MX2007003121A

MX2007003121A - Compounds, compositions containing them, preparations thereof and uses thereof ii.

Info

Publication number: MX2007003121A
Application number: MX2007003121A
Authority: MX
Inventors: Christopher Walpole; Claire Milburn; Helene Desfosses; Hua Yang; John Wei; Daniel Page; Sanjay Srivastava
Original assignee: Astrazeneca Ab
Priority date: 2004-09-24
Filing date: 2005-09-22
Publication date: 2007-07-18
Also published as: UY29129A1; NO20072090L; BRPI0515876A; IL182021A0; AR053096A1; TW200626577A

Abstract

Compounds of Formulae I, or pharmaceutically acceptable salts thereof: (I)wherein R1, R2, R3, R4 and G are as definedin the specification as well as salts and pharmaceutical compositions includingthe compounds are prepared. They are useful in therapy, in particular in the managementof pain.

Description

DERIVATIVES OF BENZYMIDAZOLE, COMPOUNDS, COMPOSITIONS THAT CONTAIN THEM, PREPARATION AND USES OF THEMSELVES II FIELD OF THE INVENTION The invention is related to the therapeutic compounds, to the pharmaceutical compositions containing these compounds, to the manufacturing processes thereof and to the uses thereof. Particularly, the present invention is related to the compounds that may be effective in the treatment of pain, cancer, multiple sclerosis, Parkinson's disease, Huntington's chorea, Alzheimer's disease, anxiety disorders, gastrointestinal disorders and / or cardiovascular disorders. BACKGROUND OF THE INVENTION Pain management has been studied for many years. It is known that ligands of the cannabinoid receptor (eg, the CBi receptor, the CB2 receptor, including agonists, antagonists and inverse agonists produce pain relief in a variety of animal models by interaction with CBi and / or CB receptors. In general, CBi receptors are located predominantly in the central nervous system, whereas CB2 receptors are located mainly in the periphery and are mainly restricted to derived cells and tissues REF .: 180132 of the immune system. While CBi receptor agonists such as? 9-tetrahydrocannabinol (? 9-THC) and anadamide, are useful in anti-nociception models in animals, they tend to exert undesirable side effects in the central nervous system (CNS) ), for example, psychoactive side effects, the potential for abuse, dependence on drugs or drugs and tolerance to them, etc. These unwanted side effects are known to be mediated by CBi receptors located in the CNS. There are lines of evidence, however, that suggest that CBi agonists that act at peripheral sites or with limited exposure in the CNS can manage pain in humans or animals with a much improved overall in vivo profile. Therefore, there is a need for new CBi receptor ligands such as agonists that may be useful in the management of pain or treatment of other symptoms or related diseases, with unwanted, reduced or minimal side effects of the central nervous system. BRIEF DESCRIPTION OF THE INVENTION The present invention provides the CBi receptor ligands that may be useful in the treatment of pain and / or other related symptoms or diseases. The term "Cm_n" or "Cm-n group" used alone or as a prefix, it refers to any group that has m to n carbon atoms. The term "alkyl" refers to a straight chain or branched, monovalent, saturated hydrocarbon radical comprising 1 to about 12 carbon atoms. Illustrative examples of alkyl include, but are not limited to, alkyl groups of 1 to 4 carbon atoms, such as, methyl, ethyl, propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, Butyl, isobutyl, t-butyl. The term "cycloalkyl" refers to a saturated monovalent ring-containing hydrocarbon radical comprising at least 3 to about 12 carbon atoms. Examples of cycloalkyls include, but are not limited to, cycloalkyl groups of 3 to 7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, and saturated cyclic and bicyclic terpenes. A cycloalkyl can be unsubstituted or substituted with one or two suitable substituents. Preferably, the cycloalkyl is a monocyclic ring or bicyclic ring. The term "alkoxy" refers to the radicals of the general formula -O-R, wherein R is an alkyl. Exemplary alkoxy includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, t-butoxy, and isobutoxy.

The term "heterocycle" used alone or as a suffix or prefix, refers to a structure that contains a molecular structure that contains a ring that has one or more multivalent heteroatoms, independently selected from nitrogen, oxygen, phosphorus and sulfur, as a part of the ring structure, and including at least 3 and up to about 20 ring atoms. The heterocycle may be saturated or unsaturated, containing one or more double bonds, and the heterocycle may contain more than one ring. When a heterocycle contains more than one ring, the rings may be fused or not fused. The fused rings generally refer to at least two rings that share two atoms between them. The heterocycle may have an aromatic character or may not have an aromatic character. The heterocycle includes, for example, monocyclic heterocycles such as: aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, pyrroline, imidazolidine, pyrazolidine, pyrazoline, dioxolane, sulfolan-2, 3-dihydrofuran, 2,5-dihydrofuran. , tetrahydrofuran, thiophane, piperidine, 1, 2, 3, 6-tetrahydro-pyridine, piperazine, morpholine, thiomorpholine, pyran, thiopyran, 2,3-dihydropyran, tetrahydropyran, 1,4-dihydropyridine, 1,4-dioxane, 1 , 3-dioxane, dioxane, homopiperidine, 2,3,4,7-tetrahydro-lH-azepine, homopiperazine, 1,3-dioxepane, 4,7- dihydro-1, 3-dioxepine, and hexamethylene oxide. In addition, the heterocycle includes aromatic heterocycles, for example, pyridine, pyrazine, pyrimidine, thiophene, furan, furazano, pyrrole, imidazole, thiazole, oxazole, pyrazole, isothiazole, isoxazole, 1,2,3-triazole, tetrazole, 1,2 , 3-thiadiazole, 1,2,3-oxadiazole, 1, 2,4-triazole, 1, 2,4-thiadiazole, 1,2,4-oxadiazole, 1,3-triazole, 1,3, - thiadiazole, and 1,3,4-oxadiazole. In addition, the heterocycle embraces polycyclic heterocycles, for example, indole, indoline, isoindoline, quinoline, tetrahydroquinoline, isoquinoline, tetrahydroisoquinoline, 1,4-benzodioxane, coumarin, dihydrocoumarin, benzofuran, 2,3-dihydrobenzofuran, isobenzofuran, chromene, chroman, isochromane, xanthene, phenoxathine, thianthrene, indolizine, isoindol, indazole, purine, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, phenanthridine, perimidine, phenanthroline, phenazine, phenothiazine, phenoxazine, 1,2-benzisoxazole, benzothiophene, benzoxazole, benzthiazole, benzimidazole, benztriazole, thioxanthine, carbazole, carboline, acridine, pyrolizidine, and quinolizidine. In addition to the polycyclic heterocycles described above, the heterocycle includes polycyclic heterocycles wherein ring fusion between two or more rings includes more than one bond common to both rings, and more of two atoms common to both rings. Examples of such bridged heterocycles include quinuclidine, diazabicyclo [2.2.1] heptane and 7-oxabicyclo [2.2.1] heptane. Preferably, the heterocycle is a monocyclic or bicyclic ring1, more preferably a monocyclic ring, wherein the ring comprises from 2 to 6 carbon atoms, and from 1 to 3 heteroatoms, referred to herein as a heterocycle of 2 to 6 carbon atoms . The term "heterocycloalkyl" used alone or as a suffix or prefix, refers to a monocyclic or polycyclic ring comprising carbon and hydrogen atoms, and at least one heteroatom preferably 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, and It has no instauration. Examples of heterocycloalkyl groups include pyrrolidinyl, pyrrolidino, piperidinyl, piperidino, piperazinyl, piperazino, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, and pyranyl. A heterocycloalkyl group can be unsubstituted or substituted with one or two suitable substituents. Preferably, the heterocycloalkyl group is a monocyclic or bicyclic ring, more preferably, a monocyclic ring, wherein the ring comprises from 2 to 5 carbon atoms and from 1 to 3 heteroatoms, referred to herein as heterocycloalkyl of 2 to 5 carbon atoms. carbon. The term "heterocyclyl" refers to a radical monovalent derived from a heterocycle by removing a hydrogen from it. Halogen includes fluorine, chlorine, bromine, and iodine. "TA" or "ta" means room temperature. "Acyl" refers to -C (= 0) -R, where R is an alkyl. Acyl groups of 2 to 5 carbon atoms include, for example, acetyl, propionyl, 2,2-dimethylpropionyl, and methyl-propionyl. "Link", "linked" or "link", unless otherwise specified, means linked or covalently linked. DETAILED DESCRIPTION OF THE INVENTION In one aspect, one embodiment of the invention provides a compound of the formula I, a pharmaceutically acceptable salt thereof, the diastereoisomers, enantiomers or mixtures thereof: Wherein: G is selected from -O-, -CHF-, and -CF2-; R1 is heterocyclyl of 2 to 6 carbon atoms, in wherein the heterocyclyl of 2 to 6 carbon atoms includes at least one nitrogen on the heterocyclyl ring of 2 to 6 carbon atoms, at least one of nitrogen, is directly linked to the sulfonyl group of the formula I, and the heterocyclyl of 2 to 6 carbon atoms, is optionally substituted with one or more groups selected from halogen, hydroxyl, R5-C (= 0) -, R5-C (= 0) -NH-, R5R6-NH-C (= 0) -, R5R6-NH-C (= 0) -NH-, R5-0-C (= 0) -, R5-0-C (= 0) - NH-, alkoxy of 1 to 6 carbon atoms and alkylamino of 1 to 6 carbon atoms, wherein R 5 and R 6 are independently selected from -H, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, alkenyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 2 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms halogenated, and hydroxy- (alkyl of 1 to 6 carbon atoms); and R2, R3 and R4 are independently selected from fluoro and methyl. In still another embodiment, the compounds are those of the formula I, wherein G is selected from -O- and -CF2-; R1 is heterocycloalkyl of 2 to 6 carbon atoms, wherein the heterocycloalkyl of 2 to 6 carbon atoms includes at least one nitrogen on the heterocycloalkyl ring of 2 to 6 carbon atoms, one at less than one nitrogen is directly linked to the sulfonyl group of the formula I, and the heterocycloalkyl of 2 to 6 carbon atoms, is optionally substituted with one or more groups selected from halogen, hydroxyl, R5-C (= 0) -, R5 - C (= 0) -NH-, R5R6-NH-C (= 0) -, R5R6-NH-C (= 0) -NH-, R5-0-C (= 0) -, R5-0-C (= 0) - NH-, alkoxy of 1 to 6 carbon atoms and alkylamino of 1 to 6 carbon atoms, wherein R 5 and R 6 are independently selected from -H, alkyl of 1 to 6 carbon atoms, alkenyl from 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, heterocycloalkyl of 2 to 5 carbon atoms, alkyl of 1 6 carbon atoms halogenated, and hydroxy- (alkyl of 1 to 6 carbon atoms); and R2, R3 and R4 are independently selected from fluoro and methyl. Yet another embodiment of the invention provides a compound of the formula I, wherein G is selected from -0- and -CF2-; R1 is selected from heterocycloalkyl of 3 to 5 carbon atoms, and heteroaryl of 2 to 5 carbon atoms, wherein the heterocycloalkyl of 3 to 5 carbon atoms or the heteroaryl of 3 to 5 carbon atoms, includes at least one atom of nitrogen on the heterocycloalkyl rings of 3 to 5 carbon atoms or heteroaryl rings of 2 to 5 carbon atoms, respectively, one of at least one nitrogen is directly linked to the sulfonyl group of the formula I, and the heterocycloalkyl of 3 to 5 carbon atoms or the heteroaryl of 2 to 5 carbon atoms are optionally substituted with one or more groups selected from halogen, alkoxy from 1 to 3 carbon atoms, alkylamino of 1 to 3 carbon atoms and acylamino of 2 to 5 carbon atoms; R2, R3 and R4 are independently selected from fluoro and methyl. A further embodiment of the invention provides a compound of the formula I, wherein G is selected from -O- and -CF2-; R1 is selected from piperidinyl, imidazolyl, pyrazolyl, morpholinyl, pyrrolidinyl, azetidinyl, and isoxazolidinyl, wherein the piperidinyl, imidazolyl, pyrazolyl, morpholinyl, pyrrolidinyl, azetidinyl, and isoxazolidinyl are optionally substituted with one or more groups selected from fluoro and acylamino from 2 to 5 carbon atoms; R2, R3 and R4 are selected from fluoro and methyl, with the proviso that R2, R3 and R4 are the same. A further embodiment of the invention provides a compound of formula I, wherein G is selected from -0- and -CF2-; Where the groups They are optionally replaced R 'R and R are selected from fluoro and methyl, with the proviso that R2, R3 and R4 are the same. A further embodiment of the invention provides a compound selected from The pharmaceutically acceptable salts thereof. In another embodiment, the compound of the formula I, is selected from: N- (l- { [ {2-tert-butyl-l- [(, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl}. (Methyl) amino] sulfonyl.}. piperidin-4-yl) acetamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylazetidin-1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylpyrrolidin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylmorpholin-suphonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperidin-1-suifonamide; N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl) -N-methylpiperidin-1-sulfonamide; N- [2- (1,1-difluoroethyl) -1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide; N- (l- { [[2- (1,1-difluoroethyl) -1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl. piperidin-4-yl) acetamide; l-. { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl) -N-cyclopropylpiperidine-4-carboxamide; l-. { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl-N-isopropylpiperidin-4-carboxamide; l- { [[ 2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.) - N -cyclobutylpiperidine-4-carboxamide; l- { [ [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl) -N-cyclopentyl-piperidine-4-carboxamide, 1-1 [[ 2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl) -N-pyrrolidin-1- ilpiperidin-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl) -N-lH-pyrrol-1-ylpiperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethylpiperidine-4-carboxy ida; N- (tert-butyl) -l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl) -N, N-dimethylpiperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-diethylpiperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methylpiperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.] - N-propylpiperidine-4-carboxamide; N-butyl- l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl] piperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (2,2,2-trifluoroethyl) piperidin -carboxamide; N-alil-l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isobutylpiperidin-4-carboxamide; l-[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (2-hydroxy-l-methylethyl) piperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl) -N- (2-hydroxyethyl) piperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} ethyl piperidin-4-carboxylate; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.] Azetidin-3-yl ) cyclopropanecarboxamide, N- (1- { 1 [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl. azetidin-3-yl) -2-methylpropanamide; N- (l- { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -IH- benzimidazol-5-yl] (methyl) amino] sulfonyl} azetidin-3-yl) cyclobutanecarboxamide; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] Azetidin-3 -butanamide; N- (l- { [[2-tert-butyl-l- (tetrahydro-2H-? iran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.] azetidin -3-yl) propanamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl. methyl azetidine-3-carboxylate, N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] hexahydro-N- methyl-lH-azepin-1-sulfonamide; N- [2- (1,1-dimethylethyl) -1- [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -N, -dimethyl-l-piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1- [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -3- (hydroxymethyl) -N-methyl-1- piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -4-hydroxy-N-methyl-1-piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -4-methoxy-N-methyl-1-piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1- [(tetrahydro-2H-pyran-4-yl) methyl] -lH-benzimidazol-5-yl] -3-hydroxy-N-methyl-1-piperidine sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4,4-difluoro-N-methylpiperidin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -3,3-difluoro-N-methylpyrrolidin-1-sulfonamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} methyl piperidin-4-carboxylate; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide; (4R) -N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-hydroxy-N, 4-dimethylisoxazolidin-2-sulfonamide; N- (l- { [[2-tert -Butyl-l- (tetrahydro-2H-? Iran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} Piperidin- 4-yl) acetamide; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] Piperidin-4 -yl) -2, 2-dimethylpropanamide; [1- (. {Methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperidin-4-yl] carbamate of tert-butyl; 4- (. {Methylf [l- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperazine-1-carboxylate of ter- butyl; 4-. { [(cyclopropylamino) carbonyl] amino} -N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -1H-benzimidazol-5-yl] piperidin-1-suifonamide; N-cyclopropyl-4- (. {Methyl [[1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperazin-1 -carboxamide; 4-. { [(isopropylamino) carbonyl] amino} -N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperidin-1-sulfonamide; N-isopropyl-4- (. {Methyl} 1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperazin-1- carboxamide; N- [1- ( { Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperidin-4-yl ] acetamide; 2, 2-dimethyl-N- [1- (. {Methyl} [[1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -benzimidazol-5-yl] amino.} Sulfonyl) piperidin-yl] propanamide; 2-methyl-N- [l- ( { Methyl [[1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperidin-4-yl] propanamide; 4-Acetyl-N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide; 4- (2,2-dimethylpropanoyl) -N-methyl-N-. { 1- (Tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide; N- (l- { [ {2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} - (methyl) amino] sulfonyl. piperidin-4-yl) acetamide; N- (l- { [ {2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl.} - (methyl) amino] sulfonyl.] Piperidin -4-yl) -2,2-dimethylpropanamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methylmorpholin-4-sulfonamide; N-. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl) -N-methylpyrrolidin-1-suifonamide; N-. { 2-Ten-butyl-l- [(4, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} 3, 3-difluoro-N-methylpyrrolidin-1-sulfonamide; N-. { 2-tert-butyl-l- [(, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-i1-N-methylisoxazolidin-2-suifonamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -4, 4-difluoro-N-methylpiperidin-1- sulfonamide; 4-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl (methyl) amino] sulfonyl} tert-butyl piperazin-1-carboxylate; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-isopropylpiperazine-1-carboxamide; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-methylpiperazine-1-carboxamide; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclopropylpiperazine-1-carboxamide; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl) -N-cyclobutylpiperazine-1-carboxamide; N-. { 2-tert-butyl-l- [(, 4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-4-. { [(methylamino) carbonyl] amino} piperidin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-suifonamide; 4-Acetyl-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperazin-1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -4- (2,2-dimethylpropanoyl) -N-methylpiperazine- 1-suifonamide; 4-benzoyl-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazin-1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4- (3-methylbutanoyl) piperazine-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (cyclopropylcarbonyl) -N-methyl-piperazine-1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4-propionylpiperazine-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-isobutyryl-N-methyl-piperazine-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (cyclobutylcarbonyl) - N -methylpiperazine-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-butyryl-N-methylpiperazine-1-sulfonamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-dimethylpiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- isopropylpiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] suifoni1} -N-cyclopentylpiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methylpiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropylpiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclobutylpiperazine-1-carboxamide; N- (tert-butyl) -4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-l-carboxamide; N-butyl-4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-1-carboxamide; N-allyl-4- [[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methylamino] sulfonyl.] Piperazine-l-carboxamide; - { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.} - N -ethylpiperazine-l-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.] - N-propylpiperazine-1-carboxamide; . [[2-tert-Butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl] -. N- (cyclopropylmethyl) piperazine-1- carboxamide; N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -4- (1H-imidazol-1-ylcarbonyl) -N-methylpiperazine- 1-suifonamide; 4- {[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl}. Piperazine- isopropyl l-carboxylate; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl pyrrolidin-3-acetamide, N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl)] amino] sulfonyl, pyrrolidin-3-yl) -2,2-dimethylpropanamide, N- (l-. {[[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H] -benzimidazol-5-yl] (methyl) amino] sulfonyl.} azetidin- 3-yl) acetamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methy1-lH-imidazole-l-sulfonamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-lH-1, 2,4-triazole-1-suifonamide; N-. { 2-Ten-butyl-l- [(, 4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl) -N-methyl-lH-1,2, 3-triazole-l-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-formyl-N-methyl-1 H-pyrazole-1-sulfonamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropy1-1H-pyrazole-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethyl-lH-pyrazole-4-carboxamide; N-alil-l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxamide; l-. { ([2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl) -N-propyl-1H-pyrazole-4-carboxamide; { [[2-tert-Butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl) -N, N-dimethyl-lH-pyrazole-4 -carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl] -N- methyl-lH-pyrazole -carboxamide; N- (tert-butyl) -l- { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazole-5- il] (methyl) amino] sulfonyl.}. - lH-pyrazole-4-carboxamide; N- (l-. {[[[2-tert -Butyl-l- (tetrahydro-2H-? Iran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl]. -pyrazol-3-yl) acetamide; N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-formyl-N-methyl-lH-imidazole-1-sulfonamide; l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl] -. N -cyclopropyl-1H-imidazole-4-carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} - N-cyclopropy1-1H -pyrazol-3-carboxamide; l-. {[[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl] -N-isopropy1-1H-pyrazole-3-carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] ( methyl) amino] sulfonyl.} - N-propyl-1H-pyrazole-3-carboxamide; N-allyl-1- [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H -benzimidazol-5-yl] (methyl) amino] sulfonyl.} - lH-pyrazole-3-carboxamide; l- { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl ) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} - N-ethyl-lH-pyrazole-3-carboxamide; N- [2-tert-butyl-1- (tetrahydro-2H-pyran 4-ylmethyl) -IH- benzimidazol-5-yl] -N-methyl-4- (morpholin-4-ylcarbonyl) piperazin-1-suifonamide; 4-. { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.} - N - (2-hydroxyethyl) piperazine-1-carboxamide; N- [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-4- (lH-pyrazol-1-ylcarbonyl) piperazine- 1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-4- (pyrrolidin-1-ylcarbonyl) piperazine -1-suifonamide, and pharmaceutically acceptable salts thereof It will be understood that when the compounds of the present invention contain one or more chiral centers, the compounds of the invention may exist, and be isolated as enantiomeric or diastereoisomeric forms, or as a racemic mixture The present invention includes any possible enantiomers, diastereomers, racemates or mixtures thereof, of a compound of formula I. Optically active forms of the compound of the invention can be prepared, for example, by separating chiral chromatographic ation of a racemate, by synthesis from optically active starting materials or by asymmetric synthesis based on procedures described below. It will also be appreciated that certain compounds of the present invention can exist as geometric isomers, for example, E and Z isomers of alkenes. The present invention includes any geometric isomer of a compound of the formula I. It will be further understood that the present invention encompasses the tautomers of the compounds of the formula I. It will also be understood that certain compounds of the present invention can exist in solvated forms, for example, hydrated, as well as in unsolvated forms. It will be further understood that the present invention encompasses all such solvated forms of the compounds of the formula I. Within the scope of the invention are also the salts of the compounds of the formula I. In general, the pharmaceutically acceptable salts of the The present invention can be obtained using standard procedures well known in the art, for example, by reacting a sufficiently alkaline compound, for example, an alkylamine with a suitable acid, for example, hydrochloric acid or acetic acid, to provide an anion physiologically acceptable. It may also be possible to make a corresponding alkali metal salt (such as sodium, potassium or lithium) or an alkaline earth metal salt (such as a calcium salt) by treatment with a compound of the present invention which has a suitably acidic proton, such as a carboxylic acid or a phenol, with one equivalent of an alkali metal or alkali metal hydroxide or alkoxide (such as ethoxide or methoxide) or an appropriately basic organic amine (such as choline or meglubine) ) in an aqueous medium, followed by conventional purification techniques. In one embodiment, the compound of formula I above may be converted to a pharmaceutically acceptable salt or solvate thereof, particularly, a salt by acid addition such as a hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate. , methanesulfonate or p-toluenesulfonate. It has now been found that the compounds of the invention have activity as pharmaceuticals, in particular as modulators or ligands such as agonists, partial agonists, inverse agonists or antagonists of CBi receptors. More particularly, the compounds of the invention show selective activity as CBi receptor agonists and are useful in therapy, especially for the relief of various painful conditions such as chronic pain, neuropathic pain, acute pain, pain from cancer, pain caused by rheumatoid arthritis, migraine, visceral pain, etc. This list, however, should not be interpreted as exhaustive. In addition, the compounds of the present invention are useful in other disease systems in which dysfunction of CBi receptors is present or involved. In addition, the compounds of the invention can be used to treat cancer, multiple sclerosis, Parkinson's disease, Huntington's chorea, Alzheimer's disease, anxiety disorders, gastrointestinal disorders and cardiovascular disorders. The compounds of the invention are useful as immunomodulators, especially for autoimmune diseases, such as arthritis, for skin grafts, organ transplants and similar surgical needs, for collagen diseases, various allergies, for use as anti-tumor agents and agents anti-viral. The compounds of the invention are useful in disease states where degeneration or dysfunction of cannabinoid receptors is present or involved in that paradigm. This may involve the use of isotopically-labeled versions of the compounds of the invention, in diagnostic techniques and imaging applications such as positron emission tomography (PET). The compounds of the invention are useful for the treatment of diarrhea, depression, anxiety, and stress-related disorders such as post-traumatic stress disorders, panic disorder, generalized anxiety disorder, social phobia and obsessive-compulsive disorder, urinary incontinence. , premature ejaculation, various mental illnesses, cough, pulmonary edema, various gastrointestinal disorders, for example, constipation, functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia, Parkinson's disease and other motor disorders, traumatic brain injury, stroke, cardioprotection after myocardial infarction , spinal damage and drug addiction, including the treatment of alcohol, nicotine, opioid and other drug or drug abuse and for sympathetic nervous system disorders, for example, hypertension. The compounds of the invention are useful as an analgesic agent for use during general anesthesia and the care of monitored anesthesia. Combinations of agents with different properties are often used to achieve a balance of the examples needed to maintain the anesthetic state (for example, amnesia, analgesia, muscle relaxation and sedation). Included in this combination are inhaled anesthetics, hypnotics, anxiolytics, neuromuscular blockers and opioids. Also, within the scope of the invention is the use of any of the compounds according to formula I above, for the manufacture of a medicament for the treatment of any of the conditions discussed above. A further aspect of the invention is a method for the treatment of a subject suffering from any of the conditions discussed above, whereby an effective amount of a compound according to formula I above is administered to a patient in need of such treatment. Thus, the invention provides a compound of the formula I or the pharmaceutically acceptable salt or solvate thereof, as defined hereinbefore, for use in therapy. In a further aspect, the present invention provides the use of a compound of formula I in a pharmaceutically acceptable salt or solvate thereof, as defined hereinbefore, in the manufacture of a medicament for use in therapy. In the context of the present specification, the term "therapy" also includes "prophylaxis", unless there are specific indications to the contrary. The term "therapeutic" and "therapeutically" must be constructed accordingly. The term "therapy" within the context of the present invention further encompasses administering an effective amount of a compound of the present invention to mitigate either a pre-existing, acute or chronic disease state or a recurring condition. This definition also covers prophylactic therapies for the prevention of conditions recurrent and continuous therapy for chronic disorders. The compounds of the present invention are useful in therapy, especially for the therapy of various painful conditions, including but not limited to: acute pain, chronic pain, neuropathic pain, back pain, pain from cancer, and visceral pain. In use for therapy in a warm-blooded animal such as a human, the compound of the invention can be administered in the form of a conventional pharmaceutical composition by any route, including orally, intramuscularly, subcutaneously, topically, intranasally, intraperitoneally, intrathoraxically , intravenously, epidurally, intrathecally, transdermally, intracerebroventricularly and by injection into the joints. In one embodiment of the invention, the route of administration may be oral, intravenous or intramuscular. The dose will depend on the route of administration, the severity of the disease, the age and weight of the patient and other factors normally considered by the attending physician, when determining the individual regimen and the most appropriate dosage level for a particular patient. . To prepare pharmaceutical compositions from the compounds of this invention, the inert, pharmaceutically acceptable carriers can be either solid or liquids. The solid form preparations include powders, tablets, dispersible granules, capsules, sacks and suppositories. A solid carrier may be one or more substances, which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders or tablet disintegrating agents; This can also be an encapsulation material. In the powders the carrier is a finely divided solid, which is in a mixture with the finely divided compound of the invention or the active component. In tablets, the active component is mixed with the carrier having the necessary binding properties in suitable proportions, and compacted in the desired shape and size. To prepare suppository compositions, a low melting point wax such as a mixture of fatty acid glycerides and cocoa butter is first melted and the active ingredient is dispersed therein for example, by stirring. The molten homogeneous mixture is then poured into molds of suitable size and allowed to cool and solidify. Suitable carriers are magnesium carbonate, magnesium stearate, talc, lactose, sugar, pectin, dextrin, cotton, tragacanth, methylcellulose, Sodium carboxymethylcellulose, a low melting point wax, cocoa butter and the like. The term "composition" is also intended to include the formation of the active component with the encapsulating material as a carrier by providing a capsule in which the active component (with or without other carriers) is surrounded by a carrier which is thus association with it. Similarly, sacks are included. The tablets, powders, sacks and capsules can be used as solid dosage forms, suitable for oral administration. Liquid form compositions include solutions, suspensions and emulsions. For example, the sterile water or the aqueous propylene glycol solutions of the active compounds may be liquid preparations suitable for parenteral administration. The liquid compositions can also be formulated in solution in an aqueous solution of polyethylene glycol. Aqueous solutions for oral administration can be prepared by dissolving the active component in water and adding suitable colorants, flavoring agents, stabilizers and thickening agents, as desired. Aqueous suspensions for oral use can be made by dispersing the active component finely divided in water, together with a viscous material such as synthetic or natural gums, resins, methyl cellulose, sodium carboxymethyl cellulose, and other suspending agents known in the pharmaceutical formulating art. Depending on the mode of administration, the pharmaceutical composition will preferably include 0.05% a 99% by weight (percentage by weight), more preferably from 0.10 to 5% by weight, of the compound of the invention, all percentages by weight being based on the total composition. A therapeutically effective amount for the practice of the present invention can be determined by using the known criteria that include the age, weight and response of the individual patient, and interpreted within the context of the disease being treated or that is being treated. being prevented, by a person of ordinary skill in the art. Within the scope of the invention is the use of any compound of the formula I as defined above, for the manufacture of a medicament. Also within the scope of the invention is the use of any compound of the formula I for the manufacture of a medicament for pain therapy. The use is also provided for any compound according to formula I for the manufacture of a medication for the therapy of various painful conditions including, but not limited to: acute pain, chronic pain, neuropathic pain, back pain, pain from cancer and visceral pain. A further aspect of the invention is a method for therapy of a subject suffering from any of the conditions discussed above, whereby an effective amount of the compound according to formula I above is administered to a patient in need of such therapy. . In addition, a pharmaceutical composition comprising a compound of the formula I or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable carrier is provided. Particularly, a pharmaceutical composition comprising a compound of the formula I or a pharmaceutically acceptable salt thereof is provided in association with a pharmaceutically acceptable carrier for therapy, more particularly for pain therapy. In addition, a pharmaceutical composition comprising a compound of the formula I or a pharmaceutically acceptable salt thereof is provided in association with a pharmaceutically acceptable carrier for use in any of the conditions discussed above. In a further aspect, the present invention provides a method for preparing the compounds of the present invention. In one embodiment, the invention provides a process for preparing a compound of formula I, comprising: reacting a compound of the formula II, with a compound of the formula III, followed by treatment of the reaction product with MeOTf and subsequently with R1H, wherein R1, R2, R3, R4 and G are as defined above. The compounds of the present invention can also be prepared according to the synthetic routes as described in Reaction Schemes 1-5.

