BENZIMIDAZOLE-BASED CINNAMIDE DERIVATIVE AS A TRANSIENT POTENTIAL VANILLOID RECEPTOR SUBTYPE 1 (TRPV1) ANTAGONIST AND PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OR PREVENTION OF PAIN CONTAINING THE SAME AS AN ACTIVE INGREDIENT

Abstract

The present invention relates to a benzimidazolone-based cinnamamide derivative as a TRPV1 antagonist and a pharmaceutical composition for treating or preventing pain containing the same as an active ingredient. The example compounds provided in one aspect of the present invention block the activation of TRPV1 caused by capsaicin, a TRPV1 receptor activator, but induce appropriate inhibition at approximately pH 20% to 80%, thereby the compounds have pain-relieving effects and effectively reduce side effects such as abnormal body temperature.

Description

BENZIMIDAZOLE-BASED CINAMAMIDE DERIVATIVE AS A VANILLOID TRANSIENT POTENTIAL RECEPTOR ANTAGONIST SUBTYPE 1 (TRPV1) AND PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OR PREVENTION OF PAIN CONTAINING THE SAME AS ACTIVE INGREDIENT ML / a / ZUZZ / U 1 U JO» Field of Invention The present invention relates to a benzimidazolone-based cinnamamide derivative as a TRPV1 antagonist and a pharmaceutical composition for treating or preventing pain containing the same as an active ingredient. Background of the Invention The vanilloid transient receptor potential 1 (TRPV1) is one of the TRP (transient receptor potential) channel subfamily, a cation channel protein found in various animal tissues. It is a non-selective cation channel primarily expressed in primary sensory neurons. TRPV1 plays a crucial role in pain transmission as a pain-sensitive nociceptor and transducer involved in transduction, the first step in the nociceptive pathway, which is the process of pain perception. TRPV1 also maintains the inflammatory state that follows tissue damage caused by trauma, infection, surgery, burns, and disease. Ref. 336482 involved in the inflammatory reaction of temperature hypersensitivity. In other words, TRPV1 is a pain gateway that recognizes and transmits pain in the human body, and by inhibiting TRPV1 function, it can selectively block inappropriate pain perception while maintaining normal sensation, which is why TRPV1 is being targeted for analgesic development. Research into the development of analgesics targeting TRPV1 is largely divided into two mechanisms: agonists and antagonists. Agonists, like ligands, bind to receptors and induce pain, and their analgesic effects occur through desensitization beyond the threshold. Therefore, agonists have side effects such as initial pain, burning, and discomfort, and are thus being developed only as transdermal analgesics. In contrast, TRPV1 antagonists bind to TRPV1 receptors competitively with ligands and inhibit pain transmission by TRPV1. Therefore, TRPV1 antagonists do not have side effects such as the burning sensation and initial pain induced by agonists, nor do they cause strong irritation, allowing them to be developed as oral formulations. Specifically, TRPV1 antagonists stand out as a target for the development of novel non-opioid analgesics applicable to neuropathic, inflammatory, and cancer pain, conditions that require specialized therapeutic agents due to their low efficacy and side effects. In fact, several multinational pharmaceutical companies, including Abbott and Amgen, have undertaken the development of TRPV1 antagonists. As a result of evaluating the efficacy of low-molecular-weight TRPV1 antagonists in non-clinical animal experiments, the efficacy of these antagonists, which exhibit strong and selective antagonism, was confirmed. However, the first-generation TRPV1 antagonist ABT-102, reported as a potent TRPV1 antagonist, has been shown to increase body temperature for more than two days in rodents. Amgen's AMG 517 demonstrated excellent analgesic efficacy as an antagonist, but it was known to cause subject body temperature to rise to 40.2 °C for one to five days during clinical trials, resulting in a potentially fatal side effect. Furthermore, some TRPV1 antagonists, including Amgen's AMG7905 and AMG8562, have been confirmed to cause hypothermia even in the absence of partial agonism. Therefore, addressing abnormal body temperature is a critical issue in the development of TRPV1 antagonists. It is presumed that the temperature-raising side effect of most first-generation TRPV1 antagonists developed to date is due to antagonism against all activators (capsaicin, heat, pH, nothing, etc.) of the TRPV1 receptor. In particular, capsaicin, one of the alkaloids, when ingested, stimulates TRPV1, one of the receptor's activation channels, and does not actually raise the temperature, but induces a high fever. Furthermore, it has been reported that 100% pH blockade of TRPV1 receptor activators led to an increase in body temperature, while 20% or less blockade resulted in proton activation at high concentrations, causing a decrease in body temperature. Therefore, in the development of TRPV1 antagonists, while blocking TRPV1 activation due to capsaicin and heat, the most important task is to overcome the phenomenon of abnormal body temperature by deriving a selective key strategy that moderately inhibits pH (20%–80%). With reference to the prior art, patent reference 1 (document WO 2011 / 120604 Al) describes a TRPV1 antagonist compound and a pharmaceutical composition comprising the same as an active ingredient, and the compound inhibits the TRPV1 vanilloid receptor, thereby relieving pain and treating diseases such as dry eyes. On the other hand, the compound of the present invention inhibits the activation of TRPV1 caused by capsaicin, but exhibits TRPV1 inhibitory activity of 20%-80% with respect to pH, thus providing an analgesic effect without any side effects related to changes in body temperature and exhibiting an excellent absorption rate in the body. Therefore, the compound of the present invention differs from the content of Patent Reference 1 (document WO 2011 / 120604 Al) mentioned above, as described below. First, in the compound of the present invention, region A is a 4-amino-l,3-dihydro-2H-benzo[d]imidazol-2-one derivative, region B (the linking portion) is acrylamide, propanamide, or cyclopropan-l-carboxamide, and region C is phenyl, pyridine, pyrazole, or tlazole. Furthermore, in the compound described in patent reference 1 (document WO 2011 / 120604 A1), region A is often a benzoheterocycloalkene, region B is urea or amide, and other substituents, including region C, are different. Therefore, the compound has a different chemical structure from the compound of the present invention as a whole. Furthermore, the compound of the present invention blocks the activation of TRPV1 caused by capsaicin and heat, but exhibits TRPV1 inhibitory activity of 20%-80% with respect to pH. Therefore, it is possible to prepare an analgesic that has an analgesic effect without causing abnormal body temperature changes and has an excellent absorption rate. On the other hand, Patent Reference 1 (document WO 2011 / 120604 A1), mentioned above, only describes an inhibitory effect on TRPV1 activation caused by capsaicin in experimental examples, but does not describe the TRPV1 inhibitory activity over a certain pH range, the side effect of changes in body temperature, or the absorption rate of the compound. Therefore, there is a difference between the compound of the present invention and the compound of Patent Reference 1 with respect to the efficacy of the invention. In other words, the compound of the present invention inhibits the activation of TRPV1 caused by capsaicin, but exhibits TRPV1 inhibitory activity of 20%-80% with respect to pH, thus providing an analgesic effect, no side effect of altered body temperature, and excellent absorption rate in the body. Therefore, the present inventors have completed the present invention, demonstrating that the compound can be used effectively as an analgesic. Brief Description of the Invention It is an objective of the present invention to provide a benzimidazolone-based cinnamamide derivative compound that blocks the activation of TRPV1 caused by capsaicin, a TRPV1 receptor activator, but induces appropriate inhibition at pH 20% to 80% to relieve pain and effectively reduce side effects such as abnormal body temperature. Another objective of the present invention is to provide a pharmaceutical composition for preventing or treating pain that contains the above compound as an active ingredient. Another objective of the present invention is to provide a health-functional food composition for preventing or relieving pain that contains the above compound as an active ingredient. Another objective of the present invention is to provide a method for treating pain comprising a step of administering the above compound to a subject in need. Another objective of the present invention is to provide the above compound for use in the prevention or treatment of pain. Another objective of the present invention is to provide a use of the above compound for the preparation of a medicament for the prevention or treatment of pain. To achieve the above objectives, in one aspect of the present invention, the present invention provides a compound represented by the formula 1 described herein, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof. In another aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating pain containing the above compound as an active ingredient. In another aspect of the present invention, the present invention provides a health-functional food composition for preventing or relieving pain containing the above compound as an active ingredient. In another aspect of the present invention, the present invention provides a method for treating pain comprising a step of administering the above compound to a subject in need. In another aspect of the present invention, the present invention provides the above compound for use in the prevention or treatment of pain. In another aspect of the present invention, the present invention provides a use of the above compound for the preparation of a medicament for the prevention or treatment of pain. ADVANTAGEOUS EFFECT The example compounds provided in one aspect of the present invention block the activation of TRPV1 caused by capsaicin, an activator of the TRPV1 receptor, but induce appropriate inhibition at approximately 20% to 80% pH, thereby the compounds have pain-relieving effects and effectively reduce side effects such as abnormal body temperature. Detailed Description of the Invention The present invention is described in detail below. The embodiments of this invention can be modified in several other ways, and the scope of the present invention is not limited to the embodiments described below. It is well understood by those in the art of average knowledge in this field that the embodiments of the present invention are given to explain the present invention more precisely. Furthermore, the inclusion of an element throughout the description does not exclude other elements, but may include other elements, unless specifically stated otherwise. ΜΛ / a / zuzz / uiu jo» opposite. In one aspect of the present invention, the present invention provides a compound represented by formula 1 below, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt 5 thereof. [Formula 1] EITHER A X2HN--\ • · = ·. X1o In the previous Formula 1, X1 and X2 are independently hydrogen, or form a C=C double bond by bonding with the carbon atom to which they are attached, or form a 3-6 membered cycloalkylene by bonding with the carbon atom to which they are attached; and / is a substituted or unsubstituted 5-10 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, or a substituted or unsubstituted Ce-ium aryl, wherein the substituted 5-10 membered heteroaryl and Cs-ium aryl are independently 5-10 membered heteroaryl and Cs-ium aryl with at least one substituent ML / a / zuzz / uiu jo» selected from the group consisting of linear or branched C1-12 alkyl substituted or unsubstituted with at least one halogen or hydroxyl group, linear or branched C1-12 alkynyl, C3-10 cycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl, 5-8 membered heterocycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NR2R2, -OR3, -SR4, Cg-io aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-8 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched C1-10 alkyl, R3 is a linear or branched C1-10 alkyl substituted or unsubstituted with at least one halogen, a C3-10 cycloalkyl, or a C3-10 cycloalkyl, or a linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl group. R4 is linear or branched C1-10 alkyl substituted or unsubstituted with at least one halogen, C3-10 cycloalkyl, or C3-10 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl. In another aspect, X1 and X2 are independently hydrogen, or ML / a / ZUZZ / U 1 U JO» form a C=C double bond per bond with the carbon atom to which they are attached, or form 3-5 membered cycloalkylene per bond with the carbon atom to which they are attached; and is heteroaryl of 5-8 members substituted or unsubstituted containing at least one heteroatom selected from the group consisting of N, O and S, or substituted or unsubstituted Ce-8 aryl, wherein the substituted 5-8 membered heteroaryl and Cg-s aryl are independently 5-8 membered heteroaryl and substituted Ce-8 aryl with at least one substituent selected from the group consisting of linear or branched Ci-io alkyl substituted or unsubstituted with at least one halogen or hydroxy group, linear or branched Ci-io algynyl, C3-8 cycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl, 5-6 membered heterocycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NR3R2, -OR3, -SR4, Cg-s aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-6 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched Ci-8 alkyl, R3 is a linear or branched C3-g alkyl substituted or unsubstituted with at least one halogen, a C3-8 cycloalkyl, or a linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl group. R4 is linear or branched C1-8 alkyl substituted or unsubstituted with at least one halogen, C3-8 cycloalkyl, or C3-8 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl. In another aspect, X1 and X2 are independently hydrogen, or form a C=C double bond by bonding with the carbon atom to which they are attached, or form a 3-4 membered cycloalkylene by bonding with the carbon atom to which they are attached; and / is a substituted or unsubstituted 5-6 membered heteroaryl containing at least one heteroatom selected from the group consisting of N and S, or a substituted or unsubstituted Ce aryl, wherein the substituted 5-6 membered heteroaryl and Ce aryl are independently 5-6 membered heteroaryl and Ce aryl substituted with at least one substituent selected from the group consisting of linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen or hydroxy group, linear or branched C1-7 alkynyl, substituted or unsubstituted C3-6 cycloalkyl with at least one linear or branched C1-5 alkyl,5-6 membered heterocycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NRXR2, -OR3, -SR4, Ce aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched C1-5 alkyl, R3 is a linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, a C3-6 cycloalkyl, or a linear or branched C3-6 cycloalkyl, or a C1-5 alkyl substituted or unsubstituted with at least one methyl group. R4 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl, or C3-6 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl. In another aspect, X1 and X2 are independently hydrogen, or form a C=C double bond by bonding with the carbon atom to which they are attached, or form cyclopropylene by bonding with the carbon atom to which they are attached; and The compound represented by formula 1 can be any compound selected from the following group of compounds. (1) (Ε)-3-(2-(4-methylpiperidin-l-yl)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (2) (E)-3-(2-(4-ethylpiperidin-l-yl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[diimidazol-4-yl)acrylamide; (3) (E)-N-(2-OXO-2,3-dihydro-lH-benzo[d]imidazol-4-yl)-3-(2-(pyrrolidin-l-yl)-6-(trifluoromethyl)pyridin-3yl)acrylamide; (4) (E)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)-3-(2-(piperidin-l-yl)-6-(trifluoromethyl)pyridin-Syl) acrylamide; (5) (E)-3-(2-morpholino-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)acrylamide; (6) (E)-3-(2-(diethylamino)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (7) (E)-3-(2-(dipropylamino)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (8) (E)-3 - (2-butoxy-6-(trifluoromethyl)pyridin-3-yl)-N- (2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)acrylamida; (9) (E)-3-(2-(hexiloxi)-6-(trifluoromethyl)pyridine- 3-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4ΜΛ / a / ZUZZ / U 1 U JO' 11)acrylamide; (10) (E)-3- (2-isobutoxy-6-(trifluoromethyl)pyridine- 3-yl)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4yl)acrylamida; (11) (E)-3-(2-cyclobutoxy-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (12) (E)-3-(2-(cyclopentyloxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (13) (E)-3-(2-(cyclopropylmethoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (14) (E)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol- 