FORM 2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENTS RULES, 2003 COMPLETE SPECIFICATION [See section 10, Rule 13] NOVEL COMPOUNDS, ISOMER THEREOF, OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF AS VANILLOID RECEPTOR ANTAGONIST; AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME; AMOREPACIFIC CORPORATION, A CORPORATION ORGANIZED AND EXISTING UNDER THE LAWS OF REPUBLIC OF KOREA, WHOSE ADDRESS IS 181, 2-GA HANGANG-RO, YONGSAN-GU, SEOUL 140-777, REPUBLIC OF KOREA. THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED. 1 Technical field The present disclosure relates to novel compounds, isomer thereof or pharmaceutically acceptable salts thereof as TRPV1 antagonist; and a pharmaceutical composition containing the same. Background Art The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1, TRPV1) is the receptor for capsaicin (8-methyl-N-vanillyl-6-nonenamide), a pungent ingredient in hot peppers. The molecular cloning of TRPV1 was reported in 1997 (Caterina et al., 1997, Nature, 389, pp816-824), which belongs to the TRP channel family of non-selective cation channel. TRPV1 is activated or sensitized by stimuli such as capsaicin, resiniferatoxin, heat, acid, anandamide, lipid metabolites or the like ; thus it plays a crucial role as a molecular integrator of noxious stimuli in mammals (Tominaga et a!., 1998, Neuron, 21 pp531-543; Hwang et al., 2000, PNAS, 97, pp6155-6160). The TRPVI is highly expressed in primary afferent sensory neurons, and also reportedly expressed in various organs and tissues such as bladder, kidney, lung, intestine, skin, central nervous system (CNS), and non-neuronal tissues (Mezey et al., 2000, PNAS, 97, pp3655-3660; Stander et al., 2004, Exp. Dermatol. 13, pp 129-139; Cortright et al, 2001, BBRC, 281, ppl 183-1189), and besides TRPV1 protein is upregulated in painful disease conditions. Activation of the TRPV1 by endogenous/exogenous stimuli leads to not only transmission of noxious stimuli, but also liberation of neuropeptides such as substance P, CGRP (Calcitonin Gene-Related Peptide) in the neurons, thereby causing neurogenic inflammation. TRPV1 knock-out mice show normal responses in a wide range of behavioural tests including noxious mechanical and acute thermal stimuli, but exhibit little thermal hypersensitivity in inflammation states. (Caterina et a!., 2000, Science, 288, pp306-3J3; Davis et al., 2000, Nature, 405, ppl83-187; Karai et al., 2004, J. Clin. Invest., 113, ppl344-1352). As mentioned above, the TRPV1 knock-out mice exhibit reduced responses to thermal or noxious stimuli, which has been supported by the effects of TRPV1 antagonists in various animal models of pain (Immke et a!., 2006, Semin. Cell. Dev. Biol., 17(5), pp582-91; Ma et al., 2007, Expert Opin. Ther. Targets, 11(3), pp307-20). The well-known TRPV1 antagonist, capsazepine, decreases hyperalgesia caused by physical stimuli in several models of inflammatory and neuropathic pain (Walker et al., 2003, J PET, 304, pp56-62; Garcia-Martinez et al., 2002, PNAS, 99, 2374-2379). In addition, treatment of the primary culture of afferent sensory neurons with the TRPV1 agonist, capsaicin etc., results in damage to nerve functions and furthermore death of nerve cells. The TRPV1 antagonist exerts defense actions against such damage to nerve functions and nerve cell death (Holzer P., 1991, Pharmacological Reviews, 43, ppl43-201; Mezey et al, 2000, PNAS, 97, 3655-3660). The TRPV1 is expressed on sensory neurons distributed in all regions of the gastrointestinal tract and is highly expressed in inflammatory disorders such as irritable bowel syndrome and inflammatory bowel disease (Chan et al, 2003, Lancet, 361, pp385-391 ; Yiangou et al, 2001, Lancet, 357, ppl338-1339). In addition, activation of the TRPV1 stimulates sensory nerves, which in turn causes release of neuropeptides which are known to play a critical role in pathogenesis of gastrointestinal disorders such as gastroesophageal reflux disease (GERD) and stomach duodenal ulcer (Holzer P, 2004, Eur. J. Pharmacol. 500, pp231-241; Geppetti et al, 2004, Br. J. Pharmacol, 141, pp!313-1320). The TRPV1-expressing afferent nerves are abundantly distributed in airway mucosa, and bronchial hypersensitivity is very similar mechanism to hyperalgesia. Protons and lipoxygenase products, known as endogenous ligands for the TRPV1, are well known as crucial factors responsible for development of asthma and chronic obstructive pulmonary diseases (Hwang et al., 2002, Curr. Opin. Pharmacol. pp235-242; Spina et al., 2002, Curr. Opin. Pharmacol. pp264-272). Moreover, it has been reported that air-polluting substances which are a kind of asthma-causing substances, i.e., particulate matter specifically acts on the TR.PV1 and such action is inhibited by capsazepine (Veronesi et al., 2001, NeuroToxicology, 22, pp795-810). Urinary bladder hypersensitiveness and urinary incontinence are caused by various central/peripheral nerve disorders or injury, and TRPV1 expressed in afferent nerves and urothelial cells play an important role in bladder inflammation. (Birder et al., 2001, PNAS, 98, ppl3396-13401). Further, TRPV1 knock-out mice are anatomically normal but have higher frequency of low-amplitude, non-voiding bladder contractions and reduced reflex voiding during bladder filling as compared to wild type mice, which is thus indicating that the TRPV1 affects functions of the bladder (Birder et al., 2002, Nat. Neuroscience, 5, pp856-860). The TRPV1 is distributed in human epidermal keratinocytes as well as in primary afferent sensory nerves (Denda et al., 2001, Biochem. Biophys. Res. Commun., 285, ppl250-1252; Inoue et al., 2002, Biochem. Biophys- Res. Commun., 291, ppl24-129), and it is then involved in transmission of various noxious stimuli and pains such as skin irritation and pruritus, thereby having close correlation with etiology of dermatological diseases and disorders, such as skin inflammation, due to neurogenic/non-neurogenic factors. This is supported by the report that the TRPV1 antagonist, capsazepine inhibits inflammatory mediators in human skin cells (Southall et al., 2003, J. Pharmacol. Exp. Ther., 304, pp217-222). Over recent years, evidence has been accumulation on other roles of TRPV1. TRPV1 might be involved in the blood flow/pressure regulation via sensory vasoactive neuropeptide release and in the regulation of plasma glucose levels or in the pathogenesis of type 1 diabetes (Inoue et al., Cir. Res., 2006, 99, pp 119-31; Razavi et al., 2006, Cell, 127, pp 1123-35; Gram etal., 2007, Eur. J. Neurosci., 25, pp213-23). Further, it is reported that TRPV1 knock-out mice show less anxiety-related behavior than their wild type littermates with no differences in locomotion (Marsch et al., 2007, J. Neurosci.,27(4), pp832-9). Based on the above-mentioned information, development of various TRPV1 antagonists is under way, and some patents and patent applications relating to TRPV1 antagonists under development were published. (Szallasi et al., 2007 , Nat. Rev. Drug Discov., 6, pp357-72; Appendino et al., 2006, Progress in Medicinal Chemistry, 44, ppl45-180 ; Rami et al., 2004, Drug Discovery Today: Therapeutic Strategies, 1, pp97-104 ; Correll et al., 2006, Expert Opin. Ther. Patents, 16, pp783-795 ; Kyle et al., 2006, Expert Opin. Ther. Patents, 16, pp977-996 ) Compounds of the present disclosure, are useful for prophylaxis and treatment of diseases associated with the activity of TRPV1 (Nagy et al., 2004, Eur. J. Pharmacol. 500, 351-369) including but not limited to. pain such as acute pain, chronic pain, neuropathic pain, post-operative pain, rheumatic arthritic pain, osteoarthritic pain, postherpetic neuralgia, neuralgia, headache, dental pain, pelvic pain, migraine, bone cancer pain, mastalgia and visceral pain (Petersen et al., 2000, Pain 88, ppl.25-133; Walker et al., 2003, J. Pharmacol. Exp. Ther., 304, pp56-62; Morgan et al.,2005, J. Orofac. Pain, 19, pp248-60 ; Dinis et al., 2005, Eur. Urol., 48, pp 162-7; Akerman et al., 2004, Br. J. Pharmcol., 142, pp 1354-1360; Ghilardi et al., 2005, J. Neurosci., 25, 3126-31; Gopinath et al., 2005, BMC Womens Health, 5, 2-9) ; nerve-related diseases such as neuropathies, HIV-related neuropathy, nerve injury, neurodegeneration, and stroke (Park et al., 1999, Arch. Pharm. Res. 22, pp432-434; Kim et al., 2005, J. Neurosci. 25(3), pp662-671); diabetic neuropathy (Kamei et al., 2001, Eur. J. Pharmacol. 422, pp83-86); fecal urgency; irritable bowel syndrome (Chan et al., 2003, Lancet, 361, pp385-391); inflammatory bowel disease (Yiangou et al., 2001, Lancet 357, ppl338-1339); gastrointestinal disorders such as gastro-esophageal reflux disease (GERD), stomach duodenal ulcer and Crohn's disease (Holzer P, 2004, Eur. J. Pharm., 500, pp231-241; Geppetti et al., 2004, Br. J. Pharmacol., 141, ppl313-1320); respiratory diseases such as asthma, chronic obstructive pulmonary disease, cough (Hwang et al., 2002, Curr. Opin. Pharmacol. pp235-242; Spina et al., 2002, Curr. Opin. Pharmacol. pp264-272; Geppetti et al., 2006, Eur. J. Pharmacol., 533, pp207-214 ; McLeod et al., 2006, Cough, 2, 10); urinary incontinence (Birder et al., 2002, Nat. Neuroscience 5, pp856-860); urinary bladder hypersensitiveness (Birder et al., 2001, PNAS, 98, ppl3396-13401); neurotic/allergic/inflammatory skin diseases such as psoriasis, pruritus, prurigo and dermatitis (Southall et al., 2003, J. Pharmacol. Exp. Ther., 304, pp217-222); irritation of skin, eye or mucous membrane (Tominaga et al., 1998, Neuron 21 pp531-543); hyperacusis; tinnitus: vestibular hypersensitiveness (Balaban et al., 2003, Hear Res. 175, ppl65-70); cardiac diseases such as myocardial ischemia (Scotland et al., 2004, Circ. Res. 95, ppl027-1034; Pan et al., 2004, Circulation 110, ppl826-1831); haemorrhagic shock (Akabori et al., 2007, Ann. Surg., 245(6), pp964-70) ; hair growth-related disorders such as hirsutism, effluvium, alopecia (Bodo et al., 2005, Am. J. Patho. 166, pp985-998; Biro et al., 2006, J. Invest. Dermatol, ppl-4) ; rhinitis (Seki et al., 2006, Rhinology, 44, pp 128-34) ; pancreatitis (Hutter et al., 2005, Pancreas, 30, pp260-5) ; cystitis (Dinis et al., 2004, J. Neurosci., 24, ppl 1253-63; Sculptoreanu et al., 2005, Neurosci. Lett. 381, pp42-6) ; vulvodynia (Tympanidis et al.,,2004, Eur. J. Pain, 8, ppl2-33); psychiatric disorders such as anxiety or fear (Marsch et al., 2007, J. Neurosci.,27(4), pp832-9). Compounds that are related to VRI activities are discussed e.g. in WO 02/61317, WO 02/090326, WO 02/16318, WO 02/16319, WO 03/053945, WO 03/099284, WO 03/049702, WO 03/049702, WO 03/029199, WO 03/70247, WO 04/07495, WO 04/72068, WO 04/035549, WO 04/014871, WO 04/024154, WO 04/024710, WO 04/02903], WO 04/089877, WO 04/089881, WO 04/072069, WO 04/111009, WO 05/03084, WO 05/073193, WO 05/051390, WO 05/049613, WO 05/049601, WO 05/047280, WO 05/047279, WO 05/044802, WO 05/044786, WO 06/097817, WO 06/098554, WO 06/100520, WO 06/101321, WO 06/102645, WO 06/103503, WO 06/111346, WO 06/101321, WO 06/101318, WO 06/1113769, WO 06/116563, WO 06/120481, WO 06/122250, WO 06/122799, WO 06/129164, WO 06/51378, WO 06/95263, WO 07/42906, WO 07/45462, WO 07/50732, WO 07/54474, WO 07/54480, WO 07/63925. WO 07/65663, WO 07/65888, WO 07/67619, WO 07/67710, WO 07/67711, WO 07/67756, WO 07/67757, WO07/63925, WO07/65662, WO07/65663, WO07/65888, WO07/69773, US20070149517, or US20070149513. More specifically, WO 06/101321 and WO 06/101318 relate to VRi modulators with a biphenyl partial structure. As a result of extensive and intensive studies, the present inventors have consequently synthesized novel compounds having VR1 antagonistic activity. Said new compounds have biphenylic structures, wherein one phenyl ring is substituted in para position to its attachment position to the rest of the molecule with a trifluoromethyl group or a fluoro, and has at least one additional substituent in ortho position (relative to said attachment position). Compared to the specific compounds disclosed in WO 06/101321 or WO 06/101318, which do not show this particular combination of features, the present compounds show remarkable improvement of their physicochemical characteristics, such as metabolic stability or pharmacokinetic profiles. Therefore, it is an object of the present disclosure to provide novel compounds useful as a potent antagonist for a TRPV1, isomer thereof and pharmaceutical^ acceptable salts thereof; and a pharmaceutical composition comprising the same. Detailed description of the disclosure The present disclosure provides a novel compound of the following formula (la), an isomer, or a pharmaceutically acceptable salt thereof: 3 formula (la) wherein, A is -C=C- or -CH-CH-; Ri is hydrogen, orCl-C3 alkyl; R? and R3 are independently hydrogen, halogen, cyano, CI-C3 alkyl, C1-C3 alkoxy, halo(Cl-C3)alkyl, (C2-C5)alkenyl, or (C2-C5)alkynyl; R4 is halo(Cl-C3)alkyl or halogen; R5 is C2-C10 alkyl, C2-C10 alkoxy, C1-C5 alkoxy (C1-C5) alkoxy, C1-C5 alkoxy (Cl- C5) alkylamino, C2-C10 alkylamino, di(C1-C5 alkyl)amino, C3-C6 cyctoalkylamino, C3-C6 cycloalkoxy, or (C3-C6)cycloalkyl(C1-C3)alkyloxy; and R6 is hydrogen, C1-C10 alkyl, C1-C10 alkoxy, or C1-C10 alkylamino. The present disclosure also provides a novel compound of the following formula (I), an isomer, or a pharmaceutically acceptable salt thereof: Re R3 formula (I) wherein, Ri is hydrogen, methyl, or ethyl; R2 and R3 are independently hydrogen, halogen, cya.no, methyl, ethyl, methoxy, trifluoromethyl, vinyl, or acetylenyl; R4 is trifluoromethyl or fluoro; R5 is C2-C5 alkyl, C2-C5 alkoxy, C1-C2 alkoxy (Cl-Q) alkoxy, C1-C2 alkoxy (Cl-C3) alkylamino, C2-C5 alkylamino, di(Cl-C3 alkyl)amino, C3-C6 cycloalkylamino, C3-C6 cycloalkoxy, or (C3-C6)cycloalkyl(Cl-C3)alkyloxy; and Rg is hydrogen, C1-C5 alkyl, C1-C5 alkoxy, or C1-C5 alkylamino. Another aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; as described above wherein if R5 is ethoxy, butoxy, pentoxy, (C3-C6)cycloalkoxy, or (C3-C6)cycloalkyl(Cl-C3)alkyloxy, then R] is methyl. In another embodiment in the compounds of formula (la) or (I) as disclosed further above, if R5 is ethoxy, butoxy, or pentoxy, and R4 is simultaneously fluoro, then Ri is methyl. In another embodiment in the compounds of formula (la) or (I) as disclosed further above, if R5 is ethoxy, butoxy, or pentoxy, then R4 is trifluoromethyl. in this specific embodiment, R[ is preferably methyl. Another aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, R| is hydrogen; R2 is halogen; and R5 is C2-C4 alky] or C2-C4 alkylamino. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, R| is hydrogen; R2 is fluoro; R3 is hydrogen, fluoro, cyano, methyl, vinyl, or acetylenyl; R4 is trifluoromethyl; R5 is C2-C4 alkyl or C2-C4 alkylamino; and R<; is hydrogen. Another aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, R1 is hydrogen, methyl, ethyl, or preferably methyl. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, Rj is methyl; R2 is halogen; and R5 is C2-C4 alkyl, C2-C4 alkyloxy, or C2-C4 alkylamino. Another aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, Ri is methyl; R2 is fluoro; R3 is hydrogen, fluoro, vinyl, methyl, or acetylenyl; R5 is C2-C4 alkyl, C2-C4 alkyloxy, or C2-C4 alkylamino; and Re is hydrogen or C1-C3 alkyl. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, R2 and R3 are independently hydrogen, fluoro, cyano, methyl, ethyl, methoxy, trifluoromethyl, vinyl, acetylenyl, or preferably hydrogen, fluoro, cyano, methyl, vinyl, or acetylenyl. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, R2 and R3 are both fluoro. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharanaceutically acceptable salt thereof; wherein., R4 is fluoro, or preferably trifiuoromethyl. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, Rj and R6 are both C1-C3 alkyl; or preferably methyl, ethyl, or propyl; or more preferably propyl. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutical ly acceptable salt thereof; wherein, Rg is hydrogen. One aspect of the present disclosure is a compound according to the above formula (la) or (I), an isomer, or a pharmaceutically acceptable salt thereof; wherein, R3 is ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, ethylamino, propylamine isopropylamino, n-butylamino, isobutylamino, sec-butylamino, or eyelohexyImethoxy, provided that if R5 is ethoxy, butoxy, pentoxy, or cyclohexylmethoxy, then R] is methyl. Another aspect of the present disclosure is a compound of the formula (la) or (1) as further described herein, an isomer, or a pharmaceutically acceptable salt thereof, wherein, if Rt is methyl or ethyl, then the compound may be a pure enantiomer or may be a mixture of the (R) and (S)-enantiomer; and then, the C-atom to which R1 is attached is preferably in the (R)-configuration. Another aspect of the present disclosure are compounds of the formula (la) or (I) as further described herein, an isomer, or a pharmaceutically acceptable salt thereof wherein, R5 is C2-C5 alkyl, (C2-C5)alkyloxy, C1-C4 alkylamino, or (C3-C6)cycloalkylalkoxyoxy, wherein preferably, R5 is C2-C4 alkyl, (C2-C4)alkyloxy, or C2-C4 alkylamino; wherein particularly preferably, Rs is C2-C4 alkyl, or C1-C3 alkylamino; wherein particularly preferably, Rs is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, or cyclohexylmethoxy, wherein particularly preferably, Rs is C2-C4 alkyl, propoxy, isopropoxy, or C2-C4 alkylamino; wherein even more preferably, R5 is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, propoxy, isopropoxy, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, or sec-butylamino, wherein even more preferably, R5 is n-propyl, n-butyl, isobutyl, isopropoxy, sec-butoxy, ethylamino, n-propylamino, isopropylamino, n-butylamino, wherein more preferably, R5 is n-propyl, n-butyl, isobutyl, n-propoxy, ethylamino, propylamino, isopropylamino, n-butylamino, wherein even more preferably, Rs is propyl, butyl, isobutyl, ethylamino, propylamino, or isopropylamino, wherein even more preferably, Rs is propyl, butyl, ethylamino, propylamino, or isopropylamino. Preferred examples of compounds according to the disclosure are selected from the group consisting of; N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Butylamino-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylarnide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propoxy-4-trifluoromethyI-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2,6-dipropyl-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-ethoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-ethyIamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-methyl-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-vinyl-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Cyano-5-ttuoro-4-methanesulfonylamino-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Ethynyl-5-fluoro-4-tnethanesuJfonyJamino-benzyi)-3-(2-propoxy-4-trifluoromethyl-phenyl)-acry!amide3 (R)-3-(256-Dibutyl-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-3-(2,6-Diethy]-4-trifluoromethyl-phenyl)-N-[l-(3s5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylatnide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-ethylamino-4-trifluoromethyl-phenyl)-acrylamide, 3-(2-Ethylamino-4-trifluoromethyl-phenyl)-N-(3-fluoro-4-methanesulfonylamino-5-methyl-benzyl)-acrylamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propyl-4-trifluoromethy(-phenyl)-acryIamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-methyl-benzyl)-3-(2-propyl-4- trifluoromethyl-phenyl)-acrylamide, (JR)-3-(2-Butyl-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-propyl]-3-(2-propyl-4-trifluoromethyl-phenyl)-acryIamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2- isopropoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesuifonyiamino-phenyl)-ethyl]-3-(4-fluoro-2- propoxy-phenyl)-acry lam ide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl].-3-(4-fluoro-2- propy lamino-pheny l)-acrylam ide, (R)-3-(2-Butoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide, (i?)-3-(2-Butoxy-4-fluoro-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino- phenyl)-ethyl]-acrylamide3 N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-propyl-4- trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Butyl-4-trifluoromethyl-phenyl)-N-[l-(3-fluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide. (R)-3-(2-sec-Butoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4- methanesulfonytamino-phenyl)-ethyl]-acrylamide, (i?)-3-(2-sec-Butoxy-4-fluoro-phenyl)-N-[ 1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2- ethylamino-4-fluoro-phenyl)-acrylamide, N-(3,5 -Difluoro-4-methanesulfony] amino-benzyl)-3 -(2-ethy lamino-4-fluoro- phenyl)-acrylamide, (R)-N-(2-Fluoro-4-{l-[3-(2-propyl-4-trifluoromethyl-phenyl)-atlylamino]- ethyi}-phenyl)-methanesulfonamide, (R)-3-(2-Butylamino-4-nuoro-phenyl)-N-[I-(3,5-difluoro-4-methanesulfonylamino-pheny[)-ethy[]-acrylamide, 3-(2-Buty]amino-4-fluoro-phenyl)-N-(3,5-difluoro-4-methaneSLilibnylamino-benzyl)-acrylam ide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-isobutyl-4-trifluoromethyl-phenyl)-acrylamides (R)-3-(2-Cyclohexylmethoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4methanesulfonylarnino-phenyl)-ethyl]-acrylamide, (S)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(4-fluoro-2-pfopyl-phenyl)-acrylamide, N-(3-FIuoro-4-methanesulfonylamino-5-vinyl-benzyl)-3-(2-isopropylamino-4-trifluoromethyl-phenyl)-acrylamide, and (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifluoromethy!-phenyl)-propionamide. Particularly preferred examples of compounds according to the disclosure are selected from the group consisting of; N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifluoromethy!-phenyl)-acrylamide, (R)-3-(2-Buty]amino-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propoxy-4-trifluoromethyl-phenyl)-acrylarnide, (R)-N-[I-(3,5-Difluoro-4-methanesuIfonylamino-phenyl)-ethyl]-3-(2;6- dipropyI-4-trifluoromethyl-phenyl)-acrylamide. (R)-N-[l-(3,5-Difluoro-4-methanesuifonyiamino-phenyij-ethyl]-3-(2-ethoxy-4- trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3s5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2- ethylamino-4-trifluoromethy 1-pheny l)-acry lam ide, N-(3-Fluoro-4-methanesulfony!amino-5-methyl-benzy!)-3-(2-propylamino-4- trifluoromethyl-phenyl)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-vinyt-benzyl)-3-(2-propylamino-4- trifluoromethyl-phenyl)-acrylamide, N-(3-Cyano-5-fluoro-4-methanesulfonylamino-ben2yl)-3-(2-propylamino-4- trifluoromethyl-phenyl)-acrylamide, (R)-3-(2,6-Diethyl-4-trifluoromethy!-phenyl)-N-[l-(3,5-difluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-ethylamino-4- trifluoromethyl-phenyl)-acrylamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-isopropoxy-4- trifluoromethyl-phenyl)-acrylamide, (R)-N-[I-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propyl-4- trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Butyl-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2- isopropoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Butoxy-4-trifiuoromethyl-phenyl)-N-[ 1 -(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-3-(2-Butoxy-4-fluoro-phenyl)-N-[l-(3,5-dif]uoro-4-methanesulfoiiylamino-phenyl)-ethyl]-acrylamide, N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Butyl-4-trifluoromethyl-phenyl)-N-[l-(3-fluoro-4-niethanesuifonylamino-phenyl)-ethyl]-acrylamide; (R)-3-(2-sec-Butoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-diftuoro-4-methanesulfonylamino-phenyi)-ethyl]-acrylamide, (R)-3-(2-sec-Butoxy-4-fluoro-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acry]amide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-ethy!amino-4-fluoro-phenyl)-acrylamide, (R)-N-(2-Fluoro-4-{l-[3-(2-propyl-4-trifluoromethyl-phenyl)-altylamino]-ethyl}-phenyl)-methanesulfonamide, (R)-3-(2-Butylamino-4-fluoro-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-isobutyl-4-trifluoromethyl-phenyl)-acrylamide, and N-(3-Fluoro-4-methanesul fbnylam ino-5 -vinyl-benzyl)-3 -(2-isopropylamino-4-trifluoromethyl-phenyl)-acrylamide. The compounds of the formula (la) or (I) of the present disclosure can chemically be synthesized by the following reaction schemes. However, these are given only for illustration of the disclosure and not intended to limit to them. [Scheme l] r"1 ? i6 Rl 9 Re R2^Y^NHz + HCT^V^S DMTMM, NMM Riy^X^K^f^y^ MsHN^V R5^^R4 THF rt MsHN'S^ H Rs'^^R* R3 ' R3 1 2 3 The Scheme I shows a proposed process for synthesizing acrylamide compound with various substituents. Substituted benzylamine (1) is reacted with phenylacrylic acid (2) to yield benzyl phenylacrylamide (3) using DMTMM {4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride} (Tetrahedron Lett., 1999, 40, 5327). [Scheme 2] N°2 NH2 reductive HN' a .y,. .... . ,„. HOOC.X Pd/C, H2 ^ HOOC.X amination, HOOC.X NHMe(OMe).HCI ^ 4 4 5 " 6 A 0 HN" a O HN'Ra o HN'Ra /°My^K, LAH u A^L Wittig reaction u t LiOH 7 * 8 R< 9^R< Rl R R2Y!!T'NH2 Bi O HN'"a 1 ^ a M3HNV ^NVA |l J »~ MsHN^T ^i^R4 ^^R4 DMTMM. NMM R, *A 10 J 11 The Scheme 2 shows a proposed process for synthesizing acrylamide compound (11) with various substituents. 4-Substituted 2-aminobenzoic acid (5), which is prepared by hydrogenation of 4-substituted 2-nitrobenzoic acid (4), is converted to the corresponding alkylamino benzoic acid (6) via reductive amination. The substituted benzoic acid (6) is converted to the corresponding Weinreb amide (7), which is reduced by lithium aluminum hydride to yield substituted benzaldehyde (8). The benzaldehyde (8) is converted to methyi phenyl acrylic ester (9) by Wittig reaction. The methyl phenyl acrylic ester (9) is hydrolyzed with lithium hydroxide to yield phenyl acrylic acid (10). The phenyl acrylic acid (10) is reacted with substituted benzylamine (1) as shown in scheme 1 to yield benzyl phenylacrylamide (11). [Scheme 3] N02 HN"Ra HOOCv^L j) Ra-CHO , CH3CQ2H HOOC.A. ^"R4 ii) Pd/C, H2 ^^R4 4 6 The Scheme 3 shows a more efficient process for synthesizing alkylamino benzoic acid (6) which is an intermediate to benzyl phenylacrylamide (11). One pot hydrogenation reaction of 4-substituted 2-nitrobenzoic acid (4) in the presence of an aldehyde and acetic acid replaces the two-step process including hydrogenation of 4 and reductive amination of the corresponding 2-aminobenzoic acid 5. [Scheme 4] NO, ,„ 0 NO? 0 HN' a HOOcJL2 NHMe(OMe).HCI ^ ^N-K1 1) Pd/C, Ha ^ ^ uKl^o NMM, DMTMM ' K^-a 2) reductive amination ' K^a K4 K4 "4 4 12 7 The Scheme 4 shows an alternative process for synthesizing Weinreb amide (7) which is an intermediate to benzyl phenylacrylamide (11). 4-Substituted 2-nitrobenzoic acid (4) is converted to the corresponding Weinreb amide (12). Hydrogenation of the weinreb amide (12) followed by reductive amination with an aldehyde yields Weinreb amide (7). TScheme 5) OH 0'Rb rVRt> H00C^A *b~X RbOOC Jk LiOH ^ HOOC JL NHMe(OMe).HCI ^ l^LR K2CO3 KA~D TIX NMM, DMTMM 13 14 1S K4 o A X. LAH ft l' Wittig reaction 0 o"Rb LiOH 1Q l-AR4 DMTMM. NMM " MsHN £ ,„ ^R< 19 K3 20 The Scheme 5 shows a proposed process for synthesizing acrylamide compound (20) with various substituents. 4-Substituted 2-hydroxybenzoic acid (13) is reacted with an alkyl halide and potassium carbonate to yield corresponding alkoxy benzoate (14), which is hydrolyzed with lithium hydroxide to give atkoxy benzoic acid (15). The substituted benzoic acid (15) is converted to benzyl phenylacrylamide (20) by similar processes used for benzyl phenylacrylamide (11) shown in Scheme 2. [Scheme 6] XX Wittig reaction ° 0H Rb-x ° fRb 21 *4 22 *4 18 R" The Scheme 6 shows an alternative process for synthesizing methyl phenyl acrylic ester (18) which is an intermediate to benzyl phenylacrylamide (20). 4- Substituted 2-hydroxybenzaldehyde (21) is converted to corresponding methyl phenyl acrylic ester (22) by Wirtig reaction, which is reacted with an alkyl halide and potassium carbonate to yield methyl phenyl acrylic ester (18). [Scheme 7] F?c O Rc O "OH Kc U Kc U R\*A. t-^n^- 3 Melhtylacrylate F3C R<= F3C Rc 24 R2-^-|^JH2 Ri O Rc SHN-V 1 R2YT"N Mil "^ ' - MSHNV " ^. DMTMM, NMM R3 25 The Scheme 7 shows a proposed process for synthesizing acrylamide compound (25) with various substituents. 4-Trifluromethyl iodobenzene is converted to substituted phenyl acrylic acid methyl ester (23) by palladium catalyzed coupling reaction. The phenyl acrylic acid methyl ester (23) is hydrolyzed with lithium hydroxide to yield phenyl acrylic acid (24). The phenyl acrylic acid (24) is reacted with substituted benzylamine (1) as described in Scheme 1 to yield benzyl phenylacrylamide (25). [Scheme 8] o X NH2 1}HO.