyl)-carbamic acid ethyl ester. lE NMR (CDCI3): 1.28 (t, 3H), 2.16 (s, 3H, Me), 3.62 (br. s, 2H, NH2), 4.19 (q, 2H), 6.16 (br. s, 1H, ArH), 6.5 (m, 2H), 7.31 (br. s, 1H, NH). LC/MS (m/z) 195.1 ([M+H]*); RT = 0.75, (UV, ELSD) 70%, 95%. (4-Amino-2-trifluoromethylphenyl)-carbamic acid ethyl ester. 'H NMR (CDCb): 1.30 (t, 3H), 3.77 (br. s, 2H, NH2), 4.20 (q, 2H), 6.52 (br. s, 1H, ArH), 6.82 (dd, 1H), 6.87 (unres. d, 1H), 7.65 (br. s, 1H, NH).). LC/MS (m/z) 248.1 (M4); RT = 1.65, (UV, ELSD) 94%, 90%. (4-Amino-2-trifluoromethylphenyl)-carbamic acid propyl ester. *H NMR (CDCI3): 0.96 (t, 3H), 1.69 (m, 2H), 3.76 (br. s, 2H, NH2), 4.11 (t, 2H), 6.51 (br. s, 1H, ArH), 6.81 (dd, 1H), 6.87 (d, 1H), 7.61 (br. s, 1H, NH). LC/MS (m/z) 261.9 (M1); RT = 2.06, (UV, ELSD) 92%, 98%. (4-Amiiio-2-cyanophenyl)-carbamic acid ethyl ester. !H NMR (DMSO-d6): 1.21 (t, 3H), 4.07 (q, 2H), 5.49 (br. s, 2H, NH2), 6.81 (m, 2H, ArH), 7.04 (d, 1H), 9.09 (br. s, 1H, NH). LC/MS (m/z) 204.9 (M4); RT 1.05, (UV, ELSD) 98%, 99%. (4-Amino-2-cyanophenyl)-carbamic acid propyl ester. 'H NMR (CDC13): 0.98 (t, 3H), 1.71 (m, 2H), 3.72 (br. s, 2H, NH2), 4.13 (t, 2H), 6.81 (br. s, ArH), 6.82 (d, 1H), 6.89 (dd, 1H), 7.83 (br. s, 1H, NH). LC/MS (m/z) 220.1 ([M+H]4); RT = 1.52, (UV, ELSD) 98%, 100%. N-(4-Amino-2-methoxyphenyl)-butyramide. LC/MS (m/z) 208.9 ([M+Hf); RT = 0.77, (UV, ELSD) 81%, 95%. *H NMR (DMSO-d6): 0.89 (t, 3H), 1.56 (m, 2H), 2.22 (t, 2H), 3.4 (very br. s, NH2), 3.69 (s, 3H, OMe), 6.08 (dd, 1H), 6.25 (d, 1H), 7.27 (d, 1H), 8.62 (s, 1H, NH). N-(4-Amino-2-methoxyphenyl)-3,4-dichlorobenzamide. LC/MS (m/z) 311.2 (M4); RT = 1.93, (UV, ELSD) 100%, 100%. ]H NMR (DMSO-d6): 3.70 (s, 3H, OMe), 5.12 (br. s, 2H, NH2), 6.15 (dd, 1H), 6.30 (d, 1H), 7.09 (d, 1H), 7.77 (d, 1H), 7.91 (dd, 1H), 8.17 (d, 1H), 9.46 (s, 1H, NH). N-(4-Amino-2-methylphenyl)-3,3-dimethylbutyramide. LC/MS (m/z) 221.1 ([M+H]4); RT = 1.22, (UV, ELSD) 53.7%, 92.3%. !H NMR (DMSO-d6): 1.02 (s, 9H), 2.02 (s, 3H), 2.11 (s, 2H), 4.89 (br. s, 2H, NH2), 6.33 (dd, 1H), 6.38 (d, 1H), 6.82 (d, 1H), 8.83 (s, 1H, NH). N-(4-Amino-2-methylphenyl)-2-(4-fluorophenyl)-acetamide. LC/MS (m/z) 259.1 ([M+H]4); RT = 1.36, (UV, ELSD) 48.1%, 91.4%. 'H NMR (DMSO-ds): 1.95 (s, 3H), 3.56 (s, 2H), 4.88 (br. s, 2H, NH2), 6.31 (dd, 1H), 6.38 (d, 1H), 6.83 (d, 1H), 7.14 (t, 2H), 7.35 (dd, 2H), 9.16 (s, 1H, NH). N-(4-Amino-2-methylphenyl)-2,2-dimethylpropionamide. LC/MS (m/z) 206.9 ([M+H]4); RT = 0.59, (UV, ELSD) 93%, 95%. !H NMR (DMSO-d6): 1.19 (s, 9H), 1.98 (s, 2H), 4.87 (br. s, 2H, NH2), 6.33 (dd, 1H), 6.39 (d, 1H), 6.71 (d, 1H), 8.55 (s, 1H, NH). [4~Amino-2-(furan-2-yl)-phenyl]--carhamic acid propyl ester. lE NMR (CDCI3): 0.96 (t, 3H), L68 (m9 2H), 3.65 (br. s, 2H, NH2), 4.10 (t, 2H), 6.50 (dd, 1H, furan), 6.58 (d, 1H, furan), 6.66 (dd, 1H)> 6.91 (br. s (unresolved d), 1H), 7.26 (br. s9 ArH), 7.52 (d, 1H), 7.72 (br. s, 1H, NH). LC/MS (m/z) 261.0 ([M+H]*); RT = 1.57. (2-Phenyl-4-aminophenyl)-carbamic acid propyl ester. LC/MS (m/z) 271.1 ([M+Hf); RT = 1.75, (UV, ELSD) 57%, 99%. (4-Amino~2-bromophenyl)-carbamic acid propyl ester. A suspension of iron powder (20 g, excess) and (2-Bromo-4-nitrophenyl)-carbamic acid propyl ester (2.183 g, 7.20 mmol) in ethanol (80 mL) and 6 M aqueous hydrochloric acid (20 mL) was sonicated at room temperature for 10 minutes. The mixture was slowly poured into saturated aqueous sodium bicarbonate (NaHCOs) solution, filtered and extracted with ethyl acetate. The combined organic solution was washed 3 times with saturated aqueous NaHC03, dried over sodium sulfate (Na2S04) and evaporated in vacuo to give 1.67 g of the title compound as pale yellow oil which solidified. Yield 85%. LC/MS (m/z) 271.9,273.8 (M4); RT « 1.30, (UV, ELSD) 99%, 100%. *H NMR (DMSO-d6): 0.90 (br. s (unresolved t), 3H), 1.59 (br. s (unresolved m), 2H), 3.94 (t, 2H), 5.31 (s, 2H, NH2), 6.50 (dd, 1H), 6.80 (unresolved d, 1H), 6.96 (br.d,lH),8.51(br.s,NHCO). The following compound was prepared analogously: (4-Amino~2~iodophenyl)-carbamic acid propyl ester. {H NMR (CDCI3): 0.97 (t, 3H), 1.69 (m, 2H), 3.59 (br, s, 2H, NH2), 4.11 (t, 2H), 6.53 (br. s, 1H, ArH), 6.66 (dd, 1H), 7.11 (d, 1H), 7.61 (br. s, 1H, NH). LC/MS (m/z) 320.7 ([M+H]4); RT «1.71, (UV, ELSD) 98%, 99%. Synthesis of intermediates of the general formulas Xni - XXIII: N-(4-Ammo-2-chlorophenyl)-2,2,2-trifluoroacetamide. To a suspension of 4-nitro-2-chloroaniline (17.2 g, 0.1 mol) in 1,2-dichloroethane (100 mL) trifluoroacetic anhydride (16 mL, 0.113 mol) was added. Obtained yellow solution was evaporated in vacuo after 5 minutes. The obtained yellow solid of N-(4-nitrO"2-chlorophenyl)-2,2,2-trifluoroacetamide was reduced with the Zn-powder in tetrahydrofuran (THF)-acetic acid as described above. The obtained crude product was treated with 2 M hydrochloric acid (150 mL) and diethyl ether. The obtained white precipitate was filtered to give 14.7 g of the title product as hydrochloride salt. The aqueous solution was neutralized with saturated aqueous sodium bicarbonate (NaHCCb) and filtered to give 4.58 g of the pure title compound as a pale grey solid. !H NMR (DMSO-dc): 5.54 (br. s, 2H, NH2), 6.53 (dd, 1H), 6.70 (d, 1H), 7.02 (d, 1H), 10.79 (br. s, 1H, NHCO). LC/MS (m/z) 239.8 ([M+Hf); RT = 1.67, (UV) 100%. N~{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-ami?io]-phenyl}-2,2,2-trifluoroacetamide. A solution of Ar-(4-Amino-2-chlorophenyl)-2,2,2-trifluoroacetamide (4.567 g, 19.14 rnmol) and 5-chloro-thiophene-2-carboxaldehyde (3.97 g, 27.1 mmol) in anhydrous ethanol (50 mL) was heated to reflux for 15 minutes and evaporated in vacuo at 70°C (0.1 mbar, 30 min). The obtained crude imine as a crystalline solid was dissolved in methanol followed by addition of sodium cyanoborohydride (NaBH3CN) in methanol (50 mL) and acetic acid (9 mL) by portions. The obtained reaction mixture was stirred at room temperature for 60 minutes and evaporated in vacuo to small volume. The concentrated solution was quenched with water and filtered after 30 minutes to give 6.98 g (99% yield) of the title compound as a brown-yellow solid. lE NMR (DMSO-d6): 4.43 (d, 2H), 6.63 (dd, 1H), 6.77 (d, 1H), 6.79 (t, 1H, NH), 6.94 (d, 1H), 6.97 (d, 1H), 7.10 (d, 1H), 10.85 (br. s, 1H, NHCO). LC/MS (m/z) 367.9 (M4); RT = 3.36, (UV,ELSD)99%,100%. N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2-trifluoroacetamide. To a mixture of N-{2-Chloro-4-[(5-chloro-thiophenyl-2-ylmethyl)-amino]-phenyl 2,2,2-trifluoroacetamide (3.28 g, 8.88 mmol), 37% aqueous formaldehyde (5 mL), and acetic acid (3 mL), sodium cyanoborohydride (NaBH3CN) (1.1 g) in methanol (10 mL) was added dropwise with stirring during 30 minutes. The reaction mixture was allowed to stand at room temperature for 2 hours and poured into water. After the oil solidified, it was filtered, washed with water and dried in vacuo to give 3.26 g of pale yellow-brown solid. Yield 95%. 1H NMR (DMSO-d6): 2.97 (s, 3H, NMe), 4.72 (s, 2H), 6.82 (m, 1H), 6.91 (m, 2H), 6.97 (d, 1H), 7.21 (d, 1H), 10.92 (br. s, 1H, NHCO). LC/MS (m/z) 382.0 (M*); RT = 3.66, (UV, ELSD) 85%, 98%. (5-Chloro-thiophen-2-ylmethyl)-[3-chloro-4-(2,2,2-trifluoro-acetylamino)-phenyl]- carbamic acid tert-butyl ester. A mixture of N-2-Chloro-4-[(5~chloro-thiophen-2-ylmethyl)-amino]-phenyl}-2,2,2- trifluoroacetamide (2.219 g, 6.01 mmol), di-tert-butyl dicarbonate (2 g), and acetonitrile (3 mL) was heated to +80°C until reaction completion (36 hours). During this time additional amount of di-tert-butyl dicarbonate was added (2 x 1.5 g). The obtained reaction mixture was evaporated in vacuo (80°C, 0.1 mbar) to give the crude title compound which was used in the next step without further purification. 1H NMR (DMSO-d6): 1.44 (s, 9H), 4.94 (s, 2H), 6.81 (d, 1H), 6.93 (d, 1H), 7.25 (dd, 1H), 7.43 (d, 1H), 7.50 (d, 1H), 11.24 (br. s, 1H, NHCO). LC/MS (m/z) 366.9 ([M-Boc]4); RT = 3.99, (UV, ELSD) 87%, 96%. 