Reaction scheme 1 XX n or XXtí G, R, R and R4 are as defined above Reaction scheme 2 H, N G, R2, R3 and R4 are as defined above Reaction scheme 3 G, R, R and R are as defined above @ It is a heterocyclyl of 2 to 6 carbon atoms as used in the definition of R1 above X is acyl-O- or halogen Reaction scheme 4 base, p. ex. base of Hunig R «-N = solvent CO, p. ex. CH2CI2 G, R2, R3 and R4 are as defined com T Is a heterocyclyl of 2 to 6 carbon atoms or is used in the definition of R1 above X is acyl-O- or halogen Reaction scheme 5 G, R2, R3 and R4 is as defined above R6 is alkyl of 1 to 6 carbon atoms or cycloalkyl of 3 6 carbon atoms It is a heterocyclyl of 2 to 6 carbon atoms as used in the definition of R1 above X is acyl-O- or halogen BIOLOGICAL EVALUATION Linkage of the hCBi receptor and hCB2 The CBi receptor from the biology of the receptor (hCBi) or of the human CB2 receptor of BioSignal membranes (hCB2) are thawed at 37 ° C, passed 3 times through a 25 gauge blunt-ended needle, diluted in the cannabinoid binding buffer (50 mM Tris, EDTA 2.5 mM, 5 mM magnesium chloride, and 0.5 mg / ml free BSA fatty acid, pH 7.4) and aliquots containing the appropriate amount of the protein are distributed in 96-well plates. The IC50 of the compounds of the invention in hCBi and hCB2 are evaluated from the 10-point dose-response curve made with 3H-CP55.940 at 20,000 and 25,000 dpm per well (0.17-0.21 mm) in a final volume of 300 μl. The total and non-specific binding are determined in the absence and presence of 0.2 μM of HU210, respectively. The plates are vortexed and incubated for 60 minutes at room temperature, filtered through a Unifilters GF / B (pre-wetted in 0.1% polyethyleneimine) with the Tomtec or Packard harvester using 3 ml of wash buffer (50 mM Tris, 5 mM magnesium chloride, 0.5 mg / ml BSA, pH 7.0). The filters are dried for 1 hour at 55 ° C. Radioactivity (cpm) is counted in a TopCount (Packard) after adding 65 μl / well of the MS-20 scintillation fluid. Link from GTP? S to hCBj and hCB2 The human CBi receptor of the Receptor Biology (hCBi) or the membranes of the human CB2 receptor (BioSignal) are thawed at 37 ° C, passed 3 times through a blunt end needle 25 gauge and diluted in GTP? S binding buffer (50 mM Hepes, 20 mM NaOH, 100 mM NaCl, 1 mM EDTA, 5 mM MgCl2, pH 7.4, 0.1% BSA). The EC50 and Emax of the compounds of the invention are evaluated from the 10-point dose-response curves performed in 300 μl with the appropriate amount of the membrane protein and 100000-130000 dpm of GTPg35S per well (0.11 -0.14 nM). The basal and maximum stimulated binding is determined in the absence and presence of 1 μM (hCB2) or 10 μM (hCBi) of Win 55,212-2, respectively. The membranes are pre-incubated for 5 minutes with 56.25 μM of hCB2 or 112.5 of GDP before distribution in the plates (15 μM (hCB2) or 30 μM (hCBi) final GDP). The plates are vortexed and incubated for 60 minutes at room temperature, filtered on Unifilters GF / B (pre-moistened in water) with the Tomtec or Packard harvester using 3 ml of wash buffer (50 mM Tris, 5 mM MgCl2, 50 mM NaCl, pH 7.0). The filters are dried for 1 hour at 55 ° C. Radioactivity (cpm) is counted in a TopCount (Packard) after adding 65 μl / well in the MS-20 scintillation fluid. Inverse antagonist studies are performed in the same manner except that (a) is to elaborate a dose-response curve of the agonist in the presence of a constant concentration of the antagonist, or (b) a dose-response curve of the antagonist in presence of a constant concentration of the agonist. Based on the above tests, the dissociation constant (Ki) for a particular compound of the invention towards a particular receptor is determined using the following equation: Ki = IC 50 / (l + [rad] / Kd), wherein IC 50 is the concentration of the compound of the invention to which a 50% displacement has been observed; [rad] is a concentration of the standard radioactive ligand or reference, at that time; and Kd is the dissociation constant of the radioactive ligand to the particular receptor. Using the above-mentioned assays the Ki towards the human CBi receptors for certain compounds of the invention are in the range of 1 nM and 2897 nM. The EC50 for these compounds are in the range of 0.58 nM to 7647 nM. The Emax for these compounds are in the range of between 72% and 161%. EXAMPLES The invention will be further described in more detail by the following examples which describe the methods by which the compounds of the present invention can be prepared, purified, analyzed and biologically tested, and which should not be considered as limiting the invention.

Example 1 N- (l- { [ {2-tert-Butyl-l- [(, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} - (methyl) amino] sulfonyl. piperidin-4-yl) acetamide Step A: N- (l- { L {2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl) (methyl) amino] sulfonyl} piperidin-4-yl) acetamide «• O Acetic anhydride (2.0 mmol) was added into a solution of triethylamine (2.0 mmol) and 4-amino-N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpiperidin-1-sulfonamide (crude product from step J, 0.9 mmol) in CH2C12 (20 ml). After being stirred at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was purified then by chromatography on silica gel (AcOEt to MeOH / AcOEt (1: 9)) to give the N- (l- { [ { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl.}. (methyl) amino] sulfonyl.] piperidin-4-yl) acetamide as a solid (235 mg, 48% for steps AD). NMR XH (400 MHz, CD3OD, TFA salt) d 1.28 (m, 2H), 1.40-1.76 (, 8H), 1.64 (s, 9H), 1.88 (s, 3H), 2.04 (m, 2H), 2.24 (m, ÍH), 2.90 (m, 2H), 3.28 (s, 3H), 3.68 (m, 3H), 4.50 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz, ÍH) , 7.77 (s, ÍH), 7.86 (d, J = 8.0 Hz, ÍH). Step B. N- (4-fluoro-3-nitrophenyl) acetamide 4-Fluoro-3-nitro-aniline (45.0 g, 0.288 mol) was added in portions to 150 ml of acetic anhydride at room temperature. The reaction mixture was stirred at room temperature for 2 hours. The white solid was collected and dried under vacuum to give the title compound (42.0 g, 70%). XH NMR (400 MHz, CDC13): d 2.23 (s, 3 H), 7.26 (m, 1 H), 7.50 (s broad, 1 H), 7.87 (m, 1 H), 8.23 (dd, J = 6.44 2.73 Hz, 1 H).

Step C. N- (4-fluoro-3-nitrophenyl) -N-methylacetamide Sodium hydride (2.40 g, 60 mmol) was added in portions to a solution of N- (4-f luoro-3-nitrofenyl) acetamide (7.93 g, 40 mmol) in 120 mL of THF at 0 ° C. Stirring for 20 minutes, iodomethane (17.0 g, 120 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours, quenched with 30 ml of saturated NaHCO 3 and extracted with 3 100 ml portions of ethyl acetate. The combined organic phases were washed with saturated sodium chloride (2 x 30 ml). After filtration and concentration, 8.73 g (100%) of the title compound was obtained as a brown solid. X H NMR (400 MHz, CDC13): d 1.92 (s, 3 H), 3.30 (s, 3 H), 7.38 (s, 1 H), 7.52 (s, 1 H), 7.95 (s, 1 H). Step D. N- (4-. {[[(4, -difl oryclohexyl) methyl] amino.}. -3-nitrophenyl) -N-methylacetamide The TFA salt of the. { (4,4-difluorocyclohexyl) methyl] amine (780 mg, 2.96 mmol) was added to a mixture of N- (4-fluoro-3-nitrophenyl) -N-methylacetamide (628 mg, 2.96 mmol) and DIPEA (1.29 ml, 7.40 mmol) in 15 ml of ethanol at room temperature. The reaction mixture was heated for 18 hours at 70 ° C. After removal of the solvent, the crude product was purified by MPLC using 70-100% EtOAc / Heptane to give 855 mg (85%) of the title compound as an orange-red solid (84%). MS (ESI) (M + H) +: 341.96. Step E. N- (3-amino-4-l [(4,4-difluorocyclohexyl) methyl] amino.}. Phenyl) -N-methylacetamide N- (4-l { [(4,4-difluorocyclohexyl) methyl] amino) -3-nitrophenyl) -N-methylacetamide (855 mg, 2.50 mmol) was hydrogenated in 50 ml of ethyl acetate, catalyzed with 10% Pd / C in H2 at 3.51 kg / cm2 (50 psi) in a Parr shaker for 18 hours at room temperature. After filtration through celite and concentration, 716 mg (92%) of a white solid was obtained, which was used in the next step without further purification. MS (ESI) (M + H) 1: 311.99.

Step F. N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] lH-benzimidazo-5-yl} -N-methylacetamide Trimethylacetyl chloride (0.29 ml, 2.41 mmol) was added dropwise to a solution of the N- (3-amino-4. {[[(4, -difluorocyclohexyl) methyl] amino] phenyl) -N- methylacetamide (716 mg, 2.30 mmol) and Et3N (0.38 mL, 2.75 mmol) in dichloromethane (100 mL) at 0 ° C. The resulting mixture was stirred for 4 hours at room temperature. After evaporation of the solvent, the residue was dissolved in 16 ml of acetic acid and then divided into 4 sealed test tubes. The mixture was heated to 150 ° C in a Personal Chemistry Smith Synthesizer microwave instrument for 3 hours. The combined reaction mixture was evaporated and then dissolved in 200 ml of ethyl acetate, washed with saturated sodium bicarbonate solution, with brine and dried over sodium sulfate. After filtration and evaporation, the residue was purified by MPLC using 5% methanol and 10% acetone in DCM as eluent on silica gel to give 570 mg (65%) of the title compound as a white solid. MS (ESI) (M + H) +: 378.23. Step G. 2-tert-Butyl-l- [(4,4-difluoro-cyclo-exyl) -methyl] -N-methyl-1H-benzimidazole-5-amine The N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylacetamide (570 mg, 1.51 mmol) and 15 ml of concentrated hydrochloric acid were heated together at 80 ° C for 18 hours. After cooling to room temperature, the reaction mixture was vacuum in 100 ml of ice water, brought to a pH of 13 by the use of concentrated sodium hydroxide and extracted with 3 50 ml portions of ethyl acetate. The combined organic layers were washed with brine and dried with sodium sulfate. After filtration and evaporation, 459 mg (90%) of the title compound was obtained as a white solid. MS (ESI) (M + H) +: 336.04.

Step H: triflate of l-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl-1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazole-3-io The triflate of 3- (imidazol-1-sulfonyl) -l-methyl-3H-imidazol-1-io (508 mg, 1.4 mmol) was added to a solution of 2-tert-butyl-1 - [(4, 4-difluorocyclohexyl) methyl] -N-methyl-lH-benzimidazol-5-amine (300 mg, 0.9 mmol) in 10 ml of acetonitrile. After stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure. The residue was then dissolved in 60 ml of ethyl acetate, washed with brine, and dried over sodium sulfate. Removal of the solvents provided a mixture (1: 1) of the N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methyl-1H-imidazole-1-sulfonamide and l- triflate. { [(2-ter-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io, which was dissolved in 10 ml of dichloromethane. The resulting solution was treated with methyl trifluoromethanesulfonate (0.5 mmol) at 0 ° C for 2 hours. The reaction mixture was then concentrated under reduced pressure to give the triflate of I-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io as a solid, which was used in step I without further purification. Step I: (l- { [ { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} - (methyl) amino] sulfonyl. piperidin-4-yl) tertiary butyl carbamate A solution of Hunig's base (1.0 mmol), triflate of l-. { [. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (crude product from Step H, 0.9 mmol) and piperidin-4-ylcarbamate from tert-butyl (200 mg, 1.0 mmol) in 20 ml of MeCN was heated for 1 hour at 80 ° C. The reaction mixture was then concentrated under reduced pressure to give (l- { [. {2-tert-Butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl.} Terbutyl (methyl) amino] sulfonyl, piperidin-4-yl) carbamate as a solid, which was used directly in Step J. Step J: 4-amino-N-. { 2-tert-butyl-14 (4,4-difluorocyclohexyl) ethyl-lH-benzimidazol-5-yl} -N-methylpiperidin-1-sulfonamide A solution of (l- { [ { 2-tert-butyl-l- [(, 4-difluorooxyhexyl) methyl] -lH-benzimidazol-5-yl} - (methyl) amino] sulfonyl. piperidin-4-yl) tert-butyl carbamate (crude product from Step I, 0.9 mmol) in 10 ml of methylene chloride was treated with 10 ml of TFA at room temperature. After being stirred at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was then dissolved in 60 ml of ethyl acetate, washed with sodium carbonate solution and brine, and dried over sodium sulfate. Removal of the solvents gave 4-amino-N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} Crude -N-methylpiperidin-1-sulfonamide, which was used in Step A without further purification. Example 2 N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide Step A: N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide Following the procedure in Step I of Example 1, the triflate of l- was reacted. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (crude product from Step G, 1.67 mmol) with isoxazolidine hydrochloride (220.mg, 2.0 mmol) and Hunig's base (0.72 ml, 4.2 ml), after purification by chromatography on silica gel by using 20-30% ethyl acetate in dichloromethane, provided the N- [ 2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide (TFA salt, 807 mg, 88%): XH NMR (600 MHz, CD3OD) d 1.43-1.56 (m, 4H), 1.60 (s, 9H), 2.22-2.35 (m, 3H), 3.26 (t, J = 11.14 Hz, 2H), 3.37 (s, 3H) , 3.47 (t, J = 7.17 Hz, 2H), 3.85 (d, J = 11.26, 3.33 Hz, 2H), 4.03 (t, J = 7.30Hz, 2H), 4.46 (d, J = 7.17Hz, 2H) , 7.63 (dd, J = 8.70, 1.02 Hz, ÍH), 7.80-7.84 (d, J = 1.28 Hz, ÍH), 7.88 (d, J = 8.96 Hz, ÍH). Step B: Methyl (4-fluoro-3-nitrophenyl) carbamate Methyl chloroformate (13.2 ml, 170.2 mmol) was added dropwise to a solution cooled to 0 ° C, to 200 ml of dichloromethane of 4-fluoro-3-nitroaniline (24.15 g, 154.7 mmol) and DIPEA (35 g). ml, 201 mmol). The reaction mixture was stirred at room temperature overnight. The solution was then diluted with 200 ml of dichloromethane and washed with 2M HCl, brine and dried over anhydrous magnesium sulfate. The solvent was concentrated and the product was directly used for the next step without further purification. Yield: 35.5 g (99%); XH NMR (400 MHz, CHLOROFORM-D): d 3.81 (s, 3H), 7.02 (s, ÍH), 7.23 (m, ÍH), 7.72 (d, J = 8.59 Hz, ÍH), 8.17 (dd, J = 6.35, 2.64 Hz, ÍH). Step C. { 3-Nitro-4- [(tetrahydro-2 H -pyran-4-ylmethyl) amino] phenyl} methy carbamate The methyl (4-fluoro-3-nitrophenyl) carbamate (2.0 g, 9.32 mmol) and the 4-aminomethyl-tetrahydropyran (1.28 g, 11.2 mmol) were stirred in 50 ml of ethanol containing TEA (2.0 ml, 14.0 mmol ) at 75 ° C for 48 hours. The solvent was evaporated. The residue was dissolved in ethyl acetate and washed with 5% aqueous KHS04, with saturated aqueous solution of NaHCO3, with brine and dried over anhydrous magnesium sulfate. The crude product was purified by flash chromatography on silica gel using hexanes: ethyl acetate 1: 1 as the eluent. Yield: 2.53 g (88%); 1 H NMR (400 MHz, CHLOROFORM-D): d 1.42 (m, 4.49 Hz, 2 H), 1.73 (d, J = 1.76 Hz, 1 H), 1.76 (d, J = 1.95 Hz, 1 H), 1.88 -2.01 (m, 1 H), 3.22 (dd, J = 6.74, 5.57 Hz, 2 H), 3.42 (m, 2 H), 3.78 (s, 3 H), 4.01 (d, J = 4.30 Hz, 1 H), 4.04 (d, J3.51 Hz, 1 H), 6.48 (s broad, 1 H), 6.85 (d, J = 9.37 Hz, 1 H), 7.65 (broad s, 1 H), 8.03-8.09 (m, 2 H).

Step D. { 3-amino-4- [(tetrahydro-2 H -pyran-4-ylmethyl) amino] phenyl} methyl carbamate He . { 3-Nitro-4- [(tetrahydro-2 H -pyran-4-ylmethyl) amino] phenyl} Methyl carbamate (2.53 g, 8.18 mmol) was dissolved in 50 ml of ethyl acetate containing a catalytic amount of 10% Pd / C. The solution was stirred under an atmosphere of hydrogen 2.81 kg / cm2 (40 psi) using a Parr hydrogenation apparatus overnight at room temperature. The solution was filtered through celite and the solvent was evaporated. Yield: 2.29 g (99%); X H NMR (400 MHz, CHLOROFORM-D): d 1.40 (m, 2 H), 1.70-1.74 (m, 1 H), 1.74-1.77 (m, 1 H), 1.81-1.92 (m, 1 H), 2.99 (d, J = 6.64 Hz, 2 H), 3.34 (broad s, 2 H), 3.41 (m, 2 H), 3.74 (s, 3 H), 3.99 (d, J = 3.51 Hz, 1 H) , 4.02 (d, J = 3.51 Hz, ÍH), 6.38 (broad s, 1 H), 6.55 - 6.60 (m, 1 H), 6.62-6.68 (m, 1 H), 6.95 (broad s, 1 H) .

Step E. [Methyl 2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] carbamate He . { 3-amino-4- [(tetrahydro-2 H -pyran-4-ylmethyl) amino] phenyl} methyl carbamate (2.29 g, 8.20 mmol) and DMAP (0.20 g, 1.64 mmol) were dissolved in 75 ml of DCM. Trimethylacetyl chloride (1.10 ml, 9.02 mmol) was added dropwise and the solution was stirred at room temperature for 2 hours. The solution was washed with an aqueous solution of NaHCO 3, with brine, and dried over anhydrous magnesium sulfate. The residue was dissolved in 25 ml of AcOH and heated at 125 ° C for 1 hour, using a Personal Chemistry microwave apparatus. The solvent was evaporated. The residue was dissolved in ethyl acetate and washed with aqueous sodium hydrogen carbonate solution, with brine and dried over anhydrous magnesium sulfate. The crude product was purified by flash chromatography on silica gel using hexanes: acetone 4: 3 as the eluent. Yield: 1.81 g (64%); XH NMR (400 MHz, CHLOROFORM-D): d 1.48-1.54 (m, 4 H) 1.56 (s, 9 H) 2.23-2.35 (m, 1 H) 3.27-3.35 (m, 2 H) 3.78 (s, 3 H) 3.96 (t, J = 2.93 Hz, 1 H) 3.99 (t, J = 3.03 Hz, 1 H) 4.18 (d, J = 7.42 Hz, 2 H) 6.63 (broad s, 1 H) 7.24-7.28 (m, 1 H) 7.41 (broad s, 1 H) 7.61 (d, J = 1.95 Hz, 1 H). Step F: 2-tert-butyl-N-methyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazole-5-amine Methyl [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] carbamate (1.80 g, 5.21 mmol) (for preparation, see Steps B through E ) was dissolved in 75 ml of THF at 0 ° C. LM HCl / ether (7.3 mL, 7.29 mmol) was added dropwise and the solution was stirred at 0 ° C for 15 minutes. LiAlH4 (988 mg, 26.1 mmol) was slowly added and the solution was stirred at room temperature overnight. The reaction was quenched at 0 ° C by the addition of 5 ml of methanol, followed by 10 ml of water and the solution was allowed to stir at room temperature for 30 minutes. 10 g of anhydrous sodium sulfate were added and the solution was stirred at room temperature for another 30 minutes. The solution was filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate and washed with aqueous NaHCO 3 solution, with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated.

Yield: 1.54g (98%); XH NMR (400 MHz, CHLOROFORM-D): d 1.49-1.53 (m, 4 H), 1.53-1.57 (m, 9 H), 2.22-2.32 (m, 1 H), 2.87 (s, 3 H), 3.26-3.35 (m, 2 H), 3.95 (t, J = 3.03 Hz, ÍH), 3.97-4.00 (m, 1 H), 4.13 (d, J = 7.42 Hz, 2 H), 6.61 (dd, J = 8.59, 2.15 Hz, 1 H), 6.99 (d, J = 1.95 Hz, 1 H), 7.11 (d, J = 8.59 Hz, 1 H). Step G: triflate of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -3-methyl-lH-imidazole-3-io Following the procedure of Step H of Example 1, 2-tert-butyl-N-methyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-amine (1.51 g, 5.0 mmol) was converted to l- triflate. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methy1-lH-imidazol-3-io, which was used in Step A without any purification.

EXAMPLE 3 N- [2-tert-Butyl-1- (tetra-2-H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide Following the procedure in Step A of Example 2, the triflate of 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io (3.33 mmol) was reacted with trimethyleneamine (4.99 mmol), after purification by chromatography on silica gel using 20-50% ethyl acetate in dichloromethane, to provide N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide (TFA salt, 675 mg, 38%). MS (M + 1): 421.01. 1 H NMR (600 MHz, CD3OD) d 1. 40-1.53 (m, 4H), 1.57 (s, 9H), 2.14 (quintuplete, J = 7.68 Hz, 2H), 2.23-2.33 (m, ÍH), 3.22 (s, 3H), 3.25 (m, 2H) , 3.80 (t, J = 7.68 Hz, 4H), 3.84 (m, 2H), 4.41 (d, J = 7.42 Hz, 2H), 7.51 (d, J = 8.70 Hz, ÍH), 7.67 (d, J = 1.79 Hz, ÍH), 7.80 (d, J = 8.45 Hz, ÍH). Example 4 N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylpyrrolidin-1-sulfonamide Step A: N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylpyrrolidin-1-sulfonamide N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylsulfamide (for the preparation see the following steps B to H) (45 mg, 0.118 mmol) was dissolved in 5 ml of DMF at 0 ° C. Sodium hydroxide (60% dispersion in oil) (14 mg, 0.354 mmol) was added and the solution was stirred at 0 ° C for 10 minutes. 1,4-Dibromobutane (0.014 ml, 0.118 mmol) was added and the solution was stirred at room temperature for 3 hours. Another 0.118 mmol of 1,4-dibromobutane was added and the solution was stirred at room temperature for another 3 hours. The reaction was quenched by the addition of a saturated aqueous solution of NaHCO 3 and the solvent was evaporated. The residue was dissolved in ethyl acetate and washed with saturated aqueous solution of NaHCO 3., brine and dried over anhydrous magnesium sulfate. The product was purified by reverse phase HPLC using 10-60% CH3CN / H20 and lyophilized to give the title compound as the corresponding TFA salt. Yield: 53 mg (82%). XH NMR (400 MHz, METAN0L-D4) d 1.52-1.58 (m, 2 H), 1.59-1.67 (m, 2 H), 1.69 (s, 9 H), 1.87-1.92 (m, 4 H), 2.35 -2.43 (m, 1 H), 3.29-3.32 (m, 7 H), 3.35 (m, 2 H), 3.93 (d, J = 3.12 Hz, 1 H), 3.96 (d, J = 3.71 Hz, 1 H), 4.55 (d, J = 7.42 Hz, 2 H), 7.67 (dd, J = 8.98, 1.95 Hz, 1 H), 7.81 (d, J = 2.15 Hz, 1 H), 7.97 (d, J = 8.98 Hz, 1 H); MS (ESI) (M + H) + 435.0; Calculated Analysis (%) for C22H34N403S + 2.4 TFA + 0.2 H20: C, 45.22; H, 5.21; N, 7.87. Found: C, 45.20; H, 5.27; N, 7.90.

Step B: (tert-butoxycarbonyl). { [4- (dimethyliminium) pyridin-1 (4H) -yl] sulfonyl} azanida Chlorosulfonyl isocyanate (1.2 ml, 13.8 mmol) was added dropwise to a DCM solution with stirring (10 ml) of t-butanol (1.3 ml, 13.8 mmol). DMAP (3.45 g, 27.6 mmol) was slowly added and the solution was stirred at room temperature for 2 hours. The solution was diluted with DCM and washed with 3 portions of water, with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated. The product was recrystallized from acetonitrile. Yield (1.68 g (40%). XH NMR (400 MHz, DMSO-D6) d 1.25 (s, 9 H), 3.21 (s, 6 H), 6.96 (d, J = 8.20 Hz, 2 H), 8.45 (d, J = 8.01 Hz, 2 H) Step C: N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylsulfamide 2-tert-Butyl-N-methyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-amine (60 mg, 0.199 mmol) (for preparation, see Example 2, Steps B to F) and (tert-butoxycarbonyl). { [4- (dimethyliminium) pyridin-1 (4H) -yl] sulfonyl} azanide (66 mg, 5 0.219 mmol) was stirred in 3 ml of DCE at 70 ° C for 2 hours. The solution was then passed through a plug of silica gel using ethyl acetate as eluent. The solvent was evaporated. The residue was dissolved in 3 ml of lM HCl / AcOH and the solution was stirred at room temperature for 1 hour. The solvent was evaporated. The product was evaporated by reverse phase HPLC using 10-60% CH3CN / H20 and then lyophilized to give the title compound as the corresponding TFA salt. The fractions were combined and the solvent was concentrated. The residue was dissolved in 2M sodium carbonate and extracted with DCM 3 times. The organic phase was dried over anhydrous magnesium sulfate and the solvent was evaporated. Yield: 45 mg (59%). XH NMR. (salt of TFA) (400 MHz, METAN0L-D) d 1.50-1.56 (m, 2 H), 1.57-1.62 (m, 2 H), 1.67 (s, 9 H), 2.33-2.42 (m, 1 H), 3.28 (s, 3 H), 3.34 (m, 2 H), 3.93 (m, 2 H), 4.53 (d, J = 7.62 Hz, 2 H), 7.64 (dd, J = 8.98, 1.95 Hz, ÍH), 7.77 (d, J = 1.56 Hz, 1 H), 7.91 (d, J = 8.98 Hz, 1 H ); MS (ESI) (M + H) + 381.0.

Example 5 N- [2-tert-butyl-1- (tetra-2-pyro-2-ylmethyl) -1H-benzimidazol-5-yl] -N-methylmorpholin-4-sulfonamide Following Step A in Example 4 using N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylsulfamide (45 mg, 0.118 mmol), sodium hydride (14 mg, 0.354 mmol) and 2-bromoethyl ether (0.030 mL, 0.236 mmol) in 4 mL of DMF. The product was purified by reverse phase HPLC using 10-60% CH3CN / H20 and lyophilized to give the title compound as the corresponding TFA salt. Yield: 42 mg (63%). 1 H NMR (400 MHz, METHANOL-Da) d 1.52-1.58 (m, 2 H), 1.59-1.66 (m, 2 H), 1.69 (s, 9 H), 2.34-2.43 (m, 1 H), 3.20 -3.24 (m, 4 H), 3.32-3.40 (m, 5 H), 3.63-3.67 (m, 4 H), 3.93 (d, J = 3.32 Hz, 1 H), 3.96 (d, J = 3.71 Hz , 1 H), 4.54 (d, J = 7.42 Hz, 2 H), 7.69 (dd, J = 8.98, 1.95 Hz, 1 H), 7.82 (d, J = 1.76 Hz, 1 H), 7.96 (d, J = 8.98 Hz, ÍH); MS (ESI) (M + H) + 451.0; Calculated Analysis (%) for C22H3N404S + 1.2 TFA + 1.0 H20: C, 48.41; H, 6.19; N, 9.25. Found: C, 48.29; H, 6.00; N, 9.53.