4-yl)-3-(2-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin3-yl)acrylamide; (15) (E)-3-(2-(neopentyloxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (16) (E) -3-(2-((2-methylcyclopropyl)methoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (17) (E)-3-(6-(chlorodifluoromethyl)-2-(cyclopropylmethoxy)pyridin-3-yl)-N-(2-oxo-2, 3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamida; (18) (Ε)-3-(6-cyclopropyl-2-(cyclopropylmethoxy)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamida; (19) (E)-3-(2-(cyclopropylmethoxy)-6- isopropylpyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[di imidazol-4-yl)acrylamide; (20) (E) -3-(2-(cyclopropylmethoxy)-6- (1- methylcyclopropyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (21) (E)-3-(2-(cyclopropylmethoxy)-6- (difluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (22) (E)-3-(2-(cyclopropylmethoxy)-6-(1,1- difluoroethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[di imidazol-4-yl)acrylamide; (23) (E)-3-(6-(tert-butyl)-2- (cyclopropylmethoxy)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (24) (E) -3-(2-(cyclopropylmethoxy)-6- (2- hydroxypropan-2-yl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (25) (E)-3-(2-(cyclobutylmethoxy)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (26) (E)-3-(2-(cyclopentylmethoxy)-6 ΜΛ / a / ZUZZ / U 1 U JO» (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[di imidazol-4-yl)acrylamida; (27) (E)-3-(2-(isobutylthio)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (28) (E) -3-(2-((cyclopropylmethyl)thio)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (29) (E)-3-(2-(cyclohexylthio)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (30) (E)-3-(2-(3-fluorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (31) (E)-3-(2-(3-chlorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (32) (E) -3-(2-(3-isopropylphenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (33) (E)-3-(2-(3-chloro-4-fluorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (34) (E)-3-(2-(4-fluorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lH ΜΛ / a / ZUZZ / U 1 U JO» benzo[djimidazol-4-yl)acrylamida; (35) (E)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol- 4-yl)-3-(2-(thiophen-2-yl)-6-(trifluoromethyl)pyridin-3yl)acrylamide; (36) (E)-3-(2-(furan-2-yl)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[dIimidazol-4-yl)acrylamide; (37) (E)-3-(2-(oxazol-2-yl)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (38) (E)-3-(2-(oxazol-5-yl)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (39) (E)-3-(2-(3,3-dimethyl-l-butyn-l-yl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[diimidazol-4-yl)acrylamide; (40) (E)-3-(2-(3,3-dimethylbutyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[djimidazol-4-yl)acrylamide; (41) (E)-3-(2-cyclopentyl-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (42) (E)-3-(2-isobutoxy-4-(trifluoromethyl)phenyl)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)acrylamide; (43) (E)-3-(2-(cyclopropylmethoxy)-4-(trifluoromethyl)phenyl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (44) (E)-3-(2-(cyclopropylmethoxy)-4-(2-hydroxypropan-2-yl)phenyl)-N-(2-oxo-2,3-dihydro-1Hbenzo[dJimidazol-4-yl)acrylamide; (45) (E)-3-(4-(terc-butyl)-2-(cyclopropylmethoxy)phenyl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamida; (46) (E)-3-(4-cyclopropyl-2-(cyclopropylmethoxy)phenyl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (47) (E) -3-(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)acrylamide; (48) (E)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazole- 4-yl)-3-(1-(m-tolyl)-3-(trifluoromethyl)-lH-pyrazol-5yl)acrylamide; (49) (E)-3-(1-(3-chloro-4-fluorophenyl)-3- (trifluoromethyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[diimidazol-4-yl)acrylamide; (50) (E)-3-(1-(3-isopropylphenyl)-3- (trifluoromethyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[djimidazol-4-yl)acrylamide; (51) (E)-3-(1-(3-chlorophenyl)-3-isopropyl-lH- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4ΜΛ / a / ZUZZ / U 1 U JO» 11)acrylamide; (52) (E)-3-(1-(3-chlorophenyl)-3- (1- methylcyclopropyl)-lH-pyrazol-5-yl)-N- (2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (53) (E) -3-(3-(tert-butyl)-1-(3-chlorophenyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)acrylamide; (54) (E)-3-(4-(3-chlorophenyl)-2- (trifluoromethyl)thiazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (55) (E)-3- (4- (3-chlorophenyl)-2-isopropylthiazol-5- yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)acrylamide; (56) (E)-3- (4- (3-chlorophenyl)-2-cyclopropylthiazol-5- yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)acrylamide; (57) (E)-3-(4-(3-chlorophenyl)-2-(1- methylcyclopropyl)thiazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (58) (E)-3- (2- (tert-butyl)-4-(3-chlorophenyl)thiazol- 5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazole-4yl)acrylamide; (5 9) 3- (2-isobutoxy-6-(trifluoromethyl)pyridin-3yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)propanoamide; (60) 3-(2-(cyclopropylmethoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lH ΜΛ / a / ZUZZ / U 1 U JO» benzo[di imidazol-4-yl)propanoimide; (61) 2- (2-isobutoxy-6-(trifluoromethyl)pyridine-3- 11)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazole-4yl)cyclopropan-l-carboxamide; (62) 2-(2-(cyclopropylmethoxy)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[dIimidazol-4-yl)cyclopropan-l-carboxamide; (63) 2- (1- (3-chlorophenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropane-l-carboxamide; (64) 2- (1- (3-chlorophenyl)-3-(1,1-difluoroethyl) -1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropane-l-carboxamide; (65) 2- (1- (3-chlorophenyl)-3-isopropyl-lH-pyrazol-5- yl)-N-(2-oxo-2, 3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropane-l-carboxamide; (66) 2- (1-(3-chlorophenyl)-3-cyclopropyl-lH-pyrazole- 5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazole-4yl)cyclopropan-l-carboxamide; (67) 2-(1-(3-chlorophenyl)-3-(1-methylcyclopropyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropan-l-carboxamide; and (68) 2-(3-(tert-butyl)-1-(3-chlorophenyl)-lH-pyrazol5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropan-l-carboxamide. In another respect, / is a substituted or unsubstituted 5-6 member heteroaryl containing at least one heteroatom selected from the group consisting of NYS, wherein the substituted 5-6 member heteroaryl is a substituted 5-6 member heteroaryl with two substituents selected from the group consisting of linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen or hydroxy group, linear or branched C1-7 alkynyl, substituted or unsubstituted C3-6 cycloalkyl with at least one linear or branched C1-5 alkyl, substituted or unsubstituted 5-6 member heterocycloalkyl with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NRlR2, -OR3, -SR4, substituted or unsubstituted Ce aryl with at least one halogen or linear or branched C1-5 alkyl, and 5-membered heteroaryl containing at least one heteroatom selected from the group consisting of N,O and S, R1 and R2 are independently linear or branched C1-5 alkyl, ML / a / ZUZZ / U 1 U JO» R3 is a linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, a C3-6 cycloalkyl, or a linear or branched C3-6 cycloalkyl, or a C1-5 alkyl substituted or unsubstituted with at least one methyl group. R4 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl, or C3-6 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl. In another aspect, ML / a / ZUZZ / U 1 U JO» is substituted or unsubstituted pyridine, wherein the substituted pyridine is pyridine substituted with two substituents selected from the group consisting of linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen or hydroxy group, linear or branched C1-7 alkynyl, C3-6 cycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl, 5-6-membered heterocycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NR4R2, -OR3, -SR4, Cs aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched C1-5 alkyl, R3 is a linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, a C3-6 cycloalkyl, or a linear or branched C3-6 cycloalkyl, or a C1-5 alkyl substituted or unsubstituted with at least one methyl group. R4 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl, or C3-6 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl. The compound represented by Formula 1 of the present invention can be used as a form of a pharmaceutically acceptable salt, wherein the salt is preferably an acid addition salt formed from pharmaceutically acceptable free acids. The acid addition salt of the present invention can be obtained from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, and phosphorous acid; non-toxic organic acids such as aliphatic mono / dicarboxylate, phenyl-substituted alkanoate, hydroxyalkanoate, alkanoate, aromatic acids, and aliphatic / aromatic sulfonic acids; or organic acids such as trifluoroacetic acid, acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, toluenesulfonic acid, tartaric acid and fumaric acid.Las sales farmacéuticamente no tóxicas son, por ejemplo, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutylate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, cabacate, fumarate, maliate, butyne-1,4-dioate, hexano-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, bencenosulfonate, toluenosulfonate, chlorobencenosulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutylate, citrate, lactate, hydroxybutylate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-l-sulfonate, naphthalene-2-sulfonate, and mandelate. The acid addition salt according to the present invention can be prepared by a conventional method known to those skilled in the art. For example, the derivative represented by formula 1 is dissolved in an organic solvent such as methanol, ethanol, acetone, methylene chloride, or acetonitrile, to which an organic or inorganic acid is added to induce precipitation. The precipitate is then filtered and dried to give the salt. Alternatively, the solvent and excess acid are distilled under reduced pressure and dried to give the salt. Or, the precipitate is crystallized in an organic solvent to give the same. A pharmaceutically acceptable metal salt can be prepared using a base. The alkali metal or alkaline earth metal salt is obtained by the following processes: dissolving the compound in an excessive solution of alkali metal hydroxide or alkaline earth metal hydroxide; filtering the insoluble compound salt; evaporating the remaining solution; and drying. At this point, the metal salt is preferably prepared in the pharmaceutically suitable form of a sodium, potassium, or calcium salt. The corresponding salt is prepared by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate). Furthermore, the present invention includes not only the compound represented by formula 1 but also a pharmaceutically acceptable salt thereof and a solvate, an optical isomer or a hydrate possibly produced therefrom. The term hydrate refers to a compound or a salt thereof of the present invention that contains a stoichiometric or non-stoichiometric amount of water bound by a non-covalent intermolecular force. The hydrate of the compound represented by formula 1 of the present invention may contain a stoichiometric or non-stoichiometric amount of water bound by a non-covalent intermolecular force. The hydrate may contain 1 or more equivalents of water, preferably from 1 to 5 equivalents of water. The hydrate may be prepared by crystallizing the compound represented by formula 1, an isomer thereof, or a pharmaceutically acceptable salt thereof in water or a water-containing solvent. The term solvate refers to a compound or salt thereof of the present invention containing a stoichiometric or non-stoichiometric amount of solvent bound by a non-covalent intermolecular force. Preferred solvents for this purpose include volatile, non-toxic solvents and / or solvents suitable for administration to humans. The term isomer refers to a compound or salt thereof of the present invention that has the same chemical or molecular formula but is structurally or spherically different. Such isomers include structural isomers such as tautomers, R or S isomers having an asymmetric carbon center, stereoisomers such as geometric isomers (trans, cis), and optical isomers (enantiomers). All such isomers and mixtures thereof are also included within the scope of the present invention. In another aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating pain, comprising the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. The compound may exhibit pain-preventive or therapeutic activity by inhibiting TRPV1 receptor activators (transient receptor potential vanilloid 1). Preferably, the compound prevents or treats pain by suppressing capsaicin, a TRPV1 receptor activator (transient receptor potential vanilloid 1 subtype), and inhibits pH in the range of 20% to 80% to reduce side effects such as abnormal body temperature. The compound represented by formula 1 of the present invention, or a pharmaceutically acceptable salt thereof, can be administered orally or parenterally and used in general pharmaceutical formulations. That is, the compound or a pharmaceutically acceptable salt thereof can be prepared for oral or parenteral administration by mixing it with commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid formulations for oral administration include tablets, pills, powders, granules, and capsules. These solid formulations are prepared by mixing one or more compounds with one or more suitable excipients such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. Besides simple excipients, lubricants, such as magnesium stearate, talc, etc., may be used. Liquid formulations for oral administration include suspensions, solutions, emulsions, and syrups. These formulations may contain various excipients such as humectants, sweeteners, flavorings, and preservatives, in addition to common diluents like water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, water-insoluble excipients, suspensions, and emulsions.Excipients and water-insoluble suspensions may contain, in addition to the active compound or compounds, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethylate, etc. The pharmaceutical composition comprising the compound represented by formula 1 or the pharmaceutically acceptable salt thereof as an active ingredient may be administered parenterally, and parenteral administration includes subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection. ML / a / ZUZZ / U 1 U JO» Currently, to prepare the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof as a parenteral formulation, the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is mixed with a stabilizer or buffer in water to produce a solution or suspension, which is then formulated as ampoules or vials. The composition described herein may be sterilized and may also contain preservatives, stabilizers, wettable powders or emulsifiers, salts and / or buffers for osmotic pressure regulation, and other therapeutically useful materials. The composition may be formulated using conventional mixing, granulation, or coating methods. Oral formulations include tablets, pills, hard / soft capsules, solutions, suspensions, emulsions, syrups, granules, elixirs, and lozenges, etc. These formulations may include diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and / or glycine) and lubricants (e.g., silica, talc, stearate and its magnesium or calcium salt, and / or polyethylene glycol) in addition to the active ingredient. Tablets may include binding agents such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, ML / a / ZUZZ / U 1 U JO» sodium carboxymethylcellulose and / or polyvinylpyrrolidone and, if necessary, disintegrating agents such as starch, agarose, alginic acid or its sodium salt or azeotropic mixtures and / or absorbents, may be included in addition to these coloring, flavoring and sweetening agents. In another aspect of the present invention, the present invention provides an analgesic composition for treating or relieving pain, comprising the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. The compound may exhibit therapeutic or pain-relieving activity by inhibiting activators of the TRPV1 receptor (transient receptor potential vanilloid subtype 1). Preferably, the compound treats or relieves pain by suppressing capsaicin, an activator of the TRPV1 receptor (transient receptor potential vanilloid subtype 1), and inhibits pH in the range of 20% to 80% to reduce side effects such as abnormal body temperature. In another aspect of the present invention, the present invention provides a functional health food composition for preventing or relieving pain, containing the compound represented by Formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. The compound may exhibit pain-preventive or pain-relieving activity by inhibiting TRPV1 receptor activators (vanilloid transient receptor potential subtype 1). Preferably, the compound prevents or relieves pain by suppressing capsaicin, a TRPV1 receptor activator, and inhibits pH in the 20% to 80% range to reduce side effects such as abnormal body temperature. The compound represented by Formula 1 according to the present invention can be used as a food additive. In such case, the compound can be added as is or mixed with other food components according to conventional methods. The mixing ratio of the