2~Chloro-N(4)-(5-chloro-tkiopken-2-ylmethyI)~N(4)-m To a solution of N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]- phenyl}-2,2,2-trifluoroacetamide (3.118 g) in methanol (MeOH) (50 mL) solution of potassium carbonate (K2CO3) (6.4 g) in water (25 mL) was added and the reaction mixture was stirred until reaction completion (24 hours) at room temperature. The obtained reaction mixture was extracted with ethyl acetate, washed with saturated aqueous sodium bicarbonate (NaHCO3) and evaporated to give 2.26 g of dark brown oil which was used in the next step without further purification. !H NMR (DMSO-d6): 2.71 (s, 3H, NMe), 4.47 (s, 2H), 4.71 (br. s, 2H, NH2), 6.67-6.75 (m, 3H), 6.82 (d, 1H), 6.93 (d, 1H). LC/MS (m/z) 288.0 ([M+Hf); RT = 2.07, (UV, ELSD) 85%, 98%. The following compound was prepared analogously: (4-Amino-3-chlorophenyl)-(5-chlorO'thiophen-2-ylmethyl)'-carbamic acid tert-butyl ester, lE NMR (DMSO-d6): 1.39 (br. s, 9H, tert-Bu), 4.74 (s, 2H), 5.35 (br. s, 2H, NH2), 6.67-6.74 (m, 2H), 6.77 (br. d, 1H), 6.90 (d, 1H), 6.97 (d, 1H). LC/MS (m/z) 271.9 ([M-Bocf); RT = 3.73, (UV, ELSD) 77%, 97%. 4-Fluoro-24sopropoxy-l-nitrobenzene 5-Fluoro-2-nitrophenol (48 g) was dissolved in dry tetrahydrofuran (THF) (300 mL), Triphenylphosphine (88 g) and 2-propanol (47 mL) were added, and the resulting mixture was cooled to 0 °C. Diisopropylazodicarboxylate (66 mL) was added dropwise. The resulting mixture was allowed to warm to room temperature and stirred over night. The solvent was evaporated in vacuo and the resulting mixture was filtered through silica (heptane / ethyl acetate 1:1). The solvent was evaporated in vacuo and the resulting mixture was recrystallised from heptane / ethyl acetate (1:1). The organic phase was separated from the crystalline solid by filtration, the solvent was evaporated in vacuo, and the remaining product was purified by flash chromatography (silica gel, heptane / ethyl acetate 9:1), yielding the title compound as colourless oil (47.2 g, 78 %). !H NMR (DMSO-d6): 1.30 (d, 6H), 4.85 (h, 1H), 6.93 (m, 1H), 7.34 (dd, 1H), 7.96 (dd, 1H). The following compounds were prepared analogously: 2-Cyclopentyloxy~4-fluoro-l -nitrobenzene. !H NMR (DMSO-d6);1.57-1.78 (m, 6H), 1.86-1.94 (m, 2H), 6.90-6.97 (m, 1H), 7.27-7.32 (m, 1H), 7.98 (dd, 1H). 2-Benzyloxy-4-fluoro-l-nitrobenzene. ]H NMR (DMSO-d6): 5.33 (s» 2H), 6.96-7.04 (m, 1H), 7.32-7.49 (m, 6H), 8.04 (dd, 1H). (4'Fluorobefizyl)'(34sopropo^-4-nitrophenyl)-(methyl)'arnine 4-Fluoro-2-isopropoxy-l-nitrobenzene (1.0 g) was dissolved in dry dimethylsulfoxide (25 mL). Potassium carbonate (1.4 g) and (4-fluorobenzyl(methyl)-amine (0.84 g) were added. The resulting mixture was heated to 90 °C over night. After cooling to room temperature, water (75 mL) was added, and the resulting mixture was extracted with ethyl acetate (3 x 75 mL). The organic phase was dried over sodium sulfate, filtered, and evaporated in vacuo to yield the title compound as slightly yellow solid (1.6 g, 100%). LC-MS (m/z) 319.1 ([M+H]+); RT = 3.43, (UV, ELSD) 85 %, 96 % lH NMR (DMSCW& 1.21 (d, 6H), 3.18 (s, 3H), 4.71 (m, 1H), 4.73 (s, 2H), 6.26 (d, 1H), 6.41 (dd, 1H), 7.17 (m, 2H), 7.25 (m, 2H), 7.84 (d, 1H). The following compounds were prepared analogously: (3-Benzyloxy-4-nitrophenyl)(4-fluorobenzyl)methylamine. LC-MS (m/z) 320.9 ([M+H-NO2]+); RT = 3.54, (UV, ELSD) 96 % 100 %. (3-Cyclopentyloxy-4-nitrophmyl)(4-fluorobenzyl)methylamine. LC-MS (m/z) 299.2 ([M+H-NO2]4); RT - 3.64, (UV, ELSD) 96 %, 100 %. 