Example 6 N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperidine-1-sulfonamide Following Step A in Example 4 using N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylsulfamide (40 mg, 0.105) mmol), sodium hydride (13 mg, 0.315 mmol) and 1,5-dibromopentane (0.042 ml, 0.315 mmol) in 4 ml of DMF. The product was purified by reverse phase HPLC using 10-60% CH3CN / H20 and lyophilized to give the title compound as the corresponding TFA salt. Yield: 42 mg (71%). XH NMR (400 MHz, METHANOL-D4) d 1.52-1.60 (m, 8 H), 1.59-1.67 (m, 2 H), 1.69 (s, 9 H), 2.34-2.43 (m, 1 H), 3.20 -3.25 (m, 4 H), 3.31 (s, 3 H), 3.35 (m, 2 H), 3.93 (d, J = 3.12 Hz, 1 H), 3.96 (d, J = 3.91 Hz, 1 H) , 4.54 (d, J = 7.62 Hz, 2 H), 7.67 (dd, J = 8.98, 1.95 Hz, 1 H), 7.80 (d, J = 1.76 Hz, 1 H), 7.95 (d, J = 8.98 Hz , 1 HOUR); MS (ESI) (M + H) + 449.0; Calculated Analysis (%) for C23H36N403S + 1.3 TFA + 0.9 H20: C, 50.15; H, 6.43; N, 9.14. Found: C, 50.22; H, 6.52; N, 9.10.

Example 7 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methylpiperidin-1-sulfonamide 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -N-met il-lH-benzimidazol-5-amine (55 mg, 0.164 mmol) (for the preparation, see Example 1, Steps B to G) and (tert-butoxycarbonyl). { [4- (dimethyliminium) pyridin-l (4H) -yl] sulfonyl} azanide (54 mg, 0.180 mmol) was stirred in 3 ml of DCE at 70 ° C for 2 hours. The crude product was purified by flash chromatography on silica gel using hexanes: ethyl acetate 1: 1 to ethyl acetate as a gradient. The resulting product was dissolved in 3 ml of lM HCl / AcOH and stirred at room temperature for 1 hour. The solvent was evaporated. The residue was dissolved in ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate solution, with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated. The product was dissolved in 3 ml of DMF at 0 ° C and added Sodium hydride (20 mg, 0.492 mmol) followed by 1,5-dibromopentane (0.033 ml, 0.246 mmol). The solution was stirred at room temperature for 2 hours. The reaction was quenched with saturated aqueous NaHCO 3 solution and the solvent was evaporated. The residue was dissolved in ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate, in brine, and dried over anhydrous magnesium sulfate. The product was purified by reverse phase HPLC using 10-60% CH3CN / H20 and lyophilized to give the title compound as the corresponding TFA salt. Yield: 15 mg (15%). 1 Ti NMR (400 MHz, METAN0L-D4) d 1.54-1.61 (m, 8 H), 1.68 (s, 9 H), 1.71-1.85 (m, 4 H), 2.01-2.12 (m, 2 H), 2.21-2.33 (m, 1 H), 3.20-3.25 (m, 4 H), 3.31 (s, 3 H), 4.56 (d, J = 7.62 Hz, 2 H), 7.67 (dd, J = 9.08, 2.05 Hz, 1 H), 7.81 (d, J = 2.15 Hz, 1 H), 7.94 (d, J = 9.18 Hz, 1 H); MS (ESI) (M + H) + 483.0; Calculated Analysis (%) for C24H36N402SF2 + 1.8 TFA + 0.4 H20: C, 47.69; H, 5.60; N, 8.06. Found: C, 47.66; H, 5.58; N, 8.07.

Example 8 N- [2 - (1,1-difluoroethyl) -1- (tetrahydro-2H-pyran-4-ylmethyl) - lH-benzimidazol-5-yl] -N-methylisoxazolidin-2 sulfonamide Step A. N- [2- (1,1-difluoroethyl) -1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide The isoxazolidin-2-io chloride (80 mg, 0.72 mmol) and DIPEA (0.12 ml, 0.72 mmol) were added to 18 ml of the reaction mixture prepared in step B in this Example. The resulting reaction mixture was heated at 60 ° C overnight and the solvent was concentrated. The product was purified by preparative reverse phase HPLC using MeCN from 10 to 90% gradient in water to provide the TFA salt of the title compound as a white solid. Performance: 50 mg (18%); NMR XH (400 MHz, CD30D) d 1.38-1.51 (m, 4 H), 2.21 (t, J = 19.34 Hz, 3 H), 2.28-2.39 (m, 2 H), 3.29-3.35 (m, 2 H) ), 3.41 (s, 3 H), 3.53 (dd, J = 8.01, 6.64 Hz, 2 H), 3.84-3.93 (m, 2 H), 4.12 (t, J = 7.42 Hz, 2 H), 4.32 ( d, J = 7.62 Hz, 2 H), 7.51 (dd, J = 8.89, 2.05 Hz, 1 H), 7.66 (d, J = 8.98 Hz, 1 H), 7.83 (d, J = 1.95 Hz, 1 H ); MS (ESI) (M + H) + 445.0; Analysis Calculated for C? 9H26F2N404S + 0.3 for TFA + 0.1 for H20: C, 48.99; H, 5.56; N, 11.16. Found: C, 49.02; H, 5.60; N, 11.67. Step B. l-. { [[2- (1, 1-difluoroethyl) -1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -3-methyl-lH-imidazole-3-io The difluoromethanesulfonate of 1- (1H-imidazol-1-ylsulfonyl) -3-methyl-1H-imidazol-3-io (1.05 g, 2.90 mmol) was added to a solution of 2- (1, 1-dif. luoroethyl) -N-methyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-amine (0.60 g, 1.93 mmol) in 70 ml of MeCN at room temperature. The reaction mixture was stirred for 4 hours, and methyl trifluoromethylsulfone (0.21 ml, 1.93 mmol) was added. The reaction mixture was stirred for 2 hours and used directly for the next step.

Example 9 N- (1- { [[2- (1,1-Difluoroethyl) -1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl .}. piperidin-4-yl) acetamide Tert-butyl piperidin-4-ylcarbamate was added (0.43 mg, 1.45 mmol) was added to the reaction mixture (52 ml), prepared in Example 1, step B. The resulting reaction mixture was heated at 90 ° C overnight. Tert-butyl piperidin-4-ylcarbamate (0.43 mg, 1.45 mmol) was added again, and the reaction mixture was heated at 90 ° C overnight. The solvent was concentrated and 50 ml of DCM was added to the residue. The resulting precipitate was filtered and dried in air to provide 404 mg of (1- {[[2- (1,1-difluoroethyl) -1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazole -5-yl] (methyl) amino] sulfonyl.] Piperidin-4-ylcarbamate terbutyl, as an intermediate The solid was treated with 10 ml of TFA for 1.5 hours, and the solvent was concentrated. of 4-amino-N- [2- (1,1-difluoroethyl) -1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methylpiperidin-1-sulfonamide is dissolved in 100 ml of DCM and the solution was neutralized with 2 ml of triethylamine at 0 ° C. Ten drops of acetyl chloride were added to the solution at 0 ° C, the reaction mixture was allowed to warm to room temperature and stirred overnight. The solvent was concentrated and the product was purified by reverse phase preparative HPLC using MeCN from 10 to 90% gradient in water to provide the TFA salt of the title compound as a white solid. Yield: 160 mg (21%); NMR XH (400 MHz, CD3OD) d 1.35-1.54 (m, 6 H), 1.78-1.87 (m, 2 H), 1.90 (s, 3 H), 2.24 (t, J = 19.33 Hz, 3H), 2.30 (s, 1 H), 2.83-2.94 (m, 2 H), 3.27-3.30 (m, 3 H), 3.30-3.38 (m, 2 H), 3.60-3.77 (m, 4 H), 3.86-3.96 (m, 2 H), 4.35 (d, J = 7.62 Hz, 2 H), 7.51 (dd, J = 8.79, 2.15 Hz, 1 H), 7.71 (d, J = 8.98 Hz, 1 H), 7.79 ( d, J = 1.95 Hz, 1 H); MS (ESI) (M + H) + 514.0; Analysis Calculated for C23H33F2N504S + 0.7 of TFA + 0.2 of H20: C, 49.09; H, 5.76; N, 11.73. Found: C, 49.06; H, 5.69; N, 11.68. Example 10 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] - (methyl) amino] sulfonyl} -N-cyclopropylpiperidine-4-carboxamide Step A. l-. { [. { 2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropylpiperidine-4-carboxamide To a solution of l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.142 mmol, see Steps B to E for its preparation), diisopropylethylamine (0.029 ml, 0.170 mmol), and cyclopropylamine (30 μl, excess) at room temperature in DMF (3 ml), added HATU (64.6 mg, 0.170 mmol) in one portion. The solution was stirred at room temperature overnight. After evaporation of the solvent, the residue was purified by reverse phase HPLC (10-60% CH3CN in H20) to give the title compound as its TFA salt (29.1 mg, 32%). NMR XH (400 MHz, CDC13) d 0.47-0.54 (m, 2 H), 0.69-0.77 (m, 2 H), 1.52-1.70 (m, 6 H), 1.73 (s, 9 H), 1.75-1.82 (m, 2 H), 2.13-2.24 (m, 1 H), 2.26 - 2.39 (m, 1 H), 2.65-2.71 (m, 1 H), 2.71-2.81 (m, 2 H), 3.31 (s) , 3 H), 3.32-3.41 (m, 2 H), 3.57-3.65 (m, 2 H), 4.00-4.07 (m, 2 H), 4.38 15 (d, J = 7.42 Hz, 2 H), 6.43 -6.48 (m, ÍH), 7.55 (d, J = 8.98 Hz, 1 H), 7.66 (dd, J = 8.98, 1.37 Hz, ÍH), 7.90-7.93 (m, 1 H); MS (ESI) (M + H) + 532. 0; Analysis (C, H, N) calculated for C27H4? N50 S + 2. 30 CF3COOH: C 47. 80, H 5.50, N 8.82; found C 47. 93, H 5.22, N 8. 91. Step B. N- [-2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-lH-imidazole-1-sulfonamide To a solution of 2-tert-butyl-N-methyl-1- (tetrahydro-2H-pyran-methylmethyl) -lH-benzimidazol-5-amine (1.97 g, 6.54 mmol) at room temperature in 40 ml of MeCN , 1- (1H-imidazol-1-ylsulphonyl) -3-methyl-1H-imidazol-3-io (3.6 g, 9.81 mmol) was added in one portion. The solution was stirred at room temperature overnight. After evaporation of the solvent, the residue was purified by flash chromatography (0-100% ethyl acetate in hexanes, 50 minutes, 100% ethyl acetate, 10 minutes, 0-2% methanol in ethyl acetate, 10 minutes) to provide the product (1.24 g, 44%). MS (ESI) (M + H) + 432.0.

Step C. 1-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino) sulfonyl} -3-methyl-lH-imidazole-3-io To a solution of N- [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-lH-imidazole-1-sulfonamide (1.24 g, 2.88 mmol) at room temperature in 20 ml of MeCN, methyl trifluoromethanesulfonate (0.49 ml, 4.32 mmol) was added dropwise. The solution was stirred at room temperature for 5 hours. After evaporation of the solvent, the residue was used directly for the next step without purification (1.0 g, 76%). MS (ESI) (M + H) + 446.0. Step D l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino) sulfonyl} piperidin-4-carboxylate To a solution of l-. { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazole-5- il] (methyl) amino) sulfonyl} 3-methyl-1H-imidazol-3-io (1 g, 2.2 mmol) and diisopropylethylamine (0.38 ml, 2.2 mmol) at room temperature in 15 ml of MeCN, methyl isonipecotate (0.61 ml, 4.5 mmol) was added a portion. The solution was stirred at room temperature overnight. After evaporation of the solvent, the residue was purified by flash chromatography (0-100% ethyl acetate in hexanes, 50 minutes, 100% ethyl acetate, 10 minutes, 0-2% methanol in ethyl acetate, 10 minutes) to provide the title compound (1.08 g, 97%). MS (ESI) (M + H) + 507.0. Step E. l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidin-4-carboxylic To a solution of 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} methyl piperidin-4-carboxylate (1.08 g, 2.13 mmol) at 0 ° C in methanol: water (3: 1, 20 ml), lithium hydroxide (178.5 mg, 7.46 mmol) is added in a portion. The solution was stirred at 0 ° C, warmed slowly to room temperature and stirred at room temperature overnight. The solution was adjusted to pH 2 with 12 ml of IN HCl, the aqueous layer was extracted with DCM. The organic layers were dried over sodium sulfate and subjected to filtration.

Evaporation of the solvent afforded the title compound (2.2 g, 92%). MS (ESI) (M + H) + 493.0. Example 11 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] - (methyl) amino] sulfonyl} -N-isopropylpiperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (200 mg, 0.41 mmol), diisopropylethylamine (0.17 ml, 0.96 mmol), isopropylamine (0.11 ml, 1.22 mmol), DMF (6 ml), and HATU (182.6 mg, 0.48 mmol) were provided with the compound of the title as its TFA salt (150 mg, 57%) after purification by reverse phase HPLC (10-60% CH3CN in H20). 1 H NMR (400 MHz, CDC13) d 1.13 (d, J = 6.64 Hz, 6 H) 1.52-1.70 (m, 6 H) 1.72 (s, 9 H) 1.76-1.84 (m, 2 H) 2.13-2.23 (m, 1 H) 2.27- 2.40 (m, 1 H) 2.71-2.85 (in, 2 H) 3.32 (s, 3 H) 3.34-3.41 (m, 2 H) 3.62-3.72 (m, 2 H) 3.98-4.09 (m, 3 H) 4.37 (d, J = 7. 42 Hz, 2 H) 5.97 (d, J = 7.62 Hz, 1 H) 7.54 (d, J = 8.98 Hz, ÍH) 7.68 (dd, J = 8.98, 1.76 Hz, 1 H) 7.89 (d, J = 1.76 Hz, ÍH); MS (ESI) (M + H) + 534.0; Analysis (C, H, N) calculated for C27H43N504S + 2.00 CF3COOH + 0.10 CH3OH: C 48.83, H 5.98, N 9.15; found C 48.83, H 5.93, N 9.07. Example 12 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclobutylpiperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 mL, 0.17 mmol), cyclobutyl ina '(0.030 ml, excess), DMF (3 ml), and HATU (64.6 mg, 0.17 mmol) were given the title compound as their TFA salt (37.8 mg, 40%) after purification by reverse phase HPLC (10-70% CH3CN in H20). NMR XH (400 MHz, CDC13) d 1.52-1.71 (m, 10 H), 1.72 (s, 9 H), 1.77-1.95 (m, 3 H), 2.12-2.23 (m, 1 H), 2.23-2.39 (m, 3 H), 2.74-2.85 (m, 2 H), 3.33 (s, 3 H), 3.34-3.41 (m, 2 H), 3.66 (d, J = 15.04 Hz, 2 H), 4.04 ( d, J = 10.94 Hz, 2 H), 4.37 (d, J = 7.42 Hz, 2 H), 6.35 (d, J = 8.01 Hz, 1 H), 7.53 (d, J = 8.98 Hz, 1 H), 7.69 (dd, J = 9.08, 1.86 Hz, 1 H), 7.90 (d, J = 1.76 Hz, 1 H); MS (ESI) (M + H) + 546.0; Analysis (C, H, N) calculated for C28H43N50S + 2.10 CF3COOH: C 49.26, H 5.79, N 8.92; found C 49.21, H 5.65, N 9.07. Example 13 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopentylpiperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-l- (tetrahydro-2H- pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulf onyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 mL, 0.17 mmol), cyclopentylamine (0.030 mL, excess), DMF (3 mL), and HATU (64.6 mg, 0.17 mmol) were provided with the compound of title as its TFA salt (37.8 mg, 40%) after purification by reverse phase HPLC (10-70% CH3CN in H20). NMR XH (400 MHz, CDC13) d 1.32-1.42 (m, 2 H), 1.52-1.69 (m, 10 H H), 1.72 (s, 9 H), 1.76-1.85 (m, 3 H), 1.89-2.01 (m, 2 H), 2.75-2.86 (m, 2 H), 3.34 (s, 3 H), 3.34-3.41 (m, 2 H), 3.65-3.73 (m, 2 H), 4.00-4.07 (m , 2 H), 4.11-4.21 (m, 1 H), 4.36 (d, J = 6.84 Hz, 2 H), 7.52 (d, J = 8.79 Hz, 1 H), 7.67 - 7.73 (m, J = 7.81 Hz, 1 H), 7.91-7.95 (m, 1 H); MS (ESI) (M + H) + 560.0; Analysis (C, H, N) calculated for C29H45N504S + 1.70 CF3COOH + 0.20H2O +0.40 CH3OH: C 51.16, H 6.37, N 9.09; found C 51.15, H 6.34, N 9.00. Example 14 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-pyrrolidin-1-ylpiperidine-4-carboxamide Following the procedure of Step A in the Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 mL, 0.17 mmol), 1-aminopyrrolidine hydrochloride (20.8 mg, 0.17 mmol), DMF (3 mL), and HATU (64.6 mg, 0.17 mmol) the title corrodate was provided as its TFA salt (37.8 mg, 40%) after purification by reverse phase HPLC (10-60% CH3CN in water). NMR * H (400 MHz, CDC13) d 1.52-1.70 (m, 7 H), 1.72 (s, 9 H), 1.74-1.84 (m, 2 H), 2.12-2.23 (m, 4 H), 2.37- 2.48 (m, 1 H), 2.87-3.00 (m, 3 H), 3.33 (s, 3 H), 3.34-3.41 (m, 2 H), 3.44-3.53 (m, 2 H), 3.65 -3.74 ( m, 4 H), 3.99-4.07 (m, 2 H), 4.38 (d, J = 7.42 Hz, 2 H), 7.57 (d, J = 8.89 Hz, 1 H), 7.69 (dd, J = 8.89, 2.05 Hz, 1 H), 7.88 (d, J = 2.05 Hz, 1 H); MS (ESI) (M + H) + 561.0; Analysis (C, H, N) calculated for C28H44N6? S + 2.75 CF3CCOH + 0.55 H20 + 0.15 CH3OH: C 45.46, H 5.49, N 9.45; found C 45.47, H 5.49, N 9.46. Example 15 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-lH-pyrrol-l-ylpiperidine-4-carboxamide Following the procedure of Step A in the Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 mL, 0.17 mmol), 1-aminopyrrole (0.030 mL, excess), DMF (3 mL), and HATU (64.6 mg, 0.17 mmol) were given the compound of the title as its TFA salt (37.8 mg, 40%) after purification by reverse phase HPLC (10-70% CH3CN in water). NMR XH (400 MHz, CDC13) d 1.50-1.63 (m, 4 H), 1.71 (s, 9 H), 1.72-1.95 (m, 2 H), 2.26-2.50 (m, 2 H), 2.75-2.86 (m, 2 H), 3.23-3.41 (m, 6 H), 3.58-3.72 (m, 3 H), 3.96-4.08 (m, 2 H), 4.37 (d, J = 7.42 Hz, 2 H), 6.06-6.15 (m, 2 H), 6.56-6.61 (m, 2 H), 7.56 (d, J = 9.18 Hz, 1 H), 7.68 - 7.73 (m, 1 H), 7.91 (d, J = 1.17 Hz, 1 H); MS (ESI) (M + H) * 557.0; Analysis (C, H, N) calculated for C28H4oN604S + 1.75 CF3COOH +0.35 CH3OH: C 49.85, H 5.67, N 10.95; found C 49.97, H 5.61, N 10.84. Example 16 l-. { [[2-tert-butyl-l- (tetra-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethylpiperidine-4-carboxamide Following the procedure of Step A in the Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 mL, 0.17 mmol), ethylamine (0.21 mL, 0.43 mmol), DMF (3 mL), and HATU (64.6 mg, 0.17 mmol) were provided with the compound of the title as its TFA salt (41.5 mg, 46%) after purification by reverse phase HPLC (10-65% CH3CN in water). NMR XH (400 MHz, CDC13) d 1.12 (t, J = 7.13 Hz, 3 H), 1.51-1.69 (m, 6 H), 1.72 (s, 9 H), 1.75-1.86 (m, 2 H), 2.19-2.41 (m, 2 H), 2.70-2.82 (m, 2 H), 3.21-3.28 (m, 2 H), 3.30 (s, 3 H), 3.31-3.41 (m, 2 H), 3.56- 3.67 (m, 2 H), 3.98-4.08 (m, 2 H), 4.39 (d, J = 7.42 Hz, 2 H), 6.47-6.56 (m, 1 H), 7.56-7.62 (m, 1 H) 7.63-7.69 (m, 1 H), 7.87 (s, 1 H); MS (ESI) (M + H) + 520.0; Analysis (C, H, N) calculated for C26H4IN504S + 2.35 CF3COOH: C 46.81, H 5.55, N 8. 89; found C 46.49, H 5.09, N 9.32. Example 17 N- (tert-butyl) -l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino) sulfonyl} piperidine-4-carboxamide Following the procedure of Step A in Example 10, using acid 1-. { [[2-Ten-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (met il) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 mL, 0.17 mmol), t-butylamine (0.045 mL, 0.43 mmol), DMF (3 mL), and HATU (64.6 mg, 0.17 mmol) were added. gave the title compound as its TFA salt (44.2 mg, 47%) after purification by reverse phase HPLC (10-70% CH3CN in water). NMR I (400 MHz, CDC13) d 1.32 (s, 9 H), 1.52-1.70 (m, 6 H), 1.71 (s, 9 H), 1.73-1.81 (m, 2 H), 2.05-2.18 (m , 1 H), 2.26-2.40 (m, 1 H), 2.69-2.81 (m, 2 H), 3.31 (s, 3 H), 3.32-3.42 (m, 2 H), 3.63-3.71 (m, 2 H), 3.99-4.07 (m, 2 H), 4.38 (d, J = 7.42 Hz, 2 H), 5.79-5.85 (m, 1 H), 7.57 (d, J = 8.98 Hz, 1 H), 7.68 (dd, J = 8.98, 1.37 Hz, 1 H), 7.82-7.86 (m, 1 H); MS (ESI) (M + H) + 548.0; Analysis (C, H, N) calculated for C28H 5N504S + 2.10 CF3COOH + 1.25 H20: C 47.76, H 6.17, N 8.65; found C 47.45, H 5.88, N 8.96.