active ingredients can be adjusted according to the intended use (prevention or enhancement). Generally, the amount of the compound added to natural foods can range from 0.1 to 90 parts by weight based on the total weight of the food. However, if long-term administration is required for health and hygiene purposes or to regulate health status, the content can be lower than the above, but a higher content is also acceptable, as the compound has been shown to be very safe. Furthermore, the functional health beverage composition of the present invention may also include various flavorings or natural carbohydrates, etc., like other beverages, in addition to the compound represented by Formula 1. The aforementioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. Additionally, natural sweeteners (such as thaumatin, stevia extract, rebaudioside A, glycyrrhizin, etc.) and synthetic sweeteners (such as saccharin, aspartame, etc.) may be included as sweetening agents. The natural carbohydrate content is preferably 1 to 20 g, and more preferably 5 to 12 g per 100 g of the composition of the present invention. In addition to the ingredients mentioned above, the compound represented by Formula 1 according to the present invention may include a variety of nutrients, vitamins, minerals (electrolytes), flavors including natural and synthetic flavorings, coloring agents and thinners (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal viscosifiers, pH regulators, stabilizers, antiseptics, glycerin, alcohols, carbonators, which are added to the soda, etc. The compound represented by Formula 1 of the present invention may also include fruit pulp, which can be added to natural fruit juices, fruit drinks, and plant-based beverages. In another aspect of the present invention, the present invention provides a pharmaceutical kit for preventing or treating pain comprising a first component containing the compound represented by formula 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient; and a second component containing an analgesic as an active ingredient. At this time, pain relievers can be used without limitation, provided they are a known pain reliever. The pain reliever can be an anti-inflammatory analgesic (NSAID such as a COX inhibitor) or an opioid-based analgesic. Some examples of analgesics include paracetamol, aspirin, ibuprofen, ketoprofen, meloxicam, diclofenac potassium, etodolac, sulindac, indomethacin, celecoxib, valdecoxib, rofecoxib, hydrocodone, oxymorphone, buprenorphine, fentanyl, hydromorphone, tramadol, and similar medications. ML / a / ZUZZ / U 1 U JO» or a combination thereof. In another aspect of the present invention, the present invention provides a method for treating pain comprising a step of administering the above compound to a subject in need. In another aspect of the present invention, the present invention provides the above compound for use in the prevention or treatment of pain. In another aspect of the present invention, the present invention provides a use of the above compound for the preparation of a medicament for the prevention or treatment of pain. The example compounds provided in one aspect of the present invention block the activation of TRPV1 caused by capsaicin, a TRPV1 receptor activator, but induce appropriate inhibition at approximately pH 20% to 80%. Thereby, the compounds have pain-relieving effects and effectively reduce side effects such as abnormal body temperature. These effects are directly supported by the examples and experimental examples that will be described later herein. The present invention will henceforth be described in detail by the following examples and experimental examples. However, the following examples and experimental examples are only to illustrate the present invention, and the contents of the present invention are not limited to this. Synthesis 1. Synthesis of compounds 1-1. Synthesis of region A [Reaction scheme 1] Synthesis of reqion A (derivative of 4-amino-l,3-dihydro-2H-benzo[d]imidazol-2-one) ACN, pyridine, triphosgene 0°C -> ta„ 1h 10% Pd / C, MeOH, H2(g) room temperature, 2h 1-1-1. Synthesis of 4-nitro-l,3-dihydro-2Hbenzo[d]imidazol-2-one 3-Nitrobenzene η-1,2-diamine (1 equivalent) was dissolved in acetonitrile, to which triphosgene (1.2 equivalent) was added dropwise at 0°C for 3-5 minutes, followed by stirring at room temperature for 30 minutes, preferably for 1 hour. The reaction mixture was diluted by slowly adding water dropwise at 0°C, and when no more gas was generated and a dark yellow-green solid began to form, the reaction mixture was stirred at room temperature for 30 minutes, preferably for 1 hour. The resulting yellow-green solid was then filtered and washed with water to give the target product 4-nitro-1,3-dihydro-2H-benzo[d]imidazo-1,2-one. (Yield: 80- 9%) 1-1-2. Synthesis of 4-amino-l,3-dihydro-2Hbenzo[diimidazol-2-one EITHER The HN H2N ·NH4-Nitro-1,3-dihydro-2H-benzo[d]imidazo-2-one (1 equivalent) obtained in the previous reaction was hydrogenated with a reducing agent such as 10% palladium-activated carbon (Pd-C) dissolved in a lower alcohol such as methanol, filtered, and the filtrate dried under reduced pressure. The reagent was purified by flash column chromatography packed with silica gel using a mixture of methylene chloride and methyl alcohol as an elution solvent to give the target compound 4-amino-1,3-dihydro-2H-benzo[d]imidazo-1,2-one. (Yield: 80-85%) 1-2. Synthesis of region C ML / a / ZUZZ / U 1 U JO» [Reaction scheme 2] Synthesis of the C region of pyridine [Method 1 A] DBU. THF or NaH or K2CO3DMF [Method 1B] Na2CO3. Pd(PPh3)4 [Method 1C] Pd(PPh3)4,Cul. TEA.toluene AND DIBAL-H. toluene R, = CF3. C(CH3)3 X = N, C Y = CN. Br Z = OH, F, Cl, SH R, = CF3. C(CH3)3 X = N,C Y = CN, Br' R?= methyl pipendma. ethylpipendma, cyclopentyl. cyclohexyl. morpholine, diethyllamide, dipropylamine, propoxy, hexylose, isobuthose. cyclobutose, cyclopentylose, 2.2,2-tnfluoroethoxy, neopentilose, 2-methylcyclopropyl)methoxy, cyclobutylmethoxy, cyclopentylmethoxy, (2,3-dimethylcyclopropyl)methoxy, isobutyl sulfane, sulfanopropyl, cyclohemethyl 3fluorofemlo. 3-chlorophemlo, 3isopropylphenyl. 3-chloro-4-fluorofemlo, 4-fluorophenyl, thiophen-2-llo, furan-2-ylo. 3,3-dimethylbut1-in-1-ilo. 3,3-dimethylbutyl. cyclobutyl, cyclopentyl, cyclohexyl 'Y = Br: direct coupling with methyl acnlate R^CFj, C(CH3)3X = N. C R?= methyl pipendma, ethylpiperidine, cyclopentyl. cyclohexyl. morpholine. diethylam. dipropylamines. purposes. hexylose, isobuthose, cyclobutose, cyclopentylose, 2,2,2-trifluoroethose, neoppentylose, 2-methylcyclopropyl)methoxy, cyclobutiImethoxy, cic lope ntilmethoxyl, (2,3-dimethylcyclopropyl)methoxy, isobutyl sulfane, cyclopropylmethyl sulfane. cyclohexyl sulfano, 3fluorophenyl, 3-chlorophemlo, 3isopropylphenyl, 3-chlor-4-fluorophenyl, 4-fluorophenyl. thiophene-2-ilo. furan-2-ilo. 3,3-dimethylbut1-in-1-¡lo, 3.3-dimethylbutllo, cyclobutyl. cyclopentyl, cyclohexyl IVIA / a / ZUZZ / UIU ME” [Method 2A] methyl acrylate, Pd(OAC)2, P(o-tol)3, DMF R, = CF3, C(CH3)3R1= CF3, C(CH3)3 X = N. CX = N. C R?= methyl piperidine, ethylpipendin, cyclopentyl, cyclohexyl, morpholine. diethylamine, dipropylamine, propoxy, hexylose, isobuthose, cyclobuthose. cyclopentylose, 2,2,2-trifluoroethose. neopentylosis. 2-methylcyclopropyl)methoxy, cyclobutylmethoxy, cyclopentylmethoxy, (2,3-dimethylcyclopropyl)methoxy. isobutyl sulfano. cyclopropylmethyl sulfano, cyclohexyl sulfano. 3fluorophenyl, 3-chlorophenyl, 3isopropylphenyl. 3-chloro-4-fluorophenyl, 4-fluorophenyl, thiophen-2-yl furan-2-yl. 3,3-dimethylbut1-yn-1-yl. 3,3-dimethylbutyl, cyclobutyl, cyclopentyl, cyclohexyl R3= CH3, ch2ch3 Me3SOI, NaH, DMSO R, = CF3. C(CH3)3X = N. C Y = CN. Br* R?= methyl piperidine, ethyl piperidine, cyclopentyl, cyclohexyl, morpholine, diethylamine, dipropylamine, propoxy, hexyloxy, isobutoxy, cyclobutoxy. cyclopentyloxy, 2,2,2-trifluoroethoxy, neopentyloxy. 2-methylcyclopropyl)methoxy, cyclobutylmethoxy. cyclopentylmethoxy. (2,3-dimethylcyclopropyl)methoxy, isobutyl sulfano. cyclopropylmethyl sulfano. cyclohexyl sulfano. 3fluorophenyl. 3-chlorophenyl. 3isopropylphenyl. 3-chloro-4-fluorophenyl. 4-fluorophenyl. thiophen-2-yl. furan-2-yl, 3,3-dimethylbut1-yn-1-lithium, 3,3-dimethylbutyl, cyclobutyl, cyclopentyl, cyclohexyl LIOH H?O. THF, H?O R, = CF3 X = N R'= Methyl cyclopropyl. Methyl isopropyl R3 = CH3 R, = CF3 X = N R'= Methyl cyclopropyl, Methyl isopropyl R3 = CH3 1-2-1. R2-pyridine / phenyl synthesis R2 [Method 1A] NR / OR As a starting material, pyridine is phenyl where Ri is CF3o C(CH3)3, Y is CN or Br, and Z is OH, Cl, F or SH was dissolved in THF or DMF, to which DBU (2 equivalents), NaH (2 equivalents), or K₂CO₃ (2 equivalents) was added at 0°C, followed by stirring for 5 to 10 minutes. The corresponding NR, OR, haloalkyl, and SR (2 equivalents) were dissolved in THF or DMF and added to the stirring mixture, followed by stirring at room temperature for 16 hours. The reaction was stopped by adding water, and the reagent was extracted with ethyl acetate or methylene chloride. The resulting organic layer was washed with brine, dried over magnesium sulfate, and then concentrated in vacuo. The residue was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as an elution solvent to give the target compound. (Yield: 85%-92%) [IB Method] CC As a starting material, 2-chloro-6-(trifluoromethyl)nicotinonitrile (1 equivalent) was dissolved in toluene and stirred. Na₂CO₃ (24 equivalents) dissolved in water was then added, followed by stirring for 5 to 10 minutes. Pd(PPhs)₄ (0.2 equivalents) was then added. The mixture was then refluxed for 30 minutes or 3 hours, and the reactor temperature was reduced to room temperature. MA / a / ZUZZ / UI U JO» corresponding boronic acid (2 equivalents) was dissolved in toluene or 1,4-dioxane and added dropwise to this, and the mixture was refluxed and stirred for 15 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was filtered through a Celite pad filter and concentrated under reduced pressure. The resulting mixture was dissolved in ethyl acetate, washed with brine and water, dried over magnesium sulfate, and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as an elution solvent to give the target compound. (Yield: 72%-85%) [Method 1C] CC As a starting material, 2-chloro-6-(trifluoromethyl)nicotinonitrile (1 equivalent) was dissolved in toluene and stirred. The corresponding alkyl (2 equivalents), Pd(PPh3)4 (0.2 equivalents), copper(I) iodide (0.2 equivalents), and TEA (2 equivalents) were added, and the mixture was refluxed and stirred for 15 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was filtered through a Celite pad filter and concentrated under reduced pressure. The resulting mixture was dissolved in EtOAc, washed with brine and water, dried over magnesium sulfate, and concentrated in a vacuum. The resulting residue was purified by flash column chromatography packed with silica gel using a mixture of ethyl acetate and hexane as the elution solvent to give the target compound. (Yield: 65%-73%) 1-2-2. Synthesis of pyridine / phenyl aldehydeXYV r2o Pyridine / phenyl nitrile (1 equivalent) obtained in the previous reaction was dissolved in toluene and filled with nitrogen. DIBAL-H (1M in toluene, 2 equivalents) was added slowly dropwise at -78°C, followed by stirring at the same temperature for 2 hours. The reaction was stopped by adding aqueous NH4Cl solution, and the organic material was extracted with EtOAc. The resulting mixture was washed with brine and water, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by flash column chromatography packed with silica gel using a mixture of ethyl acetate and hexane as the elution solvent to give the target compound. (Yield: 61%-75%). 1-2-3. Synthesis of E-ethyl / methyl acetate r2o [Method 2A] The aldehyde (1 equivalent) obtained in the previous reaction was dissolved in toluene, to which methyl(triphenylphosphoranylidene) acetate or ethyl(triphenylphosphoranylidene) acetate (2 equivalents) was added, followed by stirring at room temperature for 24 hours. After the reaction was complete, the toluene was removed by concentration under reduced pressure. The resulting residue was purified by flash column chromatography packed with silica gel using a mixture of ethyl acetate and hexane as the elution solvent to give the target compound. (Yield: 50%-65%) [Method 2B] Synthesis of (E)-3-(2(cyclopropylmethoxy)-6-(2-hydroxypropan-2-yl)pyridin-3-yl)methyl acrylate he In the case of 2-(5-bromo-6-(cyclopropylmethoxy)pyridin-2-yl)propan-2-ol having bromine at Y, 2-(5-bromo-6-(cyclopropylmethoxy)pyridin-2-yl)propan-2-ol (1 equivalent) was dissolved in anhydrous DMF, to which methyl acrylate (4 equivalents), P(o-tol)3 (0.3 equivalents), and triethylamine (10 equivalents) were added, followed by bubbling with inert gas (nitrogen and argon) for at least 5 minutes. The reaction mixture was stirred at room temperature for 10 to 30 minutes. Pd(OAc)2 (3 mol%) was added to this, followed by bubbling with inert gas (nitrogen and argon) for 5 to 10 minutes. The reaction mixture was then stirred at 100°C for 24 hours. After the reaction was completed, the reactor temperature was reduced to room temperature. The reagent was diluted with EtOAc, washed with water and brine, dried over magnesium sulfate, and concentrated under vacuum.The residue obtained was purified by flash column chromatography filled with silica gel using a mixture of ethyl acetate and hexane as an elution solvent to give the target compound. (Yield: 65%). 1-2-4. Synthesis of trifluoromethyl pyridine cyclopropane-l-carboxylate Νχ^^χ^-Τχ^θχ. r2q R2= Methyl cyclopropyl, Methyl isopropyl Trimethyl sulfoxonium iodide (2 equivalents) was dissolved in DMSO, to which NaH (2 equivalents) was added to ML / a / ZUZZ / U 1 U JO» The mixture was heated to 0°C, followed by stirring at room temperature for 1 to 2 hours, preferably until a clear mixture was formed. The starting material, pyridine acrylate (1 equivalent), obtained in the previous reaction was dissolved in a small amount of DMSO, added slowly dropwise, and the mixture was stirred at room temperature for 2 to 4 hours. The reaction was stopped by adding water, and the organic material was extracted with ethyl acetate. The reaction mixture was washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as an elution solvent to give the target compound. (Yield: 80%-90%) 1-2-5. Synthesis of phenyl / pyridine acrylic acid and cyclopropane carboxylic acid Ii 1 Ti 1 xN R? O Rj O Pyridine, phenyl acrylate, or pyridine cyclopropane carboxylate (1 equivalent) obtained in the previous reaction was dissolved in THE, to which LiOH-H₂O (2 to 3 equivalents) and the same amount of water were added, followed by stirring at room temperature for 2 to 5 hours. After the reaction was complete, 1N HCl was added at 0°C to adjust the pH of the reagent to 2–3. The organic material was extracted with EtOAc, washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as the elution solvent to give the target compound. (Yield: 85%–98%) 1-3. Synthesis of starting material from region C [Reaction scheme 3] or X = H, Cl, CH3X = H, Cl, ch3x = h, ci, ch3x = h, ci, ch3 1-3-1. Synthesis of 2,2-difluoropropionic anhydride O or While stirring 2,2-difluoropropionic acid (1 equivalent) dissolved in methylene chloride at -10°C, oxanyl chloride (1.2 equivalents) was added dropwise, followed by stirring at room temperature for 4 hours. It was then used as a starting material for the following reaction in a crude state. 