^ ■— ~^\^ • VA""0 Rd 26 2) SOCl2 3) NaOH UR4 27 28 R4 1)HCI "N 1^ Rd 2) NHMe(OMe) NMM HCI UMBK^-R^ 2) Wittig reaction k^"R4 29 30 LiOH H02C r RlYi Nhl2 R3 1 Ri o Rd DMTMM, NMM 31 R3 32 The Scheme 8 shows a proposed process for synthesizing acrylami.de compound (32) with various substituents. Substituted benzoyl chloride (26) is reacted with 2-amino-2-methyl-J-propanol in the present of a base, and the resulting adduct is treated with thionyl chloride followed by sodium hydroxide to afford dihydro-oxazole compound (27). After treated with n-butyl lithium at low temperature, the compound 27 is reacted with an alkyt halide to give disubstituted dihydro-oxazole (28). The compound 28 is hydrolyzed with conc-HCl to the corresponding benzoic acid, which is converted to the Weinreb amide (29). After reducing compound 29 with lithium aluminum hydride, the resulting aldehyde is converted to the phenyl acrylic ester (30) under suitable Wittig reaction conditions. The acrylic ester (30) is hydrolyzed with lithium hydroxide to yield the corresponding acrylic acid (31). Substituted benzylamine (1) is reacted with acrylic acid (31) as described in Scheme I to yield benzyl phenylacrylamide (32). [Scheme 9] R, 0 R6 R, O Re MsHN'^ H R5''^-^R4 MsHN Y H R/^^R4 R3 R3 3 33 The Scheme 9 shows a proposed process for synthesizing amide compound (33) with various substituents. Substituted acrylamide (3) is reduced with Pd/C under hydrogen pressure to yield amide compound (33). The present disclosure also provides to a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof for use as a medicament. In one embodiment, the present disclosure also provides a pharmaceutical composition comprising a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient and a pharmaceutically acceptable carrier. In another embodiment, the present disclosure also provides a composition comprising a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof; and pharmaceutically acceptable carrier for preventing or treating a condition associated with the pathological stimulation and/or aberrant expression of vanilloid receptor. In one preferred aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof, for treating a condition selected from the group consisting of pain, inflammatory disease of the joints, neuropathies, HIV-related neuropathy, nerve injury, neurodegeneration, stroke, urinary bladder hypersensitivity including urinary incontinence, cystitis, stomach duodenal ulcer, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), fecal urgency, gastroesophageal reflux disease (GERD), Crohn's disease, asthma, chronic obstructive pulmonary disease, cough, neurotic/allergic/inflammatory skin disease, psoriasis, pruritus, prurigo, irritation of skin, eye or mucous membrane, hyperacusis, tinnitus, vestibular hypersensitivity, episodic vertigo, cardiac diseases such as myocardial ischemia, hair growth-related disorders such as effluvium, alopecia, rhinitis, and pancreatitis. In a particularly preferred aspect, the present disclosure relates to the pharmaceutical composition comprising a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof for treating pain as described above, wherein the pain is or is associated with a condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathic pain, post-operative pain, dental pain, non-inflammatory musculoskeletal pain (including fibromyalgia, myofascial pain syndrome and back pain), visceral pain, migraine, and other types of headaches. The present disclosure also provides a pharmaceutical composition comprising a compound of formula (la) or (I), an isomer thereof or a pharmaceutical^ acceptable salt thereof, which is characterized in that it is adapted for oral administration. In one aspect, the present disclosure relates to the use of a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof for the preparation of a medicament In another aspect, the present disclosure relates to the use of a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the prevention or treatment of a condition that is associated with the aberrant expression and/or aberrant activation of a vanilloid receptor. In a preferred aspect, the present disclosure relates to the use of a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof, in preparation of a medicament for the prevention or treatment of a condition that is selected from the group consisting of pain, inflammatory disease of the joints, neuropathies, HIV-related neuropathy, nerve injury, neurodegeneration, stroke, urinary bladder hypersensitivity including urinary incontinence, cystitis, stomach duodenal ulcer, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), fecal urgency, gastroesophageal reflux disease (GERD), Crohn's disease, asthma, chronic obstructive pulmonary disease, cough, neurotic/allergic/inflammatory skin disease, psoriasis, pruritus, prurigo, irritation of skin, eye or mucous membrane, hyperacusis, tinnitus, vestibular hypersensitivity, episodic vertigo, cardiac diseases such as myocardial ischemia, hair growth-related disorders such as effluvium, alopecia, rhinitis and. pancreatitis. Jn a particularly preferred aspect, the present disclosure relates to the use of the compound of formula (la) or (I), an isomer thereof, for preparing a medicament for preventing or treating pain as described above, wherein the condition is pain, which is or which is associated with a condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathic pain, post-operative pain, dental pain, non-inflammatory musculoskeletal pain (including fibromyalgia, myofascial pain syndrome and back pain), visceral pain, migraine, and other types of headaches. In another aspect, the present disclosure relates to a method for inhibiting vanilloid ligand from binding to vanilloid receptor in a patient, comprising contacting cells expressing vanilloid receptor in the patient with the compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof. In another aspect, the present disclosure relates to a method for preventing or treating a condition associated with the pathological stimulation and/or aberrant expression of vanilloid receptors. In another aspect, the present disclosure also provides a method for preventing or treating a condition selected from the group consisting of pain, inflammatory disease of the joints, neuropathies, HIV-related neuropathy, nerve injury, neurodegeneration, stroke, urinary bladder hypersensitivity including urinary incontinence, cystitis, stomach duodenal ulcer, irritable bowel syndrome (IBS) and inflammatory bowel disease (1BD), fecal urgency, gastro-esophageal reflux disease (GERD), Crohn's disease, asthma, chronic obstructive pulmonary disease, cough, neurotic/allergic/inflammatory skin disease, psoriasis, pruritus, prurigo, irritation of skin, eye or mucous membrane, hyperacusis, tinnitus, vestibular hypersensitivity, episodic vertigo, cardiac diseases such as myocardial ischemia, hair growth-related disorders such as effluvium, alopecia, rhinitis, and pancreatitis, which comprises administering to a mammal including a person in need thereof a therapeutically effective amount of the compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof. In a particularly preferred aspect, the present disclosure relates to the method of treating pain by administering a compound of formula (la) or (I), an isomer thereof, or a pharmaceutically acceptable salt thereof as described above, wherein the pain is or is associated with a condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathic pain, post-operative pain, dental pain, non-inflammatory musculoskeletal pain (including fibromyalgia, myofascial pain syndrome and back pain), visceral pain, migraine, and other types of headaches Hereinafter, the formulating methods and kinds of excipients will be described, but the present disclosure is not limited to them. A compound of formula (la) or (I), an isomer thereof or a pharmaceutically acceptable salt thereof according to the present disclosure can be prepared as a pharmaceutical composition containing pharmaceutically acceptable carriers, adjuvants, diluents and the like. For instance, the compounds of the present disclosure can be dissolved in oils, propylene glycol or other solvents which are commonly used to produce an injection. Suitable examples of the carriers include, but not limited to, physiological saline, polyethylene glycol, ethanol, vegetable oils, isopropyl myristate, etc. For topical administration, the compounds of the present disclosure can be formulated in the form of ointment or cream. The compound according to the present disclosure may also be used in the forms of pharmaceutically acceptable salts thereof, and may be used either alone or in combination or in admixture with other pharmaceutically active compounds. The compounds of the present disclosure may be formulated into injections by dissolving, suspending or emulsifying in water-soluble solvent such as saline and 5% dextrose, or in water-in soluble solvents such as vegetable oils, synthetic fatty acid glyceride, higher fatty acid esters and propylene glycol. The formulations of the disclosure may include any of conventional additives such as dissolving agents, isotonic agents, suspending agents, emulsifiers, stabilizers and preservatives. The preferable dose level of the compounds according to the present disclosure depends upon a variety of factors including the condition and body weight of the patient, severity of the particular disease, dosage form, and route and period of administration, but may appropriately be chosen by those skilled in the art. The compounds of the present disclosure are preferably administered in an amount ranging from 0.001 to 100 mg/kg of body weight per day, and more preferably from 0.01 to 30 mg/kg of body weight per day. Doses may be administered once a day. or several times a day with each divided portions. The compounds of the present disclosure are used in a pharmaceutical composition in an amount of 0.0001 P10% by weight, and preferably 0.001 PI % by weight, based on the total amount of the composition. The pharmaceutical composition of the present disclosure can be administered to a mammalian subject such as rat, mouse, domestic animals, human being and the like via various routes. The methods of administration which may easily be expected include oral and rectal administration; intravenous, intramuscular, subcutaneous, intrauterine, duramatral and intracerebroventricular injections. Detailed description of the definitions When describing the compounds, pharmaceutical compositions containing such compounds, methods of using such compounds and compositions, and use of such compounds and compositions, all terms used in the present application shall have the meaning usually employed by a relevant person skilled in the art, e.g. by a medicinal chemists, pharmacist or physician. By the way of example some definitions of specific groups are given below: "Alkenyl" includes monovalent olefinically unsaturated hydrocarbyl groups being straight-chained or branched and having at least 1 double bond. "Alkenyl" has preferably 2-5 carbon atoms ("C1-C5 alkenyl"), 2-4 carbon atoms ("C2-C4 alkenyl"), or only 2-3 carbon atoms ("C2-C3 alkenyl"). Particular alkenyl groups include ethenyl (-CH=CH2), n-propenyl (-CH2CH=CH2), isopropenyl (C (CH3) =CH2), and the like. A preferred "alkenyl" group is ethenyl (vinyl). "Alkoxy" includes the group -OR wherein R is "alkyl" as defined further above. Particular alkoxy groups include, by way of example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, iso-butoxy, sec-butoxy, n-pentoxy, 1,2-dimethylbutoxy, and the like. "Alkoxyalkoxy" refers to the group --OROR', wherein R and R' are the same or different "alkyl" groups as defined further above. "Alkoxyalkylamino" refers to the group -NH(ROR'), wherein R and R' are the same or different "alkyl" groups as defined further above. "Alkyl" includes monovalent saturated aliphatic hydrocarbyi groups. The hydrocarbon chain may be either straight-chained or branched. "Alkyl" has 1-6 carbon atoms ("C1-C6 alkyl"), and in some instances preferably 1-5 carbon atoms ("C1-C5 alkyl"), 1-4 carbon atoms ("C1-C4 alkyl"), or only 1-3 carbon atoms ("C1-C3 alkyl"). This term is exemplified by groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, t-amyl, and the like. "Alkynyl" includes acetylenically unsaturated hydrocarbyi groups being straight-chained or branched and having at least 1 triple bond. "Alkynyl" has preferably 2-6 carbon atoms ("C2-C6 alkynyl"), and in some instances even more preferably 2-5 carbon atoms ("C1-C5 alkynyl"), 2-4 carbon atoms ("C2-C4 alkynyl"), or only 2-3 carbon atoms ("C2-C3 alkynyl"). A preferred alkynyl group is ethynyl (acetylenyl). "Alkylamino" includes the group -NHR', wherein R' is alkyl group as defined herein. "Dialkylamino" includes the group -NR'R", wherein R' and R" are alkyl group as defined herein. "Cycloalkyl" refers to cyclic saturated aliphatic hydrocarbyi groups. The numbers of C-atoms referenced in connection with a given cycloalkyl group corresponds to the number of ring forming carbon atoms, e.g. "C3-C6 cycloalkyl" refers to a cycfoalkyJ with between three and six ring-forming C atoms. Examples of "cycloalkyl" are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl etc. [f indicated, a "cycloalkyl" group may be unsubstituted or substituted with one or more alkyl groups, e.g. with C1-C6 alkyl groups, preferably with C1-C3 alkyl groups, particularly preferably with methyl groups. If a "cycloalkyl" carries more than one alkyl substituent these substituents may be attached to the same or to different ring-forming carbon atoms. "Cycloalkoxy" refers to the group -OR, wherein R is "cycloalkyl" group as defined further above. "Cycloalkylamino" refers to the group -NHR, wherein R is "cycloalkyl" group as defined further above. "Cycloalkylalkoxy" refers to the group -OR-R', wherein R is "alkyl" group and R' is "cycloalkyl" group as defined further above. Examples of "cycloalkylalkoxy" are cyclopropylmethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, cyclopropylethoxy, etc. "Cyano" refers to the radical -C=N. "Ethenyl" or "vinyl" refers to -CH=CH2 which is also designated "vinyl" in the present application. "Ethynyl" or "acetylenyl" refers to -OCH. "Halo" or "halogen" refers to fluoro, chloro, bromo, and iodo. Preferred halo groups are either fluoro or chloro. "Haloalkyl" includes an "alkyl" group as defined further above which is substituted with one or more halogens which may be the same, e.g. in trifluoromethyl or pentafluoroethyl, or which may be different. "Isomer" refers to especially optical isomers (for example essentially pure enantiomers, essentially pure diastereomers, and mixtures thereof) as well as conformation isomers (i.e. isomers that differ only in their angles of at least one chemical bond), position isomers (particularly tautomers), and geometric isomers (e.g. cis-trans isomers). "Essentially pure", e.g. in connection with enantiomers or diastereomers means at least about 90%, preferably at least about 95%, more preferably at least about 97 or at least about 98%, even more preferably at least about 99%, and particularly preferably at least about 99.5% (w/w) of a specified compound, e.g. a particular enantiomer or diastereomer. "Pharmaceutically acceptable" means being devoid of substantial toxic effects when used in doses usually employed in a medicinal dosage, and thereby being approvable or preferably being approved by a regulatory agency of the Federal or a state government or being listed in the U. S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans. "Pharmaceutically