Example 18 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-dimethylpiperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 μl, 0.17 mmol), N, N-dimethylamine (0.21 ml, 0.43 mmol), DMF (3 ml), and HATU (64.6 mg, 0.17 mmol) the title compound was provided as its TFA salt (33.7 mg, 37%) after purification by reverse phase HPLC (10-60% CH3CN in water). H NMR (400 MHz, CDC13) d 1.52-1.65 (m, 5 H), 1.65-1.79 (m, 12H), 2.25-2.40 (m, 1 H), 2.63-2.75 (m, ÍH), 2.84-2.92 (m, 2 H), 2.93 (s, 3 H), 3.06 (s, 3 H), 3.32 (s, 3 H), 3.33-3.41 (m, 2 H), 3.68-3.77 (m, 2 H) , 3.98-4.08 (m, 2 H), 4.37 (d, J = 7.42 Hz, 2 H), 7.54 (d, J = 8.98 Hz, 1 H), 7.68 (dd, J = 8.98, 0.98 Hz, 1 H ), 7.89-7.93 (m, ÍH); MS (ESI) (M + H) + 520.0; Analysis (C, H, N) calculated for 20 C26H4? N50 S + 1.80 CF3COOH + 0.75 H20: C 48.14, H 6.05, N 9.48; found C 48.09, H 6.00, N 9.57. Example 19 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-diethylpiperidin-4 -carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 ml, 0.17 mmol), N, N-diethylamine (0.044 ml, 0.43 mmol), DMF (3 ml), and HATU (64.6 mg, 0.17 mmol) the title compound was given as its TFA salt (12.1 mg, 13%) after purification by reverse phase HPLC (10-70% CH3CN in water). NMR XH (400 MHz, CDC13) d 1.08 (t, J = 7.13 Hz, 3 H), 1.19 (t, J = 7.03 Hz, 3 H), 1.52-1.62 (m, 4 H), 1.65-1.69 (m , 1 H), 1.72 (s, 9 H), 1.72-1.87 (m, 3 H), 2.54-2.64 (m, 1 H), 2.86-2.96 (m, 2 H), 3.28-3.40 (m, 10 H), 3.71-3.80 (m, 2 H), 3.99-4.07 (m, 2 H), 4.35 (d, J = 7.42 Hz, 2 H), 7.49 (d, J = 8.98 Hz, ÍH), 7.70 (dd, J = 8.98, 1.76 Hz, 1 H), 7.93 (d, J = 1.76 Hz, ÍH); MS (ESI) (M + H) + 548.0. Example 20 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-I ilpiperidin-4-carboxamide Following the procedure of Step A in the Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.029 mL, 0.17 mmol), methylamine (0.21 mL, 0.43 mmol), DMF (3 mL), and HATU (64.6 mg, 0.17 mmol) were provided with the compound of the title as its TFA salt (22.9 mg, 26%) after purification by reverse phase HPLC (10-60% CH3CN in water). NMR XH (400 MHz, CDCl 3) d 1.57 (d, 4 H), 1.65-1.76 (m, 12 H), 1.81-1.90 (m, 3 H), 2.79 (d, J = 4.49 Hz, 3 H), 2.80-2.87 (m, 2 H), 3.33 (s, 3 H), 3.34 5-3.41 (m, 2 H), 3.61-3.69 (m, 2 H), 3.99-4.08 (m, 2 H), 4.36 (d, J = 7.42 Hz, 2 H), 7.52 (d, J = 9.18 Hz, 1 H), 7. 70 (dd, J = 9.18, 1.66 Hz, 1 H), 7.96-7.99 (m, 1 H); MS (ESI) (M + H) + 506.0; Analysis (C, H, N) calculated for C25H39N504S + 1.90 CF3COOH + 0.20 H20 +0.25 CH3OH: C 47.54, H 5. 81, N 9.54; found C 47.54, H 5.82, N 9.53. Example 21 l-. { [[2-tert-butyl-l- (tetra-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propylpiperidine-4-carboxamide Following the procedure of Step A in Example 10, using acid 1-. { [. { 2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0. 14 mmol), diisopropylethylamine (0.074 ml, 0.43 mmol), N, N-diethylamine (0.035 ml, 0.43 mmol), DMF (3 ml), and HATU (81 mg, 0.21 mmol) the title compound was given as its TFA salt (31.1 mg, 34%) after purification by reverse phase HPLC (10-70% of CH3CN in water). 1 H NMR (400 MHz, CDC13) d 0.89 (t, J = 7.42 Hz, 3 H), 1.44-1.71 (m, 8H), 1.72 (s, 9H), 1.75-1.87 (m, 2H), 2.17-2.41 (m, 2H), 2.72-2.85 (m, 2H), 3.14-3.23 (m, 2H), 3.32 (s, 3 H), 3.33-3.42 (m, 2H), 3.59-3.70 (m, 2H), 3.98-4.09 (m, 2 H), 4.38 (d, J = 7.42 Hz, 2 H), 6.30-6.42 (m, ÍH), 7.55 (d, J = 8.98 Hz, 125H), 7.68 (dd, J = 8.98, 1.76 Hz, ÍH), 7.91 (d, J = 1.76 Hz, ÍH); MS (ESI) (M + H) + 534.0; Analysis (C, H, N) calculated for C24143N50 S + 1.80 CF3COOH + 0.90 CH3OH: C 49.28, H 6.29, N 9.06; found C 49.25, H 6.29, N 9.06. Example 22 N-butyl-l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (70 mg, 0.14 mmol), diisopropylethylamine (0.074 mL, 0.43 mmol), N, N- butylamine (42 μl, 0.43 mmol), DMF (3 ml), and HATU (81 mg, 0.21 mmol) were given the title compound as their TFA salt (31.1 mg, 34%) after purification by phase HPLC. Reverse (10-70% CH3CN in water). NMR XH (400 MHz, CDC13) 6 0.90 (t, J = 7.32 Hz, 3H), 1.24-1.39 (m, 2H), 1.41-1.52 (m, 2H), 1.52-1.70 (m, 6H), 1.72 ( s, 9H), 1.77-1.87 (m, 2H), 2.15-2.41 (m, 2H), 2.74-2.87 (m, 2H), 3.16-3.26 (m, 2H), 3.32 (s, 3H), 3.33- 3.41 (m, 2 H), 3.60-3.72 (m, 2H), 3.98-4.08 (m, 2H), 4.37 (d, J = 7.42 Hz, 2H), 6.18-6.30 (m, ÍH), 7.54 (d , J = 8.98 Hz, 1 H), 7.67 (dd, J = 8.98, 1.76 Hz, 1H), 7.94 (d, J = 1.76 Hz, ÍH); MS (ESI) (M + H) + 548.0; Analysis (C, H, N) calculated for C28H45N504S + 1.55 CF3COOH: C 50.56, H 6.48, N 9.67; found C 50.95, H 5.92, N 10.27. Example 23 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (2,2,2-trifluoroethyl) piperidine-4-carboxamide Following the procedure of Step A in Example 10, using acid 1-. { [[2-tert-butyl-l- (tetrahydro-2H- pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (100 mg, 0.20 mmol), diisopropylethylamine (0.1 ml, 0.61 mmol), 2,2,2-trifluoroethylamine (0.050 ml, 0.61 mmol), DMF (3 ml), and HATU (116 mg, 0.31 mmol) the title compound was given as its TFA salt (59.2 mg, 42%) after purification by reverse phase HPLC (10-70% CH3CN in water). NMR XH (400 MHz, CDC13) d 1.51-1.70 (m, 6H), 1.72 (s, 9H), 1.76-1.85 (m, 2H), 2.25-2.39 (m, 2H), 2.72-2.84 (m, 2H) ), 3.28-3.41 (m, 5H), 3.58-3.65 (m, 2H), 3.82-3.94 (m, 2H), 4.00-4.07 (m, 2H), 4.38 (d, J = 7.42 Hz, 2H), 7.05-7.14 (m, ÍH), 7.56 (d, J = 8.98 Hz, ÍH), 7.68 (dd, J = 8.98, 1.46 Hz, ÍH), 7.91-7.94 (my h); MS (ESI) (M + H) 1 573.8; Analysis (C, H, N) calculated for C 26 H 38 F 3 N 504 S + 1.85 CF 3 COOH: C 54.44, H 6.68, N 12.21; found C 45.49, H 4.94, N 8.87. Example 24 N-alyl-l-. { ([2-tert-butyl-1- (tetra-2-piper-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.] Piperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (100 mg, 0.20 mmol), diisopropylethylamine (0.1 mL, 0.61 mmol), allylamine (0.1 mL, 0.61 mmol), DMF (3 mL), and HATU (116 mg, 0.31 mmol) were provided with the compound of the title as its TFA salt (27.6 mg, 25%) after purification by reverse phase HPLC (10-60% CH3CN in water). XH NMR (400 MHz, CDC13) d 1.51-1.79 (m, 17H), 1.80-1.90 (m, 2H), 2.76-2.88 (m, 2H), 3.33 (s, 3H), 3.34-3.41 (m, 2H) ), 3.63-3.72 (m, 2 H), 3.82-3.89 (m, 2H), 3.98-4.08 (m, 2H), 4.36 (d, J = 7.42 Hz, 2 H), 5.07-5.20 (m, 2H) ), 5.75-5.89 (m, ÍH), 6.25-6.33 (m, 1 H), 7.52 (d, J = 8.98 Hz, ÍH), 7.69 (dd, J = 8.98, 1.95 Hz, 1 H), 7.94 ( d, J = 1.95 Hz, ÍH); MS (ESI) (M + H) + 532.0; Example 25 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isobutylpiperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (200 mg, 0.41 mmol), diisopropylethylamine (0.2 mL, 1.22 mmol), isobutylamine (0.12 mL, 1.22 mmol), DMF (6 mL), and HATU (236 mg, 0.62 mmol) were provided. compound of the title as its TFA salt (99.6 mg, 37%) after purification by reverse phase HPLC (10-70% CH3CN in H20). NMR XH (400 MHz, CD3OD) d 0.87 (d, J = 6.84 Hz, 6H) 1.51-1.67 (m, 7H) 1.69 (s, 9H) 1.70-1.77 (m, 3H) 2.23-2.33 (m, ÍH) 2.81-2.91 (m, 2H) 2.91-2.99 (m, 2H) 3.33 (s, 3H) 3.33-3.39 (m, 2H) 3.66-3.74 (m, 2H) 3.90-3.97 (m, 2H) 4.54 (d, J = 7.42 Hz, 2H) 7.68 (dd, J = 8.98, 1.95Hz, HH) 7.81 (d, J = 1.95 Hz, HH) 7.96 (d, J = 8.98 Hz, HH); MS (ESI) (M + H) 1- 458.0. Example 26 l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino) sulfonyl} -N- (2-hydroxy-l-methylethyl) piperidine-4-carboxamide Following the procedure of Step A in Example 10, using l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-methylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperidine-4-carboxylic acid (175 mg, 0.36 mmol), diisopropylethylamine (0.15 ml, 0.85 mmol), DL-2-amino-1-propanol (0.08 ml, 1.07 mmol), DMF (5 ml), and HATU (162 mg) , 0.43 mmol) the title compound was given as its TFA salt (66.9 mg, 28%) after purification by reverse phase HPLC (10-40% CH3CN in water). XH NMR (400 MHz, CDC13) d 1.13 (d, J = 6.64 Hz, 3H) 1.51-1.68 (m, 7H) 1.72 (s, 9H) 1.75-1.86 (m, ÍH) 2.19-2.41 (m, 2H) 2.67-2.91 (m, 2H) 3.32 (s, 2 H) 3.33-3.41 (m, 3H) 3.43-3.70 (m, 4H) 3.97-4.09 (m, 3 H) 4.39 (d, J = 7.62 Hz, 2H ) 6.76 (d, J = 7.42 Hz, HH) 7.55-7.60 (m, HH) 7.64-7.68 (m, HH) 7.84 (d, J = 1.95 Hz, HH); MS (ESI) (M + H) 1 549.8. Example 27 l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino) sulfonyl} -N- (2-hydroxyethyl) piperidine-4-carboxamide Following the procedure of Step A in the Example 10, using the acid 1-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (meth il) amino] sulfonyl} piperidin- -carboxylic (70 mg, 0.14 mmol), diisopropylethylamine (0.042 mL, 0.24 mmol), ethanolamine (0.010 mL, 0.17 mmol), DMF (3 mL), and HATU (59.4 mg, 0.16 mmol) was provided. of the title as its TFA salt (46.4 mg, 50%) following purification by reverse phase HPLC (10-60% CH3CN in H20). NMR XH (400 MHz, CDC13) d 1.52-1.66 (m, 6 H), 1.72 (s, 9 H), 1.82 (d, J = 12.50 Hz, 2 H), 2.22-2.42 (m, 2 H), 2.71-2.83 (m, 2 H), 3.30 (s, 3 H), 3.32-3.44 (m, 4 H), 3.52-3.65 (m, 2 H), 3.66-3.78 (m, 2 H), 3.98- 4.07 (m, 2 H), 4.39 (d, J = 7.42 Hz, 2 H), 7.15-7.24 (m, J = 32.62 Hz, 1 H), 7.56-7.62 (m, 1 H), 7.63-7.67 ( m, 1 H), 7.81-7.88 (m, 1 H); MS (ESI) (M + H) + 536.0; Anal. (C, H, N) calculated for C26H4? N505S + 2.20 CF3COOH + 1.00 H20: C 45.38, H 5.66, N 8.70; found C 47.93, H 5.22, N 8.91.

Example 28 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} ethyl piperidin-4-carboxylate Following the procedure for Step J in Example 10, using 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-1H-imidazol-3-io (1.9 g, 4.25 mmol) and diisopropylethylamine (0.1 ml, 0.6 mmol) at room temperature in 40 ml of MeCN and ethyl isonipecotate (1.9 ml, 12.75 mmol), The solution was concentrated and the residue was dissolved in 100 ml of ethyl acetate. The solution was washed with water (3 x 30 ml), 30 ml of brine, dried over sodium sulfate and filtered. After evaporation of the solvent, the residue was purified by flash chromatography (0-100% ethyl acetate in hexanes, 50 minutes, 100% ethyl acetate, 10 minutes, 0-2% methanol in ethyl acetate, 10 minutes) to provide the title compound (445 mg, 20%). XH NMR (400 MHz, CDC13) d 1. 24 (t, J = 7.23 Hz, 3 H), 1.49-1.59 (m, 13 H), 1.64-1.77 (m, 2 H), 1.86-1.95 (m, 2 H), 2.22-2.39 (m, 2) H), 2.78-2.89 (m, 2 H), 3.28 (s, 3 H), 3.29-3.37 (m, 2 H), 3.63-3.71 (m, 2 H), 3.95-4.02 (m, 2 H) , 4.13 (q, J = 7.23 Hz, 2 H), 4.20 (d, J = 7.42 Hz, 2 H), 7.30 (s, 1 H), 7.32 (d, J = 1.95 Hz, 1 H), 7.72 ( d, J = 1.56 Hz, 1 H); MS (EST) (M + H) + 521.0; Analysis (C, H, N) calculated for C 26 H 0 N 4 O 5 S + 0.60 CH 3 OH: C 59.17, H 7.92, N 10.38; found C 59.23, H 8.03, N 10.45. EXAMPLE 29 N- (l- { [[2-tert -Butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} azetidine -3-yl) cyclopropanecarboxamide Step A. N- (l-. {[[[2-tert-butyl-l- (tetra idro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl. azetidin-3-yl) cyclopropanecarboxamide To a solution of 3-amino-N- [2-tert-but-il-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-met ila zet idin- 1- sulphonamide (150 mg, 0.27 mmol, see Steps B and C for its preparation), diisopropylethylamine (0.14 ml, 0.82 mmol), and cyclopropancarboxylic acid (0.33 ml, 0.41 mmol) at room temperature in DMF '(1.5 ml), HATU (125.5 mg, 0.33 mmol) was added in one portion. The solution was stirred at room temperature for 3 hours. After evaporation of the solvent, the residue was purified by reverse phase HPLC (10-65% CH3CN in water) to give the title compound as its TFA salt (27.3 mg, 16%). 1 H NMR (400 MHz, CD3OD) d 0.72-0.85 (m, 4 H) 1.50-1.68 (m, 5 H) 1.69 (s, 9 H) 2.31-2.46 (m, 1 H) 3.31-3.40 (m, 5 H) 3.80-3.86 (m, 2 H) 3.91-3.98 (m, 2 H) 4.00-4.06 (m, 2 H) 4.50-4.59 (m, 3 H) 7.67 (dd, J = 8.98, 2.15 Hz, 1 H) 7.79 (d, J = 2.15 Hz, 1 H) 7.96 (d, J = 8.98 Hz, 1 H); MS (ESI) (M + H) + 503.8; Analysis (C, H, N) calculated for C25H39N50 S + 1.80 CF3COOH + 0.05 water + 0.45 CH3OH: C 48.18, H 5.66, N 9.67; found C 48.19, H 5.67, N 9.69.

Step B. 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide To a solution of 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-1H-imidazol-3-io (2.2 g, 4.9 mmol, see Example 10, Steps BI for its preparation) and diisopropylethylamine (2.6 ml, 14.7 mmol) at room temperature in MeCN (30 ml), was added 3-N-Boc-amino-azetidine (1.0 g, 5.9 mmol). The solution was stirred at room temperature overnight. After evaporation of the solvent, the residue was purified by flash chromatography (0-100% ethyl acetate in hexanes, 50 minutes, 100% ethyl acetate, 10 minutes, 0-2% methanol in ethyl acetate, 10 minutes) to provide the title compound (0.95 g, 36%). NMR (400 MHz, CD3OD) d 1.40 (s, 9 H) 1.49-1.65 (m, 5 H) 1.68 (s, 9 H) 2.30-2.45 (m, 1 H) 3.32 (s, 3 H) 3.33-3.39 (s) m, 2 H) 3.75-3.81 (m, 2 H) 3.89-4.00 (m, 4 H) 4.53 (d, J = 7.62 Hz, 2 H) 7.65 (dd, J = 8.98, 2.15 Hz, 1 H) 7.78 (d, J = 2.15 Hz, 1 H) 7.95 (d, J = 8.98 Hz, 1 H); MS (ESI) (M + H) + 535. 8; Analysis (C, H, N) calculated for C26H4? N505S + 2. 10 CF3COOH + 0. 60 water + 0. 45 CH3CN: C 46. 44, H 5.72, N 9.49; found C 46.42, H 5.73, N 9.51.

Step C. 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide To a solution of (1- {[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} azetidin -3-yl) tert-butyl carbamate (0.95 g, 1.77 mmol, see Step B for its preparation) at 0 ° C in DCM (6 ml), TFA (6 ml, excess) was added dropwise. The solution was stirred at 0 ° C for 20 minutes. The solution was concentrated. The residue was redissolved in DCM, washed with 2 portions of IN NaOH, and the layers were extracted with DCM (x4), the combined organic layers were dried over sodium sulfate, and subjected to filtration. Evaporation of the solvent afforded the title compound (778 mg, 100%). MS (ESI) (M + H) + 436.1.

EXAMPLE 30 N- (l-. {[[2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] Azetidin -3-yl) -2-methylpropanamide To a solution of 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide (150 mg , 0.27 mmol, see Example 29, Steps B and C for its preparation) and diisopropylethylamine (0.1 ml, 0.57 mmol) in DCM (3 ml) at 0 ° C, isobutyryl chloride (0.06 ml, 0.57 mmol) was added dropwise. drop. The solution was stirred at room temperature for 1.5 hours. After evaporation of the solvent, the residue was purified by reverse phase HPLC (10-60% CH 3 CN in water) to give the title compound as its TFA salt (21.7 mg, 15%). NMR? Ti (400 MHz, CD3OD) d 1.07 (d, J = 7.03 Hz, 6 H) 1.49-1.67 (m, 5 H) 1.68 (s, 9 H) 2.32-2.46 (m, 2 H) 3.30- 3.39 (m, 5 H) 3.78-3.84 (m, 2 H) 3.90-3.97 (m , 2 H) 3.99-4.05 (m, 2 H) 4.53 (d, J = 7.42 Hz, 2 H) 7.65 (dd, J = 8.98, 1.95 Hz, 1 H) 7.78 (d, J = 1.95 Hz, 1 H) 7.95 (d, J = 8.98 Hz, 1 H); MS (ESI) (M + H) + 505.8; Analysis (C, H, N) calculated for C25H39N50 S + 1.60 CF3COOH + 0.35 CH3CN: C 49.41, H 5.98, N 10.67; found C 49.55, H 5.84, N 10.61. Example 31 N- (l- { [[12-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl) azetidin-3 -il) cyclobutanecarboxamide Following the procedure for Step A in Example 30, using 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] - N-methylazetidin-1-sulfonamide (100 mg, 0.23 mmol), diisopropylethylamine (0.1 mL, 0.57 mmol), DCM (3 mL), and cyclobutanecarbonyl chloride (0.07 mL, 0.57 mmol) afforded the title compound as its salt. TFA (11.8 mg, 8%) after purification by reverse phase HPLC (10-60% CH3CN in water). NMR * H (400 MHz, CD30D) d 1. 26-1.32 (m, 1 H) 1.49-1.66 (m, 5 H) 1.68 (s, 9 H) 1.78-1.88 (m, 1 H) 1.92-2.01 (m, 1 H) 2.04-2.24 (m, 4 H) 3.32 (s, 3 H) 3.33-3.40 (m, 2 H) 3.78-3.84 (m, 2 H) 3.90 -3.98 (m, 2 H) 3. 99-4.05 (m, 2 H) 4.47-4.56 (m 3 H) 7.64 (dd, J = 9.08, 2.05 Hz, 1 H) 7.77 (d, J = 2.05 Hz, 1 H) 7.94 (d, J = 9.08 Hz, 1 H); MS (ESI) (M + H) + 517.8. EXAMPLE 32 N- (l-. {[[2-tert -Butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} azetidin -3-il) butanamide Following the procedure for Step A in Example 30, using 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] - N-methylazetidin-1-sulfonamide (100 mg, 0.23 mmol), diisopropylethylamine (0.1 mL, 0.57 mmol), DCM (3 mL), and butyryl chloride (0.06 mL, 0.57 mmol) provided the title compound as its salt of TFA (11.8 mg, 8%) after purification by reverse phase HPLC (10-60% CH3CN in water). 1 H NMR (400 MHz, CD3OD) d 0.90 (t, J = 7.42 Hz, 3H) 1.50-1.66 (m, 7 H) 1.68 (s, 9 H) 2. 14 (t, J = 7.42 Hz, 2 H) 2.31-2.44 (m, 1 H) 3.32 (s, 3 H) 3.33-3.39 (m, 2 H) 3.78-3.84 (m, 2 H) 3.90-3.97 ( m, 2 H) 4.00-4.05 (m, 2 H) 4.53 (d, J = 7.62 Hz, 2 H) 7.65 (dd, J = 8.98, 1.95 Hz, 1 H) 7.78 (d, J = 1.95 Hz, 1 H) 7.95 (d, J = 8.98 Hz, 1 H); MS (ESI) (M + H) 1 505.8; Analysis (C, H, N) calculated for C25H39N504S + 1.75 CF3COOH + 0.20 water + 0.10 CH3CN: C 48.35, H 5.86, N 10.02; found C 48.33, H 5.86, N 10.01. Example 33 N- (l- { [[2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulf onyl. azetidin-3-yl) propanamide Following the procedure for Step A in Example 29, using 3-amino-N42-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylazetidine -1-sulfonamide (150 mg, 0.27 mmol), diisopropylethylamine (0.14 mL, 0.82 mmol), DMF (1.5 mL), propionic acid (0.031 μL, 0.41 mmol) and HATU (125.5 mg, 0.33 mmol) were provided with the compound of the title as its TFA salt (15.5 mg, 9.5%) after purification by reverse phase HPLC (10-40% CH3CN in water). NMR XH (400 MHz, CD3OD) d 1.13 (t, J = 7.62 Hz, 3 H) 1.51-1.72 (m, 5 H) 1.74 (s, 9 H) 2.28 (q, J = 7.62 Hz, 2 H) 3.31 (s, 3 H) 3.32-3.40 (m, 2 H) ) 3.71-3.77 (m, 2 H) 4.00-4.07 (m, 2 H) 4.30-4.40 (m, 4 H) 4.64-4.75 (m, 1 H) 7.50-7.54 (m, 1 H) 7.57-7.61 (m m, 1 H) 8.26-8.31 (m, 1 H) 8.34 (d, J = 1.37 Hz, 1 H); MS (ESI) (M + H) + 491.8. Example 34 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} Methyl azetidine-3-carboxylate Step A. l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} Methyl azetidine-3-carboxylate To a solution of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (100 mg, 0. 17 mmol, see Example 10, Steps BI for its preparation) and diisopropylethylamine (0.12 ml, 0.68 mmol) at room temperature in MeCN (0.8 ml), was added methyl azetidine-3-carboxylate hydrochloride (51.5 mg, 0.34 mmol ). The solution was stirred at room temperature overnight. After evaporation of the solvent, the residue was purified by flash chromatography (0-100% ethyl acetate in hexanes, 50 minutes; 100% ethyl acetate 10 minutes; 0-2% methanol in ethyl acetate; minutes) to provide the title compound (7.8 mg, 8%). NMR? Ti (400 MHz, CD30D) d 1.50-1.55 (m, 5 H) 1.56 (s, 9 H) 2.23-2.36 (m, 1 H) 3.29 (s, 3 H) 3.30-3.42 (m, 211) 3.75 (s, 3 H) 3.95-4.08 (m, 4 H) 4.10-4.23 (m, 4 H) 7.28-7.31 (m, 2 H) 7.71-7.74 (m, 1 H); MS (ESI) (M + H) + 478.8. Step B. Methyl azetidine-3-carboxylate hydrochloride To a stirred suspension of 3-azetidinecarboxylic acid in methanol at 0 ° C, S0C12 was added dropwise. After 20 minutes, the ice bath was removed, the solution was warmed to room temperature and stirred for 2 hours. The solvent was removed in vacuo to give the title compound as its hydrochloride salt (1.5g, 100%). NMR XH (400 MHz, CD30D) d 3.71-3.77 (m, 1 H) 3.77 (s, 3 H) 4. 18-4.31 (m, 4 H). Example 35 N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] hexahydro-N-methyl-lH-azepin-1 -sulfonamide Step A. N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] -lH-benzimidazol-5-yl] hexahydro-N-methyl-4H-azepine -l-sulfonamide To a solution of 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (100 mg, 0. 22 mmol, see Example 10, Steps B-I for its preparation) and diisopropylethylamine (0.045 ml, 0.26 mmol) at room temperature. environment in DMF (1.2 ml), hexamethyleneimine (0.025 ml, 0.22 mmol) was added. The solution was stirred at 80 ° C for 1 hour. After evaporation of the solvent, the residue was purified by reverse phase HPLC (20-50% MeCN in water) to give the title compound as its TFA salt (23 mg, 18%). XH NMR (400 MHz, CDC13) d 1.54-1.61 (m, 8 H), 1.71 (m, 13 H), 2.27-2.35 (m, 1 H), 3.26 (s, 3 H), 3.30-3.37 (m , 6 H), 4.01-4.03 (m, 2 H), 4.34 (d, J = 7.42 Hz, 2 H), 7.48 (d, J = 8.96 Hz, 1 H), 7.68 (dd, J = 8.96, 1.79 Hz, 1 H), 7.88 (d, J = 1.79 Hz, 1 H); MS (ESI) (M + H) + 463.0; Analysis (C, H, N) calculated for C24H3gN03S + 1.30 CF3COOH + 1.10 water: C 50.66, H 6.63, N 8.88;. found C 50.64, H 6.59, N 8.92. Example 36 N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] -lH-benzimidazol-5-yl] -N, 4-dimethyl-l-piperidine sulfonamide To a solution of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (100 mg, 0.22 mmol, see Excerpt 10, Steps B-I for its preparation) and diisopropylethylamine (0.045 ml, 0.26 mmol) at room temperature in DMF (1.0 ml), 4-methylpiperidine (0.026 ml, 0.22 mmol) was added. The solution was stirred at 80 ° C for 1.5 hours. After evaporation of the solvent, the residue was purified by reverse phase HPLC (20-50% MeCN in water) to give the title compound as its TFA salt (273 mg, 22%). NMR? Ti (600 MHz, CDC13) d 0.93 (d, 3 = 6.67 Hz, 3 H), 1.17-1.25 (m, 2 H), 1.46-1.66 (m, 7 H), 1.71 (s, 9 H) , 2.27-2.35 (m, 1 H), 2.79-2.83 (m, 2 H), 3.29 (s, 3 H), 3.33-3.37 (m, 2 H), 3.65-3.67 (m, 2 H), 4.02 -4.03 (m, 2 H), 4.34-4.35 (d, 2 H), 7.49 (d, J = 8.96 Hz, 1 H), 7.67 (d, J = 8.96 Hz, 1 H), 7.91 (s, 1 H); MS (ESI) (M + H) + 463.0; Analysis (C, H, N) calculated for C24H38N 03S + 1.40 CF3COOH + 0.30 water: C 51.28, H 6.42, N 8.93; found C 51.36, H 6.34, N 8.79. Example 37 N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2 H -pyran-4-yl) methyl] -lH-benzimidazol-5-yl] -3- (hydroxymethyl) -N-methyl -1-piperidinsulf onamide To a solution of l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (met il) amino] sui onyl} - 3-met i 1- lH-imide zol-3-io (100 mg, 0.22 mmol, see Example 10, Steps BI for its preparation) and diisopropylethylamine (0.045 ml, 0.26 mmol) at room temperature in DMF (1.0 ml), 3-piper idin-methanol (25.3 mg, 0.22 mmol) was added. ). The solution was stirred at 80 ° C for 1.5 hours. After evaporation of the solvent, the residue was purified by reverse phase HPLC (10-90% MeCN in water) to give the title compound as its TFA salt (24.3 mg, 19%). 1 H NMR. (600 MHz, CDC13) d 1.04-1.10 (m, 1 H), 1.52-1.61 (m, 5 H), 1.71 (m, 12 H), 1.79-1.87 (m, 1 H), 2.28-2.35 (m , 1 H), 2.59-2.62 (m, 1 H), 2.87-2.90 (m, 1 H), 3.31 (s, 3 H), 3.323.38 (m, 3 H), 3.60-3.65 (m, 3 H), 4.02-4.04 (m, 2 H), 4.36 (d, J = 7.42 Hz, 2 H), 7.50 (d, J = 8.70 Hz, 1 H), 7.67 (d, J = 8.70 Hz, 1 H ), 8.07 (s, 1 H); MS (EST) (M + H) + 479.0; Analysis (C, H, N) calculated for C 24 H 38 N 40 S + 1.30 CF 3 COOH + 0.90 water + 0.20 CH 3 OH: C 49.56, H 6.50, N 8.63; found C 49.53, H 6.48, N 8.58.

EXAMPLE 38 N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] -lH-benzimidazol-5-yl] -4-hydroxy-N-methyl-1 -piperidine sulfonamide To a solution of 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-methylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io (100 mg, 0.22 mmol, see Example 10, Steps BI for its preparation) and diisopropylethylamine (0.045 ml, 0.26 mmol) at room temperature in DMF (1.0 ml), was added 4-hydroxypiperidine (22.3 mg, 0.22 mmol). The solution was stirred at 80 ° C for 1.5 hours. After evaporation of the solvent, the residue was purified by reverse phase HPLC (10-95% MeCN in water) to give the title compound as its TFA salt (18.9 mg, 15%). NMR? Ti (600 MHz, CDC13) d 1.54-1.65 (m, 6 H), 1.72 (s, 9 H), 1.86-1.90 (in, 2 H), 2.28-2.36 (m, 1 H), 3.07- 3.11 (m, 2 H), 3.33 (s, 3 H), 3.33-3.38 (m, 2 H), 3.48-3.52 (m, 2 H), 3.79-3.82 (m, 1 H), 4.02-4.04 ( m, 2 H), 4. 36 (d, J = 7.42 Hz, 2 H), 7.51 (d, J = 8.96 Hz, 1 H), 7.68 (dd, J = 8.96, 1.66 Hz, 1 H), 8.07 (d, J = 1.66 Hz, 1 H); MS (ESI) (M + H) + 465.0; Analysis (C, H, N) calculated for C23H36N404S + 1.10 CF3COOH + 0.30 water + 0.40 CH3OH: C 50.55, H 6.51, N 9.21; found C 50.53, H 6.50, N 9.19. Example 39 N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] -lH-benzimidazol-5-yl] -4-methoxy-N-methyl-1 -piperidine sulfonamide To a solution of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-methylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-1H-imidazol-3-io (100 mg, 0.22 mmol, see Example 10, Steps BI for its preparation) and diisopropylethylamine (0.090 ml, 0.53 mmol) at room temperature in DMF (1.0 ml), was added 4-methoxypiperidine hydrochloride (25.3 mg, 0.22 mmol). The solution was stirred at 80 ° C for 1 hour. After evaporation of the solvent, the residue was purified by reverse phase HPLC (20-50% MeCN in water) to give the title compound as its TFA salt (6.74 mg, 5%). MS (ESI) (M + H) + 479.0.

EXAMPLE 40 N- [2- (1,1-Dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] -lH-benzimidazol-5-yl] -3-hydroxy-N-methyl-1 -piperidine sulfonamide To a solution of l-. { [[2-tert-but? Ll- (tetrahydro-2H-p? Ran-4? Lmet? L) -lH-benz? M? Dazol-5? L] (methyl) amino] sulfon? } -3-met? L-lH-? M? Dazol-3-? O (100 mg, 0.22 mmol, see Example 10, Steps BI for its preparation) and diisopropylethylamine (0.090 ml, 0.53 mmol) at room temperature in DMF ( 1.0 ml), 3-h? Drox? P? Per? Dma was added (22.3 mg, 0.22 mmol). The solution was stirred at 80 ° C for 1 hour.

After evaporation of the solvent, the residue was purified by reverse phase HPLC (10 to 90% MeCN in H20) to give the title compound as its TFA Salt (16.0 mg, 13%). MS (ESI) (M + H) + 465.0.