1-3-2. Synthesis of 4-ethoxy difluorobutenone or X = H, Cl, CH3 As starting materials, 2,2-difluoropropionic anhydride obtained from the previous reaction or commercially available 2,2-difluoroacetic anhydride and 2-chloro-2,2-difluoroacetic anhydride (1 equivalent) were dissolved in chloroform, and the reactor temperature was reduced to 0°C, followed by stirring. Ethyl vinyl ether (1.3 equivalents) and pyridine (1.3 equivalents) were added to the reaction mixture, followed by stirring at room temperature for 4 hours. The reaction was terminated by adding HCl, and the organic material was extracted with methylene chloride, washed with water and brine, and concentrated under reduced pressure at 30°C. The resulting residue was purified by flash column chromatography packed with silica gel using a mixture of ethyl acetate and hexane as the elution solvent to give the target compound. (Yield: 89-95%) 1-3-3. Synthesis of 2-hydroxynicotinonitrile OH X = H, Cl, CHj 2-Cyanoacetamide (1 equivalent) was dissolved in ethanol, to which 21% NaOEt solution in ethanol (1.5 equivalents) was added dropwise, followed by stirring at room temperature for 10 to 20 minutes. After reducing the reactor temperature to 0°C, the starting material (1 equivalent) obtained in the previous reaction was added dropwise to the reaction mixture. The reactor temperature was raised, and the reaction mixture was reacted under reflux conditions for 5 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was acidified with 4N HCl, extracted using EtOAc, and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated under vacuum. The resulting residue was purified by instant column chromatography filled with silica gel using a mixed solvent of ethyl acetate and hexane as an elution solvent to give the target compound. (Yield: 60%-75%) 1-3-4. Synthesis of 2-chloro-nicotinonitrile X = H. Cl. CHj The starting material (1 equivalent) obtained from the previous reaction was dissolved in phenyl dichlorophosphate and stirred in a sealed tube at 170°C for 3 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was extracted with EtOAc or ether and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in a vacuum. The residue was purified by flash column chromatography packed with silica gel to give the target compound. (Yield: 71%–82%) [Reaction scheme 4] or MA / a / ZUZZ / UI U JO» OH Cl 1-4-1. Synthesis of (Z)-3-cyclopropyl-3-oxoprop-len-l-olate OO NaH (1 equivalent) was placed in a reaction vessel, and nitrogen gas was charged. Toluene and ethanol were added, followed by stirring. Cyclopropyl methyl ketone (1 equivalent) and ethyl formate (1 equivalent) dissolved in toluene were added to the mixture, followed by reaction at room temperature for 15 hours. After the reaction was complete, excess toluene was added to the reactor, filtered, and concentrated under reduced pressure to give the target product. (Yield: 81%) 1-4-2. Synthesis of 6-cyclopropyl-2-hydroxynicotinonitrile ML / a / zuzz / uiu jo» The OH (Z)-3-cycloprop-1,3-oxoprop-l-en-l-olate (1 equivalent) obtained in the previous reaction was dissolved in 1,4-dioxane, to which 2-cyanoacetamide (1 equivalent) was added, followed by refluxing for 21 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was filtered. AcOH was added to the filtrate, followed by stirring for 10 to 30 minutes. The reaction mixture was then extracted with EtOAc, washed with water and brine, and the resulting mixture was dried over magnesium sulfate and concentrated in a vacuum to give the target product. (Yield: 60%-70%) 1-4-3. Synthesis of 2-chloro-6-cyclopropylnicotynonitrile Cl 6-Cyclopropyl-2-hydroxynicotinonitrile (1 equivalent) obtained in the previous reaction was dissolved in phenyl dichlorophosphate and shaken in a sealed tube at 170°C for 3 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was extracted with EtOAc or ether and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel to give the target compound. (Yield: 71%-82%) [Reaction scheme 5] och3^N^OCHj CH3COOH, piperidine, H2O R = C(CH3)2, C(CH2)2CH3, C(CH3)3cyanide acetamide, R = C(CH3)2, C(CH2)2CH3, C(CH3)3 R = C(CH3)2, C(CH2)2CH3, C(CH3)3 R = C(CH3)2, C(CH2)2CH3jC(CH3)3 1-5-1. Synthesis of dimethylamino propen / buten-l-one O Yo In a sealed tube, the starting material 3-methylbutan-2-one, or 1-(1-methyl-1-cyclopropion-1-)ethan-1-one, or 3,3-dimethylbutan-2-one was dissolved in excess dimethylformamide dimethyl acetal and stirred at 110°C for 5 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the organic layer was extracted with methylene chloride and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated under reduced pressure at 30°C. The residue obtained was purified by flash column chromatography packed with silica gel to give the target compound. (Yield: 20%–50%) 1-5-2. Synthesis of 2-hydroxynicotinonitrile ML / a / ZUZZ / U 1 U JO» And η r = c(ch3)2. C(CH2)2CH3, IC(CH3)3 OH The starting material (1 equivalent) obtained from the previous reaction and acetamide cyanide (1.3 equivalents) were added to a mixture of AcOH and piperidine (1:1.3), followed by stirring under reflux for 24 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was acidified with 4N HCl, extracted using EtOAc, and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel using a mixture of ethyl acetate and hexane as the elution solvent to give the target compound. (Yield: 60%–75%) 1-5-3. Synthesis of chloro-nicotinonitrile R = C(CH3)2, C(CH2)2CH3, C(CH3)j The starting material (1 equivalent) obtained in the previous reaction was dissolved in phenyl dichlorophosphate and stirred in a sealed tube at 170°C for 3 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was extracted with EtOAc or ether and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel to give the target compound. (Yield: 71%-82%) [Reaction Scheme 6] Cl Cl 1-6-1. Synthesis of 5-bromo-2(methoxycarbonyl)pyridine 1-oxide EITHER o' + Br The starting material Methyl 5-bromopicolinate (1.0 equivalent) was dissolved in methylene chloride, to which m-CPBA (2.0 equivalents) was added, followed by stirring under reflux conditions for 20 hours. The reactor temperature was cooled below room temperature, and the reaction was stopped by adding aqueous Na₂SO₄ solution (saturated Na₂SO₃). The organic material was extracted with methylene chloride and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel to give the target compound. (Yield: 76%–85%) 1-6-2. Synthesis of methyl 5-bromo-6-chloropicolinate ML / a / ZUZZ / U 1 U JO» An excess of POCl3 was added to 1 equivalent of 5-bromo-2-(methoxycarbonyl)pyridine 1-oxide obtained in the previous reaction at 0°C, and the mixture was stirred at 95°C for 1 hour. The reaction was stopped by adding water. The organic material was extracted with EtOAc and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in a vacuum. The residue was purified by flash column chromatography packed with silica gel to give the target compound. (Yield: 68%–90%) 1-6-3. Synthesis of 2-(5-bromo-6-chloropyridin-2-yl)propan-2-ol Methyl 5-Bromo-6-chloropicolinate (1 equivalent) obtained in the previous reaction was dissolved in THE, to which 3 M CHaMgBr solution in diethyl ether (4.0 equivalents) was added dropwise at 0°C in a nitrogen-filled reactor, followed by stirring at room temperature for 1 hour. The reaction was stopped by adding aqueous NH4Cl solution. The organic layer was extracted with EtOAc and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in vacuo to give the target compound. (Yield: 70%-85%) [Reaction scheme 7] 1-7-1. Synthesis of 2-mercapto-6(trifluoromethyl)nicotinonitrile He SH starting material 2-Chloro-659 (trifluoromethyl)nicotinonitrile (1 equivalent) was dissolved in t-butanol, to which Na₂S (1 equivalent) was added, followed by stirring at 150°C for 20 minutes in a microwave oven. The reaction was stopped by adding HCl. The organic layer was extracted with EtOAc and washed with water and brine. The resulting mixture was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel to give the target compound. (Yield: 60%-65%). [Reaction Scheme 8] Synthesis of 4-cyclopropyl2-fluorobenzonitrile MA / a / ZUZZ / UI U JO» 1-8-1. Synthesis of 4-cyclopropyl-2-fluorobenzonitrile F As a starting material, 4-bromo-2-fluorobenzenitrile (1 equivalent) was dissolved in toluene and stirred, to which Na2CO3 (24 equivalents) dissolved in water was added, followed by stirring for 5 to 10 minutes. Then, Pd(PPh3)4 (0.2 equivalent) was added to the reaction mixture. The mixture was then stirred under reflux for 2 hours, the reactor temperature was reduced to room temperature, and the corresponding boronic acid (2 equivalents) dissolved in 1,4-dioxane was added dropwise, followed by stirring under reflux for 15 hours. After the reaction was complete, the reactor temperature was reduced to room temperature, and the reagent was filtered through a Celite pad filter and concentrated under reduced pressure. The resulting mixture was dissolved in ML / a / ZUZZ / U 1 U JO» ethyl acetate was washed with brine and water, dried on magnesium sulfate, and concentrated in a vacuum. The resulting residue was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as an elution solvent to give the target compound. (Yield: 85%) [Reaction Scheme 9] Synthesis of the C region of pyrazole C Ri = CF3, CH(CH3)2iC(CH2)2CH3, C(CH3)3 Ri Boronic acid, Cu(OAc)2, Ri = CF31CH(CH3)2, C(CH2)2CH3. C(CH3)3 R2= CI,CH3, CH(CH3)2 R3 = H, F LAH, THF (i) MnO2, toluene (ii) Methyl (Triphenylphosphoraniliden) acetate R3 Ri = cf3, CH(CH3)2, C(CH2)2CH3, C(CH3)3r2= CI CH3, CH(CH3)2 R3 = H, F Me3SOI, NaH, DMSO Ri R3 1-9-1. Synthesis of NR pyrazol-5-carboxylate Ri = cf3, CH(CH3)2, C(CH2)2CH3, C(CH3)3 R2= Cl, CH3, CH(CH3)2 R3 = H, F The starting material 1H-pyrazol-5-carboxylate (1 equivalent) synthesized in reaction schemes 10 to 11 was dissolved in methylene chloride and stirred. Appropriate acid (2 equivalents), Cu(OAc)2 (1.5 equivalents), and pyridine (2 equivalents) were added, followed by reaction at room temperature for 24 hours. After the reaction was complete, the reagent was filtered through a Celite pad filter, and the filtrate was concentrated under reduced pressure. The residue was purified by instant column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane, or methylene chloride and methyl alcohol as the elution solvent to give the target compound. (Yield: 80-90%). 1-9-2. Synthesis of IH-pyrazolyl methanol Ri and-- Ri = CF3, NX OH CH(CH3)2, NC(CH2)2CH3, C(CH3)3 R2= Cl, CH3, 12ch(ch3)2R3R3 = H, F LAH (2 equivalents) was dissolved in THE in a reaction vessel and nitrogen was charged. The starting material (1 equivalent) obtained from the previous reaction, dissolved in THF, was added dropwise at 0°C, followed by stirring at room temperature for 30 minutes to 1 hour. After the reaction was complete, the reactor temperature was lowered to 0°C, and the reaction was stopped by slowly adding aqueous NaHCO3 solution. The reagent was filtered through a Celite pad filter, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography packed with silica gel using a mixture of methylene chloride and methyl alcohol as the elution solvent to give the target compound. (Yield: 90%-98%) 1-9-3. Synthesis of 1H-pyrazolyl acrylate Ri R3 Ri - CF3, CH(CH3)2, C(CH2)2CH3, C(CH3)3r2= Cl, ch3, CH(CH3)2 R3 = H, F The starting material (1 equivalent) obtained by the above reaction was dissolved in toluene, to which MnO₂ (1 equivalent) was added, followed by stirring at room temperature for 30 minutes to 1 hour. Methyl(triphenylphosphoranilidene) acetate (3.5 equivalents) was added to the mixture, followed by reaction under reflux conditions for 24 hours. After the reaction was complete, the reagent was filtered through a Celite pad filter. The organic material was extracted with EtOAc, washed with brine and water, and the filtrate was dried over magnesium sulfate and concentrated in a vacuum. The resulting residue was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as the elution solvent to give the target compound. (Yield: 75%–90%) 1-9-4. Synthesis of 1H pyrazolyl cyclopropan-l-carboxylate Ri - CF3, CH(CH3)2jC(CH2)2CH3iC(CH3)3r2= Cl, ch3iCH(CH3)2 R3 = H, F Trimethyl sulfoxonium iodide (2 equivalents) was dissolved in DMSO, to which NaH (2 equivalents) was added at 0°C, followed by stirring at room temperature for 1 to 2 hours, preferably until a clear mixture was formed. The starting material, 1H-pyrazolyl acrylate (1 equivalent), obtained in the previous reaction was dissolved in a small amount of DMSO and slowly added dropwise to the mixture, followed by stirring at room temperature for 4 hours. The reaction was stopped by adding water, and the organic material was extracted with ethyl acetate. The mixture was washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as an elution solvent to give the target compound. (Yield: 80%–90%). 1-9-5. Carboxylic acid synthesis Acrylate or cyclocarboxylate (1 equivalent) obtained in the previous reaction was dissolved in THF, to which LiOH-fRO (2 to 3 equivalents) and the same amount of water were added, followed by stirring at room temperature for 2 to 5 hours. After the reaction was complete, HCl was added at 0°C to adjust the pH of the reagent to 2–3. The organic material was extracted with ethyl acetate, washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum. The residue was purified by flash column chromatography packed with silica gel using a solvent mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as the elution solvent to give the target compound. (Yield: 85%–98%) [Reaction Scheme 10] Synthesis of 1H-pyrazole-5-carboxylate [Method A] ML / a / ZUZZ / U 1 U JO» The starting material methyl propionate (1 equivalent) was dissolved in methylene chloride, to which NaNO₃ (3 equivalents) dissolved in water was slowly added dropwise, followed by stirring for 10 to 20 minutes. The reactor temperature was reduced to 0°C, and 3,3,3-trifluorophenylamine (3 equivalents) was added dropwise to the reaction mixture, followed by stirring at 0°C for 1 to 2 hours. The reaction mixture was stirred at room temperature for 30 minutes, and the reaction was stopped by adding water. The organic material was extracted with methylene chloride, washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in vacuo. The residue obtained was purified by flash column chromatography packed with silica gel using a mixed solvent of acetate. ML / a / ZUZZ / U 1 U JO» ethyl, hexane or methylene chloride and methyl alcohol as an elution solvent to give the target compound. (Yield: 65%-88%) [Method B] R= CH(CH3)2 C(CH2)2CH3 C(CH3)3t-BuOK, THF R = CH(CH3)2 C(CH2)2CH3 C(CH3)3 1-10-2. Synthesis of lH-pyrazol-5-carboxilato R= CH(CH3)2 C(CH2)2CH3 C(CH3)3 Methyl 1-1-methyl chloropropyl ketone, isopropyl methyl ketone, or pinacolone (1 equivalent) was added to a mixture in which t-BuOK (1.5 equivalent) was dissolved in THF at 0°C. Diethyloxalate (1 equivalent) dissolved in THF was added dropwise, followed by stirring at room temperature for 15 hours. AcOH (0.15 mL / mmol) was added to hydrazine (1.1 equivalent) followed by stirring under reflux conditions, and hydrazine monohydrate was added dropwise to this mixture for 3 hours. After the reaction was complete, the reagent was concentrated under reduced pressure, water was added to the resulting solid, followed by stirring for 3 to 6 hours. The resulting solid was filtered under reduced pressure and dried to give the target product. (Yield: 80%-91%) [Reaction Scheme 11] Thiazole C Region Synthesis ML / a / ZUZZ / U 1 U JO» Dimethyl carbonate NaH. THF I) SOCI2, MC ii) NH4OH Sulfur chloride CHCI3 Reactivo Lawesson toluene or THF R = CF3, CH(CH3)2, C(CH2)2CH3. C(CH3)3 R = C(CH7)2CHj, C(CH3)3 R = CF3, CH(CH3)?, C(CH2)2CH3, C(CH3)3 LAH THF (i) MnO?. tolueno (ii) Methyl (Triphenylphosphoranes lideno (acetate LiOH H?O THF / H?O 1-11-1. Synthesis of methyl 3-(3-chlorophenyl)-3oxopropanoate O^O NaH (3 equivalents) dissolved in THF by stirring in a reaction vessel filled with nitrogen. The reactor temperature was reduced to 0°C, and the starting material 1-(3-chlorophenyl)ethan-l-one (1 equivalent) and dimethyl carbonate (3 equivalents) were added slowly dropwise, followed by stirring at room temperature for 10 to 30 minutes. The reactor temperature was raised to 50°C, and the reagent was stirred for 15 hours. The reaction was stopped by adding 1N HCl at 0°C. The organic material was extracted with ethyl acetate, washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum. The residue obtained was purified by flash column chromatography packed with silica gel using a mixture of ethyl acetate and hexane as the elution solvent to give the target compound. ΜΛ / a / ZUZZ / U 1 U JO» (Yield: 65%-88%) 1-11-2. Synthesis of methyl 2-chloro-3-(3-chlorophenyl)-3-oxopropanoate EITHER Cl Cl After dissolving the methyl 3-(3-chlorophenyl)-3-oxopropanoate (1 equivalent) obtained in the previous reaction in chloroform, the reactor was filled with nitrogen, to which sulfuryl chloride (1.1 equivalent) was added dropwise at 0°C, followed by stirring under reflux conditions for 15 hours. After the reaction was complete, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography using a mixture of ethyl acetate and hexane as the elution solvent to give the target compound. (Yield: 75%-88%) 1-11-3. Synthesis of R-carboxamide R = C(CH2)2CH3, R^NH2C <CH3)3 1-Methylcyclopropane-l-carboxylic acid or pivalic acid (1 equivalent) was dissolved in toluene in a reaction vessel filled with nitrogen, to which thionyl chloride (1.1 equivalent) was added dropwise to ML / a / ZUZZ / U 1 U JO» The mixture was heated to 0°C, followed by stirring at room temperature for 5 hours. An excess of aqueous NH4OH solution was added slowly dropwise to this mixture at sub-zero temperatures, followed by stirring at room temperature for 15 hours. The reaction was stopped by adding water. The organic material was extracted with EtOAc, washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum to give the target compound. (Yield: 71%-89%) 1-11-4. Synthesis of R-carbothiamide SR=CF3, X CH(CH3)2, R NH2C(CH2)2CH3, C(CH3)3 Using commercially available 1-methylcyclopropan-L-carboxamide and pivalamide obtained from the previous reaction, or isobutyramide and 2,2,2-trifluoroacetamide as starting materials, the compounds were dissolved in THE or toluene, to which Lawesson reagent (0.6 equivalents) was added, followed by stirring at room temperature for 15 to 30 minutes. The reaction mixture was then stirred under reflux for 2 hours, preferably 4 hours. After the reaction was complete, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography packed with silica gel using a mixture of methylene chloride and methanol as the elution solvent to give the target compound. (Yield: 45%–68%) 1-11-5. Synthesis of thiazol-5-carboxylate R ML / a / zuzz / uiu jo» Methyl 2-chloro-3-(3-chlorophenyl)-3-oxopropanoate (1 equivalent) obtained in the previous reaction was dissolved in MeOH or a mixed solution of i-PrOH:n-BuOH (1:1), to which carbotiamide (1.32 equivalent) obtained in 1-11-4 dissolved in the same solvent was added dropwise, followed by stirring at room temperature for 10 to 30 minutes. The reaction mixture was then stirred under reflux for 15 hours. The reaction was stopped by adding water. The organic material was extracted with ethyl acetate, washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum. The resulting residue was purified by instant column chromatography filled with silica gel using a mixed solvent of ethyl acetate and hexane as an elution solvent to give the target compound. (Yield: 65%-88%) 1-11-6. Synthesis of R-(3-chlorophenyl)thiazol-5-yl ML / a / zuzz / ui uóoa metanol LAH (2 equivalents) was dissolved in THF in a reaction vessel and nitrogen was charged, to which the starting material thiazole-5-carboxylate (1 equivalent) obtained in the previous reaction dissolved in THF was added dropwise at 0°C, followed by stirring at room temperature for 30 minutes to 1 hour. The reactor temperature was reduced to 0°C, and the reaction was stopped by slowly adding aqueous NaHCO3 solution. The reagent was filtered through a Celite pad filter and the resulting filtrate was concentrated under reduced pressure. The residue obtained was purified by flash column chromatography packed with silica gel using a mixture of methylene chloride and methyl alcohol as an elution solvent to give the target compound. (Yield: 90%-98%). 