acceptable salt" refers to a salt of a compound of the disclosure that is "pharmaceutically acceptable" as further defined herein, and that possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid,3- (4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesutfonic acid, 4-chiorobenzenesulfonic acid, 2naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4methylbicyclo [2.2.2]-oct-2-ene-l-carboxylic acid, glucoheptonic acid,3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound is replaced. "Pharmaceutically acceptable carrier" refers to a diluent, adjuvant, excipient or carrier with which a compound of the disclosure is administered and which is "pharmaceutically acceptable" as further defined herein. "Preventing" or "prevention" refers to a reduction in risk of acquiring a disease or disorder (i.e., causing at least one of the clinical symptoms of the disease not to develop in a subject that may be exposed to or predisposed to the disease but does not yet experience or display symptoms of the disease). "Subject" includes humans and non-human mammals. The term "patient" is used interchangeably with "subject" herein and shall include humans and non-human mammals unless specified otherwise. "Therapeutically effective amount" means the amount of a compound that, when administered to a subject for treating a disease, is sufficient to effect such treatment for the disease. The "therapeutically effective amount" can vary depending on the compound, the disease and its severity, and the age, weight, etc., of the subject to be treated. "Treating" or "treatment" of any disease or disorder refers, in one embodiment, to ameliorating the disease or disorder (i.e., arresting or reducing the development of the disease or at /east one of the dinicaf symptoms thereof), m another embodiment "treating" or "treatment" refers to ameliorating at least one physical parameter, which may not be discernible by the subject. In yet another embodiment, "treating" or "treatment" refers to modulating the disease or disorder, either physically, (e. g., stabilization of a discernible symptom), physiologically, (e. g., stabilization of a physical parameter), or both. In yet another embodiment, "treating" or "treatment" refers to delaying the onset of the disease or disorder. In yet another embodiment, "treating" or "treatment" refers to reducing, modifying or removing one or more discernible symptom of a disease or disorder without modulating the cause of the underlying disease. Mode for carrying out the disclosure The present disclosure is more specifically explained by following examples and experimental examples. However, it should be understood that the extent of the present disclosure is not limited to the following examples and experimental examples Example 1: fK;-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifiuoromethyl-phenyl)-acrylamide. H F Stepl: Synthesis of 2-amino-4-(trifluoromethyl)-benzoic acid 2-Nitro-4-trifluoromethyl-benzoic acid (3.07 g, 13.0 mmol) was stirred with Pd/C under hydrogen atmosphere for 2 hrs. The reaction mixture was filtered with celite to remove Pd/C. The filterate was concentrated in vacuo. The residue was extracted with CH2CI2 (30 mi x 3) and H2O (30 ml). The combined organic layer was dried over MgS04 and then concentrated to yield title compound (2.66 g, 99%). lH NMR (300MHz, DMSO-d6): 5 7.82 (d, 1H), 7.02 (s, 1H), 7.05(m, IH), 2.41(br, 1H) Step 2: Synthesis of 2-propylamino-4-(trifluoromethyl)-benzoic acid 2-Amino-4-(trifluoromethyl)benzoic acid (714 mg, 3.48 mmol), propionylaldehyde (0.27 ml, 3,74 mmol), acetic acid (3.49 mmol) and sodium triacetoxyborohydride (1.12g, 5.25 mmol) were added in THF(40 ml). The reaction mixture was stirred overnight. The reaction mixture was quenched by adding sat. NaHCCh (50 ml). The aqueous mixture was extracted with CH2C12 (30ml x 3). A combined organic layer was dried over MgSO4 concentrated in vacuo, and purified with column chromatography to yield title compound (155mg, 18%). ]H NMR (300MHz, CDCb): 5 8.04 (d, IH, J= 8.4 Hz), 6.89 (s, 1H), 6.79 (d, IH, J = 8.1 Hz), 3.21 (t, 2H, J= 7.2 Hz), 1.75 (m, 2H), 1.02 (t, 3H, J= 7.8Hz). Step 3: Synthesis of N-methoxy-N-methyl-2-propylamino-4-trifluoromethyl-benzamide 2-Propylamino-4-(trifluoromethyl)benzoic acid (147 mg, 0.594 mmol) in CH2Cl2was reacted with N,0-dimethylhydroxy amine (82 mg), NMM (0.2 ml) and DMTMM (222 mg) at room temperature overnight. The reaction mixture was quenched by adding H2O(3 ml). The reaction solvent was removed under reduced pressure. Water (30 ml) was added to the resulting residue, which was extracted with ethylacetate (30 ml x 3). The combined organic layer was washed with sat. NaHCO3 solution (30 ml), IN HCI aqueous solution (30 ml) and brine (30 ml), and then dried over MgSO4. The tlIterate was concentrated in vacuo. The residue was purified with column chromatography to yield the title compound (98mg, 57%). 'H NMR (300MHZ, CDCl3): 5 7.43 (d, \H,J= 7.8 Hz) 6,85 (s, 1H), 6.82 (d, IH), 3.56(s, 3H), 3.34 (s, 3H), 3.10 (t,2H,J= 6.9 Hz), 1.71 (m, 2H), 1.01 (t, 3H, J =6.9 Hz). Step 4: Synthesis of 3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylic acid methyl ester N-Methoxy-N-methyl-2-propylamino-4-trifluoromethyI-benzamide (98.3 mg, 0.339 mmol) was reacted with lM lithium aluminum hydride (0.6 ml) in THF (20ml) at -40 °C for 1 hr. The reaction mixture was quenched by adding saturated potassium hydrogen sulfate solution. The mixture was stirred for 30min. The reactions solvent was removed in vacuo. Water (30 ml) was added to the resulting residue, which was extracted with CH2CI2 (30 ml x 3). The combined organic layer was dried over MgSCU and concentrated in vacuo to yield 2-propylamino-4-trifluoromethyl-benzaldehyde (78 mg). 2-Propylamino-4-trifluoromethyI-benzaldehyde in toluene was reacted with methyl (triphenylphosphoranylidene) acetate (137 mg) at 100 °C overnight. The reaction solvent was removed in vacuo. Water (30 ml) was added to the resulting residue, which was extracted with ethyl acetate (30 ml x 3). The combined organic layer was dried over MgSO4 and filtered. The filterate was concentrated in vacuo and purified with column chromatography to yield title compound (67 mg, 69%). 'H NMR (300MHz, CDCI3): 5 7.76 (d, 1H, J = 15.9 Hz), 7.41 (d, 1H, J = 8.1 Hz), 6.92 (d, IH, J = 8.7 Hz), 6.84 (s, IH), 6.38 (d, 1H, J = 15.6 Hz), 3.82 (s, 3H), 3.17 (m, 2H), 1.70 (m, 2H), 1.04 (t, 3H, J = 7.8 Hz). Step 5: Synthesis of 3-(2-propylamino-4-trifluoromethyI-phenyl)-acrylic acid 3-(2-Propylamino-4-trifluoromethyl-phenyi)-acrylic acid methyl ester (67.3 mg, 0.234 mmol) was reacted with aqueous IN LiOH solution (5 ml) in THF/CH3OH (10ml/5ml) for 1 hr. The reaction solvent removed in vacuo. Water (30 ml) was added to the resulting residue, which was neutralized with IN HCl solution, an then extracted with ethyl acetate (30ml x 3). The combined organic layer was dried over MgS04 and concentrated in vacuo to yield title compound (55 mg, 0.201 mmol, 86%). 'H NMR (300MHz, CDCb): 5 7.80 (d, IH, J = 15.6 Hz), 7.48 (d, IH, J = 7.5 Hz), 6.82 (s, IH), 6.79 (s, IH), 6.36 (d, IH, J = 15.6 Hz), 3.10 (t, 2H, J = 6.9 Hz), 1.75 (m, 2H), 0.97 (t, 3H, J = 7.5 Hz) Step 6: Synthesis of (7?)-N-[l-(3s5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifluoromethyt-phenyl)-acrylamide (RJ-N-^-Aminoethyl-2-difluoro-phenyl)-methanesulfonamide, HCl salt (70 mg, 0.24 mmol) in THF was reacted with 3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylic acid (55mg, 0.20 mmol), NMM (0.2 ml) and DMTMM (86 mg, 0.34 mmol) at room temperature overnight. The reaction mixture was quenched by adding H2O. The reaction solvent was removed in vacuo. Water (30 ml) was added to the resulting residue, which was extracted with ethyl acetate (30 ml x 3). The combined organic layer was dried over MgSO4 The filterate was concentrate under reduced pressure and purified with column chromatography to yield the title compound (35 mg, 59%). 'H NMR (300MHZ, CDC13): 5 7.79 (d, IH, J = 15 Hz), 7.37 (d, IH, J = 7.8 Hz), 6.96 (d, IH, J = 8.4 Hz), 6.86 (d, IH, J = 8.1 Hz), 6.82 (s, IH), 6.48 (br, IH), 6.33 (d, IH, J = 15.3 Hz), 5.93 (d, IH, J = 7.2 Hz), 5.15 (t, IH, J = 7.2 Hz), 3.19 (s, 3H), 3.14 (t, 2H, J = 7.2 Hz), 1.70 (m, 2H), 0.97 (t, 3H, J = 7.5 Hz) ESI [M-H]": 504 Example 2: N-(3.5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-propylamino-4-trifUioromethyl-pheny])-acrylamide 0 HN MsHN^j^ ^^XF3 F N-(4-Aminomethyl-2,6-difluoro-phenyl)-methanesulfonamide, HC1 salt (84 mg, 0.308 mmol) was reacted with 3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylic acid (67 mg, 0.245 mmol), NMM (0.4 ml) and DMTMM (121 mg) to give the title compound (62 mg, 52%). 'H NMR (300MHz, CDC13): 5 7.75 (d, IH, J = 15.6 Hz), 7.33 (d, IH, J = 7.8 Hz), 6.95 (d, IH, J = 8.4 Hz), 6.84 (d, IH, J = 8.1 Hz), 6.79 (s, IH), 6.30 (d, IH, J = 15.6 Hz), 6.03 (br, IH), 4.59 (br, IH, J = 6.9 Hz), 4.50 (d, 2H, J = 6.0 Hz), 3.16 (s, 3H), 3.12 (t, 2H, J = 7.2 Hz), 1.64 (m, 2H), 0.96 (t, 3H, J = 7.5 Hz) Example 3: (R)-3-(2-Butylamino-4-trtfluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide I O HN'^/^ F (R)-N-[4-(l-Amino-ethyl)-2,6-difluoro-phenyl]-methanesulfonamide, HC1 salt (25mg, 0.09mmol) was reacted with 3-(2-butylamino-4-trif!uoromethyl-pheny])-acrylic acid (25mg, 0.09mmol) to give the title compound (15mg, 32%) after purification by crystallization from Hex/EtOAc. 'H NMR(300MHZ, CDCb): 5 7.75(d, 1H, J =15.3Hz), 7.37(d, 1H, J =8.4Hz), 7.00(m, 2H), 6.90(d, 1H, ,/=8.4Hz), 6.83(s, 1H), 6.33(6, 1H, J=15.3Hz), 6.12(s, 1H), 5.83(d, 1H, y =7.8Hz), 5.18(m, 1H), 4.18(bs, 1H), 3.2l(s, 3H), 3.17(m, 2H), 1.48(m, 5H), 0.97(t, 3H,J=7.5Hz). ESi[M-H]":518 Example 4: N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-propoxy-4-trifluoromethyl-phenyl)-acrylamide F Step 1: Synthesis of 2-propoxy-4-trifluoromethy!-benzoic acid propyl ester 2-Hydroxy-4-trifluoromethyl-benzoic acid (673 mg, 3.26 mmol) was reacted with propylbromide (0.85 ml) and K2C03 (1.42 g) in DMF (15 ml) at 65 °C overnight. The reaction mixture was quenched by adding 10 ml of H20. The mixture was extracted with ethylacetate (30 ml x 3). A combined organic layer was washed with H2O (50 ml x 6) and brine (50 ml), and dried over MgSO4. The filterate was concentrated in vacuo to yield title compound (908 mg, 99%) 'H NMR (300MHz, CDCh): 5 7.83 (d, 1H, J = 8.1 Hz), 7.21 (d, 1H,J = 8.I Hz), 7.15 (s, 1H), 4.28 (t, 2H, J = 6.9 Hz), 4.03 (t, 2H, J = 6.3 Hz), 1.88 (m, 2H), 1.82 (m, 2H), 1.07 (m, 6H) Step 2: Synthesis of 2-propoxy-4-trifluoromethyl-benzoic acid 2-Propoxy-4-trif!uoromethyl-benzoic acid propyl ester (957 mg, 3.44 mmol) was reacted with IN LiOH (10 ml) at room temperature for 4 hrs. The reaction solvent was removed in vacuo. Water (30 ml) was added to the resulting residue, which wasneutralized with 1 N aqueous HC1 solution. The aqueous mixture was extracted with ethylacetate (30 ml x 3). A combined organic layer was dried over MgSC>4, and concentrated in vacuo to yield quantitatively title compound. 'H NMR (300MHz, CDC13): 5 8.32 (d, 1H, J = 7.8 Hz), 7.40 (d, 1H, J = 8.1 Hz), 7.16 (s, 1H), 4.28 (t, 2H, J = 6.6 Hz), 1.98 (m, 2H), 1.26 (m, 3H) Step 3: Synthesis of N-methoxy-N-methyl-2-propoxy-4-trifiuoromethyl-benzamide 2-Propoxy-4-(trifluoromethy!)benzoic acid (457 mg, 1.93 mmol) in THF was reacted with N,0-dimethylhydroxy amine (378 mg), NMM (0.65 ml) and DMTMM (947mg) at room temperature overnight. The reaction solvent was removed in vacuo. Water (30 ml) was added to the resulting residue, which wasextracted with ethyl acetate (30 ml x 3). The combined organic layer was washed with 1 M NaHCO3 (30 ml), IN HCI (30 ml) and brine (30 ml) and dried over MgSO4. The filterate was purified with column chromatography (Hex/EtOAc = 4/1) to yield the title compound (277 mg, 49%) . 'H NMR (300MHZ, CDC13): 6 7.36 (d, IH, J = 7.8 Hz), 7.25 (d, IH, J = 8.1 Hz), 7.12 (s, IH), 4.01 (t, 2H, J = 6.3 Hz), 3.46 (s, 3H), 3.35 N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propoxy-4-trifluoromethyt-pheriyl)-acrylamide • 0 Q> F (R)-N-(4-Aminoethy[-2,6-difluoro-phenyl)4, and concentrated under reduced pressure. The crude residue was purified by column chromatography (Hex/EtOAc = 2/1) to yield the title compound (230 mg, 8%). lH NMR(300MHz, CDCI3): 5 7.50(s, 1H), 7.48(d, IH, J =7.8Hz), 7.36(d, 1H, J =7.8Hz), 3.43(bs, 3H), 3.36(bs, 3H), 2.65(t, 2H, J=7.8Hz), 1.67(m, 2H), 0.97(t, 3H, J =7.2Hz). Step 3: Synthesis of 3-(2-propyl-4-trifluoromethyl-pheny!)-acrylic acid methyl ester. To a solution of N-methoxy-N-methyl-2-propyJ-4-trifluoroinethyl-benzamide (230mg, 0.84mmol) in THF (15mL) was added dropwise 1.0M LiAlH4 (0.42mL, 0.42mmol) at -78°C. The mixture was warmed up to -20°C and stirred for 30mins. An aqueous solution of sodium potassium tartrate (10% w/v) was added to the reaction mixture and the resulting mixture was vigorously stirred for 30mins, to which was added Et20. After separation of two phases, the aqueous layer was extracted three times with ether and the combined organic layer was washed with brine, dried over anhydrous MgS04: filtered and concentrated under reduced pressure. The product was vacuum dried to yield the 2-propyl-4-trifluoromethyl-benzaldehyde. To a solution of the aldehyde obtained above in toluene was added methyl (triphenylphosphoranylidene)acetate (285mg, 0.85mmol), and the resulting mixture was heated at 80°C for 3hrs. The reaction mixture was diluted with EtOAc, and washed with water and brine. The organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (Hex/EtOAc = 4/1) to give the title compound (220mg, 96%). 'H NMR(300MHz, CDC13): 5 7.98(d, IH, J =15.9Hz), 7.63(d, IH, J =8.4Hz), 7.46(d, 1H, J=8.4Hz), 7.45(s, 1H), 6.42(d, 1H, J =15.9Hz), 3.83{s, 3H)} 2.77(t 2H, J =7.5Hz), 1.63(m, 2H), 0.98(t, 3H, J=7.5Hz). Step 4: Synthesis of 3-(2-propyl-4-trifluoromethyi-phenyl)-acrylic acid. To a suspension of 3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid methyl ester (220mg, 0.8lmmol) in THF (3mL) was added a solution of IN-LiOH (6 ml), and the mixture was stirred for 3 hours at room temperature. The reaction mixture was diluted with H2O, which was washed three times with EtOAc, acidified with IN HC1 to pH 1-2. The resulting solution was extracted three times with methylene chloride and then dried over anhydrous N4gSO4 and concentrated in vacuo to give the title compound (155mg, 74%). fH NMR(300MHz, CDCl3): 5 8.09(d, 1H, J =15.9Hz), 7.67(d, 1H, J =7.8Hz), 7.49(d, 1H, J=7.8Hz), 7.47(s, 1H), 6.44(d, 1H, J =15.9Hz), 2.79(t, 2H, / =7.5Hz), L.64(m, 2H), 0.99(t3 3H, J=7.5Hz). Step 5: Synthesis of (i?)