4-(4-Fluorobenzyl)-(methyl)-amino-2-isopropoxyaniline (4-Fluoroben2yl)-(3-isopropoxy-4-nitrophenyl)-(methyl)-amine (1.60 g) was dissolved in methanol (50 mL). Ammonium fonniate (1.91 g) and palladium (10 % on charcoal, 0.21 g) were added, and the mixture was stirred for 1.5 hours at room temperature. The reaction mixture was filtered and the solvent was evaporated in vacuo. The residue was dissolved in a small amount of methanol, and concentrated aqueous sodium hydroxide (2 mL) was added. The resulting mixture was filtered through a column of silica gel (ethyl acetate as eluent). The resulting solution was evaporated in vacuo to yield crude title compound as a black oil (0.76 g), which was directly used in the next step. LC-MS (m/z) 288.9 ([M+H]+jRT = 1.91, (UV, ELSD) 80 %, 72 % (5-Chloro-thiophen-2-ylmethyl)-(methyl)-(3-mehtyl-4-nitrophenyl)-amine A suspension of 5-chloro-thiophene-2-carbaldehyde (1.61 g, 11.0 mmol), 3-methyl-4-nitroaniline (1.52 g, 10.0 mmol), and Amberlite IRC-84 (100 mg, H+ form) in o-xylene (40 mL) was heated under nitrogen at 140°C for 5 hour. After cooling to room temperature, the resin was removed by filtration, and volatiles were evaporated. The residue was dissolved in acetonitrile (40 mL) and sodium cyanoborohydride (1.26 g, 20.0 mmol) was added in one portion, followed by acetic acid (1 mL) in several portions over 15 minutes. Formaldehyde solution (37% in water, 2.23 mL, 30.0 mmol) was then added and the mixture was stirred for a further 30 minutes. Volatiles were evaporated and the residue partitioned between saturated aqueous sodium bicarbonate (100 mL) and ethyl acetate (100 mL), and the aqueous phase was extracted with ethyl acetate (50 mL). The organic layers were dried over sodium sulfate, the solvent was evaporated, and the residue analyzed by NMR. Incomplete N-methylation mandated the reductive amination step to be repeated three times (using formaldehyde solution, 7.4 mL, 100 mmol, and sodium cyauoborohydride, 2.07 g, 33 mmol) before complete conversion was attained. After this, the crude product was purified on a FlashMaster system (silica, eluted with heptane/ethyl acetate mixtures) to yield the title compound as a yellow oil (1.85 g, 62%). !HNMR (CDC13): 2.64 (s, 3H), 3.11 (s, 3H), 4.66 (s, 3H), 6.52 (d, 1H), 6.60 (dd51H), 6.69 (d, 1H), 6.77 (d, 1H), 8.10 (d, 1H). N(4)-(5-Chloro-thiophen-2-ylmethyl)-2tN(4)-dimethyl-benzene-1,4-diamine To a suspension of (5-cUoro-thiophen-2-ylmethyl)-(methyl)-(3-methyl-4-nitrophenyl)-amine (1.85 g, 6.23 mmol) and iron powder (2.09 g, 37.4 mmol) in ethanol (60 mL) was added 6 N HC1 (12.5 mL, 75 mmol), and the mixture was stirred vigorously at +60°C for 50 minutes. It was then poured into saturated aqueous sodium bicarbonate (200 mL) to which enough sodium carbonate was added to attain a pH > 10. The resulting mixture was extracted with ethyl acetate (200 mL, then 2 x 100 mL), the extract was dried over sodium sulfate and volatiles were evaporated. The residue was purified on a FlashMaster system (silica, eluted with heptane/ethyl acetate mixtures) to yield the title compound as a brown oil (1.51 g, 91 %). lE NMR (CDCI3): 2.16 (s, 3H), 2.79 (s, 3H), 3.32 (br. s, 2H), 4.39 (s, 3H), 6.58-6.65 (m, 4H), 6.72 (d, 1H). Synthesis of intermediates of the general formulas XXXV, XXXVI, and XEX from XXXIV: (3'Methyl-4-nitropheriyl)-(4-trifluoromethylbenzyl)~amine A suspension of 4-trifluoromethylbenzaldehyde (819 pL, 6.00 mmol), 3-methyl-4-nitroaniline (609 mg, 4.00 mmol), and Amberlite IRC-84 (200 mg, H+ form) in 0-xylene (4 mL) was heated under nitrogen at 140°C for 6 hours. It was then cooled to room temperature, diluted with ethyl acetate (5 mL), dried over sodium sulfate, filtered, and volatiles were evaporated. The residue was dissolved in acetonitrile (20 mL) and sodium cyanoborohydride (503 mg, 8.00 mmol) was added in one portion, followed by acetic acid (1 mL) in several portions over 15 minutes. After a further 30 minutes solvents were evaporated and the residue was partitioned between ethyl acetate (50 mL), brine (25 mL), and 10% aqueous potassium carbonate (25 mL). The organic layer was dried over sodium sulfate, solvents were evaporated, and the residue was purified on a FlashMaster system (silica, eluted with heptane/ethyl acetate mixtures) to yield the title compound as a yellow powder (1.02 g, 82%). lE NMR (CDC13): 2.59 (s, 3H), 4.50 (d, 2H), 4.76 (tar. t, 1H), 6.40 (d, 1H), 6.43 (dd, 1H), 7.45 (d, 2H), 7.63 (d,2H), 8.05 (d, 1H). (3-Methyl~4-nitrophenyl)-(4-trifluoromehylbenzyl)-carbomic