Example 41 N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylazetidine-1-sulfonamide To a triflate solution of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimide zol-5-yl] (methyl) amino] sulfonyl} 3-methyl-1H-imide zol-3-io in acetonitrile (2.8 ml, 0.344 mmol) (for the preparation, see Example 2, Step G) azetidine (35 μl, 0.516 mmol) was added. The reaction mixture was stirred at room temperature overnight, then Hunig's base (72 μl, 0.413 mmol) was added and the reaction mixture was stirred at room temperature for another day. The reaction mixture was concentrated under reduced pressure. The residue was taken up in ethyl acetate and washed with IN hydrochloric acid, 2N sodium hydroxide, brine and water. The aqueous layers were combined and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by reverse phase chromatography provided the compound of the title (14.5 mg, 10%). NMR XH (600 MHz, CD30D) d 1.40-1.53 (m, 4H), 1.57 (s, 9H), 2.14 (q, J = 7.68Hz, 2H), 2.23-2.33 (m, ÍH), 3.22 (s, 3H), 3.25 (m, 2H), 3.80 (t, J = 7.68Hz, 4H), 3.84 (dd, J = 11.26, 3.58Hz, 2H), 4.41 (d, J = 7.42Hz, 2H), 7.51 ( d, J = 8.70 Hz, HH), 7.67 (d, J = 1.79 Hz, HH), 7.80 (d, J 8.45Hz, HH); MS (ESI) (M + H) + 421.0 Example 42 N [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4,4-dif luoro -N-methylpiperidin-1-sulfonamide Following the procedure for Step A in Example 41, using 4,4-difluoropiperidine (63 mg, 0.516 mmol) and Hunig's base (72 μl, 0.413 mmol) yielded the title compound (68.4 mg, 41%). NMR? (600 MHz, CD3OD) d 1.42-1.57 (m, 4H), 1.60 (s, 9H), 1.90 (m, 4H), 2.26-2.34 (s broad, ÍH), 3.24 (s, 3H), 3.25-3.34 (m, 6H), 3.84 (dd, J = 10.75, 2.56Hz, 2H), 4.46 (d, 6.91Hz, 2H), 7.60 (d, 8.19Hz, ÍH), 7.76 (s, ÍH), 7.90 (d , J = 8.70Hz, ÍH); MS (ESI) (M + H) + 485.0 EXAMPLE 43 N- [2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -3,3-difluoro-N-methylpyrrolidine-1-sulfonamide Following the procedure for Step A in Drill 41, using 3,3-difluoropyrrolidine (55 mg, 0.516 mmol) and Hunig's base (72 μl, 0.413 mmol) provided the title compound (40.0 mg, 24%). NMR XH (600 MHz, CDsOD) d 1.40-1.55 (m, 4H), 1.59 (s, 9H), 2.22-2.37 (m, 3H), 3.21-3.31 (m, 2H), 3.25 (s, 3H), 3.44 (t, J = 7.17Hz, 2H), 3.52 (t, J = 12.80Hz, 2H), 3.84 (m, 2H), 4.45 (d, .l = 7.17Hz, 2H), 7.59 (d, J = 7.94Hz, ÍH), 7.74 (s, ÍH), 7.89 (d, J = 8.70Hz, ÍH); MS (ESI) (M + H) + 471.0 Example 44 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} iperidin-4-carboxylic acid methyl Following the procedure for Step A in the Example 41, using methyl isonipecotate (70 μl, 0.516 mmol) and Hunig's base (72 μl, 0.413 mmol) yielded the title compound (71.5 mg, 41%). NMR XH (600 MHz, CD3OD) d 1.37-1.55 (m, 6H), 1.59 (s, 9H), 1.78 (m, 2H), 2.24-2.33 (broad s, ÍH), 2.38 (m, ÍH), 2.82 (m, 2H), 3.17-3.30 (m, 2H), 3.22 (s, 3H), 3.47-3.61 (m, 2H), 3.54 (s, 3H), 3.83 (d, J = 8.45Hz, 2H), 4.45 (d, J = 7.17Hz, 2H), 7.57 (d, J = 7.94Hz, ÍH), 7.75 (s, ÍH), 7.87 (d, J = 8.45Hz, ÍH); MS (ESI) (M + H) + 507.0 Example 45 N- [2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2 -sulfonamide Following the procedure for Step A in Example 41, using isoxazolidine (57 mg, 0.516 mmol) and Hunig's base (132 μl, 0.757 mmol) yielded the title compound (51.3 mg, 34%). 1N-NMR (600 MHz, CD3OD) d 1.43-1.56 (m, 4H), 1.60 (s, 9H), 2.22-2.35 (m, 3H), 3.26 (m, 2H), 3.37 (s, 3H), 3.47 ( t, J = 7.17Hz, 2H), 3.85 (m, 2H), 4.03 (t, J = 7.30Hz, 2H), 4.46 (d, J = 7.17Hz, 2H), 7.63 (dd, J = 8. 70, 1.02Hz, ÍH), 7.80-7.84 (d, J = 1.28Hz, ÍH), 7.88 (d, J = 8.96Hz, ÍH); MS (ESI) (M + H) + 437.0 Example 46 (4R) -N- [2-tert-butyl-1- (tetrahydro-2 H-? Iran-4-ylmethyl) -1 H -benzimidazol-5-yl] - 4-hydroxy-N, 4-dimethylisoxazolidine-2-sulfonamide Following the procedure for Step A in Example 41, using 4-methylisoxazolidin-4-ol (57 mg, 0.41 mmol) and Hunig's base (57 μl, 0.33 mmol) yielded the title compound. NMR * H (600 MHz, CD30D) d 1.35 (s, 3H), 1.41-1.55 (m, 4H), 1.57 (s, 9H), 2.22-2.33 (m, ÍH), 3.19 (s, 3H), 3.24 (m, 2H), 3.30-3.36 (m, 2H), 3.46 (d, J = 11.52Hz, ÍH), 3.77-3.90 (m, 4H), 4.43 (d, J = 7.42Hz, 2H), 7.61 ( d, J = 8.96Hz, ÍH), 7.79 (s, ÍH), 7.85 (d, J = 8.96Hz, ÍH); MS (ESI) (M + H) + 467.0 Example 47 N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino} sulfonyl. piperidin-4-yl) acetamide Step B. N- (l-. {[[[2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl. piperidin-4-yl) acetamide To a solution of 4-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylpiperidine-1-sulfonamide in dichloromethane ( 0.516 mmol) (the preparation thereof followed the same procedure as for the synthesis of a compound in Example 1, Step J, using 4-tetrahydropyranmethylamine as the coupling reagent for the SNAr reaction) was added triethylamine (143 μL; 1032 mmol) followed by acetyl chloride (44 μl, 0.619 mmol). The reaction mixture was stirred at room temperature for two hours then it was washed with water. The aqueous layer was extracted with dichloromethane. The combined dichloromethane extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by reverse phase chromatography afforded the title compound (143.8 mg, 55%). NMR XH (600 MHz, CD3OD) d 1.29-1.40 (m, 2H), 1.40-1.54 (m, 4H), 1.58 (s, 9H), 1.74 (m, 2H), 1.81 (s, 3H), 2.27 ( s broad, ÍH), 2.83 (m, 2H), 3.21 (s, 3H), 3.24 (m, 2H), 3.57 (m, 2H), 3.62 (t, J = 10.88Hz, ÍH), 3.83 (dd, J = 11.52, 2.56Hz, 2H), 4.44 (d, J = 7.42Hz, 2H), 7.58 (d, J = 8.70Hz, ÍH), 7.72 (s, ÍH), 7.87 (d, J 8.96Hz, ÍH) ); MS (ESI) (M + H) + 506.0 Example 48 N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl ] (methyl) amino] sulfonyl.}. piperidin-4-yl) -2,2-dimethylpropanamide Following the procedure for Step B in the Example 47, using trimethylacetyl chloride (76 μl; 0. 619 mmol) and triethylamine (143 μl, 1032 mmol) yielded the title compound (138.1 mg, 49%). NMR 1H (600 MHz, CD3OD) d 1.04 (s, 9H), 1.37-1.53 (m, 6H), 1.55 (s, 9H), 1.68 (m, 2H), 2.21-2.32 (m, ÍH), 2.77 (m , 2H), 3.20 (s, 3H), 3.24 (m, 2H), 3.57-3.67 (m, 3H), 3.83 (m, 2H), 4.38 (d, J = 7.42Hz, 2H), 7.48 (dd, J = 8.83, 1.41Hz, 11-1), 7.68 (d, J = 1.54Hz, ÍH), 7.75 (d, J = 8.96Hz, ÍH); MS (ESI) (M-I-H) + 548.0. Example 49 [1- ( {methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperidin-4-yl ] tert-butyl carbamate Step A. [1- ( {methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperidin-4- tert-butyl-ilicarbamate Following the procedure in Step I of Example 1, 3-methyl-1- (4-methyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} - sulfonyl) - 1H-imidazol-3-io (crude product, 1.0 mmol) (see the following Steps B), C, D, E, F, G and H for the preparation) was reacted with tert-butyl piperidin-4-ylcarbamate (0.40 g, 2.0 mmol). The crude product was purified by MPLC using hexanes / ethyl acetate (1: 1) on silica gel to give 0.33 g (55%) of a white solid as the title compound. XH NMR (400 MHz, CHLOROFORM-D): d 1.41 (s, 9H), 1.44-1.54 (m, 4H), 1.77-1.93 (m, 3 5H), 2.20-2.33 (m, ÍH), 2.83-2.97 (m, 3H), 3.29 (s, 3H), 3.32-3.44 (m, 3H), 3.57-3.69 (m, 3H), 3.88-3.97 (m, 2H), 4.33 (d, J = 7.42 Hz, 2H ), 7.58 (dd, J = 8.79, 1.95 Hz, ÍH), 7.78 (d, J = 8.79 Hz, ÍH), 7.85 (d, J = 2.15 Hz, ÍH). MS (ESI) (M + H) + = 576.0. Analysis Calculated for C25H36F3N5? 5S + 0.10 for TFA + 0.10 for H20 + 0.40 for CH3OH (624.10): C, 51.58; H, 6.38; N, 11.22; Found: C, 51.56; H, 6.31; N, 11.27. Step B. N- (4-fluoro-3-nitrophenyl) acetamide The 4-fluoro-3-nitro-aniline (45.0 g, 0.288 mol) was added in portions to 150 ml of acetic anhydride at room temperature. The reaction mixture was stirred at room temperature for 2 hours. The white solid is collected and dried in vacuo to give the title compound (42.0 g, 70%). XH NMR (400 MHz, CHLOROFORM-D): d 2.23. (s, 3H), 7.26 (m, ÍH), 7.50 (s broad, ÍH), 7.87 (m, ÍH), 8.23 (dd, J = 6.44, 2.73 Hz, ÍH). Step C. N- (4-Fluoro-3-nitrophenyl) -N-methylacetamide Sodium hydride (4.22 g, 60%, 106 mmol) was added in portions to a solution of N- (4-fluoro-3-nitrophenyl) acetamide (13.9 g, 70 mmol) (for the preparation, see Step B in Example 1) in THF (200 ml) at 0 ° C.

Stirring for 20 minutes, iodomethane (18.5 g, 130 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours, quenched with 30 ml of saturated sodium hydrogen carbonate and extracted with ethyl acetate (3x100 ml). The organic phases were washed with saturated sodium chloride (2x50 ml). After filtration and concentration, 13.1 g (88%) of the title compound was obtained as a yellow solid. NMR XH (400 MHz, CHLOROFORM-D): d 1.92 (s, 3H), 3. 30 (s, 3H), 7.38 (s, ÍH), 7.52 (s, ÍH), 7.95 (s, ÍH).

Step D. N-methyl-N-. { 3-Nitro-4- [(tetrahydro-2 H -pyran-4-ylmethyl) amino] phenyl} acetamide 4-Aminomethyltetrahydropyran (10.0 g, 86.5 mmol) was added to a mixture of N- (4-fluoro-3-nitrophenyl) -N-methylacetamide (15.6 g, 73.3 mmol) and TEA (15.3 mL, 11.1 g, 110 mmol) in 300 ml ethanol at room temperature. The reaction mixture was heated for 6 hours to reflux. After evaporation of the ethanol, the residue was dissolved in 400 ml of ethyl acetate, washed with 3 portions of 50 ml of water, 50 ml portions of saturated sodium chloride, and dried over sodium sulfate. After filtration and concentration, 21.7 g (96%) of the title compound was obtained as an orange-red solid. 1 H NMR (400 MHz, CHLOROFORM-D): d 1.38-1.52 (m, 2H), 1.72-1.81 (m, 2H), 1.90 (s, 3H), 1.93-2.02 (m, ÍH), 3.23 (s, 3H), 3.23-3.27 (m, 2H), 3.36-3.49 (m, 2H), 4.01-4.07 (m, 2H), 6.91 (d, J = 9.18 Hz, ÍH), 7.29 (dd, J = 9.08, 2.64 Hz, HH), 8.05 (d, J = 2.34 Hz, HH), 8.22 (t, J = 5.37 15 Hz, HH). MS (EST) (M + H) + = 309.12.

Step in-. { 3-amino-4- [(tetrahydro-2 H -pyran-4-ylmethyl) amino] phenyl} -N-methylacetamide The N-methyl-N-. { 3-Nitro-4- [(tetrahydro-2 H -pyran-4-ylmethyl) amino] phenyl} acetamide (21.7 g, 70.5 mmol) was hydrogenated in 500 ml of ethyl acetate catalyzed with 10% Pd / C (1.0 g) at 2.11-2.81 kg / cm2 (30-40 psi) of hydrogen on a Parr shaker by 18 hours at room temperature. After filtration through celite and concentration, 19.6 g (100%) of a purple solid was obtained. NMR? Ti (400 MHz, CHLOROFORM-D): d 1.35-1.50 (m, 2H), 1.67 (s, ÍH), 1.73-1.81 (m, 2H), 1.88 (s, 3H), 1.88-1.99 (m , ÍH), 3.04 (d, J = 6.64 Hz, 2H), 3.20 (s, 3H), 3.33-3.48 (m, 4H), 3.97-4.08 (m, 2H), 6.54 (d, J = 1.76 Hz, ÍH), 6.60-6.63 (m, 2H); MS (ESI) (M + H) + = 278.7 Step F. N -methyl-N [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] acetamide A solution of N- hydrochloride. { 3-amino-4- [(Tetrahydro-2H-pyran-4-ylmethyl) amino] phenyl] -N-methylacetamide (2.77 g, 10 mmol) in 60 ml of trifluoroacetic acid was heated to reflux for 18 hours. After evaporation of the solvent, the residue was dissolved in ethyl acetate (200 ml), washed with 2N sodium hydroxide (2x10 ml) and dried over sodium sulfate. The crude product was purified by MPLC using ethyl acetate on silica gel to give 3.18 g (90%) of a white solid as the title compound. MS (ESI) (M + H) + = 356.02. Step G. N-methyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazole-5-amine t The N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] acetamide (3.18 g, 8.95 mmol) was dissolved in hydrochloric acid ( 37%, 60 ml) and then heated to 95 ° C. After concentration, the residue was treated with 20 ml of 2N sodium hydroxide, extracted with ethyl acetate (4 × 50 ml). The combined organic phases were washed with 20 ml of brine and dried over sodium sulfate. After evaporation, 2.80 g (100%) of a white-purple solid was obtained as the product of the title, which was used directly for Step H, MS (ESI) (M + H) + = 314.20. Step H. 3-Methyl-l- (. {Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} - sulfonyl) - lH-imidazol-3-io Following the procedure in Step H of Example 1, N-methyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-amine (0.32 g, 1.0 mmol) was converted to 3-methyl-l- (. {Methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) -lH-imidazol-3-yl, which it was used in Step A without any purification.

EXAMPLE 50 4- (. {Methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperazine-1-carboxylate ter -butyl Following the procedure in Step I of Example 1, 3-methyl-l- (. {Methyl} [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) -lH-imidazol-3-io (crude product, 1.10 mmol) (for the preparation see Step H in Example 4) was reacted with tert-butyl piperazine-1-carboxylate (0.38 g, 2.0 mmol). The crude product was purified by MPLC using Hexanes / ethyl acetate (1: 1) on silica gel to give 0.28 g (45%) of a white solid as the title compound. 1 H NMR (400 MHz, CHLOROFORM-D): d 1.43 (s, 9H), 1.45-1.54 (m, 4H), 2.19-2.33 (m, ÍH), 3.15-3.22 (m, 4H), 3.32 (s, 3H), 3.33-3.37 (m, 2H), 3.38-3.45 (m, 4H), 3.87-3.97 (m, 2H), 4.33 (d, J = 7.62 Hz, 2H), 7.60 (dd, J = 8.89, 2.05 Hz, HH), 7.79 (d, J = 8.59 Hz, HH), 7.87 (d, J = 1.76 Hz, HH); MS (ESI) (M + H) + = 562. 0; Anal i s i Cal culated for C24H34 F3N5? 5S + 0. 70 ethyl acetate (623.30): C, 51.64; H, 6.40; N, 11.24; Found: C, 51.60; H, 5.80; N, 11.13. Example 51 4-. { [(cyclopropylamino) carbonyl] amino} -N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -1H-benzimidazol-5-yl] piperidin-1-sulfonamide Step A. 4-. { [(cyclopropylamino) carbonyl] amino} -N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -1H-benzimidazol-5-yl] piperidin-1-sulfonamide A solution of isocyanatocyclopropane in THF (10 mmol) (freshly prepared from cyclopropylamine and triphosgene) was added to a solution of 4-amino-N-methyl-N- [1- (tetrahydro-2H-pyran-4-) ylmethyl) -2- (trifluoromethyl) -1H-benzimidazol-5-yl] piperidin-l-sulfonamide (38 mg, 0.08 mmol) (see Step B below for preparation) in 3 mL of THF) at room temperature. The mixture was stirred for 1 hour.

After evaporation, the crude product was purified by MPLC using ethyl acetate / MeOH (20: 1) on silica gel to give 45 mg (100%) of a white solid as the title compound. XH NMR (400 MHz, METHANOL-D4): d 0.34-0.47 (m, 2H), 0.59-0.71 (m, 2H), 1.33-1.53 (m, 6H), 1.77-1.87 (m, 2H), 2.16- 2.30 (m, ÍH), 2.36-2.46 (m, ÍH), 2.83-2.94 (m, 2H), 3.28 (s, 3H), 3.30-3.37 (m, 2H), 3.51-3.59 (m, ÍH), 3.58 -3.68 (m, 2H), 3.82-3.95 (m, 2H), 4.31 (d, J = 7.62 Hz, 2H), 7.57 (dd, J = 8.89, 2.05 Hz, ÍH), 7.76 (d, J = 8.98 Hz, ÍH), 7.83 (d, J = 1.76 Hz, ÍH); MS (ESI) (M + H) + = 559.0; Analysis Calculated for C24H33N6O SF3 + 0.60 for TFA + 0.30 for H20 + 0.10 for CH3OH (635.65): C, 47.81; H, 5.49; N, 13.22; Found: C, 47.83; H, 5.45; N, 13.20. Step B. 4-Amino-N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperidin-1- 3 ml of TFA was added to a solution of [1- (. {Methyl] -1- (tetrahydro-2H-pyran-methylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino}. sulfonyl) piperidin-4-yl] tert-butyl carbamate (210 mg, 0. 365 mmol) in DCM (3 ml) at 0 ° C. The mixture was stirred for 1 hour. After evaporation, the residue was dissolved in DCM (50 ml), washed with 2N sodium hydroxide (2x5 ml), brine (5 ml) and dried over sodium sulfate. After concentration, 168 mg (97%) of a white solid was obtained as the title compound. MS (ESI) (M + H) + = 475. 99. EXAMPLE 52 N-Cyclopropyl-4- (. {Methyl} [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperazine-l-carboxamide Step A. N-Cyclopropyl-4- (. {Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperazine -1-carboxamide Following the procedure in Step A of the Example 51, using N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide (38 mg, 0.083 mmol ) (see next Step B for preparation) and an isocyanatocyclopropane solution in THE (1 mmol). The crude product was purified by MPLC using ethyl acetate / MeOH (20: 1) on silica gel to give 45 mg (99%) of a white solid as the title compound. 1 H NMR (400 MHz, METHANOL-D4): d 0.39-0.44 (, 2H), 0.60-0.68 (m, 2H), 1.44-1.47 (m, 4H), 2.19-2.35 (m, ÍH), 2.47-2.55 (m, ÍH), 3.13-3.22 (m, 4H), 3.32 (s, 3H), 3.32-3.38 (m, 6H), 3.86-3.99 (m, 2H), 4.33 (d, J = 7.81 Hz, 2H ), 7.59 (dd, J = 8.89, 2.05 Hz, ÍH), 7.79 (d, J = 8.98 Hz, ÍH), 7.86 (d, J = 1.76 Hz, ÍH); MS (ESI) (M + H) + = 545.0; Analysis Calculated for C23H3? F3N6O4S + 0.70 TFA (624.42): C, 46.94; H, 5.12; N, 13.46; Found; C, 46.90; H, 4.65; N, 13.45. Step B. N-Methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide Following the procedure in Step B of Example 51, 4- (. {Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino. Sulfonyl) piperazine-1-carboxylic acid tert-butyl ester (234 mg, 0.417 mmol) was treated with TFA (3 ml) in DCM (3 ml). 176 mg (91%) of a white solid was obtained as the title compound. MS (ESI) (M + H) + = 461.96.

Example 53 4-. { [(isopropylamino) carbonyl] amino} -N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperidin-l-sulfonamide Following the procedure in Step A of the Example 51, using 4-amino-N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperidin-1-sulfonamide (38 mg, 0.08 mmol) and 0.2 ml of 2-isocyanatopropane in 3 ml of THF. The crude product was purified by MPLC using ethyl acetate / MeOH (20: 1) on silica gel to give 38 mg (85%) of a white solid as the title compound. 1 H-NMR (400 MHz, METHANOL-D4): d8 1.07 (d, J = 6.45 Hz, 6H), 1.29-1.40 (m, 2H), 1.40-1.53 (m, 4H), 1.78-1.87 (m, 2H) , 2.17-2.31 (m, ÍH), 2.85-2.95 (m, 2H), 3.28 (s, 3H), 3.30-3.37 (m, 2H), 3.48-3.56 (m, ÍH), 3.56-3.66 (m, 2H), 3.68-3.81 (m, ÍH), 3.85-3.98 (m, 2H), 4.31 (d, J = 7.62 Hz, 2H), 7.57 (dd, J = 8.89, 2.05 Hz, ÍH), 7.76 (d , J = 8.98 Hz, 1 El), 7.83 (d, J = 1.56 Hz, ÍH); MS (ESI) (M + H) + = 561.0; Analysis Calculated for C 24 H 35 F 3 N 6 O 4 S + 0.70 TFA + (640.46): C, 47.63; H, 5.62; N, 13.12; Found: C, 47.64; H, 5.51; N, 13.26.

Example 54 N-isopropyl-4- (. {Methyl} 1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperazine- 1-carboxamide Following the procedure in Step A of the Example 51, using N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide (40 mg, 0.087 mmol ) and 0.2 ml of 2-isocyanatopropane in 3 ml of THF. The crude product was purified by MPLC using EtOAc / MeOH (20: 1) on silica gel to give 48 mg (100%) of a white solid as the title compound. XH NMR (400 MHz, METHANOL-D4): d 1.09 (d, J = 6.45 Hz, 6H), 1.38-1.53 (m, 4H), 2.15-2.34 (m, HH), 3.14-3.21 (m, 4H) , 3.31 (s, 3H), 3.33-3.40 (m, 6H), 3.78-3.87 (m, ÍH), 3.87-3.95 (m, 2H), 4.31 (d, J = 7.62 Hz, 2H), 7.58 (dd) , J = 8.89, 2.05 Hz, HH), 7.77 (d, J = 8.79 Hz, HH), 7.85 (d, J = 1.76 Hz, HH); MS (ESI) (M + H) + = 547.0; Analysis Calculated for C 23 H 33 F 3 N 6 O 4 S + 0.50 TFA + 0.20 H 20 + 0.40 CH 3 OH (613.64): C, 47.37; H, 5.70; N, 13.70; Found: C, 47.41; H, 5.62; N, 13.65.

Example 55 N- [1- (. {Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperidin-4 -il] acetamide Acetyl chloride (9 mg, 0.11 mmol) was added to a solution of 4-amino-N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH- benzimidazol-5-yl] piperidin-i-sulfonamide (45 mg, 0.094 mmol) and triethylamine (12 mg, 0.12 mmol) in 5 ml of DCM at 0 ° C. The mixture was stirred for 3 hours at room temperature. After evaporation, the crude product was purified by MPLC using ethyl acetate / MeOH (10: 1) on silica gel to give 49 mg (100%) of a white solid as the title compound. NMR - "" H (400 MHz, METHANOL-D4): d 1.36-1.55 (m, 6H), 1.79-1.87 (m, 2H), 1.90 (s, 3H), 2.19-2.33 (m, ÍH), 2.86 -2.96 (m, 2H), 3.30 (s, 3H), 3.32-3.38 (m, 2H), 3.63-3.70 (m, 2H), 3.70-3.78 (m, ÍH), 3.89-3.96 (m, 2H) , 4.33 (d, J = 7.62 Hz, 2H), 7.59 (d, J = 8.89, 2.05 Hz, HH), 7.78 (d, J = 8.98 Hz, HH), 7.85 (d, J = 1.95 Hz, HH); MS (ESI) (M + H) + = 518.0 Analáls i Calculated for C22H30F3N5O4S + 0. 60 T FA + 0. 10 CH3OH (589.19): C, 47.50; H, 5.30; N, 11.89; Found: C, 47.61; H, 5.32; N, 11.82 EXAMPLE 56 2, 2-Dimethyl-N- [1- (. {Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.}. sulfonyl) piperidin-4-yl] propanamide Following the procedure in Example 55, using 4-amino-N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperidin -1-sulfonamide (45 mg, 0.094 mmol), 2,2-dimethylpropanoyl chloride (14 mg, 0.11 mmol) and triethylamine (12 mg, 0.12 mmol) in DCM (5 mL). The crude product was purified by MPLC using ethyl acetate / Hex (2: 1) on silica gel to give 44 mg (84%) of a white solid as the title compound. X H NMR (400 MHz, METAN0L-D4): d 1.12 (s, 9H), 1.38-1.56 (m, 6H), 1.75-1.78 (m, 2H), 2.14-2.34 (m, ÍH) 2.80-2.90 (m , 2H), 3.28 (s, 3H), 3.30-3.39 (m, 2H), 3.61-3.79 (m, 3H), 3.86-3.98 (m, 2H), 4.32 (d, J = 7.62 Hz, 2H), 7.57 (dd, J = 8.98, 1.95 Hz, ÍH), 7.76 (d, J = 8.79 Hz, ÍH), 7. 84 (d, J = 1.95 Hz, ÍH); MS (ESI) (M + H) + = 560.0; Analysis Calculated for C 25 H 36 F 3 N 5 O 4 S + 0.50 TFA (616.67): C, 50.64; H, 5. 97; N, 11.36; Found: C, 50.76; H, 5.99; N, 11.37. Example 57 2-methyl-N- [1- (. {Methyl (1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl piperidin-4-yl] propanamide Following the procedure in Example 55, using 4-amino-N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperidin -1-sulfonamide (45 mg, 0.094 mmol), 2-methylpropanoyl chloride (11 mg, 0.11 mmol) and triethylamine (12 mg, 0.12 mmol) in 5 mL of DCM the crude product was purified by MPLC using ethyl acetate. Hex (2: 1) on silica gel to give 46 mg (89%) of a white solid as the title compound. 1 H NMR (400 MHz, METANOL-D4): d 1.05 (d, J = 6.84 Hz, 6H), 1.35-1.54 (m, 6H), 1.76-1.86 (m, 2H), 2.17-2.30 (m, ÍH), 2.32 -2.44 (m, ÍH), 2.83-2.95 (m, 2H), 3.28 (s, 3H), 3.29-3.37 (m, 2H), 3.58-3.76 (m, 3H), 3.85-3.98 (m, 2H), 4.31 (d, J = 7. 42 Hz, 2H), 7.57 (dd, J = 8.89, 2.05 Hz, HH) 7.76 (d, J = 8.98 Hz, HH), 7.83 (d, J = 1.95 Hz, HH); MS (ESI) (M + H) + = 546.0; Analysis Calculated for C2 H34F3N5O S + 0.10 TFA (557.03): C, 52.18; H, 6.17; N, 12.57; Found: C, 52.44; H, 6.03; N, 12.44. Example 58 4-Acetyl-N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide Following the procedure in Example 55, using N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-suifonamide (43 mg, 0.096 mmol), triethylamine (12 mg, 0.12 mmol) and acetyl chloride (9 mg, 0.12 mmol) in 5 mL of DCM. The crude product was purified by MPLC using ethyl acetate / MeOH (20: 1) on silica gel to give 45 mg (92%) of a white solid as the title compound. 1 H NMR (400 MHz, METHANOL-D4): d 1.39-1.52 (m, 4H), 2.06 (s, 3H), 2.17 2. 33 (m, ÍH), 3.17-3.27 (m, 4H), 3.31 (s, 3H), 3.32-3.36 (m, 2H), 3.49-3.59 (m, 4H), 3.86-3.96 (m, 2H), 4.31 (d, J = 7.62 Hz, 2H), 7.58 (dd, J = 8.79, 2.15 Hz, ÍH), 7.77 (d , J = 8.98 Hz, ÍH), 7.85 (d, J = 1.76 Hz, ÍH); MS (ESI) (M + H) '"= 504.0; Calculated Analysis for C2? H28F3N5O4S + 0.60 TFA +0.10 CH3OH (575.17): C, 46.57; H, 5.08; N, 12.18; Found: C, 46.67; H, 5.13; N, 12.16 Example 59 4- (2,2-Dimethylpropanoyl) -N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazole-5 -yl] piperazine-l-sulfonamide Following the procedure in Example 55, using N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-suifonamide (43 mg, 0.096 mmol), triethylamine (12 mg, 0.12 mmol) and 2,2-dimethylpropanoyl chloride (14 mg, 0.12 mmol) in 5 mL of DCM. The crude product was purified by MPLC using EtOAc / Hex (2: 1) on silica gel to give 51 mg (97%) of a white solid as the title compound. XH NMR (400 MHz, METHANOL-D4): d 1.22 (s, 9H), 1.40-1.54 (m, 4H), 2.17-2.31 (m, ÍH), 3.17-3.23 (in, 4H), 3.30-3.36 ( m, 2H), 3.31 (s, 3H), 3.61-3.68 (m, 4H), 3.86-3.95 (m, 2H), 4.31 (d, J = 7.62 Hz, 2H), 7.58 (dd, J = 8.89, 2.05 Hz, HH), 7.77 (d, J = 8.79 Hz, HH), 7.85 (d, J = 1.95 Hz, HH); MS (ESI) (M + H) + = 546.0; Analysis Calculated for C 24 H 34 F 3 N 5 O 4 S + 0.30 TFA +0.20 CH 3 OH (586.24): C, 50.81; H, 6.03; N, 11.95; Found: C, 50.81; H, 5.99; N, 11.90. Example 60 N- (l- { [ {2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} - (methyl) amino] sulfonyl .}. piperidin-4-yl) acetamide Step A. N- (l- { [ {2-tert -Butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} - (methyl) amino] sulfonyl .}. piperidin-4-acetamide Acetic anhydride (2.0 mmol) was added to a solution of triethylamine (2.0 mmol) and 4-amino-N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpiperidin-1-sulfonamide (crude product from Step D, 0.9 mmol) in CH2C12 (20 ml). After shaking room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was then purified by chromatography on silica gel (ethyl acetate to MeOH / ethyl acetate (1: 9)) to give the N- (l- { [. {2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl.}. (Methyl) amino] sulfonyl.] Piperidin-4-yl) acetamide as a solid (235 mg, 48% for Steps AD ). 1 H NMR (400 MHz, CD3OD, TFA salt) d 1.28 (m, 2H), 1.40-1.76 (m, 8H), 1.64 (s, 9th), 1.88 (s, 3H), 2.04 (m, 2H), 2.24 (m, ÍH), 2.90 (m, 2H), 3.28 (s, 3H), 3.68 (m, 3H), 4.50 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz, ÍH) ), 7.77 (s, ÍH), 7.86 (d, J = 8.0 Hz, ÍH). Step B. triflate of l-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexylmethyl) -lH-benzimidazol-5-yl} - (methyl) amino] sulfonyl} - 3-methyl-1H-imidazole-3-io HN 3- (Imidazol-1-sulfonyl) -l-methyl-3H-imidazol-1-io triflate (508 mg, 1.4 mmol) was added to a solution of 2-tert-butyl-1 - [(4, 4- difluorocyclohexyl) methyl] -N-methyl-lH-benzimidazol-5-amine (300 mg, 0.9 mmol) in 10 ml of acetonitrile. After stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure. The residue was then dissolved in ethyl acetate (60 ml), washed with brine, and dried over sodium sulfate. After removing the solvents, a mixture (1: 1) of N- was provided. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl) -N-methyl-lH-imidazole-1-sulfonamide and l- triflate. { [. { 2-tert-butyl-1 - [(4,4-10 difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io, which was dissolved in 10 ml of dichloromethane. The resulting solution was treated with methyl trifluoromethanesulfonate (0.5 mmol) at 0 ° C for 2 hours. The reaction mixture was then concentrated under reduced pressure to give the triflate of I-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io as a solid, which was used in Step C without any purification.