-N-[l-(3.5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propy]-4-trifluoromethyl-phenyl)-acrylamide To a suspension of (R)-N-[4-{l-amino-ethyl)-2,6-difluoro-phenyl]- methanesulfonamide, HC1 salt (67mg, 0.23mmol) in THF (5mL) was added N- methylmorpholine (51jal, 0.46mmol). The mixture was stirred for 5 minutes, to which were added 3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid (60mg, O.23mmol) and 4-(4,6-dimethoxy[l,3,5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM, 76mg, 0.28mmol). The mixture was stirred overnight at room temperature and was concentrated under reduced pressure. The residue was diluted with EtOAc and water. The organic layer was washed with saturated sodium bicarbonate, IN HCI and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by recrystallization from n-Hex/EtOAc to give title compound (83mg, 74%). lHNMR(300MHz, CD3OD): 6 7.99 (d, 1H, J= 15.6 Hz), 7.86 (d, 1H, /= 8.7 Hz), 7.60 (bs, 2H), 7.18 (d, 2H, J= 8.7 Hz), 6.75 (d, 1H, J = 15.6 Hz), 5.20 (m, 1H), 3.17 (s, 3H), 2.90 (t, 2H, J= 7.8 Hz), 1.70 (m, 2 H), 1.61 (d, 3H, J= 7.2 Hz), 1.06 (t, 3H, J = 12 Hz). ESI [M-H]": 489 Example 22: N-(3,5-Difluoro-4-methanesiilfonylammo-benzy])-3-(2-propyl-4- trifluoromethyl-phenyl)-acrylamide N-(4-Aminomethyl-2,5-difluoro-phenyt)-methanesulfonamide, HCI salt (33mg, 0.12mmol) was reacted with 3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid (25mg, 0.097mmol) to give the title compound (30mg, 65%) after purification by column chromatography (gradient 12% to 100% EtOAc in Hex). 'H NMR(300MHz, CD3OD): 5 8.05 (d, 1H, J= 15.6 Hz), 7.87 (d, 1H, J= 8.7 Hz), 7.62 (bs, 2H), 7.16 (d, 2H, J= 8.7 Hz), 6.76 (d, 1H, J= 15.6 Hz), 4.61 (s, 2H), 3.18 (s, 3H), 2.93 (t, 2H, J= 7.8 Hz), 1.71 (m, 2 H), 1.09 (t, 3H,J= 7.5 Hz). ESI [M+H]+: Example 23: N-(3-FIiioro-4-methanesulfonylamino-5-methyl-benzyl)-3-(2-propy!-4-trifluoromethyl-phenyl)-acrylamide MsHN ^T ^^ CF3 N-(4-Aminomethy!-2-fluoro-6-methyl-phenyl)-methanesulfonamide, HC1 salt (32mg, 0.12mmol) was reacted with 3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid (25mg, 0.097mmol) to give the title compound (30mg, 63%) after purification by column chromatography (gradient 12% to 100% EtOAc in Hex). lHNMR(300MHz, CD3OD): 6 8.05 (d, 1H, J= 15.6 Hz), 7.85 (d, 1H, J= 8.1 Hz), 7.60 (m, 2H), 7.30 (m, 2H), 6.74 (d, IH, J= 15.6 Hz), 4.64 (s, 2H), 3.08 (s, 3H), 2.92 (t, 2H, J= 7.5 Hz), 2.38 (d, 3H, J= 2.1 Hz), 1.72 (m, 2 H), 1.08 (t, 3H, J= 7.5 Hz). ESI [M+H]+: Example 24: (R)-3-(2-Butyl-4-trifluoromethyl-phenyl)-N-[ 1 -(3,5-difluoro-4- m ethanes u J fon yl am ino-phenyl)-ethy l]-acry 1 amide 3-(2-Butyl-4-trifluoromethyl-phenyl)-acrylic acid was obtained by the procedure in example 21. (R)-N-[4-(l-Amino-ethyl)-2,6-difluoro-phenyl]-methanesulfonamide, HC1 salt (38mg, 0.13mmol) was reacted with 3-(2-butyl-4-trifluoromethyl-phenyl)-acrylic acid (30mg, 0.11mmol) to give the title compound (29mg, 43%) after purification by column chromatography (gradient 12% to 100% EtOAc in Hex). 'H NMR(300MHz, CD3OD): 5 7. 90 (d, IH,J= 15.6 Hz), 7.76 (d, 1H, J= 8.7 Hz), 7.51 (bs; 2H), 7.08 (d, 2H, .7=8.7 Hz), 6.65 (d, IH,J= 15.6 Hz), 5.10 (m, lH),3.07(s, 3H), 2.82 (t, 2H, J= 7.8 Hz), 1.55 (m, 2 H). 1.51 (d, 3H, J= 7.2 Hz), 1.40 (ra, 2 H), 0.94 (t, 3H, .7=7.2 Hz). ESI [M-H]": 503 Example 25: (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-propyl]-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide O F (i?)-N-[4-( 1 -Amino-propyl)-2,6-difluoro-phenyl]-methanesulfonamide, HC1 salt (15mg, 0.050mmol) was reacted with 3-(2-propyl-4-trifluoromethyl-phenyI)-acrylic acid (8mg, 0.031mmol) to give the title compound (15mg, 97%) after purification by column chromatography (gradient 12% to 100% EtOAc in Hex). 'H NMR(300MHz, DMSO-d6): 5 8.65 (d, 1H, 7= 8.1 Hz), 7.69 (m, 4H), 7.11 (d, 2H, J= 8.4 Hz), 6.75 (d, 1H, J= 15.6 Hz), 4.82 (m, IH), 2.98 (s, 3H), 2.75 (t, 2H, J = 7.8 Hz), 1.71 (m, 2 H), 1.52 (m, 2 H), 1.23 (m, 2 H), 0.89 (m, 6H). ESI [M+H]+: Example 26: (R)-N-[l-(3>5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acrylamide ■ 0 0' ^ F O OH 2-Bromopropane ? ° 1.0.5N-UOH.THF ? 9 nU ~-\ *- ^ ~ ■" y || L A DMF :- -;■-. ' ^^'-v. ■^'^^-r-c " PF ^-^ CF Stepl tjr» Step2 CF, C4.ni ^r3 st , i,r. 1.LAH.THF 2.Wittig,toluene I Step3 I 0 0^- 1.LAH.THF >F - ,1 J. _-,-. A. 2.Wittig,toluene V : Stepl: Synthesis of 2-isopropoxy-4-trifluoromethyl-benzoic acid isopropyl ester A mixture of 2-hydroxy-4-trifluoromethyl-benzoic acid (500 mg, 2.42 mrnol) in DMF (5 mL) was added potassium carbonate (837 mg, 6.06 mmol) and 2-bromopropane (906 mg, 5.33 mmol). The resulting mixture was stirred for 48 hours at 110 °C. The reaction mixture was diluted with EtOAc, which was washed with IN HC1, water, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography(Hex/EtOAc=5/l) to give the title compound (200 mg, 28 %). 'HNMR(300MHz, CDC13): 5 7.73 (d, 1H, J= 8.1 Hz), 7.19 (d, 1H, J = 8.4 Hz), 7.15 (s, 1H), 5.31 -5.29 (m, 1H), 4.68-4.60 (m, 1H), 1.40 (d, 6H, J= 6.9 Hz), 1.36 (d,6H, J= 6.6 Hz). Step 2: Synthesis of 2-isopropoxy-N-methoxy-N-methyl-4-trifluoromethyl-benzamide. To a suspension of 2-isopropoxy-4-trifiuoromethyl-benzoic acid isopropyl ester (35 mg, 0.12 mmol) in THF (1 ml) was added a solution of 0.5 N-LiOH (2 eq), and the resulting mixture was stirred for 2 hours at room temperature. The reaction mixture was acidified with IN HCL and hthen extracted with EtOAc. The combined organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was vacuum dried to yield the 2-isopropoxy-4-trifluoromethyl-benzoic acid. To an ice-cold suspension of 2-isopropoxy-4-trifluoromethyl-benzoic acid and N,O-dimethylhydroxylamine hydrochloride (13 mg, 0.132 mmol) in CH2C12 (1 mL) was added N-methylmorpholine (0.015 ml, 0.132 mmol), and the resulting mixture was stirred for 5 minutes, to which were added N-(3-dimethylaminopropyl)-jV'-ethylcarbodiimide hydrochloride (26 mg, 0.132 mmol). The resulting mixture was stirred for 2 hours at room temperature, and then diluted with EtOAc. The organic layer was washed with 1N HO, water, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography(Hex/EtOAc=3/l) to give the title compound {28 mg, 80 %). 'H NMR(300MHZ, CDC13): 5 7.26 - 7.18 (m, 2H), 7.11 (s, 1H), 4.66 - 4.60 (m, IH), 3.46 (s, 3H), 3.35 (s, 3H), 1.34 (d, 6H, J= 6.0 Hz). Step 3: Synthesis of 3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acrylic acid methyl ester. To a suspension of 2-isopropoxy-N-methoxy-N-methyl-4-trifluoromethyl-benzamide (28 mg, 0.096 mmol) in THF (1.5 mL) was added dropwise 1.0M LiAlH4 (0.048 ml, 0.5 eq) at -60°C. The mixture was slowly warmed up to -20°C until the reaction was completed. The reaction was slowly quenched with sat'd KHSO4 (1 mL) and then diluted with water (1mL). The reaction mixture was extracted with ether and the combined organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The resulting compound was vacuum dried to yield the 2-isopropoxy-4-trifluoromethyl-benzaldehyde. To the aldehyde prepared above was added toluene (1 mL) followed by portionwise addition of methyl (triphenylphosphoranylidene)acetate (32 mg, 0.105 mmol) (exothermic). Toluene (1 mL) was added to the reaction mixture, and the resulting mixture was heated at 80°C for 3 hours. The reaction mixture was cooled to room temperature, and then was directly loaded to a short silica-gel column and eluted with the solvent (Hex/EtOAc = 20/1) to give the title compound (20 mg, 72 %). 'H NMR(300MHz, CDC13): 5 7.96 (d, 1H, J= 16.2 Hz), 7.58 (d, 1H, J= 8.1 Hz), 7.17 (d, 1H,/=7.8 Hz), 7.11 (s, 1H), 6.57 (d, 1H, J= 16.2 Hz), 4.71 -4.63 (m, 1H), 3.81 (s, 3H), 1.41 (d, 6H, J= 6.3 Hz). Step 4: Synthesis of N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acrylamide. . o o^ F To a suspension of 3-(2-isopropoxy-4-trifiuoromethyl-phenyl)-acrylic acid methyl ester (15 mg, 0.052 mmol) in THF (1 ml) was added a solution of 0.5 N-LiOH (0.2 ml), and the resulting mixture was stirred for 3 hours at room temperature. The reaction mixture was acidified with IN HCI to pH 1~2. The mixture solution was extracted three times with methylene chloride, and the combined organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to give 3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acrylic acid (14 mg, 98 %). To a suspension of 3-(2- isopropoxy-4-trifluoromethyl-phenyl)-acrylic acid {14 mg, 0.051 mmol) and N-[4-(l-amino-ethyl)-2,6-difluoro-phenyl]-methanesiiltbnamide, HCI salt (17.2 mg, 0.060 mmol) in DMF (2 mL) was added N-methylmorpholine (0.007 ml, 0.060 mmol). The mixture was stirred for 5 minutes, to which were added iV-(3-dimethylaminopropyl)-iV'-ethylcarbodiimide hydrochloride (26 mg, 0.132 mmol). The mixture was stirred for 12 hours at room temperature, and then diluted with EtOAc (4 mL). The organic layer was washed with IN HCI, water, and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by chromatography (Hex/EtOAc = 1/1) to give the title compound (24 mg, 79 %). [H NMR(300MHz, CDCl3); 5 7.93 (d, 1H, J= 15.6 Hz), 7.56 (d, 1H, J = 7.8 Hz), 7.16 (d, 1H, J= 8.1 Hz), 7.10 (s, 1H), 7.01 (d, 1H, J= 8.4 Hz), 6.54 (d, 1H, J = 15.6 Hz), 5.82 (d, 1H, J= 6.9 Hz), 5.19 (t, 1H, J= 6.9 Hz), 4.67 - 4.63 (m, 1H), 3.20 (s, 3H), 1.56 (d, 6H, J= 6.3 Hz). 1.40 (d, 3H, J= 5.4 Hz). ESI [M-H]': 505 Example 27: (7?J-N-[l-(3,5-Difluoro-4-methanesuifonylamino-phenyI)-ethyl]-3-(4-fluoro-2-propoxy-phenyl)-acrylamide F Step 1: Synthesis of 3-(4-fluoro-2-hydroxy-phenyl)-acrylic acid methyl ester. 2-Hydroxy-4-fluoro-benzaldehyde (306 mg, 1.99 mmol) was reacted with methyl (triphenylphosphoranylidene)acetate (681 g, 2.044 mmol) at 110 °C overnight as described above to yield title compound (334 mg, 85%). 'H NMR (300MHZ, CDCl3): 5 7.93 (d, 1H, J = 15.9 Hs), 7.45 (m, IH), 6.65 (m, 1H), 6.59 (m, IH), 6.56 (s, IH), 6.53 (d, IH, J = 16.2 Hz), 5.27 (br, IH), 3.82 (s, 3H). Step 2: Synthesis of 3-(4-fluoro-2-propoxy-phenyl)-acrylic acid methyl ester 3-(4-Fluoro-2-hydroxy-phenyl)-acry[ic acid methyl ester (110.5 mg) was reacted with K2CO3 (111 mg) and propane iodide (0.1 ml) at 80 °C overnight as described above to yield title compound (134mg, 100%) 'HNMR (300MHz, CDCb): 5 7.90 (d, IH, J = 15.9 Hz), 7.45 (t, IH, J = 7.5 Hz), 6.65 (m, IH), 6.59 (m, IH), 6.49 (d, IH, J = 15.9 Hz), 3.96 (t, 2H, J = 6.6 Hz), 3.78 (s, 3H), 1.89 (m, 2H), 1.07 (t, 3H, J = 7.5 Hz). Step 3: Synthesis of 3-(4-fluoro-2-propoxy-phenyl)-acrylic acid 3-(4-Fluoro-2-propoxy-phenyl)-acrylic acid methyl ester (134 mg, 0.563 mmol) was reacted with aqueous IN LiOH (5 ml) as described above to yield title compound (117 mg, 92%). LH NMR (300MHz, CDC13): 5 8.00 (d, IH, J = 16.5 Hz), 7.49 (t, IH, J = 8.4 Hz), 6.67 (m, 2H) 6.50 (d, IH, J= 15.9 Hz), 3.98 (t, 2H, J = 6.6 Hz), 1.91 (m,2H), 1.09(t,3H,J = 7.2 Hz). Step 4: Synthesis of (R)-N-[1-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(4-fluoro-2-propoxy-phenyt)-acrylamide (R)-N-(4-Aminoethyl-2,6-difluoro-phenyl)-methanesulfonamide, HC1 salt (85 mg, 0.29 mmol) was reacted with 3-(4-fluoro-2-propoxy-phenyl)-acrylic acid (65 mg, 0.29 mmol), NMM (0.15 ml) and DMTMM (98 mg) at room temperature overnight to yield the title compound (77 mg, 58%) after column chromatography( Hex/EtOAc = 1/1). 'H NMR (300MHZ, CDC13): 5 7.84 (d, 1H, J = 15.6 Hz), 7.43 (t, 1H, J = 6.9 Hz), 6.98 (d, 1H, J = 8.7 Hz), 6.63 (m, 2H), 6.47 (d, 1H, J = 15.6 Hz), 5.87 (br, J H), 5.18 (m, 1H), 4.11 (t,2H, J = 6.9 Hz), 3.19 (s, 3H), 1.87 (m,2H), 1.09 (t, 3H, J = 7.5 Hz) Example 28: N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(4-fluoro-2-propoxy-phenyl)-acrylam ide F N-(4-Aminomethyl-2,6-difluoro-phenyl)-methanesulfonamide, HC1 salt (66 mg, 0.24 mmol) was reacted with 3-(4-fluoro-2-propoxy-phenyl)-acrylic acid (51 mg, 0.23 mmol), NMM (0.15 ml) and DMTMM (78 mg) at room temperature overnight to yield the title compound (52 mg, 0.12 mmol, 53%) after column chromatography( Hex/EtOAc = 1/1). 'H NMR (300MHz, CDC13): 5 7.90 (d, 1H, J = 15.9 Hz), 7.44 (t, 1H, J = 6.6 Hz), 6.99 (d, 1H, J= 8.1 Hz), 6.65 (m, 2H), 6.52 (d, 1H, J = 15.6 Hz), 5.89 (br, 1H), 4.55 (d, 2H, J = 6.0 Hz), 3.98 (t, 2H, J = 6.6 Hz), 3.21 (s, 3H), 1.90 (m, 2H), 1.08 (t, 3H3 J = 7.5 Hz). Step 1. Synthesis of N-methoxy-N-methyl-4-fluoro-2-nitro-benzamide Example 29: (S>N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)ethy!]-3-(4-fluoro-2-propylaminophenyl)-acrylamide To a solution of 4-fluoro-2-nitrobenzoic acid (1 g, 5.4 mmol), N,O-dimethylhydroxyiamine hydrochloride (0.58 g, 5.95 mmol) and N-methylmorpholine (0.65 mL, 5.91 mmol) in dichloromethane (20 mL) was added l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.14 g, 5.95 mmol). The mixture was stirred for 80 minutes at room temperature. The mixture was concentrated under reduced pressure and then diluted with EtOAc and water. The organic layer was washed with 3 N HC1, saturated aqueous NaHCOj solution and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give N-methoxy-N-methyl-4-fluoro-2-mtro-benzamide (1.15 g, 95%). 'H NMR(300MHz. CDCb): 5 7.89 ~ 7.85 (m, 1 H),, 7.58 - 7.54 (m, 1 H), 7.47 ~ 7.41 (m, 1 H), 3.37 (s, 3 H), 3.36 (s, 3 H). Step 2. Synthesis of N-methoxy-N-methyl-2-arnino-4-fluoro-benzamide A mixture of N-methoxy-N-methyl-4-fluoro-2-nitro-benzamide (1.15 g, 5.04 mmol) and 5% palladium charcoal (190 mg) in EtOH (30 mL) was shaken overnight under hydrogen atmosphere (3 atm). The mixture was filtered and concentrated under reduced pressure to give N-methoxy-N-methyl-2-amino-4-fluoro-benzamide (0.9 g, 90%). lH NMR(300MHz, CDC13): 5 7.44 ~ 7.39 (m, 1 H), 6.40 ~ 6.30 (m, 2 H), 4.90 (bs, 2 H), 3.57(s, 3H), 3.34(s, 3 H). Step 3. Synthesis of N-methoxy-N-methyl-4-fluoro-2-propylamino-benzamide To a solution of N-methoxy-N-rnethyl-2-amino-4-fluoro-benzamide (0.27 g. 1.36 mmol), propionaldehyde (0.15 mL, 2.08 mmol), and AcOH (0.12 mL, 2.1 mmol) in dichloromethane (20 mL) was added sodium triaceto^yborohydride (576 mg, 2.72 mmol) at 5°C. The mixture was stirred for 90 minutes at the same temperature and then 40 minutes at room temperature. The reaction was quenched by adding water. The organic layer was washed with saturated aqueous NaHCCb solution and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give N-methoxy-N-methyl-4-fluoro-2-propylamino-benzamide quantitatively. 