1-11-7. Synthesis of R-(3-chlorophenyl)thiazol-5ΜΛ / a / ZUZZ / U 1 U JO»yl)methyl acrylate The starting material (1 equivalent) obtained in 1-11-6 was dissolved in toluene, to which MnCg (1 equivalent) was added, followed by stirring at room temperature for 30 minutes to 1 hour. Methyl(triphenylphosphoranylidene) acetate or ethyl(triphenylphosphoranylidene) acetate (3.5 equivalents) was added to the mixture, followed by stirring under reflux conditions for 24 hours. After the reaction was complete, the reagent was filtered through a Celite pad filter, and the organic material was extracted with ethyl acetate, washed with water and brine. The resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum. The resulting residue was purified by instant column chromatography filled with silica gel using a mixed solvent of ethyl acetate, hexane or methylene chloride and methyl alcohol as an elution solvent to give the target compound. (Yield: 75%-90%). 1-11-8. Synthesis of (E)-R-(3u jo» chlorophenyl)thiazolyl-acrylic acid The acrylate (1 equivalent) obtained in 11-7 was dissolved in THE, to which LiOH-H2O (2 to 3 equivalents) and the same amount of water were added, followed by stirring at room temperature for 2 to 5 hours. After the reaction was complete, HCl was added at 0°C to adjust the pH of the reagent to 2–3. The organic material was extracted with EtOAc, washed with water and brine, and the resulting filtrate was dried over magnesium sulfate and concentrated in a vacuum. The residue was purified by flash column chromatography packed with silica gel using a mixture of ethyl acetate, hexane or methylene chloride, and methyl alcohol as the elution solvent to yield the target compound. (Yield: 85%–98%) 1-3. Synthesis of region B ML / a / ZUZZ / U 1 U JO» [Reaction scheme 12] coupling with EDC 1-12-1. EDC Coupling The acrylic acid or cyclopropane-1-carboxylic acid obtained in the previous reaction was dissolved in DMA, to which EDC-HC1 (1.5 equivalents) and DMAP (1.5 equivalents) were added, followed by stirring at room temperature for 10 to 20 minutes. After adding the 4-aminobenzo[d]imidazol-2-one derivative (4-aminobenzo[d]imidazol-2-one) (2 equivalents) obtained in reaction schemes 1A and 1B, the mixture was stirred at room temperature for 3 to preferably 5 hours. The reaction was stopped by adding water. The organic layer was extracted with ethyl acetate or methylene chloride and concentrated under reduced pressure. The resulting residue was purified by column chromatography to give the target compound. (Yield: 60-88%). [Reaction scheme 13] R = OCH2CH(CH3)2, OCH2CH(CH2)2R = OCH2CH(CH3)2, OCH2CH(CH2)2 1-13-1. Synthesis of 6-(trifluoromethyl)pyridin-3yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)propanamide(6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)propanamide) (E)-3- (2-isobutoxy-6-(trifluoromethyl)pyridin-3-yl) or (E)-3-(2(cyclopropylmethoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo2,3-dihydro-1H-benzo[d]imidazol-4-yl)acrylamide((E)-3-(2(cyclopropylmethoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo2,3-dihydro-1H-benzo[d]imidazol-4-yl)acrylamide) (1 equivalent) obtained in 1-12-1 was hydrogenated with a reducing agent such as 10% palladium-activated carbon (Pd-C) dissolved in lower alcohol such as methanol, filtered with a celite pad, and the filtrate was dried under reduced pressure.The reagent was purified by instant column chromatography filled with silica gel using a mixed solvent of methylene chloride and methyl alcohol as an elution solvent to give the target compound. (Performance: 90%-98%). The compounds in Examples 1 to 68 were synthesized via reaction schemes 1 to 13, and the NMR data for each example compound are as follows. Representatively, the compound of<Ejemplo 1> It was prepared using a compound in which Ri is CF3, X is N, and R2 is methyl piperidine in [Reaction Scheme 2] as a starting material in [Reaction Scheme 12], and reaction with region A. <Ejemplo 1> (E)-3-(2-(4-methylpiperidin-l-yl)-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Solid yellow, 72% yield; NMR (500 MHz, DMSO) δ 10.72 (s, 1H) , 10.15 (s, 1H), 9.96 (s, 1H), 8.05 (d, J = 7.65 Hz, 1H). 7.70 (m , 1H), 7.59 (d, J = 10.20 Hz,1H), 7.42 (d, J = 7.75 Hz, 1H) , 7.24 (d, J = 8.05 Hz, 1H) ,6.93 (t, J = 7.90 Hz, 1H) , 6.86 (d, J = 15.70 Hz, 6.7 = 8) , 1H) , 4.20 (m, 1H) , 3.63 (d, J = 12.55 Hz, 2H) , 2.86 (t, J = 12.15Hz, 2H), 1.96 (m, 1H), 1.72 (d, J = 11.45 Hz, 2H) , 1.58 (m, 1H) , 1.31-1.26 (m, 2H) , 1.25 (s, 4H) ,0.95 (d, J = 6.45 Hz, 3H); Mass (FAB) m / z 446 [M+H]+<Ejemplo 2> (E)-3-(2-(4-ethylpiperidine-l-yl)-6(trifluoromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide IVIA / a / ZUZZ / UIU ME” White solid, Yield 88%; RMN4H (400 MHz, DMSO) δ 10.69 (s, 1H) , 10.09 (s, 1H), 9.88 (s, 1H), 8.01 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 7.8 Hz (15.6 Hz), Hz, 1H) , 7.20 (d, J = 8.4 Hz, 1H) , 6.89 (t, J = 8.0 Hz, 1H) , 6.81 (d, J = 15.6 Hz, 1H), 6.74 (d, J = 7.4 Hz, 3. Hz, 1H 2H) , 2.81 (t, J = 11.6 Hz, 2H) , 1.74 (d, J = 10.4 Hz, 2H), 1.27-1.19 (m, 4H) , 1.15 -1.13 (t, J = 7.6 Hz), (m 0. 1H); Mass (FAB) m / z 460 [M+H]+<Ejemplo 3> (E)-N- (2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)-3-(2-(pyrrolidin-l-yl)-6(trifluoromethyl)pyridin-3-yl)acrylamide White solid, Yield 65%; RMN4H (400 MHz, DMSO) δ 10.67 (s, 1H) , 10.08 (s, 1H) , 9.08 (s, 1H) , 7.83 (d, J = 7.2 Hz, 1H), 7.78 (d, J = 15.6 Hz, 1 0 H 7.11 (d, J = 8.0 Hz, 1H) , 6.88 (t, J = 8.0 Hz, 1H) , 6.72 (d, J = 7.6 Hz, 1H), 6.50 (d, J = 15.2 Hz, 1H), 3.49); Mass (FAB) m / z 418 [M+H]+<Ejemplo 4> (E)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)-3-(2-(piperidine-l-yl)-6(trifluoromethyl)pyridin-3-yl)acrylamide ΜΛ / a / ZUZZ / U 1 U JO» Yellow solid, yield 61%; RMN3H (300MHz, DMSO) δ 10.73 (s, 1H) , 10.14 (s, 1H) , 9.92 (s, 1H) , 8.06 (d, J = 7.71 Hz, 1H) , 7.46 1,7 (d.1 = J (d, J = 7.68 Hz, 1H), 7.23 (d, J = 7.89 Hz, 1H) , 6.95-6.84 (m, 2H) , 6.77 (d, J = 7.86 Hz, 1H), 3.24 (m, 8H6) ;, 1. Mass (ESI) m / z 432 [M+H]+<Ejemplo 5> (E)-3-(2-morpholino-6(trifluoromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Yellow solid, yield 82%; RMN3H (300MHz, CD3OD) δ 8.06 (d, J = 7.9 Hz, 1H), 7.84 (d, J = 15.8 Hz, 1H), 7.38 (d, J = 7.9 Hz, 1H), 7.05 (s, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6.93 - 6.87(m,2H), 3.86(m,4H), 3.33(m,4H); Mass (ESI) m / z 434 [M+H]+<Ejemplo 6> (E)-3-(2-(diethylamino)-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Solid yellow, yield 80%; RMN4Η (500 MHz, DMSO) δ 10.72(s, 1H), 10.12(s, 1H), 9.90(s, 1H), 7.99 (d, J = 7.60 Hz, 1H), 7.59 (d, J = 15.55 Hz, 1H), respectively. 7.33 (d, J = 7.75 Hz, 1H), 7.25 (d, J = 8.10 Hz, 1H), 6.92 (t, J = 7.95 Hz, 1H), 6.78 (d, J = 11.76 Hz, 1H), 6.76 (s, 1H), 2.94 (m, 4H) 1.14 (t, J = 6.90Hz, 6H); Mass (FAB) m / z 420 [M+H]+<Ejemplo 7> (E)-3-(2-(dipropylamine)-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lH benzo[d]imidazol-4-yl)acrylamide Solid yellow, yield 82%; NMR4H (500 MHz, DMSO) δ 10.72(s,1Η); 7.97 (d, J = 7.60 Hz, 1H) , 7.59 (d, J = 15.55 Hz,1H), 7.31 (d, J = 7.70 Hz, 1H) , 7.25 (d, J = 8.10 Hz,1H), 6.93 (t, J = 7.90 Hz, 1H) , 6.75–6.78 (dd, J = 3.35 Hz, 7.95 Hz, 2H), 3.28 (t, J = 7.50 Hz, 4H), 1.60 (q, J = 7.25 Hz, 4H) , 0.81 (t, J = 7.35 Hz, 6H) ; Mass (FAB) m / z 448 [M+H]+<Ejemplo 8> (E)-3-(2-butoxy-6(triflucromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lH ΜΛ / a / ZUZZ / U 1 U JO» benzo[d]imidazole-4-yl)acrylamide White solid, Yield 63%; NMRN2Η (300 MHz, DMSO) δ 10.71 (s, 1H), 10.15 (s, 1H), 9.95 (s, 1H), 8.24 (d, J = 7.5 Hz, 1H) , 7.71 (d, J = 15.8 Hz, 1H), 7.7 Hz, 1.27 (1H (d, J = 8.2 Hz, 1H), 7.05 (d, J = 15.8 Hz, 1H), 6.93 (t, J = 7.5 Hz, 1H), 6.78 (d, J = 7.7 Hz, 1H), 4.44 (t, J. = 86 (H6), 1m Hz), (m, 2H) , 0.96 (t, J = 7.32 Hz, 3H) ; Mass (FAB) m / z 421 [M+H]+<Ejemplo 9> (E)-3-(2-(Hexyloxy)-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide White solid, Yield 73%; NMR1H (300 MHz, DMSO) δ 10.71(s, 1H), 10.15(s, 1H), 9.95(s, 1H), 8.24 (d, J = 7.71 Hz, 1H), 7.70 (d, J = 15.75 Hz, 1H), 7.56 (d, J = 7.68 Hz, 1H), 7.21 (d, J = 8.25 Hz, 1H), 7.05 (d, J = 15.75 Hz, 1H), 6.93 (t, 1H), 6.77 (d, J = 7.89 Hz, 1H), 4.43 (t, J = 6.57 Hz, 2H), 1.82 (m, 2H), 1.43–1.23 (m, 7H), 0.88–0.86 (m, 3H); Mass (FAB) m / z 449 [M+H]+<Ejemplo 10> (E)-3-(2-isobutoxy-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide White solid, Yield 73%; RMNXH (300MHz, DMSO) δ 10.72(s,1H), 10.16(s,1H), 7.95(s,1H), 8.25(d,1). J = 7.71 Hz, 1H), 7.74 (d, J = 15.75 Hz, 1H), 7.57 (d, J = 7.69 Ηζ, 1Η) , 7.19 (d, J = 7.71 Hz, 1H) , 7.04 (d, J = 15.72 Hz, 1H) , 6.93 (t, J = 8.04 Hz, 1H) , 7.6, J = 6.78 4.21 (d, J = 6.78 Hz, 1H) , 2.17 (p, J = 6.57 Hz, 1H) , 1.02 (d, J= 6.78 Hz, 6H) ; Mass (ESI) m / z 421 [M+H]+<Ejemplo 11> (E) -3-(2-cyclobuthoxy-6(triflucromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide derived” White solid, Yield 82%; RMNXH (300 MHz, DMSO) δ 10.71 (s, 1H) , 10.14 (s, 1H) , 9.98 (s, 1H) , 8.23 ​​(d, J = 7.7 Hz, 1H), 7.68 (d, J.6) J = 1,5 = 7.5 Hz, 1H) , 7.18 (d, J = 7.9 Hz, 1H) , 7.09 (d, J = 7.5 Hz, 1H) , 6.93 (t, J = 7.9 Hz, 1H), 6.78 (d, J = 7.9 Hz) (H 2.50 (m, 2H) , 2.22 (m, 2H) , 1.78 (m, 2H) ; Mass (ESI) m / z 419 [M+H]+<Ejemplo 12> (E)-3-(2-(cyclopentyloxy)-6(trifluoromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide White solid, Yield 62%; RMNXH (400 MHz, DMSO-D6) δ 10.66 (s, 1Η) , 10.09 (s, 1H) , 9.90 (s, 1H) , 8.18 (d, J = 7.8 Hz, 1H) , 7.63 (d, J = 16.1 Hz, 1H) , 7.50 (d, J = 7.4 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 6.99 (d, J = 16.1 Hz, 1H), 6.89 (t, J = 7.8 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 5.45 (s, 1H), 2.01 (t, J = 6.4 (Hz, 3H) , 1.92 (s, 2H) , 1.69-1.79 (m, 4H) , 1.59 (d, J = 8.3 Hz, 3H) ; Masas (ESI) m / z 433 [M+H]+<Ejemplo 13> (E)-3-(2-(ciclopropilmetoxi)-6(triflucrómetil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida U JO» Sólido amarillo pallido, rendimiento 82%; RMN4Η (600MHz, DMSO) δ 10.70 (s, 1H), 10.14 (s, 1H), 9.95 (s, 1H) , 8.24 (d, J = 7.80 Hz, 1H), 7.73 (d, J = 16.02 Hz, 1H), 7.57 (d, J = 7.38 Hz, 1H), 7.20 (d, J 7, J = 8.1 =H7), 16.02 Hz, 1H), 6.93 (t, J = 8.28 Hz, 1H), 6.77 (d, J = 7.80 Hz, 1H), 4.29 (d, J = 6.84 Hz, 2H), 1.35 (m, 16 (q H2), J = 6 = 0. 0.42 (q, J = 5.04 Hz, 2H); Mass (ESI) m / z 419 [M+H]+<Ejemplo 14> (E)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)-3-(2-(2,2,2-trifluoroethoxy)-6(trifluoromethyl)pyridine-3-yl)acrylamide cf3 Pale yellow solid, yield 62%; NMR (400 MHz, DMSO) δ 10.68 (s, 1H), 10.14 (s, 1H), 9.98 (s. 1H), 8.33 (d, J = 7.2 Hz, 1H) , 7.69 (m, 2H) 1 .6, J = 7.1 6.96 (d, J = 15.6 Hz, 1H) , 6.89 (t, J = 8.0 Hz, 1H) , 6.74 (d, J = 8.8 Hz, 1H) , 5.11(q, J = 8.8 Hz, 2H) ; Mass (FAB) m / z 447 [M+H]+<Ejemplo 15> (E)-3-(2-(neoppentyloxy)-6(trifluoromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide ΜΛ / a / ZUZZ / U 1 U JO» Solid yellow, yield 52%; NMR2Η (400 MHz, DMSO) δ 10.68(s, 1H), 10.13(s, 1H), 9.91(s, 1H), 8.22(d, 20). J = 7.6 Hz, 1H), 7.74 (d, J = 16.0 Hz, 1H), 7.75 (d, J = 0.80). Hz, 1H) , 7.15 (d, J = 8.4 Hz, 1H) , 6.95 (d, J = 8.4 Hz, 1H) , 6.88 (t, J = 8.4 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 4.60 (s, 2H), 1.02 (s, 9H); Mass (FAB) m / z 435 [M+H]+<Ejemplo 16> (E)-3-(2-((2-methylcyclopropyl)methoxy)6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Solid amarillo, yield 63%; RMN3H (400 MHz, DMSO) δ 10.69 (s, 1H) , 10.15 (s, 1H) , 9.94 (s, 1H), 8.20 (d, J = 7.6 Hz, 1H), 7.72-7.66 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 7.03 (d, J = 16.0 Hz, 1H), 6.89 (t, J = 8.0 Hz, 1H), 6.74 (d, J = 7.2 Hz, 1H), 4.32-4.18 (m, 2H), 0.99 (d, J = 6.0 Hz, 3H), 0.81-0.80 (m, 2H) , 0.54 (m, 1H) , 0.32 (m, 1H) ; Masas (FAB) m / z 433 [M+H]+<Ejemplo 17> (E)-3-(6-(chlorodifluoromethyl)-2(cyclopropylmethoxy)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamida White solid, yield 71%; RMN7H (400MHz, DMSO) δ 10.67 (s, 1H), 10.23 (s, 1H), 10.02 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 16.0 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.05 (d, J = 16.0 Hz, 1H), 6.88 (t, J = 8.4 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 4.26 (d, J = 7.2 Hz, 2H), 1.33 (m, 1H), 0.55 (d, J = 8.0 Hz, 2H), 0.38 (d, J = 5.2 Hz, 2H); Masas (ESI) m / z 435 [M+H]+<Ejemplo 18> (E)-3-(6-ciclopropil-2(ciclopropilmetoxi)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida / \oo HNNH Sólido blanco, Rendimiento 82%; RMNXH (400MHz, DMSO) δ 10.66 (s, 1H), 10.09 (s, 1H), 9.75 (s, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.64 (d, J = 16.0 Hz, 1H), 7.19 (t, J = 8.0 Hz, 1H), 6.96 (d, J = 7.8 Hz, 1H), 6.79-6.90 (m, 2H), 6.71 (d, J = 7.3 Hz, 1H), 4.14 (d, J = 6.9 Hz, 2H), 1.99-2.05 (m, 1H), 0.93 (d, J = 6.4 Hz, 4H), 0.81 (t, J = 6.9 Hz, 1H), 0.53 (d, J = 6.9 Hz, 2H), 0.31 (d, J = 4.6 Hz, 2H) ; Masas (FAB) m / z 391 [M+H]+<Ejemplo 19> (E)-3-(2-(ciclopropilmetoxi)-6isopropilpiridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida U JO» Sólido blanco, Rendimiento 52%; RMN2H(400 MHz, DMSO) δ 10.67 (s, 1Η), 10.10 (s, 1H), 9.77 (s, 1H), 7.87 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 16.0 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 6.92-6.83 (m, 3H), 6.72 (d, J = 7.2 Hz, 1H), 4.23 (d, J = 6.8 Hz, 2H), 2.942.87 (m, 1H), 1.36-1.27 (m, 1H), 1.19 (d, J = 6.8 Hz, (6H), 0.56-0.51 (m, 2H), 0.35-0.33 (m, 2H); Masas (FAB) m / z 393 [M+H]+<Ejemplo 20> (E)-3-(2-(ciclopropilmetoxi)-6-(1metilciclopropil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 61%; RMN3H (400 MHz, DMSO) δ 10.65 (s, 1H), 10.23(s, 1H), 9.87 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 16.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.89-6.84 (m, 2H), 6.70 (d, J = 8.0 Hz, 1H), 4.13 (d, J = 6.8 Hz, 2H), 1.42 (s, 3H), 1.27-1.25(m, 1H) , 1.18-1.17 (m, 2H) , 0.81-0.78 (m, 2H) , 0.55-0.52 (m, 2H) , 0.32-0.31 (m, 2H) ; Masas (FAB) m / z 405 [M+H]+<Ejemplo 21> (E)-3-(2-(ciclopropilmetoxi)-6IVIA / a / ZUZZ / UIU JO» (difluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lH benzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 70%; RMN1H (DMSO, 400 MHz) δ 10.68 (s, 1H), 10.21(s, 1H), 9.97 (s, 1H), 8.14 (d, J = 7.2 Hz, 1H), 7.69 (d, J = 16.0 Hz, 1H), 7.32 (d, J = 7.2 Hz, 1H), 7.18 (d, J= 8.0Hz, 1H), 7.02-6.72 (m, 4H), 4.23 (d, J = 6.8 Hz, 2H), 1.33-1.28 (m, 1H), 0.57-0.53 (m, 2H), 0.380.34 (m, 2H); Masas (FAB) m / z 401 [M+H]+<Ejemplo 22> (E)-3-(2-(ciclopropilmetoxi)-6-(1,1difluoroetil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 59%; RMN1H (DMSO, 400 MHz) δ 10.67 (s, 1H), 10.20(s, 1H), 9.97 (s, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 16.0 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 7.19 (d, J = 8.4Hz, 1H), 6.99 (d, J = 16.0 Hz, 1H), 6.89 (t, J = 8.0 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 4.25 (d, J = 6.8 Hz, 2H), 1.95 (t, J = 18.8 Hz, 3H), 1.35-1.30 (m, 1H), 0.58-0.53 (m, 2H), 0.38-0.35 (m, 2H); Masas (FAB) m / z 415 [M+H]+<Ejemplo 23> (E)-3-(6-(terc-butil)-2(ciclopropilmetoxi)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida U JO» Sólido amarillo, rendimiento 59%; RMN2Η (DMSO, 400 MHz) δ 10.66 (s, 1H), 10.17(s, 1H), 9.84 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 15.6 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 7.6 Hz, 1H), 6.89-6.85 (m, 2H), 6.71 (d, J = 8.0 Hz, 1H), 4.23 (d, J = 6.8 Hz, 2H), 1.36-1.30 (m, 1H), 1.26 (s, 9H), 0.56-0.51(m, 2H), 0.35-0.33(m, 2H); Masas (FAB) m / z 407 [M+H]+<Ejemplo 24> (E)-3-(2-(ciclopropilmetoxi)-6-(2hidroxipropan-2-il)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida OH Sólido amarillo, rendimiento 63%; RMN2Η(DMSO, 400 MHz) δ 10.65 (s, 1H) , 10.33 (s, 1H) , 9.98 (s, 1H) , 7.95 (d, J=7.6 Hz, 1H) , 7.68 (d, J=16.0 Hz, 1H) , 7.25 (d, J=7.6 Hz, 1H), 6.93-6.86 (m, 2H), 6.71 (d, J=7.6 Hz), 5.12 (s, 1H), 4.22 (d, J=7.2 Hz, 2H), 1.39 (s, 6H), 1.34-1.27 (m, 1H), 0.56-0.51 (m, 2H) , 0.36-0.32 (m, 2H) ; Mass (FAB) m / z 409 [M+H] +<Ejemplo 25> (E)-3-(2-(ciclobutilmetoxi)-6(trifluorometil)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrilamida Sólido amarillo, yield 83%; 1H NMR (300 MHz, DMSO) δ 10.72 (s, 1H), 10.10 (s, 1H), 9.91 (s, (d, J = 15.93 Ηζ, 1H), 6.92 (m, 1H), 6.78 (d, J = 7.95 Ηζ, 1H), 4.40 (d, J = 6.96 Ηζ, 2H), 2.01 (m, 2H), 1.89 (m, 3H), 1.21 (m, 2H); Masas (FAB) m / z 433 [M+H]+<Ejemplo 26> (E)-3-(2-(ciclopentilmetoxi)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 63%; RMN4H (300 MHz, DMSO) δ 10.72 (s, 1H), 10.16 (s, 1H), 9.94 (s, 1H), 8.24 (d, J = 7.71 Hz, 1H), 7.72 (d, J = 15.75 Hz, 1H), 7.57 (d, J = 7.68 Hz, 1H), 7.19 (d, J = 7.89 Hz, 1H), 7.04 (d, J = 15.75 Hz, 1H), 6.93 (t, J = 7.86 Hz, 1H), 6.78 (d, J = 7.71 Hz, 1H), 4.31 (d, J = 7.14 Hz, 2H), 2.46 (m, 1H), 1.80 (m, 2H), 1.61 (m, 4H), 1.37 (m, 2H); Masas (FAB) m / z 447 [M+H]+<Ejemplo 27> (E)-3-(2-(isobutiltio)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida White solid, Yield 55%; NMR (400MHz, DMSO) δ 10.73 (s, 1H), 10.22 (s, 1H), 10.08 (s, 1H), 8.15 (d, J = 8.43 Hz, 1H) , 7.22 (d, J = 8.43 Hz, 1H) , 7.73 (d, J = 16.11 Hz, 1H), 7.71 (m,1H), 6.96 (d, J = 15.93 Hz, 1H), 6.92 (d,J = 7.89 Hz, 1H), 6.78 (d, J = 7.86 Hz, 1H), 4 J 3,6 (d 1.94 (m,1H), 1.00 (d, J = 6.42 Hz, 6H) ; Mass (FAB) m / z 437 [M+H]+<Ejemplo 28> (E)-3-(2-((cyclopropylmethyl)thio)-6(triflucromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide IVIA / a / ZUZZ / UIU ME” White solid, Yield 55%; RMNXH (400 MHz, DMSO) 510.67 (s, 1H), 10.11 (s, 1H), 9.98 (s, 1H), 8.14 (d, J = 7.88 Hz, 1H), 7.70 (d, J = 7.85 ( J = 7.85), J 7. Hz, 1H Hz, 1H), 7.22 (d, J = 8.12 Hz, 1H) , 6.94 (d, J = 8.24Hz, 1H) , 6.62 (d, J = 7.64 Hz, 1H) , 6.78 (d, J = 7.68 Hz,1H) , 6.93 (d, J = 15.88 Hz, 1H), 3.21 (d, J = 7.20 Hz, 2H), 1.16 (m, 1H), 0.55 (m, 2H), 0.3469 (m, 2H); Masas (FAB) m / z 435 [M+H]+<Ejemplo 29> (E)-3-(2-(ciclohexiltio)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido blanco, Rendimiento 59%; RMN4Η(400MHz, DMSO) δ 10.72 (s, 1H), 10.19 (s, 1H), 10.04 (s, 1H), 8.14 (d, J = 8.07 Hz, 1H), 7.70 (d, J = 8.04 Hz, 1H), 7.67 (d, J = 15.36 Hz, 1H), 7.22 (d, J = 8.07 Hz, 1H), 6.94 (d, J = 7.32 Hz, 1H), 6.93 (d, J = 15.75 Hz, 1H), 6.78 (d, J = 7.68 Hz, 1H), 3.91 (m, 1H), 2.03 (m,2H), 1.72 (m,2H), 1.51 (m, 6H); Masas (FAB) m / z 463 [M+H]+<Ejemplo 30> (E)-3-(2-(3-fluorofenil)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida ΜΛ / a / ZUZZ / U 1 U JO» Sólido blanco, Rendimiento 75%; RMN2H (400MHz, DMSO) 510.72 (s, 1H), 10.13 (s, 1H), 9.99 (s, 1H), 8.45 (d, J = 8.43 Hz, 1H), 8.07 (d, J = 8.58 Hz, 1H), 7.55 (m, 2H), 7.43 (m, 3H),7.20 (d, J = 8.25 Hz, 1H), 6.93 (m, 2H), 6.76 (d, J = 7.86 Hz, 1H); Masas (FAB) m / z 443 [M+H]+<Ejemplo 31> (E)-3-(2-(3-chlorofenil)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido blanco, Rendimiento 62%; RMN2Η (300MHz, DMSO) δ 10.72 (s, 1H), 10.11 (s, 1H), 9.98 (s, 1H), 8.45 (d, J = 8.2 Hz, 1H), 8.07 (d, J = 8.3 Hz, 1H), 7.51-7.65 (m, 5H), 7.20 (d, J = 8.3 Hz, 1H), 6.89-6.98 (m, 2), 6.71 (d, J = 7.50 Hz, 1H); Masas (ESI) m / z 459 [M+H]+<Ejemplo 32> (E)-3-(2-(3-isopropilfenil)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida ΜΛ / a / ZUZZ / U 1 U JO» White solid, Yield 82%; NMR2Η (300 MHz, DMSO) δ 10.71(s, 1H), 10.05(s, 1H), 9.95(s, 1H), 8.42 (d, J = 7.7 Hz, 1H), 8.02 (d, J = 8.1 Hz, 1H), 7.59 (d, J = 15.8 Hz, 1H) , 7.39–7.51 (m, 4H) , 7.20 (d, J = 8.4 Hz, 1H) , 6,896.97 (m, 2H) , 6.76 (d, J = 7.7 Hz, 1H) , 2.98 (m, 1H) , 1.24 (d, J = 6.8 Hz, 6H); Mass (FAB) m / z 467 [M+H]+<Ejemplo 33> (E)-3-(2-(3-chloro-4-fluorophenyl)-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide White solid, Yield 82%; NMR1H (300 MHz, DMSO) δ 10.72 (s, 1H), 10.10 (s, 1H), 9.98 (s, 1H), 8.44 (d, J= 6.1 Hz, 1H), .07 (d, J= 8.2 Hz, 1H), 7.81 (dd, J=1.8, 7.1 Hz, 1H) , 7.59-7.66 (m, 2H), 7.53 (d, J = 15.4 Hz, 1H), 7.21 (d, J = 8.3 Hz, 1H), .6.89–6.97 (m, 2H), 6.77 (d, J = 7.50 Hz, 1H); Mass (FAB) m / z 477 [M+H]+<Ejemplo 34> (E)-3-(2-(4-fluorophenyl)-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Sólido blanco, Rendimiento 69%; RMN2H(400MHz, DMSO) δ 10.71 (s, 1H), 10.13 (s, 1H), 10.00 (s, 1H), 8.41 (d, J = 8.07 Hz, 1H), 8.01 (d, J = 8.25 Hz, 1H), 7.63 (m, 2H), .53 (d, J = 15.54 Hz, 1H), 7.39 (m, 2H), 7.20 (d, J = 8.22 Hz, 1H), 6.93 (m, 2H), 6.75 (d, J = 7.68 Hz, 1H); Masas (FAB) m / z 443 [M+H]+<Ejemplo 35> (E)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)-3-(2-(tiofen-2-il)-6(trifluorometil)piridin-3-il)acrilamida Sólido amarillo, rendimiento 71%; RMN2Η (400MHz, DMSO) δ 10.70 (s, 1H), 10.14 (s, 1H), 10.01 (s, 1H), 8.27 (d, J = 7.8 Hz, 1H), 7.83-7.91 (m, 3H), 7.48-7.48 (m, 1H), 7.25 (dd, J = 5.3, 3.9 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 6.856.92 (m, 2H), 6.75 (d, J = 7.8 Hz, 1H); Masas (FAB) m / z 431 [M+H]+<Ejemplo 36> (E)-3-(2-(furan-2-il)-6(triflucrómetil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido marrón pálido, rendimiento 61%; RMN2H (400 MHz, DMSO) δ 10.69 (s, 1H), 10.12 (s, 1H), 9.97 (s, 1H), 8.29 (d, J = 8.0 Hz, 1H), 8.00-8.07 (m, 2H), 7.89 (d, J = 8.2 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.08 (d, J = 3.7 Hz, 1H), 6.83-6.92 (m, 2H), 6.73-6.76 (m, 2H); Masas (FAB) m / z 415 [M+H]+<Ejemplo 37> (E)-3-(2-(oxazol-2-il)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido marrón pálido, rendimiento 58%; RMN2H(300 MHz, DMSO) δ 10.69 (s, 1Η) , 10.12 (s, 1H), 9.97 (s, 1H), 8.29 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.15 (m, 2H), 6.83-6.92 (m, 2H), 6.73-6.76 (m, 2H); Masas (FAB) m / z 416 [M+H]+<Ejemplo 38> (E)-3-(2-(oxazol-5-il)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida ΜΛ / a / ZUZZ / U 1 U JO» Sólido marrón pálido, rendimiento 51%; RMN2H (400 MHz, DMSO) δ 10.69 (s, 1H), 10.12 (s, 1H), 9.97 (s, 1H), 8.29 (s, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 8.2 Hz, 1H), 7.09(m, 2H), 6.83-6.92(m, 2H), 6.73-6.76(m, 2H); Masas (FAB) m / z 416 [M+H]+<Ejemplo 39> (E)-3-(2-(3,3-dimetil-l-butin-l-il)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 67%; RMNXH(400MHz, DMSO) δ 10.70 (s, 1H), 10.16 (s, 1H), 9.99 (s, 1H), 8.35 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 16.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 16.0 Hz, 1H), 6.89 (t, J = 8.0 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 1.35 (s, 9H); Masas (FAB) m / z 429 [M+H]+<Ejemplo 40> (E)-3-(2-(3,3-dimetilbutil)-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida IVIA / a / ZUZZ / UIU JO» Sólido amarillo, rendimiento 82%; RMNXH (400 MHz, DMSO) δ 10.70 (s, 1H), 10.14 (s, 1H), 9.97 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.80 (m, 2H), 7.19 (d, J = 8.0 Hz, 1H), 6.87-6.91 (m, 2H), 6.72 (d, J = 8.0 Hz, 1H), 2.88 (m, 2H), 1.47(m, 2H); Masas (FAB) m / z 433 [M+H]+<Ejemplo 41> (E)-3-(2-cyclopentil-6(trifluorometil)piridin-3-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 82%; RMNXH(400MHz, DMSO) δ 10.69 (s, 1H), 10.13 (s, 1H), 9.95 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 15.6 Hz, 1H), 7.76 (d, J = 8.0 100 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 6.89 (t, J = 7.6 Hz, 1H), 6.80-6.73 (m, 2H), 3.62-3.54 (m, 1H), 1.95 (m, 2H), 1.85-1.76 (m, 4H), 1.65(m, 2H); Masas (FAB) m / z 417 [M+H]+<Ejemplo 42> (E)-3-(2-isobutoxi-4(trifluorometil)fenil)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida ΜΛ / a / ZUZZ / U 1 U JO» Sólido amarillo, rendimiento 71%; RMNXH (300 MHz, DMSO) δ 10.69 (s, 1H), 10.10 (s, 1H), 9.85 (s, 1H), 7.89 (d, J = 15.2 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.36 (m, 2H), 7.20 (d, J = 8.2 Hz, 1H) , 6.88 - 6.93 (m, 2H) , 6.75 (d, J = 7.7 Hz, 1H) , 3.95 (d, J = 6.2 Hz, 2H) , 1.97-2.12 (m, 1H) , 1.02 (d, J = 6.6 Hz, 6H) ; Masas (ESI) m / z 420 [M+H]+<Ejemplo 43> (E)-3-(2-(ciclopropilmetoxi)-4(trifluorometil)fenil)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 65%; RMN3Η (300MHz, DMSO) δ 10.70 (s, 1H), 10.12 (s, 1H), 9.88, (s, 1H), 7.89 (d, J = 15.8 Hz, 1H), 7.81 (d, J = 7.7 Hz, 1H), 7.34-7.38 (m, 101 2Η), 7.22 (d, J = 8.8 Hz, 1H), 6.90-6.96 (m, 2H), 6.76 (d, J = 7.7 Hz, 1H), 4.03 (d, J = 7.1 Hz, 2H), 1.31-1.16 (m, 1H), 0.62 (m, 2H), 0.38 (m, 2H) ; Masas (FAB) m / z 418 [M+H]+<Ejemplo 44> (E)-3-(2-(ciclopropilmetoxi)-4-(2hidroxipropan-2-il)fenil)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido amarillo, rendimiento 60%; RMN2Η (400MHz, DMSO) δ 10.66 (s, 1H), 10.07 (s, 1H), 9.70 (s, 1H), 7.85 (d, J = 15.6 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 8.2 Hz, 1H), 6.99-7.01 (m, 2H), 6.88 (t, J = 8.0 Hz, 1H), 6.706.75 (m, 2H), 3.91 (d, J = 6.9 Hz, 2H), 1.24 (s, 6H), 0.57 (t, J = 6.2 Hz, 2H), 0.34 (t, J = 5.0 Hz, 2H) ; Masas (FAB) m / z 408 [M+H]+<Ejemplo 45> (E)-3-(4-(terc-butil)-2(ciclopropilmetoxi)fenil)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida S ó1 ido love the 11th, yield 70%; RMN1H κ c NN (400MHz, DMSO) δ 10.66 (s, 1H), 10.07 (s, 1H), 9.70 (s, 1H), 7.85 (d, J = 15.6 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 8.2 Hz, 1H), 6.99-7.01 (m, 2H), 6.88 (t, J = 8.0 Hz, 1H), 6.70-6.76 (m, 2H), 3.92 (d, J = 6.9 Hz, 2H), 1.25 (s, 10H), 0.57 (t, J = 6.2 Hz, 2H) , 0.34 (t, J = 5.0 Hz, 2H); Masas (FAB) m / z 406 [M+H]+<Ej emplo 46> (E)-3-(4-cyclopropyl-2(cyclopropylmethoxy)phenyl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamida Solid white Yield 82%; RMN2H (400 MHz, DMSO) δ 10.66 (s, 1H), 10.05 (s, 1H), 9.66(s, 1H), 7.82 (d, J = 15.6 Hz, 1H), 7.43 (d, J = 7.8Hz, 1H) , 7.21 (d, J = 7.8 Hz, 1H), 6.87 (t, J = 8.0Hz, 1H), 6.66-6.72 (m, 4H), 3.88 (d, J = 6.9 Hz,2H), 1.87-1.95 (m, 1H), 1.25 (m, 1H), 0.95 (t, J = 6.4Hz, 2H) , 0.71 (d, J = 4.6 Hz, 2H), 0.57 (d, J = 7.8Hz, (2H), 0.32 (d, J = 4.6 Hz, 2H); Masas (FAB) m / z390 [M+H]+ 103<Ejemplo 47> (E)-3-(1-(3-chlorofenil)-3(trifluorometil)-lH-pirazol-5-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido blanco, Rendimiento 82%; RMN4Η (300 MHz, DMSO) δ 10.73 (s, 1H), 10.14 (s, 1H), 10.02 (s, 1H), 7.78 (m, 1H), 7.67 (m, 2H), 7.60 (m, 1H), 7.50 (s, 1H), 7.26 (d, J = 15.54 Hz, 1H) , 7.15 (d, J = 7.86 Hz, 1H) , 6.91 (t, J = 8.04 Hz, 1H) , 6.88 (d, J = 15.6 Hz, 1H) , 6.76 (d, J = 7.68 Hz, 1H); Masas (FAB) m / z 448 [M+H]+<Ejemplo 48> (E)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)-3-(1-(m-tolil)-3-(trifluorometil)-1Hpirazol-5-il)acrilamida White solid, Yield 60%; NMR4H (300 MHz, DMSO) δ 10.69(s, 1H), 10.11(s, 1H), 9.99, (s, 1H), 7,427.55(m, 4H), 7.35 (d, J = 7.9 Hz, 1H), 7.26 (d, J = 15.7). Hz, 1H), 7.15 (d, J = 7.9 Hz, 1H), 6.86–6.93 (m, 2H), 6.76 (d, J = 7.7 Hz, 1H), 2.42 (s, 3H); Mass (FAB) m / z 428 [M+H]+ 104<Ejemplo 49> (E)-3-(1-(3-chloro-4-fluorophenyl)-3(trifluoromethyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide U JO» F Light Solid yellow, yield 73%; NMR (300 MHz, DMSO) δ 10.70(s,1H); 7.99 (dd, J = 6.78, 2.55 Hz, 1H), 7.69–7.74 (m, 2H), 7.48 (s, 1H) , 7.24 (d, J = 15.8 Hz, 1H) , 7.15 (d, J = 8.1 Hz, 1H) , 6.92 (d, J = 8.0 Hz, 1H), 6.85 (d, J = 16.3 Hz, 1H), 6.76 (d, J = 7.9 Hz, 1H); Masas (FAB) m / z 466 [M+H]+<Ejemplo 50> (E)-3-(1-(3-isopropylfenil)-3(trifluorometil)-lH-pirazol-5-il)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-il)acrilamide Sólido amarillo claro, rendimiento 66%; RMN2H(300 7.15 MHz, DMSO) (d, J = 8.25 Hz, 1H), 6.93 - 6.80 (m, 2H), 6.76 (d, J = 105 7.5 Hz, 1H), 3.02 (m, 1H), 1.26 (s, 3H), 1.24 (s, 3H); Masas (FAB) m / z 456 [M+H]+<Ejemplo 51> (E)-3-(1-(3-chlorofenil)-3-isopropillH-pirazol-5-il)-N-(2-oxo-2,3-dihidro-lH-benzo[d]imidazol-4 IVIA / a / ZUZZ / UIU JO» il)acrilamida Solid yellow, yield 46%; NMR Ή (300 MHz, DMSO) δ 10.70(s,1H), 10.10(s,1H), 9.90(s,1H), 7.59(m,3H) , 7.46(m,1H) , 7.31(d,J = 15.39Hz,1H), 7.19(m,14). 1H), 6.90(m,1H), 6.81(m,3H), 3.0(m,1H), 1.28(d, J = 6.96 Hz, 4H); Mass (FAB) m / z 422 [M+H]+<Ejemplo 52> (E)-3-(1-(3-chlorophenyl)-3-(1methylcyclopropyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Solid yellow, yield 87%; NMRτΗ (300 MHz, DMSO) δ 10.70 (s, 1H), 10.10 (s, 1H), 9.90 (s, 1H), 7.61–7.58 (m, 3H), 7.44 (m, 1H), 7.28 (d, J = 15.39 Hz, 1H), 7.20 (d, J.Sc 106 = 8.25 Hz, 1H), 6.90 (m, 1H), 6.78-6.71 (m, 3H), 1.45 (s, 3H), 1.23(s,1H), 0.99(m,2H), 0.80(m,2H); Mass (FAB) m / z 434 [M+H]+<Ejemplo 53> (E) -3-(3-(tert-butyl)-1-(3chlorophenyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Sólido amarillo, rendimiento 88%; RMN2Η (300 MHz, DMSO-D6) δ 10.73 (s, 1H), 10.09 (s, 1H), 9.87, (s, 1H), 7.577.64 (m, 3H), 7.44-7.47 (m, 1H), 7.32 (d, J = 15.4 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 6.86-6.93 (m, 2H), 6.74-6.79 (m, 2H), 1.33 (s, 9H); Masas (FAB) m / z 436 [M+H]+<Ejemplo 54> (E)-3-(4-(3-chlorofenil)-2(triflucrómetil)tiazol-5-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida Sólido marrón pálido, rendimiento 77%; RMN7H (400 MHz, DMSO) δ 10.70 (s, 1H), 10.08 (s, 1H), 10.02 (s, 1H), 7.66 (d, J = 10.8 Hz, 1H), 7.59 (m, 4H), 7.12 (d, J = 8.0 Hz, 107 1Η), 6.88 (t, J = 8.4 Ηζ, 1H), 6.80 (d, J = 15.6 Ηζ, 1H), 6.74 (d, J = 8.0 Ηζ, 1H) ; Masas (FAB) m / z 465 [M+H]+<Ejemplo 55> (E)-3-(4-(3-chlorofenil)-2isopropiltiazol-5-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)acrilamida ΜΛ / a / ZUZZ / U 1 U JO» Pale yellow solid, yield 78%; iH NMR (400MHz, DMSO) δ 10.69(s,1H), 10.05(s,1H), 9.85(s,1H), 7.63 (d, J = 15.2 Ηζ, 1H), 7.63 (s, 1H), 7.56-7.52 (m,3H), 7.17 (d, J = 8.4 Ηζ, 1H), 6.88 (t, J = 8.0 Ηζ, 1H), 6.73 (d, J = 7.6 Ηζ, 1H), 6.56 (d, J = 15.6 Ηζ, 1H), 3.35 (m,1H), 1.37 (d, J = 6.8 Ηζ, 6H); Mass (FAB) m / z 439 [M+H]+<Ejemplo 56> (E)-3-(4-(3-chlorophenyl)-2cyclopropylthiazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Pale yellow solid, yield 78%; NMRτΗ (400MHz, DMSO) δΐθ.69 (s, 1H), 10.05 (s, 1H), 9.84 (s, 1H), 7.61 (s, 1H), 7.60 (d, J = 15.6 Ηζ, 1H), 7.56 -7.53 (m 3H), 108 7.17 (d, J = 8.0 Hz, 1H), 6.88 (t, J = 8.4 Hz, 1H), 6.73 (d, J = 7.2 Hz, 1H), 6.50 (d, J = 15.6 Hz, 1H), 1.21 (m, 3H), 1.10 (m, 2H); Mass (FAB) m / z 437[M+H]+<Ejemplo 57> (E)-3-(4-(3-chlorophenyl)-2-(1methylcyclopropyl)thiazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Pale brown solid, yield 66%; RMNXH (400MHz, DMSO) δ 10.68(s,1H), 10.03(s,1H), 9.81(s,1H), 7.59 (m, 1H), 7.58 (d, J = 15.2 Hz, 1H), 7.54 -7.49 (m,3H), 7.15 (d, J = 8.4 Hz, 1H), 6.86 (t, J = 8.0 Hz, 1H), 6.71 (d, J = 7.2 Hz, 1H), 6.51 (d, J = 15.2 Hz, 1H), 1.55 (s,3H), 1.31 (m, 2H), 1.08 (m, 2H); Mass (FAB) m / z 451 [M+H]+<Ejemplo 58> (E)-3-(2-(tert-butyl)-4-(3chlorophenyl)thiazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide Pale brown solid, yield 66%; RMNXH (400 MHz, DMSO) δ 10.66(s,1H), 10.01(s,1H), 9.82(s,1H), 7.67(d,J = 109 15.2 Hz, 1H) , 7.66 (m, 1H) , 7.58 (m, 3H) , 7.21 (d, J = 8.12 Hz, 1H) , 6.91 (t, J = 7.96 Hz, 1H) , 7.2 J) = 7.75 (m, 1H). 6.60 (d, J = 15.2 Hz, 1H), 1.46 (s, 9H) ; Mass (FAB) m / z 453 [M+H]+<Ejemplo 59> 3-(2-isobutoxy-6(triflucromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)propanoamide JO» Pale yellow solid, yield 86%; RMN1H (500 MHz, CDC13) δ 9.14 (s, 1H) , 8.16 (s, 1H) , 7.58 (d,J = 7.35 Hz, 1H) , 7.27 (s, 1H) , 7.16 (d, J = 7.40 Hz, 1H),6.93 (t, J = 7.90 Hz, 1H), 6.81 (d, J = 7.75 Hz, 1,8 (d) = 6.5. 4.16 (d, J = 6.45 Hz, 2H) , 3.05 (t, J =7.25 Hz, 2H), 2.74 (t, J = 7.25 Hz, 2H) , 2.11 (p, J = 6.70 Hz, 1H), 1.03 (d, J = 6.65 Hz, 6H) ; Mass (FAB) m / z 423 [M+H]+<Ejemplo 60> 3-(2-(cyclopropylmethoxy)-6(triflucromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)propanoimide White solid, Yield 77%; RMN4H (300 MHz, DMSO) δ 10.66 (s, 1H), 10.08 (s, 1H), 9.53 (s, 110 1H) , 7.80 (d, J = 7.50 Hz, 1H), 7.41 (d, J = 6.00 Hz, 1H) , 7.07 (d, J = 8.25 Hz, 1H), 6.87 (t, J = 7.86 Hz, 7. d, 6 =H7) 2 1H), 4.20 (d, J = 6.96 Hz, 2H), 2.96 (t, J = 7.14 Hz. 2H), 2.70 (t, J = 7.50 Hz, 2H) , 1.28 (m, 1H), 0.55 (q, J = 5.70 Hz, 2H) , 0.40 (q, J = 5.70 Hz, 2H); Mass (FAB) m / z 421 [M + H]+<Ejemplo 61> 2-(2-isobutoxy-6(trifluoromethyl)pyridine-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)cyclopropane-l-carboxamide Solid pale amarillo, yield 72%; RMN1H (500 MHz, CDC13) δ 9.14 (s, 1H), 8.16 (s, 1H), 7.58 (d, J= 7.35 Hz, 1H) , 7.27 (s, 1H) , 7.16 (d, J= 7.40 Hz, 1H), 6.93 (t, J= 7.90 Hz, 1H) , 6.81 (d, J = 7.75 Hz, 1H) , 6.58 (d, J = 8.05 Hz, 1H) , 4.16 (d, J = 6.45 Hz, 2H) , 3.11 (s, 1H) , 2.89 (s, 1H), 2.11 (p, J = 6.70 Hz, 1H), 1.23 (m, 2H) , 1.03 (d, J = 6.65 Hz, 6H) , 0.89 (m, 1H) ; Masas (FAB) m / z 435 [M+H]+ 111<Ejemplo 62> 2-(2-(cyclopropylmethoxy)-6(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-yl)cyclopropan-l-carboxamida ινΐΛ / a / zuzz / uiu jo» White solid, yield 65%; RMN1H (300 MHz, DMSO) δ 10.66 (s, 1H), 10.08 (s, 1H), 9.53 (s, 1H), 7.80 (d, J = 7.50 Hz, 1H) , 7.41 (d, J = 6.00 Hz, 1H) , 7.07 (d, J = 8.25 Hz, 1H), 6.87 (t, J = 7.86 Hz, 1H) , 6.72 (d, J = 7.86 Hz, 1H) , 4.20 (d, J = 6.96 Hz, 2H) , 2.96 (t, J = 7.14 Hz . 