Step C. (l- { [ {2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} - (methyl) amino] sulfonyl. piperidin-4-yl) tertiary butyl carbamate A solution of Hunig's base (1.0 mmol), triflate of l-. { [. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (crude product from Step B, 0.9 mmol) and tert-butyl piperidin-4-ylcarbamate (200 mg, 1.0 mmol) in MeCN (20 mL) was heated for 1 hour at 80 ° C. The reaction mixture was then concentrated under reduced pressure to give (l- { [. {2-tert-Butyl-1- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (tert-butyl) amino] sulfonyl}. piperidin-4-yl) carbamate as a solid, which was used directly in Step D.

Step D. 4-amino-N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpiperidin-1-sulfonamide A solution of (1- {[[{{2-tert-butyl-l- [(, 4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (meth i) amino] sulfonyl} piperidin-4 -i 1) tert-butyl carbamate (crude product from Step C, 0.9 mmol) in 10 ml of CH2C12 was treated with 10 ml TFA at room temperature. After stirring at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was then dissolved in 60 ml of ethyl acetate, washed with sodium carbonate solution and brine, and dried over sodium sulfate. After removing the solvents, 4-amino-N- was provided. { 2-t er-but il-1 - [(4, -di fluorocyclohexyl) methyl] -lH-benzimide zol-5-yl} -N-methyl-piperidin-1-sulfonamide crude, which was used in Step A without purification.

Example 61 N- (l- { [ {2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} - (methyl) amino] sulfonyl} piperidin-4-yl) -2,2-dimethylpropanamide Following the procedure in Step A of Example 60, the 4-amino-N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpiperidin-1-sulfonamide (50 mg, 0.1 mmol) was reacted with 2,2-dimethylpropanoyl chloride (24 mg, 0.2 mmol), after purification by reverse phase HPLC, to give the N- (l - { [ { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl.} - (methyl) amino] sulfonyl.] Piperidin-4-yl. ) -2,2-dimethylpropanamide (TFA salt, 7 mg, 10%). 1 H-NMR (400 MHz, CD30D, TFA salt) d 1.13 (s, 9H), 1.28 (m, 2H), 1.53 (m, 3H), 1.64 (s, 9H), 1.76 (m, 5H), 2.04 ( m, 2H), 2.24 (m, 1H), 2.87 (m, 2H), 3.28 (s, 3H), 3.68 (m, 3H), 4.50 (d, J = 7.6 Hz, 2H), 7.60 (d, J = 9.0 Hz, ÍH), 7.77 (s, ÍH), 7.86 (d, J = 9.0 Hz, 1H); MS (ESI) (M + H) + 582.0.

Example 62 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methylmorpholin-4-sulfonamide Following the procedure in Step C of the Example 60, the triflate of l-. { [. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} 3-methyl-1H-imidazol-3-io (0.1 mmol) was reacted with morpholine (35 mg, 0.4 mmol), after purification by reverse phase HPLC, to give N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylmorpholin-4-sulfonamide (TFA salt, 56 mg, 93%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.40-1.76 (m, 6H), 1.64 (s, 9H), 2.04 (m, 2H), 2.24 (m, ÍH), 3.19 (m, 4H), 3.33 (s, 3H), 3.62 (m, 4H), 4.50 (d, J = 7.4 Hz, 2H), 7.61 (d, J = 9.0 Hz, ÍH), 7.79 (s, ÍH), 7.87 (d, J = 9.0 Hz, ÍH).

Example 63 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methylpyrrolidin-1-sulfonamide Following the procedure in Step C of the Example 60, the triflate of l-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (0.1 mmol) was reacted with pyrrolidine (28 mg, 0.4 mmol), after purification by reverse phase HPLC, to give the N-. { 2-tert-butyl-l- [(, 4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpyrrolidin-1-sulfonamide (TFA salt, 26 mg, 48%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.23 (m, 2H), 1.40-1.76 (m, 6H), 1.64 (s, 9H), 1.86 (m, 2H), 2.01 (m, 2H), 2.24 (m, ÍH), 3.04 (m, 2H), 3.27 (m, 2H), 3.28 (s, 3H), 4.49 (d, J = 7.4 Hz, 2H), 7.58 (d, J = 9.0 Hz, ÍH ), 7.77 (s, ÍH), 7.84 (d, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 469.0.

Example 64 N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -3,3-difluoro-N-methylpyrrolidin-1-sulfonamide Following the procedure in Step C of the Example 60, the triflate of l-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} 3-methyl-1H-imidazol-3-io (0.1 mmol) was reacted with 3,3-difluoropyrrolidine (42 mg, 0.4 mmol), after purification by reverse phase HPLC, to give the N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} 3, 3-difluoro-N-methylpyrrolidin-1-sulfonamide (TFA salt, 18 mg, 26%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.40-1.76 (m, 6H), 1.64 (s, 9H), 2.04 (m, 2H), 2.24 (m, ÍH), 2.38 (m, 2H), 3.32 (s, 3H), 3.52 (m, 2H), 3.60 (m, 2H), 4.50 (d, J = 7.4 Hz, 2H), 7.59 (d, J = 9.0 Hz, ÍH), 7.77 (s, ÍH) ), 7.86 (d, J = 9.0 Hz, ÍH); MS (EST) (M + H) + 505.0.

Example 65 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-Methylisoxazolidin-2-sulfonamide Following the procedure in Step C of Example 60, the triflate of l-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} 3-methyl-1H-imidazol-3-io (0.1 mmol) was reacted with isoxazolidine hydrochloride (44 mg, 0.4 mmol) and Hunig's base (1.0 ml), after purification by reverse phase HPLC, to provide the N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-Methylisoxazolidin-2-sulfonamide (TFA salt, 58 mg, 99%). X H NMR (400 MHz, CD3OD, TFA Salt) d 1.401.76 (m, 6H), 1.64 (s, 9H), 2.04 (m, 2H), 2.31 (m, ÍH), 2.33 (m, 2H), 3.44 (s, 3H), 3.55 (m, 2H), 4.11 (m, 2H), 4.51 (d, J = 7.4 Hz, 2H), 7.60 (m, ÍH), 7.87 (m, 21 * 1); MS (ESI) (M + H) + 471.0.

Example 66 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -4, 4-difluoro-N-methylpiperidin-1-sulfonamide Following the procedure in Step C of the Example 60, the triflate of 1-. { [. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io (0.1 mmol) was reacted with 4,4-difluoropiperidine hydrochloride (62 mg, 0.4 mmol) and Hunig's base (1.0 ml), after being purified by HPLC of reverse phase, to provide the N-. { 2-tert-butyl-l- [(, 4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -4,4-difluoro-N-methylpiperidine-1-sulfonamide (TFA salt, 36 mg, 57%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.40-1.76 (m, 6H), 1.64 (s, 9H), 1.97 (m, 6H), 2.24 (m, ÍH), 3.31 (s, 3H), 3.38 (m, 4H), 4.50 (m, 2H), 7.60 (d, J = 9.0 Hz, ÍH), 7.78 (s, ÍH), 7.87 (d, J = 9.0 Hz, ÍH); MS (EST) (M + H) + 519.0.

Example 67 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} tert-butyl piperazin-l-carboxylate Following the procedure in Step C of the Example 60, the triflate of 1-. { [. { 2-tert-butyl-l- [(, 4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (2.0 mmol) was reacted with tert-butyl piperazine-1-carboxylate (930 mg, 5.0 mmol) and Hunig's base (1.0 mL), after being purified by chromatography on silica gel, to provide 4-. { [. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} piperazin-1-tert-butyl carboxylate (730 mg, 63%). NMR XH (400 MHz, CDC13) d 1.39 (s, 9H), 1.46 (m, 3H), 1.51 (s, 9H), 1.67 (m, 3H), 2.09 (m, 3H), 3.12 (m, 4H) , 3.25 (s, 3H), 3.35 (m, 4H), 4.16 (m, 2H), 7.22 (m, 2H), 7.28 (d, J = 8.6 Hz, ÍH), 7.67 (s, ÍH); MS (ESI) (M + H) 1 584.0.

Example 68 4-. { [. { 2-tert-butyl- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-isopropylpiperazine-1-carboxamide Step A. 4-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl) -N-isopropylpiperazine-1-carboxamide Isopropyl isocyanate (85 mg, 1.0 mmol) was added to a solution of triethylamine (1.0 mmol) and N-. { 2-tert-butyl-1- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpiperazine-l-sulfonamide (100 mg, 0.21 mmol) in CH2C12 (10 mL). After stirring at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was then purified by chromatography on silica gel (Hexane to ethyl acetate) to give 4-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-isopropylpiperazine-1-carboxamide (114 mg, TFA salt, 81%). NMR? H (400 MHz, CDC13) d 1.14 (d, J = 6.5 Hz, 6H), 1.52 (m, 3H), 1.56 (s, 9H), 1.72 (m, 3H), 2.14 (m, 3H), 3.20 (m, 4H), 3.30 (s, 3H), 3.35 (m, 4H), 3.94 (m, ÍH), 4.22 (m, 2H), 4.35 (m, ÍH), 7.28 (d, J = 8.6 Hz , ÍH), 7.32 (d, J = 8.6 Hz, ÍH), 7.72 (s, ÍH); MS (ESI) (M + H) + 569.0. Step B. N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methyl-piperazine-1-sulfonamide A solution of 4-. { [. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} Terbutyl piperazine-l-carboxylate (720 mg, 1.23 mmol) in 10 mL CH2C12 was treated with 10 mL of TFA at room temperature. After stirring at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure. The residue was then dissolved in 60 ml of ethyl acetate, washed with a solution of Sodium carbonate and brine, and dried over sodium sulfate. The elimination of the solvents gave N-. { 2-tert-Butyl-1- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} Crude -N-methylpiperazine-1-sulfonamide (434 mg, 73%), which was used in Step A without purification. Example 69 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-methylpiperazine-1-carboxamide Following the procedure in Step A of the Example 68, the N-. { 2-tert-butyl-l- [(, 4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-Methylpiperazine-1-sulfonamide (56 mg, 0.116 mmol) was reacted with methyl isocyanate (57 mg, 1.0 mmol), after being purified by chromatography on silica gel, to give 4-. { [. { 2-tert-butyl-l- [(4,4-difluorooxyhexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-methylpiperazine-l-carboxamide (TFA salt, 49 mg, 64%). NMR XH (400 MHz, CDC13) d 1.46 (m, 3H), 1.50 (s, 9H), 1.67 (m, 3H), 2.10 (m, 3H), 2.71 (m, 3H), 3.14 (m, 4H) , 3.23 (s, 3H), 3.31 (m, 4H), 4.16 (d, J = 7.4 Hz, 2H), 4.68 (m, ÍH), 7.22 (d, J = 8.6 Hz, ÍH), 7.25 (d, J = 8.6 Hz, ÍH), 7.65 (s, ÍH); MS (ESI) (M + H) + 541.0. Example 70 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclopropylpiperazine-1-carboxamide Step A. 4-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclopropylpiperazine-1-carboxamide Following the procedure in Step A of Example 68, the N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpiperazine-1-sulfonamide (54 mg, 0.112 mmol) was reacted with cyclopropyl isocyanate (1.0 mmol), after being purified by chromatography on silica gel, to provide 4 -. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclopropylpiperazin-1- carboxamide (TFA salt, 48 mg, 63%). XH NMR (400 MHz, CDC13) d 0.45 (m, ÍH), 0.54 (m, ÍH), 0.72 (m, 2H), 1.54 (m, 2H), 1.56 (s, 9H), 1.72 (m, 3H), 2.14 (m, 3H), 2.50 (m, 1H), 2.60 (m, ÍH), 3.18 (m, 4H), 3.29 (s, 3H), 3.34 (m, 4H), 4.22 ( d, J = 7.4 Hz, 2H), 5.01 (m, ÍH), 7.28 (d, J = 8.6 Hz, ÍH), 7.32 (d, J = 8.6 Hz, ÍH), 7.71 (s, ÍH); MS (ESI) (M + H) + 567.0. Step B. Cyclopropyl Isocyanate O H2N) > i? A solution of cyclopropylamine (57 mg, 1.0 mmol) and DIPEA (3.0 mmol) in 5 mL of THF was slowly added to a solution of triphosgene (105 mg, 0.35 mmol) in 10 mL of THF a 0 ° C. After 30 minutes, the cyclopropyl isocyanate solution was used directly in Step A. Example 71 4-. { [. { 2-tert-butyl-l-4 (4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclobutylpiperazine-1-carboxamide Step A. 4-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclobutylpiperazine-1-carboxamide Following the procedure in Step A of Example 68, the N-. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methyl-piperazine-1-sulfonamide (58 mg, 0.12 mmol) was reacted with cyclobutyl isocyanate (1.0 mmol), after being purified by chromatography on silica gel, to give 4-. { [. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclobutylpiperazine-1-carboxamide (TFA salt, 39 mg, 47%). 1 H NMR (400 MHz, CDC13) d 1.52 (m, 2 H), 1.56 (s, 9 H), 1.72 (m, 8 H), 2.04 (m, 3 H), 2.32 (m, 2 H), 3.19 (m, 4 H) , 3.30 (s, 3H), 3.34 (m, 4H), 4.21 (m, 2H), 4.25 (m, ÍH), 4.65 (m, ÍH), 7.27 (d, J = 8.6 Hz, ÍH), 7.32 ( d, J = 8.6 Hz, ÍH), 7.72 (s, ÍH); MS (ESI) (M + H) + 581.0.

Step B. Cyclobutyl isocyanate A solution of cyclobutylamine (71 mg, 1.0 mmol) and DIPEA (3.0 mmol) in 5 mL of THF was slowly added to a solution of triphosgene (105 mg, 0.35 mmol) in 10 mL of THF at 0 ° C. After 30 minutes, the cyclopropyl isocyanate solution was used directly in Step A. Example 72 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-4-. { [(methylamino) carbonyl] amino} piperidin-l-sulfonamide Following the procedure in Step A of the Example 68, the 4-amino-N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methylpiperidin-1-sulfonamide (50 mg, 0.1 mmol) was reacted with methyl isocyanate (57 mg, 1.0 mmol), after being purified by gel chromatography. silica, to provide the N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methyl-4-. { [(methylamino) carbonyl] amino} piperidin-1-sulfonamide (TFA salt, 49 mg, 73%). NMR XH (400 MHz, CDC13) d 1.39 (m, 2H), 1.52 (m, 3H), 1.56 (s, 9H), 1.72 (m, 3H), 1.89 (m, 2H), 2.15 (m, 3H) , 2.72 (s, 3H), 2.83 (m, 2H), 3.27 (s, 3H), 3.63 (m, 3H), 4.22 (d, J = 8.0 Hz, 2H), 5.15 (m, ÍH), 7.30 ( m, 2H), 7.71 (s, 1H); MS (ESI) (MAI) + 555.0. EXAMPLE 73 N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H- Following the procedure in Step C of Example 60, the triflate of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (500 mg, 0.84 mmol) was reacted with tert-butyl piperazine-1-carboxylate (558 mg, 3.0 mmol), after purification by chromatography on silica gel, to provide the 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazin-1-tert-butyl carboxylate (460 mg, 100%). MS (ESI) (M + H) + 550.0.

EXAMPLE 74 4-Acetyl-N- [2-tert-butyl-1- (tetrahydro-2H-yran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide Step A 4-Acetyl-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide Following the procedure in Step A of Example 60, N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide trifluoroacetate (100 mg, 0.18 mmol) was reacted with acetyl chloride (79 mg, 1.0 mmol), after purification by reverse phase HPLC, to give 4-acetyl-N- [2-tert-butyl-1- (tetrahydro-2H-pyran -4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (TFA salt, 58 mg, 53%). XH NMR (400 MHz, CD3OD, TFA salt) d 1.54 (m, 4H), 1.66 (s, 9H), 2.07 (s, 3H), 2.36 (m, ÍH), 3.20 (m, 2H), 3.33 (s, 3H), 3.34 (m, 4H), 3.55 (m, 4H), 3.91 ( m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 7.65 (d, J = 9.0 Hz, ÍH), 7.79 (s, ÍH), 7.92 (d, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 492.0. Step B. N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide A solution of 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} Terbutyl piperazine-l-carboxylate (460 mg, 0.84 mmol) in 10 mL of CH2C12 was treated with 10 mL of TEA at room temperature. After stirring at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure to provide N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazole-5 il] -N-methylpiperazine-1-sulfonamide (TFA salt, 100%), which was used in Step A without purification.

Example 75 N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (2,2-dimethylpropanoyl) -N-methyl-piperazin-1- sulfonamide H-N N- rS-N Following the procedure in Step A of the Example 60, N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide trifluoroacetate (100 mg, 0.18 mmol ) was reacted with 2,2-dimethylpropanoyl chloride (120 mg, 1.0 mmol), after being purified by reverse phase HPLC, to give the N- [2-tert-butyl-1- (tetrahydro-2H-pyran 4-ylmethyl) -lH-benzimidazol-5-yl] -4- (2,2-dimethylpropanoyl) - N -methylpiperazine-1-sulfonamide (TFA salt, 24 mg, 21%). NMR XH (400 MHz, CD3OD, TFA salt) d 1.23 (s, 9H), 1.56 (m, 4H), 1.66 (s, 9H), 2.36 (m, ÍH), 3.23 (m, 4H), 3.33 (s, 3H), 3.36 (m, 2H), 3.66 (m, 4H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 7.65 (d, J = 9.2 Hz, ÍH), 7.79 ( s, ÍH), 7.92 (d, J = 9.2 Hz, ÍH); MS (ESI) (M + H) + 534.0.

Example 76 4-benzoyl-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide Following the procedure in Step A of Example 60, N- [2-tert-butyl-tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (45) mg, 0.10 mmol) was reacted with benzoyl chloride (28 mg, 0.2 mmol), after purification by reverse phase HPLC, to give 4-benzoyl-N- [2-tert-butyl-1- (tetrahydro- 2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (TFA salt, 64 mg, 96%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.58 (m, 4H), 1.67 (s, 9H), 2.36 (m, ÍH), 3.28 (m, 6H), 3.33 (s, 3H), 3.47 ( m, 2H), 3.74 (m, 2H), 3.92 (m, 2H), 4.52 (d, J = 7.6 Hz, 2H), 7.40 (m, 2H), 7.46 (m, 3H), 7.68 (d, J = 9.0 Hz, ÍH), 7.80 (s, ÍH), 7.95 (d, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 554.0.

Example 77 N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-4- (3-methylbutanoyl) piperazine-1- sulfonamide Following the procedure in Step A of the Example 60, N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (45 mg, 0.10 mmol) was Reacted with 3-methylbutanoyl chloride (24 mg, 0.2 mmol), after purification by reverse phase HPLC, to give N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-4- (3-methylbutanoyl) piperazine-1-sulfonamide (TFA salt, 63 mg, 97%). XH NMR (400 MHz, CD3OD, TFA salt) d 0.87 (d, J = 7.4 Hz, 6H), 1.45 (m, 4H), 1.49 (s, 9H), 2.00 (m, ÍH), 2.09 (d, J = 6.9 Hz, 2H), 2.22 (m, ÍH), 3.06 (m, 2H), 3.16 (m, 214), 3.22 (s, 3H), 3.23 (, 21-1), 3.39 (, 2H), 3.52 (m, 2H), 3.91 (in, 2H), 4.12 (d, J = 7.6 Hz, 2H), 4.83 (m, HI), 7.23 (m, 2H), 7.64 (s, ÍH); MS (ESI) (M + H) + 534.0.

EXAMPLE 78 N- [2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (cyclopropylcarbonyl) -N-methyl-piperazine-1-sulfonamide Following the procedure in Step A of the Example 60, N- [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (50 mg, 0.11 mmol) was Reacted with cyclopropanecarbonyl chloride (21 mg, 0.2 mmol), after purification by reverse phase HPLC, to give N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (cyclopropylcarbonyl) -N-methylpiperazine-1-sulfonamide (TFA salt, 45 mg, 71%). NMR XH (400 MHz, (m, 2H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 (m, 2H), 7.72 (s, 114), MS (ESI) ( M + H) + 518.0.

Example 79 N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4-propionylpiperazine-1-sulfonamide Following the procedure in Step A of Example 60, N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperazin-1- Sulfonamide (60 mg, 0.13 mmol) was reacted with the propanoic anhydride (26 mg, 0.2 mmol), after purification by reverse phase HPLC to give N- [2-tert-butyl-1- (tetrahydro-2H- pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-4-propionylpiperazine-1-sulfamide (TFA salt, 28 mg, 35%). NMR XH (400 MHz, CDC13) d 1.13 (5, J = 7.4 Hz, 3H), 1.53 (m, 4H), 1.57 (s, 9H), 2.32 (m, 3H), 3.14 (m, 2H), 3.25 (m, 2H), 3.30 (s, 3H), 3.33 (m, 2H), 3.45 (m, 2H), 3.60 (m, 2H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 506.0.

Example 80 N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-isobutyryl-N-methylpiperazine-1-sulfonamide 0 Following the procedure in Step A of the Example 60, N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (50 mg, 0.11 mmol) was reacted with 2-methylpropanoyl chloride (22 mg, 0.2 mmol), after being purified by reverse phase 5-phase HPLC to provide N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl. ] -4- isobutyryl-N-methylpiperazine-1-sulfonamide (TFA salt, 35 mg, 50%). NMR XH (400 MHz, CDC13) d 1.10 (d, J = 6.6 Hz, 6H), 1.53 (m, 4H), 1.57 (s, 9H), 2.30 (m, ÍH), 2.73 (m, ÍH), 3.15 (m, 0 2H), 3.30 (m, 2H), 3.31 (s, 3H), 3.33 (m, 2H), 3.50 (m, 2H), 3.60 (m, 2H), 3.99 (, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 520.0. 5 EXAMPLE 81 N- [2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (cyclobutylcarbonyl) -N-methyl-piperazine-1-sulfonamide Following the procedure in Step A of the Example 60, N- [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (50 mg, 0.11 mmol) was reacted with cyclobutanecarbonyl chloride (24 mg, 0.2 mmol), after purification by reverse phase HPLC, to give N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl. ] -4- (cyclobutylcarbonyl) -N-methylpiperazine-1-sulfonamide (TFA salt, 34 mg, 48%). NMR XH (400 MHz, CDC13) d 1.53 (m, 4H), 1.57 (s, 9H), 1.80-2.00 (m, 2H), 2.13 (m, 2H), 2.31 (m, 3H), 3.14 (m, 2H), 3.20 (, 3H), 3.30 (s, 3H), 3.32 (m, 4H), 3.35 (m, 2H), 3.91 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 (m, 2H), 7.72 (s, ÍH); M? (ESI) (M + H) + 532.0.

EXAMPLE 82 N- [2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-butyryl-N-methylpiperazine-1-sulfonamide Following the procedure in Step A of Example 60, N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperazin-1- Sulfonamide (50 mg, 0.11 mmol) was reacted with butanoyl chloride (21 mg, 0.2 mmol), after being purified by reverse phase HPLC, to give N- [2-tert-butyl-1- (tetrahydro-2H) -piran-4-ylmethyl) -lH-benzimidazol-5-yl] -4-butyryl-N-methylpiperazine-1-sulfonamide (TFA salt, 28 mg, 40%). NMR XH (400 MHz, CDC13) d 0.96 (t, J = 7.4 Hz, 3H), 1.53 (m, 4H), 1.57 (s, 9H), 1.65 (m, 2H), 2.27 (t, J = 7.4 Hz, 2H), 2.30 (m, ÍH), 3.14 (m, 2H), 3. 24 (m, 2H), 3.30 (s, 3H), 3.33 (m, 2H), 3.45 (m, 2H), 3.60 (m, 2H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz , 213), 7.32 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 520.0.

Example 83 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-dimethylpiperazine-1-carboxamide Following the procedure in Step A of the Example 60, N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (45 mg, 0. 1 mmol) was reacted with dimethylcarbamoyl chloride (22 mg, 0.2 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-dimethylpiperazine-l-carboxamide (TFA salt, 56 mg, 88%). RM? XH (400 MHz, CD30D, TFA salt) d 1.54 (m, 4H), 1.67 (s, 9H), 2.37 (m, ÍH), 2.82 (s, 6H), 3.23 (m, 6H), 3.33 (s) , 3H), 3.36 (m, 4H), 3.91 (m, 2H), 4.53 (d, J = 7.6 Hz, 2H), 7.68 (d, J = 9.2 Hz, ÍH), 7.81 (s, ÍH), 7.96 (d, 3 = 9.2 Hz, ÍH); MS (ESI) (M + H) + 521.0.

Example 84 4-. { [[2-tert-Butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isopropylpiperazine-1-carboxamide Following the procedure in Step A of Example 68, N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperazin-1- Sulfonamide (45 mg, 0.1 mmol) was reacted with isopropyl isocyanate (17 mg, 0.2 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isopropypiperazine-1-carboxamide (TFA salt, 64 mg, 98%). XH NMR (400 MHz, CD3OD, TFA salt) d 1.10 (d, J = 6.4 Hz, 6H), 1.58 (m, 4H), 1.67 (s, 9H), 2.35 (m, ÍH), 3.20 (m, 4H), 3.33 (s, 3H), 3.37 (m, 6H), 3.85 (m, ÍH), 3.91 (m, 2H), 4.53 (d, J = 7.6 Hz, 2H), 7.67 (d, J = 9.2 Hz, ÍH), 7.81 (s, ÍH), 7.96 (d, J = 9.2 Hz, ÍH); MS (ESI) (M + H) + 535.0.