'H NMR(300MHz, CDCb): 5 7.40 (t, 1 H, J= 7.2 Hz), 6.34 ~ 6.25 (m, 2 H), 3.58 (s, 3 H), 3.33 (s, 3 H), 3.03 (t, 2H,/= 6.9 Hz), 1.72 - 1.59 (m, 2 H), 1.00 (t, 3 H, J = 12 Hz). Step 4. Synthesis of 3-(4-fluoro-2-propylamino-phenyl)-acrylic acid methyl ester To a solution of N-methoxy-N-methyl-4-fluoro-2-propylamino-benzamide (0.33 g, 1.37 mmol) in THF (4 mL) was added dropvvise LiAlH4 (1 M in THF, 0.7 mL) at -45°C, The mixture was stirred for 40 minutes at -35°C and then quenched by adding saturated aqueous KHSO4 solution. The mixture was diluted with EtOAc, washed with 3 N HC1, and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was reacted with methyl (triphenylphosphoranylidene)acetate (0.5 g, 1.5 mmol) in toluene (4 mL) overnight at 100°C. The mixture was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (0.23 g, 69%) after purification by column chromatography (EtOAc : hexane =1 : 10). lH NMR(300MHz, CDCl3): 5 7.72 (d, 1 H, J= 15.6 Hz), 7.34 ~ 7.29 (m, I H), 6.41 ~ 6.29 (m, 2 H), 6.27 (d, 1 H,J= 15.6 Hz), 4.16 (bs, 1 H), 3.80 (s, 3 H), 3.12 -3.07 (m, 2 H), 1.76 - 1.63 (m, 2 H), 1.02 (t, 3 H, J= 7.2 Hz). Step 5. Synthesis of (R)-N-[l-(3,5-difluoro-4-methanesulfonylaminophenyl)ethy]]-3-(4-fluoro-2-propylamino-phenyl)-acrytamide To a solution of 3-(4-fluoro-2-propylamino-phenyl)-acrylic acid methyl ester (0.23 g, 0.95 mmol) in THF (4 mL) and MeOH (2 mL) was added 1 N LiOH (4 mL). The mixture was stirred for 2 hours at room temperature, concentrated under reduced pressure, and then acidified with 3 N HC1. The mixture was diluted with EtOAc, washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give 3-(4-fliioro-2-propylamino-phenyl)-acrylic acid (0.17 g, 79%) after purification by crystallization form EtOAc and hexane. To a mixture of 3-(4-fluoro-2-propylamino-phenyl)-acryUc acid (50 mg, 0.22 mmol), (R)-[l-(3,5-difluoro-4-methanesulfonylaminophenyl)ethylamine hydrochloride (64 mg, 0.22 mmol) and N- methylmorphoiine (36 µL, 0.33 mmol) in THF (5 mL) was added 4-(4,6- dimethoxy[l,3,5]triazin-2-yl)-.4-methylmorpholirium chloride hydrate (DMTMM, 68 mg, 0.25 mmol). The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was diluted with EtOAc and water, and the aqueous layer was washed with 2 N HCI and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (35 mg, 34%) after purification by crystallization form EtOAc and hexane. 'H NMR(300MHZ, CDCI3): 5 7.78 (d, 1 H, J= 15 Hz), 7.32 ~ 7.26 (m, I. H), 6.93 (d, 2 H, J= 8.4 Hz), 6.78 (s, 1 H), 6.37 ~ 6.29 (m, 2 H), 6.22 (d, 1 H, J= 15 Hz), 5.87 (d, 1 H, J = 6.9 Hz), 5.13 (t, 1 H, J= 6.9 Hz), 4.48 (bs, 1 H), 3.18 (s, 3 H), 3.08 (t, 2 H, J= 6.9 Hz), 1.71-1.58 (m, 2 H), 1.49 (d, 3 H, J= 6.9 Hz), 0.99 (t, 3 H, J= 7.2 Hz). Example 30: N-[l-(3,5-Difluoro-4-methanesulfonylaminobenzyl]-3-(4-fluoro-2-«- propylamino-phenyl)-acrylamide o HN ""--"' F To a mixture of 3-(4-fluoro-2-propylamino-phenyl)-acrylic acid (50 mg, 0.22 mmol), (3,5-difluoro-4-methanesiilfonylamino)benzylamine hydrochloride (61 mg, 0.22 mmol) and N-methylmorpholine (36 (JL, 0.33 mmol) in THF (5 mL) was added 4-(4,6- dimethoxy[l,3,5]triazin-2-yl)-4-methylmorpholirium chloride hydrate (DMTMM, 68 mg, 0.25 mmol). The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. The residue was diluted with EtOAc and water, and the aqueous layer was washed with 2 N HO and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to give the title compound (9 mg, 9%) after purification by column chromatography (EtOAc : hexane = 1:1). 'H NMR(300MHz, CDCI3): 6 7.60 (d, 1 H, J = 15 Hz), 7.32 ~ 7.26 (m, 1 H), 6.96 (d, 2 H, 7=8.1 Hz), 6.93 -6.32 (m, 2 H), 6.14 (d, 1 H,./= 15 Hz), 6.13 (br, 1 H), 5.95 (br, 1 H), 4.53 (d, 2 H, J= 5.7 Hz), 4.25 (br, 1 H), 3.21 (s, 3 H), 3.09 (m, 2 H), 1.72 ~ 1.65 (m, 2H), 1.01 (t, 3 H, J =7.2 Hz). Example 31: (R)-3-(2-Butoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide 1 0 0 MsHN^f V'^CFS F Step 1: Synthesis of 2-butoxy-4-trifluoromethyl-benzoic acid butyl ester 2-Hydroxy-4-trifluoromethy[-benzoic acid (755 mg) was reacted with butylbromide (0.96 ml) and K2CO3 (1.15 g) in DMF solution as described above to yield title compound. !H NMR (300MHz, CDC13): 5 8.01 (s, 1H), 7.801 (d, 1H, J = 7.8 Hz), 7.19 (m, 2H), 4.32 (t, 2H, J = 6.6 Hz), 4.06 (t, 2H, J - 6.3 Hz), 1.82 (m, 2H), 1.75 (m, 2H), 0.98 (m, 6H) Step 2: Synthesis of 2-butoxy-4-trifluoromethyl-benzoic acid 2-Butoxy-4-trifluoromethyl-benzoic acid butyl ester was reacted with IN LiOH (10 ml) as described above to yield title compound (687 mg). 'H NMR (300MHz, CDCI3): 5 8.29 (d, 1H, J = 8.4 Hz), 7.38 (d, 1H, J = 8.1 Hz), 4.31 (t, 2H, J = 6.3 Hz), 1.94 (m, 2H), 1.53 (m, 2H), 1.02 (t, 3H, J = 7.5 Hz) Step 3: Synthesis of 2-butoxy-N-methoxy-N-methyl-4-trifluoromethyl-benzamide 2-Butoxy-4-trifluoromethyl-benzoic acid (687 mg) was reacted with N,0-dimethylhydroxy amine (331 mg), NMM (0.65 ml) and DMTMM (911 mg) as described above to yield the title compound (825 mg) after column chromatography (Hex/EtOAc = 7.5/1). 'H NMR (300MHz, CDCI3): 5 7.36 (br, 1H), 7.22 (d, 1H, J = 8.1 Hz), 7.11 (s, 1H), 4.04 (t, 2H, J = 6.3 Hz), 3.45 (s, 3H), 3.35 (s, 3H), 1.77 (m, 2H), 1.46 (m, 2H), 0.99 (t, 3H, J = 7.5 Hz) Step 4: Synthesis of 2-butoxy-4-trifluoromethyl-benzaldehyde 2-Butoxy-N-methoxy-N-methy]-4-trifluoromethyl-benzamide (825 mg) was reacted with 1 M LAH (31 ml) at -50 °C for I hour as described above to yield title compound (423 mg) after column chromatography (Hex/EtOAc = 20/1). 'H NMR (300MHZ3 CDC13): 5 10.53 (s, 1H), 7.92 (d, IH, J = 7.8 Hz), 7.27 (d, IH, J = 8.7 Hz), 7.21 (s, 1H), 4.10 (t, 2H, J = 6.3 Hz), 1.89 (m, 2H), 1.57 (m, 2H), 1.01 (t, 3H, J = 7.2 Hz) Step 5: Synthesis of 3-(2-butoxy-4-trifluoromethyl-phenyl)-acrylic acid methyl ester 2-Butoxy-4-trifluoromethyl-benzaldehyde (420 mg) was reacted with methyl (triphenylphosphoranylidene)acetate (679 mg) at 110 °C overnight as described above to yield title compound (464 mg) after column chromatography (Hex/EtOAc = 20/1). LH NMR (300MHz, CDCI3): 5 7.91 (d, 1H, J = 16.5 Hz), 7.53 (d, 1H, J - 7.8 Hz), 7.13 (m, 1H), 7.06 (s, 1H), 6.54 (d, IH, J = 16.2 Hz), 4.03 (t, 2H, J = 6.6 Hz), 3.77 (s, 3H), 1.82 (m, 2H), 1.48 (m, 2H), 0.96 (t, 3H, J = 7.5 Hz) Step 6: Synthesis of 3-(2-butoxy-4-trifluoromethyl-phenyl)-acrylic acid 3-(2-Butoxy-4-trifluoromethyl-phenyl)-acrylic acid methyl ester (464 mg) was reacted with IN LiOH (10 ml) in THF and CH3OH for 1 hr as described above to yield title compound !H NMR (300MHz, CDC13): 5 8.05 (d, IH, J = 16.2 Hz), 7.60 (d, IH, J = 8.1 Hz), 7.20 (m, IH), 7.12 (s, IH), 6.62 (d, IH, J = 16.2 Hz), 4.09 (t, 2H, J = 6.0 Hz), 1.85 (m, 2H), 1.56 (m, 2H), 1.04 (t, 3H, J = 7.5 Hz) Step 7: Synthesis of (R;-3-(2-butoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4- methanesulfony]amino-phenyl)-ethyl]-acrylarnide (R)-N-(4-Aminoethyl-2,6-difluoro-phenyl)-methanesulfonamide, HCI salt (75 mg, 0.26 mmol) was reacted with 3-(2-butoxy-4-trifluoromethyl-phenyl)-acrylic acid (63 mg, 0.230 mmol), NMM (0.15 ml) and DMTMM (75 mg) at room temperature overnight to yield the title compound (52 mg, 0.10 mmol, 43%) after column chromatography( Hex/EtOAc= 1/1). 'H NMR (300MHZ, CDC13): 5 7.93 (d, 1H, J = 15.6 Hz), 7.55 (d, 1H, J = 7.8 Hz), 7.18 (d, 1H, J = 8.1 Hz), 6.99 (d, 1H, J = 6.6 Hz), 6.75 (d, 1H, J = 8.4 Hz), 6.52 (d, 1H, J = 15.6 Hz), 5.89 (br, 1PI), 5.18 (t, 1H), 4.10 (d, 2H, J = 6.0 Hz), 3.19 (s, 3H), 1.87 (m, 2H), 1.52 (m, 2H), 0.99 (t, 3H, J = 7.2 Hz). ESI[M-H]-:519 Example 32: 3-(2-Butoxy-4-trifluoromethyl-phenyl)-N-(3,5-difluoro-4- methanesulfonylamino-benzyl)-acrylamide F N-(4-Aminomethyl-2,6-difluoro-phenyl)-methanesulfonamide, HCI salt (65 mg, 0.24 mmol) was reacted with 3-(2-butoxy-4-trifluoromethyl-phenyl)-acrylic acid (57 mg, 0.20 mmol), NMM (0.2 ml) and DMTMM (66 mg) to give the title compound (62 mg, 012 mmol, 62%) after column chromatography( Hex/EtOAc = 1/1). 'H NMR (300MHz, CDC13): 5 7.96 (d, 1H, J = 15.6 Hz), 7.56 (d, 1H, J = 8.1 Hz), 7.20 (d, 1H, J = 7.2 Hz), 7.11 (s, 1H), 6.99 (d, 1H, J = 8.1 Hz), 6.75 (d, 1H, J = 8.1 Hz), 6.52 (d, 1H, J = 15.6 Hz), 6.05 (br, 1H), 4.55 (d, 2H, J = 6.3 Hz), 4.10 (d, 2H, J = 6.9 Hz), 3.20 (s, 3H), 1.88 (m, 2H), 1.57 (m, 2H), 0.98 (t, 3H, J = 7.2 Hz). Example 33: (??>3<2-Butoxy-4-iliioro-phenyI}-N-[l-(3,5-difluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide F Step 1: Synthesis of 3-(2-butoxy-4-fluoro-phenyl)-acrylic acid methyl ester 3-(4-Fluoro-2-hydroxy-phenyl)-acrylic acid methyl ester (106 mg) was reacted with K2CO3 (125 mg) and butyl iodide (0.1 ml) at 80 °C for 3 hrs as described above to yield title compound (121 mg). 'H NMR (300MHZ, CDCI3): 6 7.90 (d, 1H, J = 16.2 Hz), 7.45 (m, 1H), 6.64 (m, 2H), 6.47 (d, 1H, J = 15.9 Hz), 4.00 (t, 2H, J = 6.6 Hz), 3.79 (s, 3H), 1.84 (m, 2H), 1.53 (m, 2H), 0.99 (t, 3H, J = 7.2 Hz) Step 2: Synthesis of 3-(2-butoxy-4-fIuoro-phenyl)-acrylic acid 3-(2-Butoxy-4-fluoro-phenyl)-acryiic acid methyl ester (121 mg) was reacted with IN LiOH (5ml) in THF and CH3OH for 2 hrs as described above to yield title compound (116 mg). 'H NMR (300MHz, CDC13): 5 7.99 (d, 1H, J = 16.2 Hz), 7.48 (m, 1H), 6.65 (m, 2H), 6.49 (d, 1H, J = 16.2 Hz), 4.02 (t, 2H, J = 6.3 Hz), 1.86 (m, 2H), 1.54 (m, 2H), 1.00 (t, 3H, J = 7.2 Hz). Step 3: Synthesis of (R)-3-(2-butoxy-4-fluoro-phenyl)-N-[l-(3,5-difluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide (R)-N-(4-Aminoethyl-2,6-difluoro-phenyl)-methanesulfonamide, HC1 salt (75 mg, 0.26 mmol) was reacted with 3-(2-butoxy-4-fluoro-phenyl)-acrylic acid (60 mg, 0.25 mmol), NMM (0.15 ml) and DMTMM (82 mg) at room temperature overnight to yield the title compound (87 mg, 0.19 mmol, 74%) after column chromatography (Hex/EtOAc= 1/1). lH NMR (300MHz, CDC13): 5 7.85 (d, IH, J = 15.9 Hz), 7.42 (m, IH), 6.94 (d, 2H, J = 8.4 Hz), 6.62 (m, 2H), 6.47 (d, IH, J= 15.6 Hz), 6.23 (d, IH, J = 7.2 Hz), 5.13 (t, IH), 4.11 (t, 2H, J = 6.3 Hz), 3.17 (s, 3H), 1.81 (m5 2H), 1.54 (m, 2H), 1.46 (d, 3H, J = 6.6 Hz), 0.90 (t, 3H, /= 7.2 Hz). ESI [M-H]": 469 Example 34: 3-(2-Biitoxy-4-fluoro-pheny!)-N-(3,5-difluoro-4-methanesulfonylamino-benzyl)-acrylamide o o MsHN' F N-(4-Aminomethyl-2,6-difluoro-phenyl)-methanesulfonamide, HC1 salt (73 mg, 0.26 mmol) was reacted with 3-(4-fluoro-2-propoxy-pheny|)-acrylic acid (55 mg, 0.23 mmol), NMM (0.15 ml) and DMTMM (73 mg) at room temperature overnight to yield the title compound (85 mg, 0.19 mmol, 81%) after column chromatography( Hex/EtOAc= 1/1). 'H NMR (300MHz, CDC13): 5 7.89 (d, IH, J = 15.6 Hz), 7.45 (m, IH), 6.94 (d, 2H, J = 8.4 Hz), 6.98 (m, IH), 6.64 (m, IH), 6.50 (d, IH, J = 15.6 Hz), 6.07 (br, IH), 4.55 (d, 2H, J = 6.0 Hz), 4.13 (t, 2H, J = 63 Hz), 3.20 (s, 3H), 1.83 (m, 2H), 1.52 (m, 2H), 0.88 (t, 3H, J = 7.2 Hz). Example 35: N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide N-(4-Aminomethyl-2-ethynyl-6-fluoro-phenyl)-methanesu!fonamide, HCI salt (14mg, 0.050mmol) was reacted with 3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid (8mg, 0.031mmol) to give the title compound (12mg, 80%) after purification by column chromatography (gradient 12% to 100% EtOAc in Hex). 'H NMR(300MHz, DMSO-d6): 5 8.79 (t, 1H), 7.69 (m, 4H), 7.74 (ra, 2H), 7.60 (m, 2H), 7.26 (m, 2H), 6.72 (d, IH,J= 15.6 Hz), 4.45 (s, 1H), 4.38 (d, 1H, J- 5.4 Hz), 3.01 (s, 3H), 2.70 (t, 2H, J= 7.5 Hz), 1.54 (m, 2 H), 1.23 (m, 2 H), 0.91 (m, 3H). ESI [M+H]+: Examp le 3 6: (R)-3 -(2-Butyl-4-tri fluoromethyl-phenyl)-N- [ 1 -(3 -fluoro-4- methanesulfonylamino-phenyl)-ethyl]-acrylamide O MsHN' ^ ^ "CF3 (/f)-N-[4-(l-Amino-ethyl)-2-fluoro-phenyl]-methanesulfonamide, HCI salt (20mg, 0.074mmol) was reacted with 3-(2-butyl-4-trifluoromethyl-phenyl)-acrylic acid (8mg, 0.031mmol) to give the title compound (5mg, 35%) after purification by column chromatography (gradient 12% to 100% EtOAc in Hex). 'H NMR(300MHZ, DMSO-d6): 6 8.66 (d, 1H, J= 8.1 Hz), 7.66 (m, 3H), 7.51 (bs, 2H),7.31 (t, lH,J=8.4Hz), 7.17 (d, \H,J= 11.4 Hz), 7.09 (d, IH, 7=8.1 Hz), 6.70 (d, IH, J= 15.6 Hz), 5.00 (m, IH), 2.91 Yi- L.T3 Step 1 6 Me MsHN step 2 Step 1: Synthesis of 2-methyl-3-(2-propyl-4-trifJuoromethyl-phenyl)-acrylic acid To a suspension of N-methoxy-N-methyl-2-propyl-4-trifluoromethyl-benzamide (150mg, 0.58mmol) in THF (lOmL) was added dropwise 1.0M LiAlH4 (0.30mL, 0.30mmol) at -78°C. The mixture was warmed up to -20°C and stirred for 30 mins. An aqueous solution of sodium potassium tartarate (10% w/v) was added to the reaction mixture and the resulting mixture was vigorously stirred for 30mins, to which was added Et20. After separation of two phases, the aqueous layer was extracted three times with ether and the combined organic layer was washed with brine, dried over anhyd. MgSO4 filtered and concentrated under reduced pressure. The product was vacuum dried to yield the 2-propyl-4-triftuoromethyl-benzaldehyde. To an ice-cold suspension of NaH (60% in mineral oil, 45mg, l.l3mmol) in THF (2mL) was added triethyl-2-phosphonopropionate (0.16mL, 0.75mmol), and the resulting mixture was stirred for 10mins at ambient temperature. A solution of aldehyde obtained above in THF was added to the reaction mixture and the resulting mixture was stirred for 3 hrs at ambient temperature. The reaction mixture was diluted with water and EtOAc, and the aqueous layer was extracted three times with EtOAc. The combined organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (gradient \2% to 100% EtOAc in Hex) to give 2-methyl-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid ethyl ester (68mg, 39%). To a suspension of 2-methyl-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid ethyl ester (68mg, 0.23mmol) in THF (ImL) was added a solution of IN-LiOH (10 ml), and the mixture was stirred for 3 hours at room temperature. The resulting residue was dissolved in H2O and then washed three times with EtOAc, acidified with IN HCI to pH 1-2. The solution was extracted three times with methylene chloride and then dried over anhydrous MgSO4 and concentrated in vacuo to give the title compound (60mg, 96%). 'H NMR(300MHz, CDCl3): 6 7.9l(s, 1H), 7.48(bs, 2H), 7.30(d, 1H, J =8.7Hz), 2.63(t, 2H,/=8.1Hz), 1.96(s, 3H), 1.61(m, 2H), 0.95(t, 3H,y=7.2Hz). Step 2: Synthesis of (^)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-2- methyl-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide To a suspension of (R)-N-[4-(l-amino-ethyl)-2,6-difluoro-phenyl]- methanesulfonamide, HCI salt {30mg, 0.11mmol) in THF (2mL) was added N-methylmorpholine (23µl 0.21mmol). The mixture was stirred for 5 minutes, to which were added 2-methyl-3-(2-propyl-4-trifluoromethyl-phenyi)-acrylic acid (22mg, 0.08lmmol) and 4-(4,6-dimethoxy[l,3,5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (DMTMM, 27mg, 0.098mmol). The mixture was stirred overnight at room temperature and was concentrated under reduced pressure. The residue was diluted with EtOAc and water. The organic layer was washed with saturated sodium bicarbonate. IN HCI and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography (gradient 12% to) 00% EtOAc in Hex) to give title compound (I8mg, 44%). 'H NMR(300MHZ, DMSO-d6): 5 8.41 (d, IH, J = 7.8 Hz), 7.58 (m, 2H), 7.41 (m, 2H), 7.13 (d, 2H,J= 8.4 Hz), 5.04 (m, IH), 2.97 (s, 3H), 2.62 (t, 2H), 1.86 (s, 3H), 1.52 (m, 2 H), 1.43 (d, 3H, J= 6.9 Hz), 0.87 (t, 3H, J= 12 Hz). Example 49: (i?)-N-[l-(3-Fluoro-4-methanesulfonylamino-phenyl)-ethyl]-2-methyl-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide (^-N-^-Cl-Amino-ethyO^-fluoro-pheny^-methanesulfonamide, HC1 salt (52mg, 0.19mmol) was reacted with 2-methyl-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylic acid (40mg, 0.15mmol) to give the title compound (68mg, 93%) after purification by column chromatography (gradient 12% to 100% EtOAc in Hex). 