2H), 2.70 (t, J = 7.50 Hz, 2H), 1.28 (m, 3H), 0.80 (m, 1H), 0.55 (q, J = 5.70 Hz, 2H), 0.40 (q, J = 5.70 Hz, 2H) ; Masas (FAB) m / z 433 [M+H]+<Ejemplo 63> 2-(1-(3-chlorofenil)-3(trifluorometil)-lH-pirazol-5-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)ciclopropan-l-carboxamida Sólido blanco, Rendimiento 78%; RMNΣΗ (400MHz, DMSO) δ 10.67 (s, 1H), 9.95 (s, 1H), 9.85 (s, 1H), 7.75 (s, 1H), 7.66-7.64 (t, J = 5.88 Hz, 1H), 7.57 (s, 2H), 7.07 (d, J 112 = 6.52 Hz, 1H), 6.90 (d, 1H), 6.87 (s, 1H), 6.74 (d, J = 6.16 Hz, 1H), 2.35 (m, 1H), 2.18 (m, 1H), 1.53 (t, J = 5.92 Hz, 2H), 1.23 (s, 2H), 0.80 (m, 1H); Masas (FAB) m / z 462 [M+H]+<Ejemplo 64> 2-(1-(3-chlorofenil)-3-(1,1difluoroetil)-lH-pirazol-5-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)ciclopropan-l-carboxamida ΜΛ / a / ZUZZ / U 1 U JO» Sólido amarillo, rendimiento 65%; RMN2Η (300 MHz, DMSO) δ 10.67 (s, 1H) , 9.95 (s, 1H) , 9.87 (s, 1H) , 7.63 (s, 1H) , 7.56 (m, 1H) , 7.46 (t, J = 8.22 Hz, 1H) , 7.41 (s, 1H) , 7.10 (d, J = 7.89 Hz, 1H) , 6.88 (t, J = 7.68 Hz, 1H) , 6.73 (d, J = 8.07 Hz, 1H) , 6.05 (s, 1H) , 1.23 (m, 1H) , 0.91 (m, 1H) , 0.67 (m, 3H) ; Masas (FAB) m / z 458 [M+H]+<Ejemplo 65> 2-(1-(3-clorofenil)-3-isopropil-lHpirazol-5-il)-N-(2-oxo-2,3-dihidro-lH-benzo[d]imidazol-4il)ciclopropan-l-carboxamida Sólido marrón pálido, rendimiento 60%; RMN1H 113 (300 MHz, DMSO) δ 10.67 (s, 1H), 9.98 (s, 1H), 9.89(s, 1H) , 7.64 (s, 1H) , 7.59 (d, J = 7.68 Hz, 1H), 7.48 (t, J = 8.25 Hz, 1H), 7.42 (m, 1H), 7.16 (d, J = 8.04 Hz,1H), 6.88 (t, J = 7.53 Hz, 1H) , 6.72 (d, J = 7.62 Hz,1H), 6.21 (s, 1H) , 2.30 (m, 1H), 2.19 (m, 1H), 1.74 (s,2H), 1.51 (m, 1H), 1.23 (d, J = 6.78 Hz, 6H) ; Masas (FAB) m / z 436 [M+H]+<Ejemplo 66> 2-(l-(3-chlorofenil)-3-ciclopropillH-pirazol-5-il)-N-(2-oxo-2,3-dihidro-lH IVIA / a / ZUZZ / UIU JO» benzo[d]imidazol-4-il)ciclopropan-l-carboxamida RMN4H (300 (MHz, DMSO) δ 10.67 7.64 (s, 1H), 7.57 7.42 (m, 2H), 7.10 7.68 Hz, 1H), 6.73 2.32 (m, 1H) , 2.08 (s, 1H) , 9.98 (s, (m, 2H) , 7.49 (t, (d, J = 7.86 Hz, (d, J = 7.68 Hz), (m, 1H) , 1.95 (m, 1H), 9.89 (s, 1H), J = 8.25 Hz, 2H), 1H), 6.88 (t, J = 1H), 6.05 (s, 1H), 2H), 1.51 (m, 1H), 0.89 (m, 2H), 0.67(m, 2H); Masas (FAB) m / z 434 [M+H]+ 114<Ejemplo 67> 2-(1-(3-chlorofenil)-3-(1metilciclopropil)-lH-pirazol-5-il)-N-(2-oxo-2,3-dihidro-lHbenzo[d]imidazol-4-il)ciclopropan-l-carboxamida Sólido amarillo, rendimiento 73%; RMN (300 MHz, DMSO) δ 10.68 (s, 1H) , 9.96 (s, 1H) , 9.87 (s, 1H) , 7.64(s, 1H) , 7.57 (m, 1H) , 7.49 (t, J = 8.25 Hz, 1H) , 7.42 (m,1H) , 7.10 (d, J = 7.86 Hz, 1H) , 6.88 (t, J = 7.68 Hz, 1H) ,6.73 (d, J = 7.68 Hz, 1H) , 6.12 (s, 1H) , 1.40 (s, 3H) , 0.91(s, 2H), 0.74 (s, 2H); Masas (FAB) m / z 448 [M+H]+<Ejemplo 68> 2-(3-(terc-butil)-1-(3-clorofenil)-1Hpirazol-5-il)-N-(2-oxo-2,3-dihidro-lH-benzo[d]imidazol-4il)ciclopropan-l-carboxamida Sólido amarillo, rendimiento 82%; RMN (400 MHz, DMSO) δ 10.67 (s, 1H) , 9.93 (s, 1H) , 9.85 (s, 1H) , 7.64 (s, 1H) , 7.60 (d, J = 6.92 Hz, 1H) , 7.51 (t, J = 8.00 Hz, 1H) , 7.44 (d, J = 6.92 Hz, 1H) , 7.11 (d, J = 8.08 Hz, 1H) , 6.89 115 (t, J = 7.96 Hz, 1H) , 6.74 (d, J = 7.76 Hz, 1H) , 6.22 (s, 1H) , 2.32 (m, 1H) , 2.13 (m, 1H) , 1.53 (m, 1H) , 1.42 (m, 1H) , 1.27 (s, 9H) ; Masas (FAB) m / z 450 [M+H]+ The chemical formulas of the compounds prepared in Examples 1-68 are summarized and shown in Table 1 below. Table 1 ΜΛ / a / zuzz / u uóoa 116 IVIA / a / ZUZZ / UIU ME” 117 MA / S / ZUZZ / UI AND I” 118 ΜΛ / a / ZUZZ / UIU ME” 119 22 F 56 Λ ° Vs H 23 V oh HnH N sAqkxz NNH 0. o A 57 o Vs µ HN-^ JW-ú 24 OH h tC ov A 58 _V o Í-SH Νγ^γΝ^ΧΝ6 o 2 „ 25 FC , 25 FC 27 _ _ or 61 o 120 121 <Ejemplo Comparativo 1> Preparation of 1-(2-oxo1,3-dihydrobenzimidazol-4-yl)-3-[[2-pyrrolidin-l-yl-6(trifluoromethyl)-3-pyridyl]methyl]urea The compound of Example 39 described in Korean Patent Publication No. Compound 10-2013-0065634 (WO docket 2011 / 120604 Al) was prepared as the Comparative Example 1 compound. <Ejemplo Comparativo 2>Preparation of 1—[[2—isopropoxy-6-(trifluoromethyl)-3-pyridyl]methyl]-3-(2-oxo-1,3-dihydrobenzimidazol-4-yl)urea The compound of Example 68 described in the Korean Patent Publication No. 10-2013-0065634 (document 122 WO 2011 / 120604 Al) was prepared as the compound of Comparative Example 2. <Ejemplo Comparativo 3> Preparation of 1-(2-oxo1,3-dihydrobenzimidazol-4-yl)-3-[[2-(1-piperidyl)-6-(triflucromethyl)-3-pyridyl]methyl]urea The compound of Example 71 described in Korean Patent Publication No. 10-2013-0065634 (document WO 2011 / 120604 Al) was prepared as the compound of Comparative Example 3. <Ejemplo Experimental 1> Evaluation of antagonism against TRPV1 receptor activators (vanilloid transient receptor potential subtype 1) (in vitro) As previously emphasized, the reported side effect of increased body temperature from first-generation TRPV1 antagonists developed to date is due to the antagonism of all TRPV1 receptor activators (capsaicin, heat, pH, NADA). Specifically, 100% pH blockade among TRPV1 receptor activators has been reported to cause an increase in body temperature. 123 Excessive body temperature, and blocking 20% ​​or less caused proton activation at a high concentration to cause an excessive decrease in body temperature. That is, in the development of TRPV1 antagonists, while blocking TRPV1 activation caused by capsaicin and heat, but inducing adequate inhibition of around 20% to 80% of the pH, it can have the effect not only of relieving pain but also of reducing side effects such as abnormal body temperature. It was subsequently evaluated whether the example compounds provided in one aspect of the present invention could block the activation of TRPV1 caused by capsaicin, but induce appropriate inhibition at approximately 20% to 80% pH, thereby relieving pain as well as reducing side effects such as abnormal body temperature. We sought antagonism to capsaicin and pH, the activators of the hTRPV1 receptor, and set the target IC50 (CAP) < 15 nM (efficacy) and 80% inhibition at pH=6 (no hyperthermia). This is because the IC50 (CAP) of Mavatrep, a clinical control drug, was investigated at 13.8 nM in our own experiment, and when pH antagonism was less than 80% inhibition, no hyperthermia was considered to have occurred. 124 Ca2+ penetration test PreciSION™ hTRPV1-HEK recombinant cells (CYL3063) from Millipore were acquired and used as cells for the human TRPV1 (hTRPV1) antagonist assay. DME / F-12 (HyClone) (10% FBS, 1% NEAA, 1% penicillin-streptomycin) was used as the medium, and Fluo4-NW (Molecular Probes, F-36206) as the ELISA kit. After culturing the cells at 37°C and 5% CO2, they were inoculated into a 96-well plate at a density of 5 × 10⁴ cells / well and cultured for 16 hours. The medium was then removed, and 100 pL of a staining solution was added to each well, followed by culturing for 30 minutes at 37°C and 5% CO2. Next, the cells were acclimated to room temperature for 15 minutes and the test substances (example compounds and comparative example compounds of the present invention) were added to each well, followed by culturing at room temperature for 15 minutes.After diluting capsaicin (Sigma, M2028) to a concentration of 10 nM, it was placed in each well of the plate and fluorescence was measured (ex485 / em535). In the previous experiment, the drug's efficacy was evaluated using BCTC as a representative TRPV1 antagonist. Evaluation of human pH inhibitory activity Precision™ hTRPVl-HEK recombinant cells 125 (CYL3063) cells were purchased from Millipore and used. After culturing the above cells under conditions of 37°C and 5% CO2, the cells were inoculated into a 96-well plate at a density of 5 x 10⁴ cells / well, followed by culturing for 16 hours. The medium was then removed, and 100 pL of a staining solution was placed in each well, followed by culturing for 30 minutes under conditions of 37°C and 5% CO2. After 30 minutes, all existing staining solution was removed and replaced with 100 pL of HBSS. The cells were then acclimated to room temperature for 15 minutes, and the test substances (example compounds and comparative example compounds of the present invention) were added to each well, followed by culturing at room temperature for 15 minutes. Then, the final pH was adjusted to 6.0 using MES and fluorescence was measured (ex485 / em535).In the pH assay, the efficacy of the drug was evaluated using BCTC as a TRPV1 antagonist. The results of the in vitro test of<Ejemplo experimental 1> were combined with the results of the in vivo test of<Ejemplo experimental 2> , which are shown in Table 2 below. <Experimental Ejemplo 2> Bioavailability assessment (BA) Potency, ADME, and toxicity properties are important for new drug candidates, and as For pharmacokinetic properties, drugs must have a blood concentration profile above a certain level, and based on this, it is crucial to verify if the PK-PD correlation is good. Using the pharmacokinetic parameters of new drug candidates obtained from experimental animals such as rats or mice, the blood concentration and drug efficacy can be predicted in humans through allometric scales or pharmacokinetic prediction. To do this, it is important to measure C1 and Vss, which determine the dose and administration interval, and obtain PK parameters such as Cmax, ti / 2, and AUCall during oral administration. Furthermore, basic information related to metabolic enzymes, transporters, and tissue distribution of candidate substances can be obtained, and inappropriate physical properties can be estimated.The information obtained through the analysis can provide important decision criteria for deriving an optimal candidate, as well as help in the molecular design and development of more efficient drugs. Test method SD rats (Coatec, Hana Trading Co., Ltd., 7–8 weeks old, male, n = 4, 250–300 g) were used for the experiment. The rats were reared in a small animal breeding facility (animal experimentation center) maintained at a temperature of 22 ± 2°C, a relative humidity of 50–15%, and a IVIA / a / ZUZZ / UIU JO» 127. Lighting time of 12 hours (08:00 ~ 20:00), and a lighting intensity of 150 to 300 lux. Food was provided free of charge throughout the test period, and reverse osmosis water was provided free of charge. Before oral administration of the test substances (example compounds and comparative example compounds of the present invention), the rats were kept fasted for 16 hours. The dosage of the example compounds and the comparative example compounds of the present invention was 5 mg / kg when administered intravenously and 10 mg / kg when administered orally. For intravenous administration, a clear solution was administered in which 10% DMSO, 10% Cremophor EL, and 80% PEG400 were dissolved. For oral administration, a solution or suspension was administered in which 10% DMSO and 10% Cremophor EL were dissolved in 80% DDW. After intravenous or oral administration, blood was collected at 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours and 8 hours, and the concentrations of the test substances (example compounds and comparative example compounds of the present invention) in plasma were measured by LC-MS / MS. After adding 80 μA of acetonitrile (including internal standard) to 20 μA of plasma, a MA / a / ZUZZ / UI U JO» 128 centrifugation for 5 minutes at 15,000 rpm at 4 °C with vortex shaking. The supernatant obtained after centrifugation was analyzed by LC-MS / MS. For HPLC, the Nexera XR system (Shimadzu, Japan) was used, and for the mass spectrometer, the TSQ Vantage triple quadrupole system (Thermo, USA) was used. IVIA / a / ZUZZ / UIU JO» 1) HPLC condition HPLC system Nexera XR system (Shimadzu, Japan) Kintex XB-C18 column (2.1 x 100 mm, 2.6 µl particle size: Phenomenex, USA) Injection volume 2 µl (A) 0.1% formic acid in water Mobile phase (B) 0.1% formic acid in acetonitrile Sample analysis time 3 - 3.5 min Retention time 2 - 2.06 min ® Mass spectrometry condition TSQ vantage Triple Quadrupole Analysis System (Thermo, USA) Ion source time Turbo spray ionization The PK parameters were calculated using a non-compartmental analysis model with the Phoenix WinNonlin program version 6.4 (Pharsight, USA). The AUC (area under the plasma concentration-time curve) up to 8 hours was calculated from the measured plasma concentration using the trapezoidal rule, and the oral absorption rate (F%) was calculated 129 from the relationship with the AUC when the same dose was administered intravenously. The AUC was calculated using the linear trapezoidal rule in the phase of increasing plasma level and the logarithmic trapezoidal rule in the decreasing phase. The results are shown in Table 2 below. Table 2 Test substance hTRPVl IC50 [cap] , nM hTRPVl pH(%, 3μM) Bioavailability F (%) Example 1 36.96 78.62 Example 2 28.76 86.72 Example 3 15.74 52.56 13.2 Example 4 11.33 49.86 12.5 Example 5 16.26 94.79 Example 6 10.65 76.92 Example 7 23.30 89.87 Example 8 27.34 81.24 Example 9 >50 NT Example 10 12.95 53.26 25.9 Example 11 37.84 88.23 Example 12 31.47 81.25 Example 13 13.74 30.67 35.6 Example 14 34.5 94.03 130 Example 15 201.7 NT Example 16 86.0 97.34 Example 17 56.9 83.20 5 Example 18 116.8 NT Example 19 409.8 NT Example 20 53.5 86.79 Example 21 26.1 79.89 Example 22 31.2 90.86 10 Example 23 217.2 NT Example 24 Example 25 34.10 89.76 Example 26 54.41 95.11 15 Example 27 40.87 78.45 Example 28 >100 NT Example 29 >100 NT Example 30 14.25 48.62 Example 31 26.01 82.34 20 Example 32 23.72 67.88 Example 33 27.44 69.89 Example 34 11.09 37.85 Example 35 11.76 95.87 Example 36 11.04 100.46 MA / a / zuzz / ui uóoa 131 Example 37 Example 38 Example 39 35.4 67.89 Example 40 177.5 NT Example 41 123.1 NT Example 42 35.42 78.89 Example 43 19.66 87.68 Example 44 Example 45 79.3 48.71 Example 46 72.9 57.38 Example 47 15.89 37.26 Example 48 9.95 29.43 Example 49 19.90 21.37 Example 50 41.28 34.22 Example 51 >160 NT Example 52 >160 NT Example 53 79.78 78.21 Example 54 55.7 63.44 Example 55 >160 NT Example 56 26.04 68.23 Example 57 39.81 61.78 Example 58 102.98 NT 132 Example 59 40.71 59.32 Example 60 23.66 67.19 Example 61 Example 62 Example 63 10.33 0.53 Example 64 >160 NT Example 65 >160 NT Example 66 >160 NT Example 67 >160 NT Example 68 138.88 NT Comparative Example 1 18.45 0.78 2.3 Comparative Example 2 23.37 1 Comparative Example 3 13.50 82.51 3.0 *NT = Not Tested As shown in Table 2, the example compounds provided in one aspect of the present invention block the activation of TRPV1 caused by capsaicin, but induce appropriate inhibition at approximately 20% to 80% pH, so the compounds have pain-relieving effects and reduce side effects such as IVIA / a / ZUZZ / UIU JO» 133 abnormal body temperature. Furthermore, it was confirmed that the compounds of the present invention have a high pK value, so that the example compounds are easily absorbed into the body and, therefore, thermoneutrality is also maintained. On the other hand, the compounds in Comparative Examples 1 to 3 block capsaicin-induced TRPV1 activation, but they inhibit the pH less or more than necessary, that is, outside the appropriate range of 20% to 80%. Furthermore, it was confirmed that the compounds in the comparative examples have a low pKa value and, therefore, are not readily absorbed by the body, making them difficult to use as effective analgesics. <Ejemplo de Manufacturación 1> Powder preparation Derivative represented by the formula 1 2 g Lactose 1 g The powders were prepared by mixing all the above components, which were then filled into hermetically sealed packages. <Ejemplo de Manufacturación 2> tablet preparation Derivative represented by the formula 1 100 mg Corn starch 100 mg ML / a / ZUZZ / UI U0O» 134 Lactose 100 mg Magnesium stearate 2 mg The tablets were prepared by mixing all the above components using the conventional method for preparing tablets. <Ejemplo de Manufacturación 3> Capsule preparation Derivative represented by the formula 1 100mg Corn starch 100mg Lactose 100mg Magnesium stearate 2mg The capsules were prepared by mixing all the above components, which were then filled into gelatin capsules in accordance with the conventional method for preparing capsules. <Ejemplo de Manufacturación 4>Preparation of injectable solutions U JO» Derivative represented by the formula 1 100 mg Mannitol 180 mg Na2HPO4· 2H2O 2 6 mg Distilled water 2974 mg The injectable solutions were prepared containing all the above components in the indicated amounts in accordance with the conventional method for preparing injectable solutions. 135<Ejemplo de Manufacturación 5> Preparation of MA / a / ZUZZ / UI U JO» functional foods for health Derivative represented by the formula 1 500 mg 5 10 15 20 Vitamin complex appropriate amount Vitamin A acetate 70 mg Vitamin E 1.0 mg Vitamin B6 0.13 mg Vitamin B2 0.15 mg Vitamin B6 0.5 mg Vitamin B12 0.2 mg Vitamin C 10 mg Biotin 10 mg Nicotinamide 1.7 mg Folic acid 50 mg Calcium pantothenate 0.5 mg Minerals appropriate amount Ferrous sulfate 1.75 mg Zinc oxide 0.82 mg Magnesium carbonate 25.3 mg Potassium phosphate, monobasic 15 mg Calcium phosphate, dibasic 55 mg Potassium citrate 90 mg Calcium carbonate 100 mg Magnesium chloride 24.8 mg 25 The vitamins and minerals appropriate for food 136 functional health ingredients were mixed according to the preferred mixing ratio, but the composition ratio can be adjusted arbitrarily. After mixing the above components according to the conventional method for preparing functional health foods, the granules were prepared and used for the preparation of functional health foods according to the conventional method. <Ejemplo de Manufsaturación 6> Preparing healthy drinks Derivative represented by the formula 1 500 ng Citric acid 1000 mg Oligosaccharide 100g Maesil extract (Prunus mume) 2g Taurine 1g Purified water up to 900 MI The aforementioned constituents were mixed according to the conventional method for preparing health beverages. The mixture was heated to 85°C for 1 hour with stirring and then filtered. The filtrate was transferred to sterilized containers, which were sealed and sterilized again, and stored in a refrigerator until used for preparing a health beverage composition. The appropriate constituents for the beverages or jo» 137 favorites were mixed according to the preferred mixing ratio, but the composition ratio can be adjusted according to regional and ethnic preferences, such as demand class, demand country and purpose of use, etc. It is hereby stated that, as of this date, the best method known to the applicant for putting the aforementioned invention into practice is the one that is clear from the present description of the invention.