Example 85 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopentyl-piperazine-1-carboxamide Following the procedure in Step A of Example 68, N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperazin-1- Sulfonamide (90 mg, 0.2 mmol) was reacted with isocyanatocyclopentane (44 mg, 0.4 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopenti-piperazine-1-carboxamide (TFA salt, 135 mg, 100%). RM? XH (400 MHz, CDC13) d 1.28 (m, 2H), 1.54 (m, 4H), 1.57 (s, 9H), 1.59 (m, 4H), 1.97 (m, 2H), 2.30 (m, ÍH), 3.19 (m, 4H), 3.30 (s, 3H), 3.33 (m, 6H), 4.02 (m, 2H), 4.07 (m, ÍH), 4.20 (d, J = 7.6 Hz, 2H), 4.38 (m , ÍH), 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 561.0.

Example 86 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methylpiperazine-1-carboxamide Following the procedure in Step A of Example 68, N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazin-1- Sulfonamide (60 mg, 0.13 mmol) was reacted with methyl isocyanate (17 mg, 0.3 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-methylmethyl) -lH-benzimido-5-yl] (methyl) amino] sulfonyl} -N-methylpiperazine-1-carboxamide (TFA salt, 75 mg, 93%). NMR XH (400 MHz, CDC13) d 1.45 (m, 4H), 1.48 (s, 9H), 2.21 (m, ÍH), 2.68 (m, 3H), 3.10 (m, 4H), 3.21 (s, 3H) , 3.28 (m, 6H), 3.91 (m, 2H), 4.12 (d, J = 7.6 Hz, 2H), 4.78 (m, HI), 7.23 (m, 2H), 7.62 (s, ÍH); MS (ESI) (M + H) + 507.0.

Example 87 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropylpiperazine-1-carboxamide Following the procedure in Step A of Example 68, N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazin-1- Sulfonamide (50 mg, 0.11 mmol) was reacted with cyclopropyl isocyanate (25 mg, 0.3 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropylpiperazine-1-carboxamide (TFA salt, 56 mg, 78%). RM? XH (400 MHz, CDC13) d 0.53 (m, 2H), 0.68 (m, 2H), 1.53 (, 4H), 1.57 (s, 9H), 2.30 (m, ÍH), 2.61 (m, ÍH), 3.18 (m, 4H), 3.30 (s, 3H), 3.33 (m, 6H), 3.99 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 5.01 (s, ÍH), 7.31 (m, 2H), 7.70 (s, ÍH); MS (ESI) (M + H) + 533.0.

Example 88 4-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclobutylpiperazine-1 -carboxamide Following the procedure in Step A of Example 68, N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazin-1- Sulfonamide (50 mg, 0.11 mmol) was reacted with cyclobutyl isocyanate (29 mg, 0.3 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-methylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclobutylpiperazine-1-carboxamide (TFA salt, 39 mg, 54%) RM? XH (400 MHz, CDC13) d 1.53 (m, 4H), 1.57 (s, 9H), 1.69 (m, 2H), 1.79 (m, 2H), 2.30 (, 3H), 3.19 (m, 4H), 3.30 (s, 3H), 3.34 (m, 6H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 4.23 (m, ÍH), 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 547.0.

Example 89 N- (tert-butyl) -4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-l-carboxamide Following the procedure in Step A of Example 68, N- [2-tert-but-il-1- (tet rahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylpiperazine- 1-sulfonamide (50 mg, 0.11 mmol) was reacted with tert-butyl isocyanate (29 mg, 0.3 mmol), after purification by reverse phase HPLC, to give the N- (tert-butyl) -4- . { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-1-carboxamide (TFA salt, 29 mg, 40%). NMR XH (400 MHz, CDC13) d 1.33 (s, 9H), 1.53 (m, 4H), 1.57 (s, 9H), 2.30 (m, ÍH), 3.20 (m, 4H), 3.30 (s, 3H) , 3.33 (m, 6H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 549.0.

Example 90 N-butyl-4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-l-carboxamide Following the procedure in Step A of Example 68, N- [2-t er-but i 1-1- (t and rahydro-2H-pi ran- -ylmethyl) -lH-benzimidazol-5-yl] - N-methyl-piperazine zin-1-sulfonamide (50 mg, 0.11 mmol) was reacted with butyl isocyanate (29 mg, 0.3 mmol), after purification by reverse phase HPLC, to give N-butyl-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (met il) amino] sulfonyl} piperazine-1-carboxamide (TFA salt, 26 mg, 36%). 1 H NMR (400 MHz, CDC13) d 0.90 (t, J = 7.2 Hz, 3 H), 1.33 (m, 2 H), 1.46 (m, 2 H), 1.53 (m, 4 H), 1.57 (s, 9 H), 2.30 (m, ÍH), 3.16 (m, 6H), 3.30 (s, 3H), 3.35 (m, 4H), 3.99 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 549.0.

Example 91 N-allyl-4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-l-carboxamide Following the procedure in Step A of Example 68, N- [2-ter-but i 1-1- (t and rahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methypi piperazine-1-sulfonamide ( 50 mg, 0.11 mmol) was reacted with 3-i sociana t oprop-1-ene (25 mg, 0.3 mmol), after being purified by reverse phase HPLC, to give the N-ali 1-4 -. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (meth il) amino] sulfonyl} piperazin-1-carboxamide (TFA salt, 29 mg, 41%). NMR XH (400 MHz, CDC13) d 1.54 (m, 4H), 1.57 (s, 9H), 2.30 (m, HH), 3.21 (m, 4H), 3.30 (s, 3H), 3.37 (m, 6H) , 3.84 (m, 2H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 5.11 (m, ÍH), 5.17 (m, ÍH), 5.85 (m, ÍH), 7.31 ( m, 2H), 7.73 (s, ÍH); MS (ESI) (M + H) +533.0.

Example 92 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethylpiperazine-1-carboxamide Following the procedure in Step A of Example 68, N- [2-t er-but i 1- 1- (tertrohydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-met ilpipera zin-1-sulfonamide (50 mg, 0.11 mmol) was reacted with isocyanate oet ano (21 mg, 0.3 mmol), after purification by reverse phase HPLC, to give the 4 -. { [[2-tert-butyl] -1- (tet rahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethylpiperazine-l-carboxamide (TFA salt, 13 mg, 19%) 1 H-NMR (400 MHz, CDC13) d 1.13 (t, Hz, 3H), 1.53 (m, 4H), 1.57 (s, 9H) , 2.30 (m, ÍH), 3.20 (m, 6H), 3.30 (s, 3H), 3.33 (m, 4H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 ( m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 521.0.

Example 93 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propylpiperazine-1-carboxamide Following the procedure in Step A of the Example 68, N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (50 mg, 0.11 mmol) was Reacted with 1-isocyanatopropane (25 mg, 0.3 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propylpiperazine-1-carboxamide (TFA salt, 24 mg, 34%) 1 NMR (400 MHz, CDC13) d 0.91 (t, J = 7.6 Hz, 3H), 1.53 (m, 6H), 1.57 (s) , 9H), 2.33 (m, ÍH), 3.20 (m, 6H), 3.30 (s, 3H), 3.33 (m, 4H), 3.98 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H) 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 535.0.

Example 94 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (cyclopropylmethyl) piperazine-l-carboxamide Following the procedure in Step A of the Example 68, N- [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazin-1-sulfonamide (50 mg, 0. 11 mmol) was reacted with (isocyanatomethyl) cyclopropane (28 mg, 0.3 mmol), after purification by reverse phase HPLC, to give 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (cyclopropylmethyl) piperazine-1-carboxamide (TFA salt, 35 mg, 48%). NMR XH (400 MHz, CDC13) d 0.17 (m, 2H), 0.50 (m, 2H), 0.94 (m, ÍH), 1.54 (m, 4H), 1.57 (s, 9H), 2.30 (m, ÍH), 3.06 (m, 2H), 3.20 (m, 4H), 3.30 (s, 3H), 3.37 (m, 6H), 3.99 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 7.31 (m, 2H), 7.72 (s, ÍH); MS (ESI) (M + H) + 547.0.

EXAMPLE 95 N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (lH-imidazol-1-ylcarbonyl) -N-methylpiperazine- 1-sulfonamide A solution of N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazin-1-sulfonamide (2.25 g, 5.0 mmol) and 1, 1'-biscarbonyl-lH-imidazole (0.97 g, 6.0 mmol) in THF (40 mL) was heated at 65 ° C for two days. The reaction mixture was concentrated under reduced pressure. The residue was then dissolved in 60 ml of ethyl acetate, washed with brine, and dried over sodium sulfate. Removal of the solvents gave N- [2-tert-buty1-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -4- (lH-imidazol-1-ylcarbonyl) -N-methylpiperazine-1-sulfonamide (2.6 g, 96%), 1 H NMR (400 MHz, CD30D, TFA salt) d 1.54 (m, 4H), 1.68 (s, 9H), 2.37 (m, ÍH), 3.32 (m, 2H), 3. 34 (s, 3H), 3.42 (m, 4H), 3.65 (m, 4H), 3.92 (m, 2H), 4.54 (d, J = 7.6 Hz, 2H), 7.67 (m, 2H), 7.84 (s, ÍH), 7.90 (s, ÍH), 7.97 (d, J = 8.8 Hz, ÍH), 9.32 (s, ÍH); MS (ESI) (M + H) + 543.8.

Example 96 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} isopropyl piperazin-l-carboxylate Following the procedure in Step A of the Example 60, N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide (45 mg, 0. 10 mmol) was reacted with isopropyl chloroformate (25 mg, 0.2 mmol), after purification by reverse phase HPLC, 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-1-isopropyl carboxylate (TFA salt, 62 mg, 94%). NMR XH (400 MHz, CDC13) d 1.16 (d, J = 6.3 Hz, 6H), 1.47 (m, 4H), 1.49 (s, 9H), 2.22 (m, ÍH), 3.10 (m, 4H), 3.23 (s, 3H), 3.23 (m, 2H), 3.37 (m, 4H), 3.91 (m, 2H), 4.13 (d, J = 7.6 Hz, 2H), 4.83 (m, ÍH), 7.23 (m, 2H), 7.64 (s, ÍH); MS (ESI) (M + H) + 536.0.

Example 97 N- (l-. {[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -bensimidazol-5-yl] (methyl) amino] sulfonyl. Pyrrolidine -3-yl) acetamide Step A. N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl. pyrrolidin-3-yl) acetamide Following the procedure in Step A of Example 60, the trifluoroacetate of 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] - N-methylpyrrolidin-1-sulfonamide (100 mg, 0.18 mmol) was reacted with acetyl chloride (79 mg, 1.0 mmol), after purification by reverse phase HPLC, to give the N- (1- {. [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazole-5- il] (methyl) amino] sulfonyl} pyrrolidin-3-yl) acetamide (TFA salt, 25 mg, 23%). 1 H NMR (400 MHz, CD3OD, TFA salt) d 1.54 (m, 4H), 1.67 (s, 9H), 1.85 (m, ÍH), 1.89 (s, 3H), 2.13 (m, ÍH), 2.36 ( m, ÍH), 3.10 (m, ÍH), 3.31 (s, 3H), 3.33 (m, 3H), 3.48 (m, 2H), 3.91 (m, 2H), 4.20 (m, ÍH), 4.52 (d , 7.6 Hz, 2H), 7.65 (d, J = 9.0 Hz, ÍH), 7.79 (s, ÍH), 7.93 (d, 3 = 9.0 Hz, ÍH); MS (ESI) (M + H) + 492.0. Step B. (l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} pyrrolidin- 3-yl) tert-butyl carbamate Following the procedure in Step C of Example 60, the triflate of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-1H-imidazol-3-io (460 mg, 0.77 mmol) was reacted with tert-butyl pyrrolidin-3-ylcarbamate (558 mg, 3.0 mmol), after being purified by chromatography on silica gel, to give (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} pyrrolidin-3 il) tert-butyl carbamate (385 mg, 91%). MS (ESI) (M + H) + 550.0.

Step C. 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylpyrrolidin-1-sulfonamide A solution of (l- { [[2-tert-Butyl-l- (tetrahydro-2H-pyran--methyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl] pyrrolidin-3-yl ) tert-butyl carbamate (385 mg, 0.7 mmol) in 10 ml of CH2C12 was treated with 10 ml of TFA at room temperature. After stirring at room temperature for 1 hour, the reaction mixture was concentrated under reduced pressure to provide 3-amino-N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH -benzimidazol-5-yl] -N-methylpyrrolidin-1-sulfonamide (TFA salt, 100%), which was used in Step A without purification. EXAMPLE 98 N- (l-. {[[2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} pyrrolidine -3-yl) -2, 2-dimethylpropanamide Following the procedure in Step A of the Example 60, the trifluoroacetate of 3-amino-N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methylpyrrolidin-1-sulfonamide (100 mg, 0.18 mmol) was reacted with 2, 2-dimethylpropanoyl chloride (60 mg, 0.5 mmol), after being purified by Reverse phase HPLC, to provide N- (l-. {[[[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] ] sulfonyl, pyrrolidin-3-yl) -2,2-dimethylpropanamide (TFA salt, 39 mg, 33%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.12 (s, 9 H), 1.57 (m, 4 H), 1. 67 (s, 9 H), 1. 96 (m, 1 H), 2.11 (m, 1 H) ), 2.36 (m, ÍH), 3.10 (m, ÍH), 3.31 (s, 3H), 3.33 (m, 3H), 3.48 (m, 2H), 3. 91 (m, 2H), 3.94 (m, ÍH), 4.52 (d, J = 7.6 Hz, 2H), 7. 65 (d, J = 9.0 Hz, ÍH), 7.79 (s, ÍH), 7. 94 (d, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 534.0. Example 99 N- (l- { [[2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] Azetidin -3-yl) acetamide Following the procedure in Step A of Example 60, 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N- methylazetidin-1-sulfonamide (20 mg, 0.046 mmol) was reacted with acetic anhydride (51 mg, 0.5 mmol), after purification by reverse phase HPLC, to give the N- (l- { [[2-tert-butyl-1 - (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl.] azetidin-3-yl) acetamide (TFA salt, 9 mg, 33%). NMR * H (400 MHz, CD3OD, TFA salt) d 1.58 (m, 4H), 1.67 (s, 9H), 1.91 (s, 3H), 2.32 (m, ÍH), 3.28 (s, 3H), 3.33 (m, 2H), 3.80 (m, 2H), 3.91 (m, 2H), 3.99 (m, 2H), 4.50 (m, ÍH), 4.53 (d, J = 7.6 Hz, 2H), 7.65 (d, J = 9.2 Hz, ÍH), 7.78 (s, ÍH), 7.95 (d, J = 9.2 Hz, ÍH); MS (ESI) (M + H) +478.0. Example 100 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl] -N-methyl-1H-imidazole-1-sulfonamide The triflate of 3- (imidazol-1-sulfonyl) -1-methyl-3H-imidazol-1-yl (xx mg, 1.5 mmol) was added to a solution of 2-tert-butyl-1 - (4, 4). -difluorocyclohexyl) methyl] -N-methyl-lH-benzimidazol-5-amine (335 mg, 1.0 mmol) in 15 ml of acetonitrile. After being stirred at room temperature overnight, the reaction mixture was concentrated under reduced pressure to give a residue, which was purified by HPLC to provide the N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-met i1-lH-imidazol-1-sulfonamide (295 mg, 51%). MS (ESI) (M + H) + 466.0. Example 101 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-1H-l, 2,4-triazole-l-sulfonamide Following the procedure in Step C of Example 60, triflate of 1-. { [. { 2-tert-butyl-l- [(, -difluorocyclohexyl) methyl) -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (50 mg, 0.08 mmol) was reacted with the 1H-1,2,4-triazole (69 mg, 1.0 mmol), after purification by reverse phase HPLC to provide the N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methyl-lH-1,2, -triazol-1-sulfonamide (TFA salt, 15 mg, 32%). 1T NMR (400 MHz, CDC13) d 1.40-1.76 (m, 6H), 1.62 (s, 9H), 2.03 (m, 2H), 2.20 (m, ÍH), 3.55 (s, 3H), 4.48 (d, J = 7.4 Hz, 2H), 7.36 (d, J = 9.0 Hz, ÍH), 7.60 (s, ÍH), 7.86 (d, J = 9.0 Hz, ÍH), 8.28 (s, ÍH) 8.72 (s, ÍH); MS (ESI) (M + H) + 467.0. Example 102 N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-1H-1,2,3-triazole-1-sulfonamide Following the procedure in Step C of Example 60, triflate of l-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl) -lH-benzimidazol-5-yl} (methyl) amino] sulfonyl} -3-methyl-lH-imidazol-3-io (50 mg, 0.08 mmol) was reacted with the lH-1,2,4-triazole (69 mg, 1.0 mmol), after being purified by reverse phase HPLC for provide the N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -lH-benzimidazol-5-yl} -N-methyl-lH-1,2,4-triazole-1-sulfonamide (TFA salt, 14 mg, 30%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.40-1.76 (m, 6H), 1.59 (s, 9H), 2.03 (m, 2H), 2.20 (m, ÍH), 3.56 (s, 3H), 4.42 (d, J = 7.4 Hz, 2H), 7.22 (d, J = 9.0 Hz, ÍH), 7.47 (s, ÍH), 7.75 (d, J = 9.0 Hz, ÍH), 7.82 (d, J = 1.1 Hz, ÍH), 8.21 (d, J = 1.1 Hz, ÍH); MS (ESI) (M + H) + 467. 0 EXAMPLE 103 N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-formyl-N-methyl-lH-pyrazole-1-sulfonamide Following the procedure in Step C of Example 60, triflate of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io (1.89 mg, 3.0 mmol) was reacted with the lH-pyrazole-4-carbaldehyde (576 mg, 6.0 mmol), after being purified by chromatography on silica gel to provide N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl] -lH-benzimidazol-5-yl] -4-formyl-N-methyl-lH-pyrazole-1-sulfonamide (586 mg, 43%). XH NMR (400 MHz, CDC13) d 1.48 (m, 4H), 1.50 (s, 9H), 2.22 (m, ÍH), 3.27 (m, 2H), 3.55 (s, 3H), 3.91 (m, 2H), 4.14 (d, J = 7.2 Hz, 2H), 6.98 (dd, J = 8.8 Hz, 2.0 Hz, ÍH), 7.925 (d, J = 8.8 Hz, ÍH), 7.37 (s, ÍH), 8.14 (s, ÍH), 8.18 (s, ÍH), 9.81 (s, ÍH), MS (ESI) (M + H) + 460.0.

Example 104 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-pyrazole-4-carboxamide Step A. l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-pyrazole-4-carboxamide HATU (150 mg, 0.4 mmol) was added to a solution of acid 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxylic acid (100 mg, 0.21 mmol), cyclopropylamine (57 mg, 1.0 mmol) and DIPEA (0.2 mL) in 3.0 mL of DMF at room temperature. After 30 minutes, the reaction mixture was condensed to give a residue, which was purified by Reverse phase HPLC to provide 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropy1-lH-pyrazole-4-carboxamide (TFA salt, 29 mg, 22%). NMR XH (400 MHz, CDC13) d 0.59 (m, 2H), 0.80 (m, 2H), 1.54 (m, 4H), 1.56 (s, 9H), 2. 33 (m, ÍH), 2.82 (m, ÍH), 3.33 (m, 2H), 3.55 (s, 3H), 3.99 (m, 2H), 4.20 (d, J = 7.6 Hz, 2H), 6.40 (s, ÍH), 7.06 (dd, J = 9.01, 2.0 Hz, ÍH), 7.28 (d, J = 9.0 Hz, ÍH), 7.38 (s, ÍH), 8. 02 (s, ÍH), 8.05 (d, J = 3.5 Hz, ÍH); MS (ESI) (M + H) + 515.0. Step B. l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxyl N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -4-formyl-N-methyl-lH-pyrazole-1-sulfonamide (460 mg, 1.0 mmol) and ozone (1.0 g, 1.6 mmol) were heated in 15 ml of DMF at 50 ° C for 2 hours. The resulting solution of l- acid. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazole- 5-yl] (methyl) amino] sulf onyl} -lH-pyrazole-4-carboxylic acid in DMF was used directly in Step A. MS (ESI) (M + H) + 476.0. Example 105 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethyl-lH-pyrazole-4-carboxamide Following the procedure in Step A of Example 104, acid 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxylic acid (96 mg, 0.20 mmol) was reacted with ethylamine (90 mg, 2.0 mmol), after purification by reverse phase HPLC to give 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethyl-lH-pyrazole-4-carboxamide (TFA salt, 33 mg, 27%). NMR XH (400 MHz, CD30D) d 1.14 (d, J = 7.4 Hz, 3H), 1.52 (m, 4H), 1.65 (s, 9H), 2.33 (m, ÍH), 3.32 (m, 4H), 3.51 (s, 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 7.42 (dd, J = 9.20, 2.0 Hz, ÍH), 7.66 (d, J = 2.0 Hz, ÍH), 7.95 (d, J = 9.0 Hz, ÍH), 8.18 (s, ÍH), 8. 30 (s, ÍH); MS (ESI) (M + H) + 502.8. Example 106 N-allyl- { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxamide Following the procedure in Step A of Example 104, acid l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxylic acid (96 mg, 0.20 mmol) was reacted with allylamine (114 mg, 2.0 mmol), after purification by reverse phase HPLC to provide N-allyl-1. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl] -lH-pyrazole-4-carboxamide (TFA salt, 38 mg, 30%). NMR XH (400 MHz, CDC13) d 1.52 (m, 4H), 1.65 (s, 9H), 2.33 (m, ÍH), 3.32 (m, 4H), 3.52 (s, 3H), 3.91 (m, 4H), 4.51 (d, J = 7.6 Hz, 2H), 5.09 (m, ÍH), 5.17 (m, ÍH), 5.85 (m, ÍH), 7.42 (dd, J = 9.0, 2.0 Hz, ÍH), 7.6788 (d, J = 2.0 Hz, ÍH), 7.95 (d, J = 9.0 Hz, ÍH), 8.20 (s, ÍH), 8.32 (s, ÍH); MS (ESI) (M + H) + 515.0.

Example 107 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propyl-lH-pyrazole-4-carboxamide Following the procedure in Step A of Example 104, acid 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxylic acid (96 mg, 0.20 mmol) was reacted with propylamine (118 mg, 2.0 mmol), after purification by reverse phase HPLC to give l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propyl-lH-pyrazole-4-carboxamide (Exit TFA, 44 mg, 35%). XH NMR (400 MHz, CD30D, TFA salt) d 0.91 (d, J = 7.4 Hz, 3H), 1.52 (m, 6H), 1.65 (s, 9H), 2.33 (m, ÍH), 3.23 (t, J = 7.2 Hz, 2H), 3.32 (m, 2H), 3.52 (s, 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 7.41 (dd, J = 9. 0, 2.0 Hz, ÍH), 7.66 (d, J = 2.0 Hz, ÍH), 7.95 (d, J = 9.01 Hz, ÍH), 8.19 (s, ÍH), 8.31 (s, ÍH); MS (ESI) (M + H) + 516.8.

Example 108 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-dimethyl-lH-pyrazole-4-carboxamide Following the procedure in Step A of Example 104, acid l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -1H-pyrazole-4-carboxylic acid (96 mg, 0.20 mmol) was reacted with dimethylamine (90 mg, 2.0 mmol), after purification by reverse phase HPLC to give l-. { [[2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, -dimethyl-lH-pyrazole-4-carboxamide (TFA salt, 79 mg, 64%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.53 (m, 4H), 1.66 (s, 9H), 2.33 (m, 1H), 3.02 (s, 3H), 3.12 (s, 3H), 3.32 ( m, 2H), 3.51 (s, 3H), 3.89 (m, 2H), 4.52 (d, J = 7.6 Hz, 2H), 7.41 (dd, J = 9.0, 2.0 Hz, ÍH), 7.61 (d, J = 2.0 Hz, ÍH), 7.95 (d, J = 9.0 Hz, ÍH), 8.09 (s, ÍH), 8.16 (s, ÍH); MS (ESI) (M + H) + 502.8.

Example 109 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methyl-lH-pyrazole-4-carboxamide Following the procedure in Step A of Example 104, acid l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxylic acid (96 mg, 0.20 mmol) was reacted with methylamine (31 mg, 1.0 mmol), after purification by reverse phase HPLC to provide l-. { [[2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methyl-lH-pyrazo-1-4-carboxamide (TFA salt, 24 mg, 20%). X H NMR (400 MHz, CD3OD, TFA salt) d 1.52 (m, 4H), 1.65 (s, 9H), 2.3365 (m, ÍH), 2.81 (s, 3H), 3.32 (m, 2H), 3.52 ( s, 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 7.41 (dd, J = 9.06, 2.0 Hz, ÍH), 7.66 (d, J = 2.0 Hz, ÍH), 7.95 (d, J = 9.0 Hz, ÍH), 8.17 (s, ÍH), 8.27 (s, ÍH); MS (ESI) (M + H) + 488.7.

Example 110 N- (tert-butyl) -l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxamide Following the procedure in Step A of Example 104, acid l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -1H-pyrazole-4-carboxylic acid (96 mg, 0.20 mmol) was reacted with t-butylamine (73 mg, 1.0 mmol), after purification by reverse phase HPLC to give the N- (tert-butyl) -l. -. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxamide (TFA salt, 26 mg, 20%). 1 H NMR (400 MHz, CD3OD, TFA salt) d 1.37 (s, 9H), 1.52 (m, 4H), 1.66 (s, 9H), 2.33 (m, ÍH), 3.32 (m, 2H), 3.51 ( s, 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 7.44 (dd, J = 9.0, 2.0 Hz, ÍH), 7.66 (d, J = 2.0 Hz, ÍH), 7.96 (d, J = 9.0 Hz, ÍH), 8.17 (s, ÍH), 8.36 (s, ÍH); MS (ESI) (M + H) + 530.8.

EXAMPLE 111 N- (l-. {[[2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl. lH-pyrazol-3-yl) acetamide Step A. N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl. -lH-pyrazol-3-yl) acetamide Following the procedure in Step A of Example 60, 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N- Methyl-lH-pyrazole-1-sulfonamide (from Step B) was reacted with acetic anhydride (530 mg, 5.0 mmol), after purification by chromatography on silica gel, to give N- (1 -. {[[[ 2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} - lH-pyrazole-3- acetamide (3 mg, 2%). 1 H NMR (400 MHz, CD3OD, TFA salt) d 1.52 (m, 4H), 1.66 (s, 9H), 2.14 (s, 3H), 2.34 (, ÍH), 3.32 (m, 2H), 3.51 (s) , 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 6.75 (d, J = 2.8 Hz, ÍH), 7.41 (dd, J = 9.0, 2.2 Hz, 2H), 7.54 (s, ÍH), 7.68 (d, J = 2.8 Hz, ÍH), 7.93 (dd, J = 9.0, Hz, ÍH); MS (ESI) (M + H) + 489.0. Step B. 3-amino-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-lH-pyrazole-1-sulf onamide Following the procedure in Step C of Example 60, the triflate of 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io (189 mg, 0.3 mmol) was reacted with the lH-pyrazol-3-amine (83 mg, 1.0 mmol), after being purified by chromatography on silica gel, provide crude 3-amino-N- [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-lH-pyrazole-1-sulfonamide , which was used in Step A without further purification.

EXAMPLE 112 N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-formyl-N-methyl-lH-imidazole-1-sulfonamide Following the procedure in Step C of the Example 60, the triflate of l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} 3-methyl-lH-imidazol-3-io (630 mg, 1.0 mmol) was reacted with lH-imidazole-4-carbaldehyde (288 mg, 3.0 mmol), after being purified by chromatography on silica gel to provide the N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -4-formyl-N-methyl-lH-imidazole-1-sulfonamide (335 mg , 73%). 1 H NMR (400 MHz, CDC13) d 1.52 (m, 4H), 1.54 (s, 9H), 2.25 (m, ÍH), 3.32 (m, 2H), 3.60 (s, 3H), 3.98 (m, 2H), 4.19 (d, J = 7.6 Hz, 2H), 6.81 (s, ÍH), 7.01 (dd, J = 8.6, 1.9 Hz, ÍH), 7.32 (d, J = 8.6 Hz, ÍH), 7.41 (s, ÍH), 7.74 (s, ÍH), 10.12 (s, ÍH); MS (ESI) (M + H) + 460.0.