'H NMR(300MHZ, DMSO-d6): 5 9.51 (bs, IH), 8.41 (d, IH, J= 7.8 Hz), 7.58 (m, 2H), 7.29 (m, 5H), 5.06 (m, 1H), 3.00 (s, 3H), 2.60 (t, 2H), 1.86 (s, 3H), 1.50 (m, 2 H), 1.44 (d, 3H, J= 7.2 Hz), 0.87 (t, 3H, J= 7.5 Hz). Example 50: (tf )-3-(2-Cyclohexylmethoxy-4-trifluoromethyl-phenyl)-N-[ 1 -(3,5-difiuoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide Step 1: Synthesis of 2-cyclohexylmethoxy-4-trifluoromethyl-bertzoic acid cyclohexylmethyl ester 2-Hydroxy-4-trifluoromethyl-benzoic acid (246 mg, 1.19 mmol) was reacted with toluene-4-sulfonic acid cyclohexylmethyl ester (640 mg, 2.34 mmol) as described above to give the title compound (470 mg, 99 %) after purification by column chromatography. 'H NMR(300MHz, CDCl3): 5 7.83 (d, 1H, J= 7.8 Hz), 7.20 (d, 1H, J= 7.8 Hz), 7.13 (s, 1H), 4.13 (d, 2H, J= 6.6 Hz), 3.84 (d, 2H; J= 5.7 Hz), 2.04 - 1.74 (m, 12H), 1.33 -1.02 (m, 10H). Step 2: Synthesis of 2-cyclohexylmethoxy-N-methoxy-N-methyl-4-trifluoromethyl-benzamide 2-Cyclohexylmethoxy-4-trifluoromethyl-benzoic acid cyclohexylmethyl ester (528 mg, 1.33 mmo!) was reacted with IN LiOH (2,65 mg, 2.65 mmol) as described above to give 2-cyciohexylmethoxy-4-trifli.ioromethyl-benzoic acid (361. mg, 90 %) after drying by vacuum. 2-Cyclohexylmethoxy-4-triftuoromethyl-benzoic acid (361 mg, 1.19 mmol) was reacted with N,0-dimethylhydroxyamine, HCI salt (128 mg, 1.31 mmol) as described above to give the title compound (363 mg, 88 %) after purification by vacuum dry. 'H NMR(300MHZ, CDC13): 5 7.36 (s, 1H), 7.23 (d, 1H, J= 7.5 Hz), 7.10 (s, 1H), 3.83 (d, 2H, J= 5.7 Hz), 3.42 (s, 3H), 3.37 (s, 3H), 1.84 - 1.73 (m, 6H), 1.49 - 1.05 (m, 5H). Step 3: Synthesis of 3-(2-cyclohexylmethoxy-4-trifluoromethy]-phenyl)-acrylic acid methyl ester 2-Cyc!ohexyimethoxy-N-methoxy-N-methyl-4-trifluoromethyI-benzamide (363 mg, 1.05 mmol) was processed by LAH reduction and wlttig reaction as described above to give the title compound (250 mg, 69 %) after purification by column chromatography^- Hex/EtO Ac=2 0/1). 1HNMR(300MHz,CDCl3):δ 7.97(d, 1H, J= 16.2 Hz), 7.58 (d, 1H, J = 7.8 Hz), 7.19 (d, 1H, J= 7.8 Hz), 7.09 (s, 1H), 6.60 (d, \H,J= 16.2 Hz), 3.86 (d, 2H, J = 5.7 Hz), 3.82 (s, 3H), 1.91-1.77 (m, 6H), 1.43 - 1.05 (m, 5H). Step 4: Synthesis of 3-(2-cyclohexylmethoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide MsHN-^f^ ^^CF3 F N-[4-(l-Amino-ethyl)-2,6-diHuoro-phenyI]-methanesulfonamideJ HCI salt (28.8 mg, 0.101 mmol) was reacted with 3-(2-cyclohexylmethoxy-4-trifluoromethy!-phenyl)-acrylic acid (30 mg, 0.091 mmol) to give the title compound (33 mg, 65 %) after purification by column chromatography. 1HNMR(300MHz,CDCl3):5 7.88(d, 1H, J= 15.6 Hz), 7.50 (d, IH,J=8.1 Hz), 7.12 (d, 1H, 7= 8.1 Hz), 7.03 (s, 1H), 6.94 (d, 2H, J= 8.4 Hz), 6.51 (d, 1H, J = 15.9 Hz), 6.04 (s, 1H), 5.82 (d, 1H, J= 7.2 Hz), 5.17 - 5.10 (m, 1H), 3.80 (d, 1H, J= 5.7 Hz), 3.15 (s,3H), 1.86 - 1.65 (m,6H), 1.47 (d, 3H, J= 6.9 Hz), 1.28- 1.02 (m, 5H). Example 51: N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-piperidin-l-yl-4-trifluoromethyI-phenyl)-acrylamide F N-(4-Aminomethyl-3,5-difluoro-phenyl)-methanesulfonamide, HCI salt (59mg, 0.217mmol) was reacted with 3-(2-piperid-l-yl-4-trifluoromethyl-phenyl)-acrylic acid (65mg, 0.217mmol) to give the title compound (25mg, 22%) after purification by crystallization from Hex/EtOAc. 'H NMR(3Q0MHZ, CDCh): 5 7.98(d, IH, J= 15.6Hz), 7.60(m, 2H), 6.99(m, 2H), 6.79(d, 1H, J=8.4Hz), 6.46(d, 1H, /=15.6Hz), 6.00(s, 1H), 4.37(d, 2H, J =6.3Hz), 3.2l(s, 3H), 2.92(m, 4H), 1.77(m, H), 1.61(m, 4H) Example 52: (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-3-(2-piperidin-l-yl-4-trifluoromethyl-phenyl)-acrylamide (R)-N-[4-(1.-Amino-ethyl)-2,6-difluoro-phenyl]-methanesulfofiamide, HO salt (129mg, 0.451mmol) was reacted with 3-(2-piperid-l-yl-4-trifluoromethyl-phenyl)-acrylic acid (135mg, 0.451mmol) to give the title compound (65mg, 27%) after purification by crystallization from Hex/EtOAc. 'H NMR(300MHz, CDC13): 5 7.94(d, IH, J = 15.9Hz), 7.55(d, IH, J =8.4Hz), 7.23(m, 2H), 7.01(m, 2H), 6.43(d, IH, ,/=15.6Hz), 5.99(s, IH), 5.83(s, IH), 5.20(m, lH),3.21(s, 3H),2.92(m,4H), 1.76(m,4H), l.59(m,2H), 1.53(d, 3H, J=6Mlz). Example 53: (R)-N-[\ -(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(4-fluoro-2-propyl-phenyl)-acrylamide I O f MSHNV H ^F F 3-(4-Fluoro-2-propyl-phenyl)-acrylic acid was prepared as described above. (R)-N-(4-Aminoethyl-2,6-difluoro-phenyl)-methanesulfonamide, HC1 salt (28 mg, 0.097 mmol) was reacted with 3-(4-fluoro-2-propyl-phenyl)-acrylic acid (15 mg, 0.072 mmol), NMM (0.20 ml) and DMTMM (36 mg) at room temperature overnight to yield the title compound (12 mg, 38%) after column chromatography (Hex/EtOAc = 3/2). 'H NMR (300MHZ, CDCI3): 5 7.91 (d, IH, J = 15.3 Hz), 7.00 (d, IH, J = 8.4 Hz), 7.48 (m, IH), 6.92 (m, 2H), 6,25 (d, IH, J = 15.3 Hz), 6.05 (br, IH), 5,82 (d, IH, J = 6.9 Hz), 5.17 (t, IH, J= 7.1 Hz), 3.20 (s, IH), 2.72 (t, 2H, J = 7.5 Hz), L.60 (m, 2H), 0.95 (t, 3H, J = 7.2 Hz) Example 54: N-(3-FluQro-4-methanesulfonylamirto-5-vinyl-benzyl)-3-(2- isopropylamino-4-trifluoromethy!-phenyl)-acrylamide O HN^- N-(4-Atninomethyl-2,5-difluoro-phenyl)-methanesulfonamide, HCI salt (43mg, 0.154mmol) was reacted with 3-(2-isopropylamino-4-trifluoro-phenyl)-acrylic acid (42mg, 0.154mmol) to give the title compound (34mg, 42%) after purification by crystallization from Hex/EtOAc. 'HNMR(300MHz, DMSO-d6): 5 8.7 l(s, 1H), 7.70(d, 1H, J = 15.3Hz), 7.50(m, 2H), 7.10(m, 3H), 6.83(s, 1H), 6.57(d, 1H, .7 = 15.3Hz), 5.85(m, 1H), 5.70(m, 1H), 5.42(m, 1H), 4.42(d, 2H, J=5.4Hz), 3.58(m, 1H), 2.98(s, 3H), 1.1 g(d, 6H, J=6.0Hz}. ESI [M-H]-: 498 Example 55: (R)-N-[ 1 -(3,5-Difluoro-4-methanesulfonyIamino-phenyl)-ethyl]-3-(2-propyIarnino-4-trifluorornethyl-phenyl)-propionamide . O HN MsHN^V H ^CF3 F (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide (12 mg) was reduced with Pd/C (15 mg) under hydrogen atmosphere to yield title compound (7 mg, 60%). 'H NMR (300MHZ, CDCI3): 5 7.02 (d, IH, J = 7.5 Hz), 6.95 (d, 1H, J = 8.7 Hz), 6.87-6.71 (m, 3H), 6.17 (br, IH), 5.62 (d, 1H, J = 7.8 Hz), 4.96 (t, 1H, J = 7.2 Hz), 3.15 (s, 3H), 3.00 (m, 2H), 2.83 (m, 2H), 2.47 (m, 2H), 1.32 (d, 3H, J = 6.6 Hz), 0.96 (t, 3H, J = 7.5 Hz). Example 56: N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-propionamide 0 HN F N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide (20 mg, 0.041 mmol) was reduced with Pd/C under hydrogen atmosphere to yield title compound (12 mg, 59%). 'H NMR (300MHz, CDC13): 5 7.08 (d, IH, J = 7.5 Hz), 6.95 (d, IH, J = 8.4 Hz), 36.87 (d, IH, J = 7.8 Hz), 6.78 (s, IH), 6.76 (m, IH), 6.29 (s, IH), 5.93 (t, IH), 4.36 (d, 2H, J = 6.3 Hz), 3.19 (s, 3H), 3.09 (m, 2H), 2.91 (m, 2H), 2.55 (m, 2H), 1.70 (m, 2H), 1.02 (t, 3H, J = 7.5 Hz) Experimental example: Biological potency test 1. 4S Ca influx test 1) Separation of spinal dorsal root ganglia (DRG) in newborn rats and primary culture thereof Neonatal (2-3 day old or younger than 2-3 day old) SD rats were put in ice for 5 minutes to anesthetize and disinfected with 70% ethanol. DRG of all part of spinal cord were dissected (Wood et al., 1988, J. Neurosci. 8, pp3208-3220) and collected in DME/F12 medium to which 1.2g/l sodium bicarbonate and 50mg/l gentamycin were added. The DRG were incubated sequentially at 37°C for 30 mins in 200 U/ml collagenase and 2.5mg/ml trypsin, separately. The ganglia were washed twice with DME/F12 medium supplemented with 10% horse serum, triturated through a fire-polished Pasteur pipette, filtered through Nitex 80 membrane to obtain single cell suspension and the suspension was washed once triore. This was subjected to centrifugation, then resuspended in cell culture medium at certain level of cell density. As the cell culture medium, OME/F12 medium supplemented with. IQ% hmsje serum was diluted with identical medium conditioned by C6 glioma cells 2 days on a confluent monolayer (1:1), and NGF (Nerve Growth Factor) was added to adjust 200ng/ml as final concentration. After the ceils were grown 2 days in medium where cytosine arabinoside (Ara-C, 100 uM) was added to kill dividing nonneuronal cells, medium was changed to one without Ara-C. The resuspended cells were plated at a density of 1500-2000 neurons/weli onto Terasaki plates previously coated with 10 u.g/ml poly-D-ornithine. 2) ' Ca influx experiments DRG nerve cells from the primary culture of 2 days were equilibrated by washing 4 times with HEPES (10mM, pH 7.4)-buffered Ca2+, Mg2+-free HBSS (H-HBSS). The solution in each well was removed from the individual well. Medium containing the test compound plus capsaicin (final concentration 0.5 uM) and 45Ca (final concentration 10 µCi/ml) in H-HBSS was added to each well and incubated at room temperature for 10 mins. Terasaki plates were washed five times with H-HBSS and dried at room temperature. To each well. 0.3% SDS (10 µ1) was added to elute 43Ca. After the addition of scintillation cocktail of into each well, the amount of 45Ca influx into neuron was measured by counting radioactivity. Antagonistic activities of test compounds against vanilloid receptor were calculated as percent of the inhibition of maximal response of capsaicin at a concentration of 0.5 µM. The results are displayed in Table I below. [Table l] Results of Calcium Influx Test Examples Antagonist Examples Antagonist Calcium Uptake Test (IC50,fiM) Calcium Uptake Test (ICS0,uM) 1 0.019 29 0.16 2 0.17 30 0.41 3 0.12 31 0.11 4 0.38 32 2.2 5 0.12 33 0.15 6 0.026 34 0.98 7 0.11 35 0.092 8 0.85 36 0.046 9 0.34 37 1.7 10 0.050 38 1.1 11 0.062 39 0.022 12 0.15 40 0.10 13 0.12 41 0.55 14 0.24 42 0.11 15 2.4 43 0.32 16 0.22 44 0.091 17 0.14 45 0.065 18 0.083 46 0.18 19 0.16 47 0.094 20 0.15 48 0.53 21 0.019 49 1.4 22 0.16 50 0.21 23 0.27 51 3.3 24 0.044 52 0.34 25 0.17 53 0.17 26 0.047 54 0.027 27 0.17 55 0.19 28 1.1 56 0.35 2. Analgesic activity test: Mouse writhing test by inducing with phenyl-p-quinone Male ICR mice (mean body weight 25g) were maintained in a controlled lighting environment (12 h on/ 12 h off) for experiment. Animals received an intraperitoneal injection of 0.3ml of the chemical irritant phenyl-p-quinone (dissolved in saline containing 5% ethanol to be a dose of 4.5mg/kg) and 6 mins later, the number of abdominal constrictions was counted in the subsequent 6 mins period. Animals (10 animals/group) received 0.2ml of test compounds solution in vehicle of ethanol/Tween 80/saline (10/10/80) intraperitoneally 30 min before the injection of phenyl-p-quinone. In the case of oral administration, 0.2ml of test compounds solution in vehicle of ethanol/Tween 80/saline (5/5/90) were administered 54 min prior to the 0.2ml of 0.02% phenyl-p-quinone injection. A reduction in the number of writhes responding to the test drug compound relative to the number responding in saline control group was considered to be indicative of an analgesic effect. Analgesic effect was calculated by % inhibition equation (% inhibition=(C-T)/C x 100), wherein C and T represent the number of writhes in control and compound-treated group, respectively. Most examples of the present disclosure having good in vitro activities, were tested at various doses (ranging from 0.3 to 3 mg/kg) and all compounds tested in vivo showed analgesic effects from 8 to 59% inhibition at each dose, respectively, 3. PK study Pharmacokinetics of compounds in rats were analyzed using the following experiment. Rats were fasted overnight prior to administration and until approximately 4 hours after administration. Rats were given a single oral administration of compound at same dose. Administration volume was lOml/kg. Blood samples were collected from the retro-orbital sinus at various times over the following 7 hrs. Immediately after each collection, plasmas were separated from blood cells by centrifugation and stored at -20°C until the analysis was performed. The plasma samples were analyzed using a reverse phase high-performance chromatography (HPLC) method. The results are displayed in table 2 below, [Table 2] PK results for the compound having CF3-phenyl with meta substituent Ex# Structure IC50 Cmax (mcg/ml) Tma.x (hour) AUCpo (meg hr ml-1) TI/2 (hour) 1 F 0.019 0.466 3.500 1.939 1.399 2 H F 0.17 1.417 2.000 7.152 3.551 5 H f 0.12 2.631 3.50 22.456 4.300 21 F 0.019 2.716 2.000 16.424 3.501 22 MsHN^Y^^ ^^"CFa F 0.16 3.656 2.000 19.227 2.581 24 0.044 1.187 2.000 5.693 2.079 54 9 HI^ 0.027 0.772 2.000 5.316 4.050 4. Comparative examples As shown in Tables 2 and 3, the PK properties of the compounds of formula (I) of the present disclosure surprisingly have superior PK characteristics compared to compounds with a tert-butyl phenyl partial structure, with or without other substituents on the phenyl group, which were at least in part disclosed in the art, e.g. in WO 06/101318 or WO 06/101321 (also refer Table 3). Substantial increases in absorption and apparent half-life were observed by the replacement of tert-butyl phenyl by F-phenyl or CF3- phenyl (see Table 2 vs 3). [Table 3] PK results for the compound having tert-butyl-phenyl Ex# Structure rcso (HM) Cmax (mcg/mi) Tmax (hour) AUCpo (meg hr ml-1) Tl/2 (hour) Comp Cpd A (Ex 15a) Q FIX«'VT1/ 0.034 < 0.100 -b -b -b Comp Cpd B (Ex 4C) 0 0.31 0.069 0.500 0.072 0.462 Comp Cpd C (Ex 34a) 0.17 < 0.100 -b -b -b Comp Cpd D 0.085 < 0.100 -b -b -b Comp Cpd E F ' 2.3 < 0.100 -b -b -b a Example number in WO 06/101318 could not be determined due to low plasma concentration (detection limit: 0. lOOmcg/ml). c Example number in WO 06/101321 As shown in Tables 2 and 4, the compounds of formula (I) of the present disclosure have superior IC50 values and in some cases also improved PK characteristics compared to compounds with a CF3-phenyl partial structure but without additional substituents on the phenyl group, which were at least in part disclosed in the art, e.g. in WO 06/101318 or WO 06/101321. Surprisingly, the introduction of an additional substituent in ortho position of the phenyl's attachment position to the cinnamoyl backbone confers improved VR1 activity to the compounds. For example, whilst comparative compound "G" has an IC50 value of more than 10 uM, the compounds 1, 3,5-7,10,16-18, 21, 24, 26, 31, 39, 47, 50, and 52 of the present disclosure which all differ from "G" only by additional substituent(s) on phenyl group, all have IC50 values in a range between 0.019 and 0.34 uM. In addition, compound "G" shows only poor PK-properties, while all tested compounds of the present disclosure showed improved PK properties (in terms of T max and A L/C). Likewise, while comparative compound "F" has a moderate ICso value of 0.57 uM, the IC50 values of the corresponding examples of the present disclosure Ex 