acid tert-butyl ester A solution of (3-methyl-4-mfrophenyl)-(4-trifluoromethylbenzyl)-amine (1.02 g, 3.29 mmol), di-tert-butyl dicarbonate (1.08 g, 4.93 mmol), dimethylaminopyridine (201 mg, 1.64 mmol), and triethylamine (687 μL, 4.93 mmol) in acetonitrile (20 mL) was stirred at room temperature for 18 hours in an open flask (to allow carbon dioxide to escape). Volatiles were evaporated and the residue was dissolved in ethyl acetate (50 mL). This solution was washed with sat. ammonium chloride (2 x 50 mL), dried over sodium sulfate, volatiles were evaporated, and the residue was purified on a FlashMaster system (silica, eluted with heptane/ethyl acetate mixtures) to yield the title compound as a pale yellow, viscous oil (1.17 g, 86%), which retained traces of heptane, lK NMR (CDCI3): 1.44 (s, 9H), 2.58 (s, 3H), 4.95 (s, 2H), 7.16 (dd, 1H), 7.21 (d, 1H), 7.34 (d, 2H), 7.60 (d, 2H), 7.96 (d, 1H). (4-Amino-3'methylphenyl)~(4'trifluoromethylbenzyl)-carbamic acid tert-butyl ester A solution of Na2S204 (3.00 g, 17.2 mmol) in water (20 mL) was added to a solution of (3-methyl^nitrophenyl)-(4-trifluoromelhylbenzyl)"Carbainic acid tert-butyl ester (1.41 g, 3.44 mmol) in tetrahydrofuran (20 mL), and the resulting mixture was stirred for 20 hours at +55°C. After cooling to room temperature, the water phase was saturated with potassium carbonate, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2 x 20 mL). The combined organic layers were dried over sodium sulfate, solvents were evaporated, and the residue was purified on a FlashMaster system (silica, eluted with heptane/ethyl acetate mixtures) to yield the title compound as a white solid (1.09 g, 83%). 1H NMR (CDCI3): 1.41 (s, 9H), 2.10 (s, 3H), 3.59 (br. s, 2H), 4.78 (s, 2H), 6.56 (d, 1H), 6.76 (br. s, 2H), 7.36 (d, 2H), 7.55 (d, 2H). Compounds of the invention Example 1 la {4-[(Bemofuran'2-ylmethyl)'aminoJ-2-methylphmyl}-'Carbamic acid propyl ester. A mixture of 0.1 M solution of (4-amino-2-methylphenyl)-carbamic acid propyl ester (0.35 mL, 0.035 mmol) and 0.1 M solution of benzofiiran-2-carbaldehyde (0.35 mL) in tetrahydrofuran (THF) was kept at 55°C for 60 minutes. Volatiles were removed in vacuo. To the obtained residue 0,2 M sodium cyanoborohydride (NaBH3CN) (0.5 mL) in methanol and acetic acid (0.03 mL) were added. After sonication for 60 minutes the reaction mixture was evaporated in vacuo and the title compound was separated by preparative LC/MS to give 5.1 mg of colorless solid. Yield 43%. LC/MS (m/z) 339.2 ([M+H]+); RT = 2.92, (UV, ELSD) 94%, 94%. lb {4-[(5'Chloro-thiophm'2-ylmethyl)-aminoJ'2'methylpheriyl}-carbamic acid ethyl ester, LC/MS (m/z) 323.9 (M4); RT = 2.67, (UV, ELSD) 94%, 100%. lc {4-[(Beftzo[b]thiophen'2-ylmethyl)-aminoJ-2'methylphenyl}'Carbamic acid ethyl ester. LC/MS (m/z) 340.0 (M4); RT = 2.87, (UV, ELSD) 91%, 100%. Id {2-Methyl-4-[(5-phenyl-thiophen-2-ylmethyl)-amino]-phenyl}-carbamic acid ethyl ester. LC/MS (m/z) 365.3 ([M-Hf); RT = 2.89, (UV, ELSD) 97%, 99%. le [4-(4~Isopropyl-benzylamino)-2-methylphenyl]-carbarnic acid ethyl ester. LC/MS (m/z) 326.0 (M4); RT = 2.50, (UV, ELSD) 84%, 98%. If [4-(4-Fluoro-bemylamino)-2-methylphenyl]-carbamic acid propyl ester. LC/MS (m/z) 317.1 ([M+H]+); RT = 2.32, (UV, ELSD) 82%, 96%. LC/MS (m/z) 432.1 (M*); RT = 4.15, (UV, ELSD) 99.3% 100.0%. 2aj {2-Bromo-4-[methyl-(4'trifluoromethyl-benzyl)-amino]-phenyl}-carbamic acid propyl ester. LC/MS (m/z) 447.0 ([M+H]^; RT = 3.84, (UV, ELSD) 98.4%, 99.9%. 