Claims

Having described the invention as above, the contents of the following claims are claimed as property: 3 > tu NCNNC -jc Ca σ A compound characterized in that it is represented by the same, a pharmaceutically acceptable solvate of the same, a stereoisomer of the same, a hydrate of the same: [Formula 1] X1 formula the (In the above, X1 and X2 form a cycloalkylene of the same, a C=C double bond of carbon to which they are attached or substituted with the carbon atom to which they are heteroatom N,O and S are by 3-6 bond with the atom members joined; unsubstituted heteroaryl containing selected from the group 5-10 members less than one bond consisting of substituted or unsubstituted Cs-io aryl 139 wherein the substituted 5-10 membered heteroaryl and Cs-io aryl are independently substituted 5-10 membered heteroaryl and Cs-io aryl with at least one substituent selected from the group consisting of linear or branched C1-12 alkyl substituted or unsubstituted with at least one halogen or hydroxy group, linear or branched C1-12 alkynyl, substituted or unsubstituted C3-10 cycloalkyl with at least one linear or branched C1-5 alkyl, substituted or unsubstituted 5-8 membered heterocycloalkyl with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NRlR2, -OR3, -SR4,Cg-ium aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-8 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched C1-10 alkyl, R3 is linear or branched C1-10 alkyl substituted or unsubstituted with at least one halogen, C3-10 cycloalkyl, or C3-10 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl, R4 is linear or branched C1-10 alkyl substituted or unsubstituted with at least one halogen, C3-10 cycloalkyl, or C3-10 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl).

2. The compound, the stereoisomer thereof, the solvate thereof, the hydrate thereof, or the pharmaceutically acceptable salt thereof according to claim 1, characterized in that: X1 and X2 are independently hydrogen,or form a C=C double bond by bonding with the carbon atom to which they are attached, or form a 3-5 membered cycloalkylene by bonding with the carbon atom to which they are attached; and is a substituted or unsubstituted 5-8 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, or a substituted or unsubstituted Ce-s aryl, wherein the substituted 5-8 membered heteroaryl and Cs-s aryl are independently a 5-8 membered heteroaryl and a substituted Ce-8 aryl with at least one substituent selected from the group consisting of a linear or branched Ci-io alkyl substituted or unsubstituted with at least one halogen or hydroxy group, a linear or branched Ci-io alkynyl, a substituted or unsubstituted C3-8 cycloalkyl with at least one linear or branched C1-5 alkyl,5-6 membered heterocycloalkyl substituted or unsubstituted 141 with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NR2R2, -OR3, -SR4, Cg-s aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-6 membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched Ci-s alkyl, R3 is linear or branched C1-8 alkyl substituted or unsubstituted with at least one halogen, C3-8 cycloalkyl, or C3-8 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl, R4 is linear or branched C1-8 alkyl substituted or unsubstituted with at least a halogen, C3-8 cycloalkyl, or C3-8 cycloalkyl, C1-5 linear or branched alkyl substituted or unsubstituted with at least one methyl group.

3. The compound, the stereoisomer thereof,the solvate thereof, the hydrate thereof, or the pharmaceutically acceptable salt thereof according to claim 1, characterized in that: X1 and X2 are independently hydrogen, or form a C=C double bond by bonding with the carbon atom to which they are attached, or form a 3-4 membered cycloalkylene by bonding 142 with the carbon atom to which they are attached; and is a substituted or unsubstituted 5-6 membered heteroaryl IVIA / a / ZUZZ / UIU JO» containing at least one heteroatom selected from the group consisting of N and S, or a substituted or unsubstituted Ce aryl, wherein the substituted 5-6 membered heteroaryl and Ce aryl are independently substituted 5-6 membered heteroaryl and Ce aryl with at least one substituent selected from the group consisting of a substituted or unsubstituted linear or branched C1-7 alkyl with at least one halogen or hydroxy group, or a linear or branched C7-7 alkynyl,C3-6 cycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl, 5-6 membered heterocycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NRXR2, -OR3, -SR4, Ce aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched C1-5 alkyl, 143 R3 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl, or C3-6 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with al less one methyl, R4 is a linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, a C3-6 cycloalkyl,or linear or branched C3-6 cycloalkyl C1-5 alkyl substituted or unsubstituted with at least one methyl group.

4. The compound, the stereoisomer thereof, the solvate thereof, the hydrate thereof, or the pharmaceutically acceptable salt thereof according to claim 1, characterized in that: X1 and X2 are independently hydrogen, or form a C=C double bond by bonding with the carbon atom to which they are attached, or form cyclopropylene by bonding with the carbon atom to which they are attached; and 144 145 5. The compound, the stereoisomer thereof, the solvate thereof, the hydrate thereof or the pharmaceutically acceptable salt thereof according to claim 1, characterized in that it is selected from the group consisting of the following compounds: (E)-3-(2-(4-methylpiperidin-1-yl)-6 (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1H benzo[diimidazol-4-yl)acrylamide; (2) (E)-3-(2-(4-ethylpiperidin-l-yl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[djimidazol-4-yl)acrylamida; (3) (E)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4- yl)-3-(2-(pyrrolidin-1-yl)-6-(trifluoromethyl)pyridin-3146 11)acrylamide; (4) (E)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3yl)acrylamida; (5) (E)-3-(2-morpholino-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2, 3-dihydro-1H-benzo[d]imidazol-4-yl)acrylamide; (6) (E)-3-(2-(diethylamino)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (7) (E)-3-(2-(dipropylamino)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (8) (E)-3-(2-butoxy-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)acrylamide; (9) (E)-3- (2- (hexiloxi)-6-(trifluoromethyl)pyridin- 3-yl)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4yl)acrylamida; (10) (E)-3-(2-isobutoxy-6-(trifluoromethyl)pyridin- 3-yl)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4yl)acrylamida; (11) (E)-3-(2-cyclobutoxy-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (12) (E)-3-(2-(cyclopentyloxy)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1H IVIA / a / ZUZZ / UIU JO» 147 benzo[diimidazol-4-yl)acrylamide; (13) (E)-3-(2-(cyclopropylmethoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[dJimidazol-4-yl)acrylamide; (14) (E)-N-(2-OXO-2,3-dihydro-1H-benzo[d]imidazol- 4-yl)-3-(2-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin3-yl)acrylamide; (15) (E)-3-(2-(neopentyloxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (16) (E) -3-(2-((2-methylcyclopropyl)methoxy)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (17) (E)-3-(6-(chlorodifluoromethyl)-2- (cyclopropylmethoxy)pyridin-3-yl)-N-(2-oxo-2, 3-dihydro-lHbenzo[dIimidazol-4-yl)acrylamide; (18) (E)-3- ( 6-cyclopropyl-2- (cyclopropylmethoxy)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[di imidazol-4-yl)acrylamide; (19) (E)-3-(2-(cyclopropylmethoxy)-6- isopropylpyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (20) (E)-3-(2-(cyclopropylmethoxy)-6- (1- methylcyclopropyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; 148 (21) (Ε)-3-(2-(cyclopropylmethoxy)-6- (difluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (22) (E) -3-(2-(cyclopropylmethoxy)-6-(1,1- difluoroethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[di imidazol-4-yl)acrylamide; (23) (E)-3-(6-(terc-butyl)-2-(cyclopropylmethoxy)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamida; (24) (E) -3-(2-(cyclopropylmethoxy)-6- (2- hidroxipropan-2-yl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamida; (25) (E)-3-(2-(cyclobutylmethoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (26) (E)-3-(2-(cyclopentylmethoxy)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (27) (E)-3-(2-(isobutylthio)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (28) (E)-3-(2-((cyclopropylmethyl)thio)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (29) (E)-3-(2-(cyclohexylthio)-6 IVIA / a / ZUZZ / UIU JO» 149 (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (30) (E)-3-(2-(3-fluorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[dJimidazol-4-yl)acrylamide; (31) (E)-3-(2-(3-chlorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (32) (E)-3-(2-(3-isopropylphenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (33) (E)-3-(2-(3-chloro-4-fluorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (34) (E)-3-(2-(4-fluorophenyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (35) (E)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol- 4 — i1)-3-(2-(thiophen-2-yl)-6-(trifluoromethyl)pyridin-3yl)acrylamida; (36) (E)-3-(2-(furan-2-yl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (37) (E)-3-(2-(oxazol-2-yl)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1H 150 benzo[djimidazol-4-yl)acrylamide; (38) (E)-3-(2-(oxazol-5-yl)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (39) (E)-3-(2-(3,3-dimethyl-l-butyn-l-yl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[diimidazol-4-yl)acrylamide; (40) (E)-3-(2-(3,3-dimethylbutyl)-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (41) (E)-3-(2-cyclopentyl-6-(trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-1Hbenzo[d]imidazol-4-yl)acrylamide; (42) (E)-3-(2-isobutoxy-4-(trifluoromethyl)phenyl)-N-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-4-yl)acrylamide; (43) (E)-3-(2-(cyclopropylmethoxy)-4-(trifluoromethyl)phenyl)-N-(2-oxo-2,3-dihydro-1Hbenzo[diimidazol-4-yl)acrylamide; (44) (E)-3-(2-(cyclopropylmethoxy)-4- (2- hydroxypropan-2-yl)phenyl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (45) (E)-3-(4-(tert-butyl)-2- (cyclopropylmethoxy)phenyl)-N-(2-oxo-2,3-dihydro-lHbenzo[di imidazol-4-yl)acrylamide; (46) (E)-3- (4-cyclopropyl-2 151 (cyclopropylmethoxy)phenyl)-N-(2-oxo-2,3-dihydro-lHbenzo[diimidazol-4-yl)acrylamide; (47) (E) -3-(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)acrylamide; (48) (E)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol- 4-yl)-3-(1-(m-tolyl)-3-(trifluoromethyl)-lH-pyrazol-5yl)acrylamide; (49) (E)-3-(1-(3-chloro-4-fluorophenyl)-3- (trifluoromethyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[diimidazol-4-yl)acrylamide; (50) (E) -3-(1-(3-isopropylphenyl)-3- (trifluoromethyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[di imidazol-4-yl)acrylamide; (51) (E)-3-(1-(3-chlorophenyl)-3-isopropyl-lH- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)acrylamide; (52) (E)-3-(1-(3-chlorophenyl)-3-(1- methylcyclopropyl)-lH-pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[diimidazol-4-yl)acrylamide; (53) (E) -3-(3-(tert-butyl)-1-(3-chlorophenyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)acrylamide; (54) (E)-3-(4-(3-chlorophenyl)-2- (trifluoromethyl)thiazol-5-yl)-N-(2-oxo-2,3-dihydro-lH IVIA / a / ZUZZ / UIU JO» 152 benzo[djimidazol-4-yl)acrylamide; (55) (E)-3-(4-(3-chlorophenyl)-2-isopropylthiazol-5- yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)acrylamide; (56) (E)-3- (4- (3-chlorophenyl)-2-cyclopropylthiazol-5- yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4-yl)acrylamide; (57) (E)-3-(4-(3-chlorophenyl)-2-(1- methylcyclopropyl)thiazol-5-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)acrylamide; (58) (E)-3- (2- (tert-butyl)-4-(3-chlorophenyl)thiazol- 5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)acrylamide; (5 9) 3- (2-isobutoxy-6-(trifluoromethyl)pyridin-3yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)propanoamide; (60) 3-(2-(cyclopropylmethoxy)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)propanoimide; (61) 2- (2-isobutoxy-6-(trifluoromethyl)pyridin-3- yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropan-l-carboxamide; (62) 2-(2-(cyclopropylmethoxy)-6- (trifluoromethyl)pyridin-3-yl)-N-(2-oxo-2,3-dihydro-lHbenzo[d]imidazol-4-yl)cyclopropan-l-carboxamide; (63) 2- (1- (3-chlorophenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazole-4 153 yl)cyclopropane-l-carboxamide; (64) 2- (1-(3-chlorophenyl)-3-(1,1-difluoroethyl)-1H- pyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropane-l-carboxamide; (65) 2- (1- (3-chlorophenyl)-3-isopropyl-lH-pyrazol-5- yl)-N-(2-oxo-2, 3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropan-l-carboxamide; (66) 2- (1- (3-chlorophenyl)-3-cyclopropyl-lH-pyrazol- 5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropan-l-carboxamide; (67) 2-(1-(3-chlorophenyl)-3-(1-methylcyclopropyl)-1Hpyrazol-5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropan-l-carboxamide; and (68) 2-(3-(tert-butyl)-1-(3-chlorophenyl)-lH-pyrazol5-yl)-N-(2-oxo-2,3-dihydro-lH-benzo[d]imidazol-4yl)cyclopropan-l-carboxamide.

6. The compound, the stereoisomer thereof, the solvate thereof, the hydrate thereof, or the pharmaceutically acceptable salt thereof according to claim 1, characterized in that: IVIA / a / ZUZZ / UIU JO» f is a substituted or unsubstituted 5-6-membered heteroaryl containing at least one heteroatom selected from the group consisting of N 154 ys, wherein the substituted 5-6-membered heteroaryl is a 5-6-membered heteroaryl substituted with two substituents selected from the group consisting of a linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen or hydroxy group, a linear or branched C1-7 alkynyl,C3-6 cycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl, 5-6 membered heterocycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NR2R2, -OR3, -SR4, Ce aryl substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched C1-5 alkyl, R3 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl, or C3-6 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl, R4 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl,or C3-6 cycloalkyl C1-5 linear or branched substituted or ML / a / ZUZZ / U 1 U JO» 155 unsubstituted with at least one methyl.

7. The compound, the stereoisomer thereof, the solvate thereof, the hydrate thereof, or the pharmaceutically acceptable salt thereof according to claim 1, characterized in that: / is substituted or unsubstituted pyridine, wherein the substituted pyridine is pyridine substituted with two substituents selected from the group consisting of linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen or hydroxy group, linear or branched C1-7 alkynyl, C3-6 cycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl, 5-6 membered heterocycloalkyl substituted or unsubstituted with at least one linear or branched C1-5 alkyl containing at least one heteroatom selected from the group consisting of N and O, -NR4R2, -OR3, -SR4,aryl C1-5 substituted or unsubstituted with at least one halogen or linear or branched C1-5 alkyl, and 5-membered heteroaryl containing at least one heteroatom selected from the group consisting of N, O and S, R1 and R2 are independently linear or branched C1-5 alkyl, R3 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl, or C3-6 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl, R4 is linear or branched C1-7 alkyl substituted or unsubstituted with at least one halogen, C3-6 cycloalkyl, or C3-6 cycloalkyl linear or branched C1-5 alkyl substituted or unsubstituted with at least one methyl.

8. A pharmaceutical composition for treating pain, characterized in that it contains the compound according to claim 1, a stereoisomer thereof, a solvate thereof,a hydrate thereof or a pharmaceutically acceptable salt thereof as an active ingredient.

9. The pharmaceutical composition for preventing or treating pain according to claim 8, characterized in that the compound exhibits pain-preventive or therapeutic activity by inhibiting activators of the TRPV1 receptor (vanilloid transient receptor potential subtype 1).

10. The pharmaceutical composition for preventing or treating pain according to claim 9, characterized in that the compound prevents or treats pain by suppressing capsaicin, an activator of the TRPV1 receptor (vanilloid transient receptor potential subtype 1), and inhibits pH in the range of 20% to 80% to reduce side effects such as abnormal body temperature.

11. An analgesic composition for treating or relieving pain, characterized in that it contains the compound according to claim 1, a stereoisomer thereof,11. A health-promoting functional food composition for preventing or ameliorating pain, characterized in that it contains the compound according to claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

12. A health-promoting functional food composition for preventing or ameliorating pain according to claim 12, characterized in that the compound exhibits pain-preventive or pain-ameliorating activity by inhibiting TRPV1 (vanilloid transient receptor potential 1) receptor activators.

13. The health-promoting functional food composition for preventing or ameliorating pain according to claim 12,characterized in that the compound prevents or improves pain by suppressing capsaicin, a TRPV1 (transient receptor potential vanilloid 1) receptor activator, and inhibits pH in the 20% to 80% range to reduce side effects such as abnormal body temperature.

15. A pharmaceutical kit for preventing or treating pain, characterized in that it comprises a first component containing the compound according to claim 1, a stereoisomer thereof, a solvate thereof, a hydrate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient; and a second component containing an analgesic as an active ingredient.