Example 113 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-imidazole-4-carboxamide Step A. l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-imidazole-4-carboxamide HATU (15 mg, 0.04 mmol) was added to a solution of l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -IH-imidazole-4-carboxylic acid (10 mg, 0.02 mmol), cyclopropylamine (6 mg, 0.1 mmol) and DIPEA (0.1 mL) in 1.0 mL of DMF at room temperature. After 30 minutes, the reaction mixture was condensed to give a residue, which was purified by phase HPLC. inverse to provide the l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-1H-imidazole-4-carboxamide (TFA salt, 2 mg, 15%). 1N-NMR (400 MHz, CDC13) d 0.61 (m, 2H), 0.80 (m, 2H), 1.54 (m, 4H), 1.68 (s, 9H), 2.35 (m, ÍH), 2.80 (m, ÍH) , 3.33 (m, 2H), 3.46 (s, 3H), 3.93 (m, 2H), 4.54 (d, J = 7.6 Hz, 2H), 7.37 (dd, J = 9.0, 1.9 Hz, ÍH), 7.56 ( d, J = 1.9 Hz, HH), 7.72 (s, 1H), 7.91 (s, HH), 7.99 (d, J = 9.0 Hz, HH); MS (ESI) (M + H) + 514.8. Step B. l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -1H-imidazole-4-carboxylic acid N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -4-formyl-N-methyl-lH-imidazole-1-sulfonamide (320 mg, 0.7 mmol) and ozone (650 mg, 1.1 mmol) was heated in 6 mL of DMF at room temperature for 24 hours. The resulting solution of l- acid. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-imidazole-4-carboxylic acid in DMF was used directly in Step A. MS (ESI) (M + H) + 476.0.

Example 114 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-pyrazole-3-carboxamide Step A. l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-pyrazole-3-carboxamide HATU (250 mg, 0.66 mmol) was added to a solution of 1- [[[2-tert-b -thyl] -l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] (methylene) oxide-? 4-sulfanil} -1H-pyrazole-3-carboxylic acid (65 mg, 0.14 mmol), cyclopropylamine (57 mg, 1.0 mmol) and DIPEA (0.4 mL) in 1.0 mL of DMF at room temperature. After 30 minutes, the reaction mixture was condensed to give a residue, which was purified by reverse phase HPLC to provide l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-1H-pyrazole-3-carboxamide (TFA salt, 19 mg, 22%). NMR XH (400 MHz, CDC13) d 0.64 (m, 2H), 0.81 (m, 2H), 1.52 (m, 4H), 1.65 (s, 9H), 2.33 (m, ÍH), 2.84 (m, ÍH) , 3.33 (m, 2H), 3.56 (s, 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 6.80 (d, J = 2.8, ÍH), 7.39 (dd, J = 9.0, 2.0 Hz, ÍH), 7.52 (s, ÍH), 7.88 (d, J = 2.8 Hz, ÍH), 7.95 (d, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 514.8. Step B. N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -3-formyl-N-methyl-lH-pyrazole-1-sulfonamide Following the procedure in Step C of Example 60, triflate of 1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl] -3-methyl-lH-imidazol-3-yl ( 630 mg, 1.0 mmol) was reacted with lH-pyrazole-3-carbaldehyde (288 mg, 3.0 mmol), after being purified by chromatography on silica gel to provide N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -3-formyl-N-methyl-1H -pyrazol-1-sulfonamide (320 mg, 70%). MS (ESI) (M + H) + 460.0. Step C. 1- [[[2-tert-Butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] (methylene) -oxide-4 acid sulfanil} -lH-pyrazole-3-carboxylic acid N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -3-formyl-N-methyl-lH-pyrazole-1-sulfonamide (320 mg, 0.7 mmol) and ozone (615 mg, 1.0 mmol) was heated in 6 ml of DMF at 50 ° C for 4 hours. The resulting solution of the acid 1- [[[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] (methylene) oxide-4 -sulfanil} -lH-pyrazole-4-carboxylic acid in DMF was used directly in Step A. MS (ESI) (M + H) + 476.0.

Example 115 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isopropyl-lH-imidazole-3-carboxamide Following the procedure in Step A of Example 114, the acid 1- [[[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] ] (Methylene) -oxido-4-sulfanyl] -lH-pyrazole-3-carboxylic acid (65 mg, 0.14 mmol) was reacted with isopropylamine (59 mg, 1.0 mmol), after purification by reverse phase HPLC to provide the l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isopropy1-1H-pyrazole-3-carboxamide (TFA salt, 31 mg, 36%). NMR XH (400 MHz, CDC13) d 1.24 (d, J = 6.6 Hz, 6H), 1.52 (m, 4H), 1.65 (s, 9H), 2.33 (m, ÍH), 3.33 (m, 2H), 3.56 (s, 3H), 3.91 (m, 2H), 4.20 (m, ÍH), 4.51 (d, J = 7.6 Hz, 2H), 6.80 (d, J = 2.8 Hz, ÍH), 7.40 (dd, J = 9.0, 2.0 Hz, ÍH), 7.53 (s, ÍH), 7.88 (d, J = 2.8 Hz, ÍH), 7.95 (dd, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 516.8.

Example 116 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propyl-lH-pyrazole-3-carboxamide Following the procedure in Step A of Example 114, the acid 1- [[[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] ] (Methylene) oxido-? 4-sulfanyl] -lH-pyrazole-3-carboxylic acid (65 mg, 0.14 mmol) was reacted with propylamine (59 mg, 1.0 mmol), after being purified by reverse phase HPLC to provide the l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propyl-lH-pyrazole-3-carboxamide (TFA salt, 26 mg, 30%). NMR XH (400 MHz, CDC13) d 0.95 (t, J = 7.4 Hz, 3H), 1.52 (m, 4H), 1.62 (m, 2H), 1.65 (s, 9H), 2.33 (m, ÍH), 3.28 (s, 3H), 3.33 (m, 2H), 3.58 (s, 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 6.80 (d, J = 2.8 Hz, ÍH) , 7.39 (dd, J = 9.0, 2.0 Hz, ÍH), 7.53 (s, ÍH), 7.88 (d, J = 2.8 Hz, ÍH), 7.95 (d, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 516.8.

Example 117 N-alyl-1-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H- benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-3-carboxamide Following the procedure in Step A of Example 114, the acid 1- [[[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] ] (Methylene) oxido-? - sulfanyl] -lH-pyrazole-3-carboxylic acid (65 mg, 0.14 mmol) was reacted with allylamine (57 mg, 1.0 mmol), after being purified by reverse phase HPLC to provide the N-alil-l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H- benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-3-carboxamide (TFA salt, 18 mg, 21%). NMR XH (400 MHz, CDC13) d 1.50 (m, 4H), 1.62 (m, 2H), 1.64 (s, 9H), 2.32 (m, ÍH), 3.31 (, 2H), 3.57 (s, 3H), 3.91 (m, 2H), 3.97 (d, J = 5.3 Hz, 2H), (m, ÍH), 4.49 (d, J = 7.6 Hz, 2H), 5.11 (m, ÍH), 5.21 (m, 'ÍH), 5.88 (m, ÍH), 6.80 (d, J = 2.8 Hz, ÍH), 7.39 (dd, J = 9. 0, 2.0 Hz, ÍH), 7.52 (s, ÍH), 7.88 (d, J = 2.8 Hz, ÍH), 7.94 (d, J = 9.0 Hz, ÍH); MS (ESI) (M + H) + 514.8.

Example 118 l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethyl-lH-pyrazole-3-carboxamide Following the procedure in Step A of Example 114, the acid 1- [[[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] ] (Methylene) oxide-? 4-sulfanyl] -lH-pyrazole-3-carboxylic acid (65 mg, 0.14 mmol) was reacted with ethylamine (45 mg, 1.0 mmol), after purification by reverse phase HPLC to provide the l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethyl-lH-pyrazole-3-carboxamide (TFA salt, 30 mg, 36%). NMR XH (400 MHz, CDC13) d 1.21 (d, J = 7.4 Hz, 3H), 1.52 (m, 4H), 1.65 (s, 9H), 2.33 (m, ÍH), 3.32 (m, 2H), 3.40 (q, J = 7.4 Hz, 2H), 3.58 (s, 3H), 3.91 (m, 2H), 4.51 (d, J = 7.6 Hz, 2H), 6.80 (d, J = 2.8 Hz, ÍH), 7.40 (dd, J = 9.0, 2.0 Hz, HH), 7.53 (,, HH), 7.88 (d, J = 2.8 Hz, HH), 7.95 (d, J = 9.0 Hz, HH); MS (ESI) (M + H) + 502.8.

Example 119 N- [2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4- (morpholin-4-ylcarbonyl) piperazine-1 -sulfonamide Step A. N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-4- (morpholin-4-ylcarbonyl) piperazine- l-sulfonamide A solution of triflate of 1- [(4- {[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl .}. piperazin-1-yl) carbonyl] -3-methyl-1H-imidazol-3-io (20 mg, 0.03 mmol), morpholine (87 mg, 1 mmol), and Hunig's base (0.2 ml) in 2 ml of MeCN was stirred overnight at room temperature. The reaction mixture was then condensed to give a residue, which was purified by reverse phase HPLC to give N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-4- (morpholin-4) -carbonyl) piperazine-1-sulfonamide (TFA salt, 5 mg, 26%). NMR XH (400 MHz, CDC13) d 1.55 (m, 4H), 1.68 (s, 9H), 1.83 (m, 4H), 2.37 (m, ÍH), 3.25 (m, 8H), 3.29 (m, 6H) , 3.33 (s, 3H), 3.62 (m, 4H), 3.93 (m, 2H), 4.54 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 9.2 Hz, ÍH), 7.81 (s, ÍH), 7.97 (d, J = 9.2 Hz, ÍH); MS (ESI) (M + H) + 562.8. Step B. Triflate of 1- [(4- {[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl .}. piperazin-l-yl) carbonyl] -3-methyl-lH-imidazol-3-io N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -lH-imidazol-1-ylcarbonyl) - N -methylpiperazine-1-sulfonamide ( 1.09 g, 2.0 mmol) in 20 ml of acetonitrile was treated with methyl trifluoromethanesulfonate (1.0 g, 6.0 mmol) at room temperature for 0.5 hour. The resulting solution of triflate of 1- [(4- {[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl.}. piperazin-1-yl) carbonyl] -3-methyl-lH-imidazol-3-io in MeCN was used in Step A directly.

Example 120 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (2-hydroxyethyl) piperazine-l-carboxamide Following the procedure in Step A of the Example 119, triflate of 1- [(4- {[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl .}. piperazin-1-yl) carbonyl] -3-methyl-1H-imidazol-3-io (40 mg, 0.06 mmol) was reacted with 2-aminoethanol (61 mg, 1.0 mmol), after being purified by HPLC of reverse phase to provide the 4-. { [[2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (2-hydroxyethyl) piperazine-1-carboxamide (TFA salt, 19 mg, 52%). NMR XH (400 MHz, CDC13) d 1.55 (m, 4H), 1.68 (s, 9H), 2.37 (m, ÍH), 3.24 (m, 8H), 3.33 (s, 3H), 3.40 (m, 4H) , 3.55 (m, 2H), 3.93 (m, 2H), 4.54 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 9.2 Hz, ÍH), 7.82 (s, ÍH), 7.97 (d, J = 9.2 Hz, ÍH); MS (ESI) (M + H) + 536.8.

Example 121 N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4- (lH-pyrazol-1-ylcarbonyl) piperazine -1-sulfonamide Following the procedure in Step A of the Example 119, triflate of 1- [(4- {[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl .}. piperazin-1-yl) carbonyl] -3-methyl-lH-imidazol-3-io (40 mg, 0.06 mmol) was reacted with 1H-pyrazole (68 mg, 1.0 mmol), after being purified by HPLC of reverse phase to provide N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-1-4- (1H-pyrazole-1) -carbonyl) piperazine-1-sulfonamide (TFA salt, 29 mg, 78%). 1N-NMR (400 MHz, CDC13) d 1.56 (m, 4H), 1.68 (s, 9H), 2.37 (m, ÍH), 3.35 (m, 9H), 3.81 (m, 4H), 3.93 (m, 2H) , 4.54 (d, J = 7.6 Hz, 2H), 6.44 (m, ÍH), 7.68 (s, ÍH), 7.69 (d, J = 9.2 Hz, ÍH), 7.84 (s, ÍH), 7.97 (d, J = 9.2 Hz, ÍH), 8.11 (s, ÍH); MS (ESI) (M + H) + 543.8.

Example 122 N- [2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4- (pyrrolidin-1-ylcarbonyl) piperazine-1 -sulfonamide Following the procedure in Step A of the Example 119, triflate of 1- [(4- {[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl .}. piperazin-1-yl) carbonyl] -3-methyl-1H-imidazol-3-io (40 mg, 0.06 mmol) was reacted with pyrrolidine (71 mg, 1.0 mmol), after purification by phase HPLC. inverse to provide N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-4- (pyrrolidin-1-ylcarbonyl) piperazine -1-sulfonamide (TFA salt, 26 mg, 70%). NMR XH (400 MHz, 20 CDC13) d 1.58 (m, 4H), 1.68 (s, 9H), 1.83 (m, 4H), 2.37 (m, ÍH), 3.25 (m, 8H), 3.34 (m, 9H) ), 3.93 (m, 2H), 4.54 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 9.2 Hz, ÍH), 7.82 (s, ÍH), 7.97 (d, J = 9.2 Hz, ÍH) ); MS (ESI) (M + H) + 547.0.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. A compound of the formula I, a pharmaceutically acceptable salt thereof, the diastereomers, enantiomers, or mixtures thereof: characterized in that G is selected from -0-, -CHF-, and -CF2-; R1 is heterocyclyl of 2 to 6 carbon atoms, wherein the heterocyclyl of 2 to 6 carbon atoms includes at least one nitrogen on the heterocyclyl ring of 2 to 6 carbon atoms, one of at least one nitrogen, is directly linked to the sulfonyl group of the formula I, and the heterocyclyl of 2 to 6 carbon atoms, is optionally substituted with one or more groups selected from halogen, hydroxyl, R5-C (= 0) -, R5-C (= 0) - NH-, R5R6-NH-C (= 0) -, R5R6-NH-C (= 0) -NH-, R5-0-C (= 0) -, R5-0-C (= 0) - NH- , alkoxy of 1 to 6 carbon atoms and alkylamino of 1 to 6 carbon atoms, wherein R 5 and R 6 are independently selected from -H, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, alkenyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 2 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms halogenated, and hydroxy- (alkyl of 1 to 6 carbon atoms); and R2, R3 and R4 are independently selected from fluoro and methyl. 2. The compound according to claim 1, characterized in that G is selected from -O-, -CHF-, and -CF2-; R1 is heterocycloalkyl of 2 to 6 carbon atoms, wherein the heterocycloalkyl of 2 to 6 carbon atoms includes at least one nitrogen on the heterocycloalkyl ring of 2 to 6 carbon atoms, one of at least one nitrogen, is directly linked to the sulfonyl group of the formula I, and the heterocycloalkyl of 2 to 6 carbon atoms, is optionally substituted with one or more groups selected from halogen, hydroxyl, R5-C (= 0) -, R5-C (= 0) - NH-, R5R6-NH-C (= 0) -, R5R6-NH-C (= 0) -NH-, R5-0-C (= 0) -, R5-0-C (= 0) - NH- , alkoxy of 1 to 6 carbon atoms and alkylamino of 1 to 6 carbon atoms, wherein R 5 and R 6 are independently selected from -H, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms , cycloalkyl of 3 to 6 carbon atoms, heterocycloalkyl of 2 to 5 carbon atoms, halogenated, alkyl of 1 to 6 carbon atoms, and hydroxy- (alkyl of 1 to 6 carbon atoms); and R2, R3 and R4 are independently selected from fluoro and methyl. 3. The compound according to claim 1, characterized in that G is selected from -0-, and -CF2-; R1 is selected from piperidinyl, imidazolyl, pyrrolyl, pyrazolyl, morpholinyl, pyrrolidinyl, azetidinyl, and isoxazolidinyl, wherein the piperidinyl, imidazolyl, pyrrolyl, pyrazolyl, morpholinyl, pyrrolidinyl, azetidinyl, and isoxazolidinyl are optionally substituted with one or more selected groups fluoro and acylamino of 2 to 5 carbon atoms; R2, R3 and R4 are selected from fluoro and methyl, with the proviso that R2, R3 and R4 are the same. 4. The compound according to claim 1, characterized in that G is selected from -O- and -CF2-; R where the groups They are optionally substituted with one or more selected fluoro groups, R2, R3 and R4 are selected from fluoro and methyl, with the proviso that R2, R3 and R4 are the same. 5. The compound according to claim 1, characterized in that G is selected from -O- and -CF2-; R1 is selected from heterocycloalkyl of 3 to 5 carbon atoms, and heteroaryl of 2 to 5 carbon atoms, wherein the heterocycloalkyl of 3 to 5 carbon atoms or the heteroaryl of 3 to 5 carbon atoms, includes at least one atom of nitrogen on the heterocycloalkyl rings of 3 to 5 carbon atoms or heteroaryl rings of 2 to 5 carbon atoms, respectively, one of at least one nitrogen is directly linked to the sulfonyl group of the formula I, and the heterocycloalkyl of 3 to 5 carbon atoms or the heteroaryl of 2 to 5 carbon atoms are optionally substituted with one or more groups selected from halogen, alkoxy of 1 to 3 carbon atoms, alkylamino of 1 to 3 carbon atoms and acylamino of 2 to 5 carbon atoms carbon; R2, R3 and R4 are independently selected from fluoro and methyl. The compound characterized because it is selected from and the pharmaceutically acceptable salts thereof. 7. A compound, characterized in that it is selected from: N- (l- { [ {2-tert-Butyl-l- [(4, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl.} (methyl) amino] sulfonyl.}. piperidin-4- il) acetamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylazetidin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylpyrrolidin-1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylmorpholin-4-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperidin-1-sulfonamide; N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl) -N-methylpiperidin-1-sulfonamide; N- [2- (1,1-difluoroethyl) -1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide; N- (l- { [[2- (1,1-difluoroethyl) -1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl. piperidin-4-yl) acetamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropylpiperidinecarboxamide; l-. { [[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methylamino] sulfonyl.} - N-isopropylpiperidin-4-carboxamide; l-. { . [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -IH- benzimidazol-5-yl] (methylamino] sulfonyl.} - N -cyclobutylpiperidine-4-carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H -benzimidazol-5-yl] (methyl) amino] sulfonyl.} - N-cyclopentyl-piperidine-4-carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl] ) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} - N-pyrrolidin-1-ylpiperidinecarboxamide; 1 - { [[2-tert-butyl-1- (tetrahydro-2H -piran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} - N-lH-pyrrol-1-ylpiperidine-4-carboxamide; l- { [[2-ter -butyl- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} - N-ethylpiperidine-4-carboxamide; N- (tert-butyl) -l- { [[2-tert-Butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl.} piperidine-4-carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl] -N, N- dimethylpiperidine-4-carboxamide; l- { [[2-ter -butyl- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-diethylpiperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methylpiperidin-4- carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.] - N-propylpiperidine-4-carboxamide; N-butyl- l-. {[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl, piperidine-4-carboxamide; l-. {[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} - N- (2, 2, 2-trifluoroethyl) piperidine-4-carboxamide; N-allyl-l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] ] (methyl) amino] sulfonyl}. piperidine-4-carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] ] (methyl) amino] sulfonyl.} - N-isobutylpiperidin-4-carboxamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazole- 5-yl] (methyl) amino] sulfonyl.} - N - (2-hydroxy-1-methylethyl) piperidinecarboxamide; l-. {[[[2-tert-butyl-1- (tetrahydro-2H- pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfon il} -N- (2-hydroxyethyl) piperidine-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} ethyl piperidin-4-carboxylate; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.] Azetidin-3-yl ) cyclopropanecarboxamide; N- (l-. {1 [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl. azetidin-3-yl) -2-methylpropanamide; N- (l-. {[[[2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl]] methyl) amino] sulfonyl, azetidin-3-yl) cyclobutanecarboxamide, N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazole- 5-yl] (methyl) amino] sulfonyl.] Azetidin-3-butanamide; N- (l- { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H -benzimidazol-5-yl] (methylamino] sulfonyl.] azetidin-3-yl) propanamide; l-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] methyl azetidin-3-carboxylate; N- [2- (1,1-dimethylethyl) -1- [(tetrahydro-2H-pyran-4-yl) ) methyl] lH-benzimidazol-5-yl] hexahydro-N-methyl-lH-azepin-1-s ulfonamide; N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -N, 4-dimethyl-l-piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1- [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -3- (hydroxymethyl) -N-methyl-1- piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -4-hydroxy-N-methyl-l-piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -4-methoxy-N-methyl-l-piperidinesulfonamide; N- [2- (1,1-dimethylethyl) -1 - [(tetrahydro-2H-pyran-4-yl) methyl] lH-benzimidazol-5-yl] -3-hydroxy-N-methyl-1-piperidinesulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylazetidin-1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4,4-difluoro-N-methylpiperidin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -3,3-difluoro-N-methylpyrrolidin-1-sulfonamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} methyl piperidine-4-carboxylate; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide; (4R) -N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-hydroxy-N, 4-dimethylisoxazolidin-2- sulfonamide; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] Piperidin-4 -yl) acetamide; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] Piperidin-4 -yl) -2,2-dimethylpropanamide; [1- (. {Methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperidin-4-yl] carbamate of tert-butyl; 4- (. {Methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperazine-1-carboxylate of ter- butyl; 4-. { [(cyclopropylamino) carbonyl] amino} -N-methyl-N- [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -1H-benzimidazol-5-yl] piperidin-1-suifonamide; N-cyclopropyl-4- (. {Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperazin-1- carboxamide; 4-. { [(isopropylamino) carbonyl] amino} -N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperidin-1-sulfonamide; N-isopropyl-4- (. {Methyl} 1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperazin-1- carboxamide; N- [1- ( { Methyl [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino.} Sulfonyl) piperidin-4-yl ] acetamide; 2, 2-dimethyl-N- [1- (. {Methyl (1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -benzimidazol-5-yl] amino} sulfonyl) piperidine - 4-yl] propanamide; 2-methyl-N- [1- (. {Methyl [1- (tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] amino} sulfonyl) piperidin -4-il] propanamide; 4-Acetyl-N-methyl-N- [1- (tetrahydro-2 H -pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide; 4- (2,2-dimethylpropanoyl) -N-methyl-N-. { 1- (Tetrahydro-2H-pyran-4-ylmethyl) -2- (trifluoromethyl) -lH-benzimidazol-5-yl] piperazine-1-sulfonamide; N- (l- { [ {2-tert -Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} - (methyl) amino] sulfonyl. piperidin-4-yl) acetamide; N- (l- { [ {2-tert -Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} - (methyl) amino] sulfonyl. piperidin-4-yl) -2,2-dimethylpropanamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methylmorpholin-4-sulfonamide; N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl) -N-methylpyrrolidin-1-sulfonamide; N-. { 2-Ten-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} 3, 3-difluoro-N-methylpyrrolidin-1-sulfonamide; N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl-N-methylisoxazolidin-2-suifonamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -4,4-difluoro-N-methylpiperidin-1-sulfonamide; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} tert-butyl piperazin-1-carboxylate; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-isopropylpiperazine-1-carboxamide; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-methy1-piperazine-1-carboxamide; 4-. { [. { 2-tert-butyl-l- [(4, -difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl} -N-cyclopropipiperazine-1-carboxamide; 4-. { [. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} (methyl) amino] sulfonyl) -N-cyclobutyl-piperazine-1-carboxamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-4- . { [(methylamino) carbonyl] amino} piperidin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methylisoxazolidin-2-sulfonamide; 4-Acetyl-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-piperazine-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (2,2-dimethylpropanoyl) -N-methyl-piperazin-1-suifonamide; 4-benzoyl-N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] -N-methyl-piperazine-

1-sulfonamide; N- [

2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4- (

3-methylbutanoyl) piperazine-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (cyclopropylcarbonyl) - N -methylpiperazin-1-suifonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4-propioni-piperazin-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-isobutyryl-N-methylpiperazine-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4- (cyclobutylcarbonyl) - N -methylpiperazine-1-sulfonamide; N- [2-tert-Butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-butyryl-N-methy1-piperazine-1-sulfonamide;

4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-

5-yl] (methyl) amino] sulfonyl} -N, N-dimethylpiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isopropypiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopenti-piperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methy1-piperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropipiperazine-1-carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclobutyl-piperazine-1-carboxamide; N- (tert-butyl) -4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-1-carboxamide; N-butyl-4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazin-l- carboxamide; N-allyl-4- [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methylamino] sulfonyl.] Piperazine-1-carboxamide; - { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl} -. N -ethiIpiperazine-1-carboxamide; 4-. {[[[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl.} - N-propypiperazin-1 -carboxamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N- (cyclopropylmethyl) piperazine-1-carboxamide; N- [2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -4- (lH-imidazol-1-ylcarbonyl) - N -methylpiperazin-1- sulfonamide; 4-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} piperazine-1-isopropyl carboxylate; N- (L-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl] pyrrolidin-3 -acetamide: N- (l- { [[2-tert-Butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl. pyrrolidin-3-yl) -2,2-dimethylpropanamide; N- (l-. {[[[2-tert-butyl-l- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl.] Azetidin-3 -yl) acetamide; N-. { 2-tert-butyl-l- [(, 4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-lH-imidazole-1-sulfonamide; N-. { 2-tert-Butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl} -N-methyl-1H-1, 2,4-triazole-1-suifonamide; N-. { 2-tert-butyl-l- [(4,4-difluorocyclohexyl) methyl] -1H-benzimidazol-5-yl) -N-methyl-lH-1,2,3-triazole-1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-formyl-N-methyl-1 H-pyrazole-1-sulfonamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropy1-1H-pyrazole-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethyl-lH-pyrazole-4-carboxamide; N-alil-l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propyl-lH-pyrazole-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N, N-dimethyl-lH- pyrazole-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-methyl-lH-pyrazole-4-carboxamide; N- (tert-butyl) -l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -lH-benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-4-carboxamide; N- (l-. {[[[2-tert -Butyl-l- (tetrahydro-2H-? Iran-4-ylmethyl) -1H-benzimidazol-5-yl] (methyl) amino] sulfonyl]. -pyrazol-3-yl) acetamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -4-formyl-N-methyl-1 H-imidazole-1-sulfonamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-imidazole-4-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-cyclopropyl-lH-pyrazole-3-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-isopropy1-1H-pyrazole-3-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-propyl-lH-pyrazole-3-carboxamide; N-allyl-1- [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -lH-pyrazole-3-carboxamide; l-. { [[2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] (methyl) amino] sulfonyl} -N-ethyl-lH-pyrazole-3-carboxamide; N- [2-tert-butyl-1- (tetrahydro-2 H -pyran-4-ylmethyl) -1 H -benzimidazol-5-yl] -N-methyl-4- (morpholin-4-ylcarbonyl) piperazine-1-sulfonamide; 4-. { [[2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] (methylamino] sulfonyl.} - N - (2-hydroxyethyl) piperazine-1-carboxamide; N- [2-tert-butyl-l- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-4- (lH-pyrazol-1-ylcarbonyl) piperazine- 1-sulfonamide; N- [2-tert-butyl-1- (tetrahydro-2H-pyran-4-ylmethyl) -1H-benzimidazol-5-yl] -N-methyl-4- (pyrrolidin-1-ylcarbonyl) piperazine -1-suifonamide, and the pharmaceutically acceptable salts thereof 8. The compound according to any of claims 1 to 7, characterized in that it is for use as a medicament 9. The use of a compound in accordance with any of claims 1 to 7 in the manufacture of a medicament for pain therapy. 10. The use of a compound according to any of claims 1 to 7 in the manufacture of a medicament for the treatment of anxiety disorders. 11. The use of a compound according to any of claims 1 to 7 in the manufacture of a medicament for the treatment of cancer, multiple sclerosis, Parkinson, Huntington's chorea, Alzheimer's disease, gastrointestinal disorders and cardiovascular disorders. 12 A pharmaceutical composition characterized in that it comprises a compound according to any one of claims 1 to 7 and a pharmaceutically acceptable carrier. 13 A method for pain therapy in a warm-blooded animal, characterized in that it comprises the step of administering to the animal in need of such therapy a therapeutically effective amount of a compound according to any of claims 1 to 7. 14 A method for preparing a compound of formula I, characterized in that it comprises the steps of: a) reacting a compound of formula II with a compound of formula III, b) treating the reaction product of step a) with MeOTf; c) reacting the reaction product of step b) with wherein G is selected from -O-, -CHF-, and -CF2-; R1 is heterocyclyl of 2 to 6 carbon atoms, wherein the heterocyclyl of 2 to 6 carbon atoms includes at least one nitrogen on the heterocyclyl ring of 2 to 6 carbon atoms, one of at least one nitrogen, is directly linked to the sulfonyl group of the formula I, and the heterocyclyl of 2 to 6 carbon atoms, is optionally substituted with one or more groups selected from halogen, hydroxyl, R5-C (= 0) -, R5-C (= 0) - NH-, R5R

6-NH-C (= 0) -, R5R6-NH-C (= 0) -NH-, R5-0-C (= 0) -, R5-0-C (= 0) - NH- , alkoxy of 1 to 6 carbon atoms and alkylamino of 1 to 6 carbon atoms, wherein R 5 and R 6 are independently selected from -H, alkyl of 1 to 6 carbon atoms, aryl of 6 to 10 carbon atoms, alkenyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, heterocyclyl of 2 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms halogenated, and hydroxy- ( alkyl of 1 to 6 carbon atoms); and R2, R3 and R4 are independently selected from fluoro and methyl.