2%% N-{2-Chloro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-2,2,2- trifluoroacetamide. Data fox this comopund are reported above in the synthesis of intermediates of the general formula XDI-XXIII Example 3 3a {4-[(4-Fluorobervzyl)-(methyl)-amino]-2-isopropoxyphenyl}-carbamic acid ethyl ester 4-(4-Fluoroberizyl)-(me1hyl)-amino-2,isopropoxyaniline (0.29 g) was dissolved in dry dioxane (3 mL). N,N-Diisopropylethylamine (0.27 mL) and ethyl chloroformate (0.15 mL) were added, and the reaction mixture was stirred at room temperature over night. Water (5 mL) was added, and the resulting mixture was extracted with ethyl acetate (3 x 10 mL). The organic phase was dried over sodium sulfate and filtered. The solvent was evaporated in vacuo, and the crude product was purified by flash chromatography (silica gel, heptane / ethyl acetate 19:1,1 % triethylamine, gradient). Evaporation of the solvent in vacuo furnished the title compound (0.20 g, 55 %) as a colourless oil. LC-MS (m/z) 361.3 ([M+H]4); RT = 2.58, (UV, ELSD) 90 %, 98 %. Example 4 4a [4-(3-Fluorobenzylamino)-2-methoxyphenyl]-carbamic acid ethyl ester A solution of 3-fluorobenzaldehyde in dry methanol (84 μL, 476 mM) was added to a solution of (4-Amino-2-methyloxyphenyl)-carbamic acid ethyl ester (84 μL, 0.476 M in dry methanol). The resulting mixture was heated to 40 °C for 30 minutes. The solvent was evaporated in vacuo, and the remaining material was dissolved in 1,2-dichloroethane (1 mL). Sodium triacetoxyborohydrate (20 mg) was added, and the resulting mixture was kept at room temperature for 2 hours, under 2 periods of sonication for 10 minutes, respectively. The reaction mixture was filtered through silica gel (500 mg), and the column was washed with 1,2-dichloroethane (3 mL). The solvent was evaporated in vacuo yielding the title compound (5.7 mg, 45 %). LC-MS (m/z) 318.1 (M*); RT = 2.33, (UV, ELSD) 93 %, 100 %. The following compounds were prepared in an analogous fashion: 4b [4-(4-Isopropylbenzylamino)-2-methoxyphenyl]-carbamic acid ethyl ester LC-MS (m/z) 341.3 ([M-l]+); RT = 2.51, (UV, ELSD) 86 %, 100 %. 4c {2-Methoxy-4-[(3-methylthiophen-2-ylmethyl)-ainino]-phenyl}-carbamic acid ethyl ester LC-MS (m/z) 319.9 (M*); RT = 2.10, (UV, ELSD) 79 %, 99 % 4rf /V-(2, 4-Difluorobemylamino)~2-methoxyphenyl]-carbamic acid ethyl ester LC-MS (m/z) 337.2 ([M+H]4); RT = 2.44, (UV, ELSD) 93 % 100 %. Example 5 5a [2'Cyclopentyloxy-4-(4-methoxyben2ylamino)-phenyl]-carbamic acid ethyl ester (2-Cyclopentyloxy-4-nitrophenyl)-carbamic acid ethyl (294 mg) was dissolved in ethanol (26 mL). Zinc granules (1.63 g) and aqueous hydrochloric acid (5.0 mL, 2 M) were added. The resulting mixture was sonicated at room temperature for 6.5 hours, and then kept standing at room temperature over night Aqueous saturated sodium bicarbonate (100 mL) was added, and the mixture was extracted with ethyl acetate (2 x 100 mL). The organic phase was washed with water (100 mL) and brine (100 mL), dried over magnesium sulfate, and evaporated in vacuo. The resulting oil was dissolved in methanol (1.82 mL), and an aliquot (40 μL) of this solution was mixed with a solution of 4-methoxybenzaldehyde (40 μL, 0.466 M in methanol). The resulting mixture was heated to 40 °C for 20 minutes. The solvent was evaporated in vacuo, and the remaining material was dissolved in 1,2-dichloroethane (1 mL). Sodium triacetoxyborohydrate (20 mg) was added, and the resulting mixture was kept at room temperature for 2 hours, under 2 periods of sonication for 10 minutes, respectively. The reaction mixture was filtered through silica gel (500 mg), and the column was washed with 1,2-dichloroethane (3 mL). The solvent was evaporated in vacuo yielding the title compound (6.0 mg, 84 % from aldehyde). LC-MS (m/z) 384.1 (M*); RT = 2.40, (UV, ELSD) 76 %, 96 %. The following compounds were prepared in an analogous fashion: 5b [2-Cyclopentyloxy-4-(3'fluorO-2-methylbenzylamino)-phenylJ-carbamic acid ethyl ester The product was purified by preparative LC-MS. LC-MS (m/z) 386.2 (M*);RT = 3.22, (UV, ELSD) 80 %, 91 %. 5c [4-(3-FluorO'2'methylbenzylamino)-2~phenethyloxyphmyIJ-carbarnicacid ethyl ester The product was purified by preparative LC-MS. LC-MS (m/z) 422.3 (M*); RT = 3.389 (UV, ELSD) 84 %, 91 % 5d [2-Benzyloxy'4-(3'fluorO'2'methylbenzylamino)~phenyl]-carbamic acid ethyl ester The product was purified by preparative LC-MS. LC-MS (m/z) 409.2 ([M+Hf);RT = 3.30, (UV, ELSD) 80 %, 89 %. 