12 (0.15 uM) and 54 (0.027 uM) are significantly improved. [Table 4] PK results for the compound having CF3-phenyl Ex# Structure IC50 (jiM) Cmax (mcg/ml) Tmax (hour) AUCpo (mcghrml-1) Tl/2 (hour) Comp Cpd F (Exl8a) 0 XJ H KJ- 0.57 5.001 2.000 40.123 4.589 Comp Cpd G F >10 <0.100 j> _b _b a Exampl e number in WO 06/101318 b could not be determined due to low plasma concentration (detection limit: O.lOOmcg/ml). In summary, the presently disclosed compounds of formula (I) show a significantly improved "balance" between VRl activity and PK properties compared to the compounds disclosed in the art. Industrial Applicability As explained above, the compound according to the present disclosure is useful to prevent or to treat pain, inflammatory disease of the joints, neuropathies, HtV-related neuropathy, nerve injury, neurodegeneration, stroke, urinary bladder hypersensitivity including urinary incontinence, cystitis, stomach duodenal ulcer, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), fecal urgency, gastroesophageal reflux disease (GERD), Crohn's disease, asthma, chronic obstructive pulmonary disease, cough, neurotic/allergic/inflammatory skin disease, psoriasis, pruritus, prurigo, irritation of skin, eye or mucous membrane, hyperacusis, tinnitus, vestibular hypersensitivity, episodic vertigo, cardiac diseases such as myocardial ischemia, hair growth-related disorders such as effluvium, alopecia, rhinitis, and pancreatitis. More specifically, the compound according to the present disclosure is useful to preventing and treating of pain, which is or which is associated with a condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathic pain, post-operative pain, dental pain, noninflammatory musculoskeletal pain (including fibromyalgia, myofascial pain syndrome and back pain), migraine, and other types of headaches. We Claim : 1. A compound of, an isomer, or a pharmaceutically acceptable salt thereof; R1 O Re R3 formula (I) wherein, R1 is hydrogen, methyl, or ethyl; R2 and R3 are independently hydrogen, halogen, cyano, methyl, ethyl, methoxy, trifluoromethyl, vinyl, or acetylenyl; R4 is trifluoromethyl or fluoro; R5 is C2-C5 alkyl, C2-C5 alkoxy, C1-C2 alkoxy (C1-C3) alkoxy, C1-C2 alkoxy (Cl- C3) alkylamino, C2-C5 alkylamino, di(Cl-C3 alkyl)amino, C3-C6 cycloalkylamino, C3-C6 cycloalkoxy, or (C3-C6)cycloalkyl(C1-C3)alkyloxy; and R6 is hydrogen, C1-C5 alkyl, C1-C5 alkoxy, or C1-C5 alkylamino. 2. The compound according to claim 1, an isomer, or a pharmaceutically acceptable salt thereof; wherein, provided that if R5 is ethoxy, butoxy, pentoxy, (C3-C6)cycloalkoxy, or (C3-C6)cycloalkyl(Cl-C3)alkyloxy, then R1 is methyl. 3. The compound according to claim 1, an isomer, or a pharmaceutically acceptable salt thereof; wherein, R1 is hydrogen; R2 is halogen; and R5 is C2-C4 alkyl or C2-C4 alkylamino. 4. The compound according to claim 1, an isomer, or a pharmaceutically acceptable salt thereof; wherein, R, is hydrogen; R2 is fluoro; R3 is hydrogen, fluoro, cyano, methyl, vinyl, or acetylenyl; R4 is trifluoromethyl; R5 is C2-C4 alkyl or C2-C4 alkylamino; and R6 is hydrogen. 5. The compound according to claim 1, an isomer, or a pharmaceutically acceptable salt thereof; wherein R( is methyl. 6. The compound according to claim 1, an isomer, or a pharmaceutically acceptable salt thereof; wherein, R, is methyl; R2 is halogen; and R5 is C2-C4 alkyl, C2-C4 alkyloxy, or C2-C4 alkylamino. 7. The compound according to claim 1, an isomer, or a pharmaceutically acceptable salt thereof; wherein, R1 is methyl; R2 is fluoro; R3 is hydrogen, fluoro, vinyl, methyl, or acetylenyl; R5 is C2-C4 alkyl, C2-C4 alkyloxy, or C2-C4 alkylamino; and R6 is hydrogen or C1-C3 alkyl. 8. The compound according to claims any one of 1 to 7, an isomer, or a pharmaceutically acceptable salt thereof; wherein R.2 and R3 are both fluoro. 9. The compound according to claims any one of 1 to 8, an isomer, or a pharmaceutical^ acceptable salt thereof; wherein R6 is hydrogen. 10. The compound according to claims any one of I to 9, an isomer, or a pharmaceutically acceptable salt thereof, wherein R5 is ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, ethylamino, propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, or cyclohexylmethoxy, provided that if R3 is ethoxy, butoxy, pentoxy, or cyclohexylmethoxy, then Ri is methyl. 11. The compound according to claims any one of 1 to 10, an isomer, or a pharmaceutical ly acceptable salt thereof, wherein R5 is propyl, butyl, isobutyl, ethylamino, propylamino, or isopropylamino 12. The compound according to anyone of claims 1, 2, and 5 to 11, wherein if Ri is methyl or ethyl, then the atom to which R1 is attached is in (R)-configuration. 13. The compound according to claim 1, an isomer, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of; (i?)->J-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylarnino-4-trifluoromethyl-phenyl)-acryIamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Butylamino-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonyIamino-phenyl)-ethyi]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2,6-dipropyl-4-trifluoromethyI-phenyl)-acrylamide, (R)-N-[l-(3(5-Difluoro-4-methanesulfonyiamino-phenyl)-ethyl]-3-(2-ethoxy-4-trifluoromethy!-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-ethylamino-4-trifluoromethyl-phenyO-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-methyl-benzy[)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-vinyl-benzyI)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acry!amide, N-(3-Cyano-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-propoxy-4-trifluoromethyi-phenyl)-acrylamide, (R)-3-(2,6-Dibutyl-4-trifIuoromethyI-phenyl)-N-[l-(3,5-difluoro-4-methanesuIfonyIamino-phenyl)-ethyl]-acrylamide, (R)-3-(2,6-Diethyl-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, N-(3,5-DifIuoro-4-methanesulfonyIamino-benzyl)-3-(2-ethy]amino-4-trifluoromethyl-phenyl)-acrylamide, 3-(2-Ethylamino-4-trifluoromethyI-phenyl)-N-(3-fluoro-4-methanesuIfonylamino-5-methyl-benzyl)-acry]amide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acryiamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyI]-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide, N-(3,5-Ditluoro-4-methanesulfonyIamino-benzyl)-3-(2-propyi-4-trifluoromethyl-phenyI)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-methyl-benzyl)-3-(2-propyl-4-trifluoromethyl-phenyi)-acryIamide, (R)-3-(2-Butyl-4-trifluoromethyl-pheny])-N-[l-(3,5-difluoro-4-methanesuIfonylamino-phenyl)-ethy!]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-triethanesulfonylamino-phenyl)-propyl]-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyi]-3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(4-fluoro-2-propoxy-phenyl)-acrylamide, (R)-N-[I-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(4-f1uoro-2-propylamino-phenyl)-acrylam ide, (R)-3-(2-Butoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-3-(2-Butoxy-4-fluoro-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino- phenyl)-ethy!]-acrylam ide; N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-propyl-4- trifliioromethyl-phenyl)-acrylamide, (R)-3-(2-Butyi-4-trifluoromethyl-phenyl)-N-[l-(3-fluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamideJ (R)-3-(2-sec-Butoxy-4-trifluoromethyl-phenyl.)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-3-(2-sec-Butoxy-4-fluoro-phenyt)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2- ethylamino^-fluoro-phenylj-acrylamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-ethyiamino-4-fluoro- phenyl)-acrylamide, (R)-N-(2-Fluoro-4-{l-[3-(2-propyl-4-trifluoromethyl-phenyl)-allylamino]- ethyl}-phenyl)-methanesulfonamide; (R)-3-(2-Butylamino-4-fluoro-phenyl)-"N-[l-(3,5-difluoro-4-methanesulfotiylamino-phenyl)-ethyl]-acrylamide, 3-(2-ButyIamino-4-fluoro-phenyl)-N-(3,5-difluoro-4-methanesulfonylamino- benzyl)-acrylamide} (R)-N- [ 1 -(3,5-D i fluoro-4-methanesulfony lam ino-phenyl)-ethyl]-3 -(2-isobutyl- 4-trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Cyclohexylmethoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro- 4methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3s5-Difiuoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(4-tluoro-2-propyl-phenyt)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-vinyl-benzyl)-3-(2-isopropyIamino-4-trifluoromethyl-phenyl)-acrylamide, and (R)-N-[l-(3,5-DifIuoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifluoromethyl-phenyl)-propionamide. 14. The compound according to claim 1, an isomer, or a pharmaceutical^ acceptable salt thereof, wherein the compound is selected from the group consisting of; (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propylamino-4-trifluoromethyl-phenyi)-acrylamide, (R)-3-(2-Butylamino-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-propoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2,6-dipropyl-4-trifluoromethyl-phenyl)-acrylamide, (R-N-[1-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyly]-3-(2-ethoxy-4-trifluoromethyl-phenyl)-acrylamide, (R)-N-[1-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-ethylamino-4-trifluoromethyl-phenyl)-acryIamide, N-(3 -F luoro-4-methanesu lfonylamino-5 -methyl-benzyl)-3 -(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Fluoro-4-methanesulfonylamino-5-vinyl-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3-Cyano-5-fluoro-4-methanesulfony!amino-benzyl)-3-(2-propylamino-4-trifluoromethyl-phenyl)-acrylamide, (R)-3-(2,6-Diethyl-4-trifluoromethyl-phenyl)-N-[I-{3,5-difluoro-4-methanesulfony]amino-phenyt)-ethyt]-acrylamide, N-(3.5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-ethylamino-4-trifluoromethyl-phenyl)-acrylamide, N-(3,5-Difluoro-4-methanesulfonylamino-benzyl)-3-(2-isopropoxy-4-trif!uoromethyl-phenyl)-acrylamide, (i?)-N-[l-(3,5-Difluoro-4-methanesulfonyIamino-phenyl)-ethy]]-3-(2-propyl-4-trifluoromethy]-phenyl)-acry]amide, (R)-3-(2-Butyl-4-trifluoromethyl-phenyl)-N-[l-(3!5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-1-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-isopropoxy-4-trifluoromethyl-phenyl)-acrylamide, (R )-3-(2-Butoxy-4-trifluoromethyl-phenyl)-N-[ 1 -(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-3-(2-Butoxy-4-fluoro-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethy 1] -acrylam ide, N-(3-Ethynyl-5-fluoro-4-methanesulfonylamino-benzyl)-3-(2-propyl-4-trifluoromethyl-phenyl)-acrylamide, (R)-3-(2-Butyl-4-trifluoromethyl-phenyl)-N-[l-(3-fluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-3-(2-sec-Butoxy-4-trifluoromethyl-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamicle, (R)-3-(2-sec-Butoxy-4-fluoro-phenyj)-N-[ (-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R-N-[1-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-ethylamino-4-tluoro-phenyl)-acrylamide, (R)-N-(2-Fluoro-4-{l-[3-(2-propyl-4-trifluoromethyi-phenyl)-allyiamino]-ethyl}-phenyl)-methanesu!fonamide, (R)-3-(2-Butylamino-4-fluoro-phenyl)-N-[l-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl]-acrylamide, (R)-N-[l-(3,5-Difluoro-4-methanesulfonylamino-phenyl)-ethyl]-3-(2-isobutyl-4-trifluoromethyl-phenyl)-acrylamide, and N-(3-Fluoro-4-methanesulfonylamino-5-vinyl-benzyl)-3-(2-isopropylamino-4-trifluoromethyl-phenyl)-acrylamide. 15. A compound according to anyone of claims 1 to 14 for use as a medicament. 16. A pharmaceutical composition comprising the compound according to any one of claims 1 to 14, an isomer, or a pharmaceutically acceptable salt thereof, as an active ingredient and a pharmaceutically acceptable carrier. 17. The pharmaceutical composition according to claim 16, for preventing or treating a condition associated with the pathological stimulation and/or aberrant expression of vanilloid receptors. 18. The pharmaceutical composition according to claim 16 or 17, for treating a condition selected from the group consisting of pain, inflammatory disease of the joints, neuropathies, HIV-related neuropathy, nerve injury, neurodegeneration, stroke, urinary bladder hypersensitivity including urinary incontinence, cystitis, stomach duodenal ulcer, irritable bowel syndrome (IBS) and inflammatory bowel disease (1BD), fecal urgency, gastroesophageal reflux disease (GERD), Crohn's disease, asthma, chronic obstructive pulmonary disease, cough, neurotic/allergic/inflammatory skin disease, psoriasis, pruritus, prurigo, irritation of skin, eye or mucous membrane, hyperacusis, tinnitus, vestibular hypersensitivity, episodic vertigo, cardiac diseases such as myocardial ischemia, hair growth-related disorders such as effluvium, alopecia, rhinitis, and pancreatitis. 19. The pharmaceutical composition according to claim 18, wherein the pain is or is associated with a condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathic pain, post-operative pain, dental pain, non-inflammatory musculoskeletal pain (including fibromyalgia, myofascial pain syndrome and back pain), visceral pain, migraine, and other types of headaches. 20. Use of the compound according to any one of claims 1 to 14, an isomer, or a pharmaceutically acceptable salt thereof for the preparation of a medicament. 21. Use of the compound according to anyone of claims 1 to 14, an isomer, or a pharmaceutically acceptable salt thereof, in preparation of a medicament for prevention or treatment of a condition that is associated with the aberrant expression and/or aberrant activation of a vanilloid receptor. 22. Use of the compound according to any one of claims 1 to 14, an isomer, or a pharmaceutically acceptable salt thereof, in preparation of a medicament for prevention or treatment of a condition that is selected from the group consisting of pain, inflammatory disease of the joints, neuropathies, HIV-related neuropathy, nerve injury, neurodegeneration, stroke, urinary bladder hypersensitivity including urinary incontinence, cystitis, stomach duodenal ulcer, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), fecal urgency, gastro-esophageal reflux disease (GERD), Crohn's disease, asthma, chronic obstructive pulmonary disease, cough, neurotic/allergic/inflammatory skin disease, psoriasis, pruritus, prurigo, irritation of skin, eye or mucous membrane, hyperacusis, tinnitus, vestibular hypersensitivity, episodic vertigo, cardiac diseases such as myocardial ischemia, hair growth-related disorders such as effluvium, alopecia, rhinitis and pancreatitis. 23. The use of the compound according to claim 22, wherein the condition is pain, which is or which is associated with a condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, diabetic neuropathic pain, post-operative pain, dental pain, non-inflammatory musculoskeletal pain (including fibromyalgia, myofascial pain syndrome and back pain), visceral pain, migraine, and other types of headaches.