5e [2-Benzyloxy-4-(4~methylsulfanylbenzylamino)-phenyl]-carbamic acid ethyl ester LC-MS (m/z) 422.1 (M4); RT - 2.92, (UV, ELSD) 83 %, 89 %. 5f {4'[(Befizo[bJthiophen-3~ylmethyl)-aminoJ-2'Cyclopentyloxyphenyl}-carbamic acid ethyl ester The product was purified by preparative LC-MS. LC-MS (m/z) 411.1 ([M+Hf); RT - 3.12, (UV, ELSD) 79 %, 85 %. 5g [4-(3-Fluoro-2-methylbenzylamino)-2-isopropoxyphenyl]-carbamic acid ethyl ester The product was purified by preparative LC-MS. LC-MS (m/z) 361.2 ([M+Hf);RT = 2.95, (UV, ELSD) 77 %, 86 %. 5h [2-Benzyloxy-4-(3-methoxybenzylarnino)-phenylJ~carbamic acid ethyl ester LC-MS (m/z) 407.3 QM+ffT) RT = 2.81, (UV, ELSD) 76 %, 87 %. Si {4'[(Benzo[lJJdioxol-5-ylmethyl)-aminoJ-2-isopropoxyphenyl}-carbamic acid ethyl ester LC-MS (m/z) 372.1 (M*);RT = 2.24, (UV, ELSD) 76 % 86 %. Example 6 6o N-{2-CMoro-4-[(5-chloro-thiophen-2-ylmethyl)-(methyl)amino]-phenyl}-3- cyclohexylpropionamide. Method A: To a mixture of 2-chloroN(4)-(5-chloro-thiophen-2-ylmethyl)-N(4)-methyl-benzene-l,4-diamine (14 mg) and triethyl amine (0.04 mL) in acetonitrile (1 mL) 3-cyclohexyl-proionyl chloride (0.03 mL) was added. Volatiles were evaporated in vacuo and the title compound was separated by preparative LC-MS. Method B: To a stirred mixture of 2-ChloroN-(4)-(5-chloro-thiophen-2-ylmethyl)-N(4)-methyl-benzene-l,4-diamine (470 mg, 1.64 mmol) and sodium bicarbonate in acetonitrile (40 mL) 3-cyclohexyl-proionyl chloride (372 mg, 2.13 mmol) was added. After 1 hour the reaction mixture was quenched with water (100 mL) and ice. The title compound was separated by filtration as a grey-brown solid. Yield 0.422 g, 60%. LC/MS (m/z) 425.4 ([M+Hf); RT = 4.09, (UV, ELSD) 97%, 100%. !H NMR (DMSO-d6): 0.87 (m, 2H), 1.05-1.29 (m, 4H), 1.47 (q, 2H), 1.56-1.76 (m, 5H), 2.29 (t, 2H), 2.91 (s, 3H), 4.67 (s, 2H), 6.76 (dd, 1H), 6.83 (d, 1H), 6.88 (d, 1H), 6.96 (d, 1H), 7.27 (d, 1H). The following compounds were prepared analogously by the method A from corresponding anilines and appropriate acid chlorides, chloroformiates, carbamyl chlorides, isocyanates, or di-tert-butyl dicarbonate (Boc20). Triethyl amine was used as a base in case of acid chlorides. Pyridine was used as a base in case of chloroformiates and carbamyl chlorides. No base was used in case of isocyanates and B0C2O. In case of (4-amino-3-chlorophenyl)-(5-chloro-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester as an aniline, the residue after evaporation was treated with 2% solution of anisol in a 1:1 mixture of trifluoroacetic acid and methylene chloride for 1 hour and evaporated again before preparative LC-MS: two adjacent R together with the aromatic group form a 5-8 membered ring which optionally contains one or two heteroatoms; R6 and R6' are independently selected from the group consisting of hydrogen, C1. 6-alk(en/yn)yl, C3-8-cycloalk(en)yl, C3-g-cycloaIk(en)yl-Ci-6-alk(en/yn)yI and Ar; or salts thereof. 2 A compound according to Claim 1, wherein R1 is Ci.6-alk(en/yn)yl or a hydrogen atom. 3 A compound according to any one of Claims 1-2, wherein s is 0. 4 A compound according to any one of Claims 1-2, wherein s is 1. 5 A compound according to Claim 4 wherein U is an oxygen atom. 6 A compound according to any one of Claims 1-5, wherein R2 is selected from the group consisting of hydrogen, C1-6-alk(en/yn)yl, C3-8-cycloa!k(en)yl, Axs Ar-C1-6 alk(en/yn)yl, halogen, halo-C1-6-alk(en/yn)yl and cyano; provided that when R2 is halogen or cyano then s is 0; and provided that U is 0 or S when s is 1 and R2 is a hydrogen atom. 7 A compound according to any one of Claims 1-6, wherein Z is an oxygen atom. 8 A compound according to any one of Claims 1-6, wherein Z is a sulphur atom. 9 A compound according to any one of Claims 1-8, wherein q is 0. 10 A compound according to any one of Claims 1-8, wherein q is 1. 11 A compound according to any one of Claims 1-10, wherein X is CO. 13 A compound according to Claim 12, wherein R and R are independently selected from the group consisting of hydrogen, Ci-6-alk(en/yn)yl and Ar. 14 A compound according to any one of Claims 1-13, wherein Y is of formula XXIV. 15 A compound according to any one of Claims 1-13, wherein Y is of formula XXV. 16 A compound according to any one of Claims 14-15, wherein W is an oxygen atom. 17 A compound according to any one of Claims 14-15, wherein W is a sulphur atom. 18 A compound according to any one of Claims 1-13, wherein Y is of formula XXVII. 19 A compound according to any one of Claims 1-13, wherein Y is of formula XXXXI. 20 A compound according to Claim 19, wherein V is a nitrogen atom. 21 A compound according to Claim 19, wherein V is CH. 22 A compound according to anyone of Claims 1-13, wherein Y is of formula xxxxn. 23 A compound according to Claim 22, wherein T is a nitrogen atom. 24 A compound according to Claim 22, wherein T is an oxygen atom. 25 A compound according to any one of Claims 1-24, wherein each R5 is independently selected from the group consisting of a C1_6-alk(en/yn)yl, C1-6 alk(en/yn)yl-heterocycloalk(en)yl, Ar, C1-6-alk(en/yn)yloxy, Ar-oxy, C1-6-alk(en/yn)yloxy-carbonyl, halogen, halo-C1-.6-alk(en/yn)yl, NR7Rr, S-R8 and S02R8, or two adjacent R5 together with the aromatic group form a 5-8 membered ring, which optionally contains one or two heteroatoms. 26 A compound according to Claim 25, wherein both R7 and Rr are C1-6 alk(en/yn)yl 27 A compound according to Claim 25, wherein R8 is selected from the group consisting of C1-6-alk(en/yn)yl and Ar. 28 A compound according to any one of Claims 1-27, said compound being selected from the group consisting of: {4-[(Benzofuran-2-ylmethyl)-amino]-2-methylphenyl}-carbamic acid propyl ester; or salts thereof 29 A pharmaceutical composition comprising one or more pharmaceutical acceptable carriers or diluents and a compound according to any one of claims 1- 28. 30 Use of a pharmaceutical composition according to Claim 29 for increasing ion flow in a potassium channel of a mammal such as a human. 31 Use according to Claim 30 for the prevention, treatment or inhibition of a disorder or condition being responsive to an increased ion flow in a potassium channel, such disorder or condition is preferably a disorder or condition of the central nervous system. 32 Use according to Claim 31, wherein said disorder or disease is selected from the group consisting of seizure disorders such as convulsions, epilepsy and status epilepticus. 33 Use according to claim 31 characterized in that the disorder or condition is selected from the group consisting of neuropathic and migraine pain disorders such as allodynia, hyperalgesic pain, phantom pain, neuropathic pain related to diabetic neuropathy and neuropathic pain related to migraine. 34. Use according to claim 31 characterized in that the disorder or condition is selected from the group consisting of anxiety disorders such as anxiety, generalized anxiety disorder, panic anxiety, obsessive compulsive disorder, social phobia, performance anxiety, post-traumatic stress disorder, acute stress reaction, adjustment disorders, hypochondriacal disorders, separation anxiety disorder, agoraphobia, specific phobias, anxiety disorder due to general medical condition and substance-induced anxiety disorder. 3 5 Use according to claim 31 characterized in that the disorder or condition is selected from the group consisting of and neurodegenerative disorders such as Alzheimer's disease, Huntington's chorea, multiple sclerosis, amyotrophic lateral sclerosis, AIDS-induced encephalopathy and other infection-related encephalopathies being caused by rubella viruses, herpes viruses, borrelia and by unknown pathogens, Creutzfeld-Jakob disease, Parkinson's disease, trauma-induced neurodegenerations. 36 Use according to claim 31 characterized in that the disorder or condition is selected from the group consisting of neuronal hyperexcitation states such as in medicament withdrawal or by intoxication.

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