TW200408628A - Resorcinol and its derivatives - Google Patents

Abstract

The present invention relates to a compound of the following formula (I), [wherein, X:CH or N; R1: a C1-6 alkyl group, a C3-7 cycloalkyl group, a C2-6 alkenyl group, a C6-10 aryl group, a C7-16 aralkyl group, a 4-10 membered heterocyclic group with 1-3 heteroatom; R2: a C7-16 aralkyl group, a C9-16 aralkenyl group, a 5-10 membered heteroaromatic-cyclic group with 1-3 heteroatom, etc.; R3: a hydrogen atom, a Cl-6 alkyl group, a C6-10 aryl group etc.; m=1-2, n=1-3] ; or the pharmaceutically acceptable salt or ester thereof, having an excellent activity and safty, useful as the prophylactic or therapeutic agent for diabetes.

Description

200408628 (ii) Description of the invention [Technical field to which the invention belongs] The present invention relates to novel phenylpropionic acid derivatives, pharmacologically acceptable salts and pharmacologically acceptable esters thereof. In addition, the present invention relates to phenylpropionic acid derivatives having excellent PPAR (peroxysome activation receptor) r activation, improving insulin resistance, lowering blood glucose, lowering lipids, anti-inflammatory, and inhibiting colonization of cancer cells, and Its pharmacologically acceptable salt and its pharmacologically acceptable ester. Furthermore, the present invention relates to diabetes, hyperglycemia, insufficient glucose tolerance, obesity, hyperlipidemia, diabetic dysfunction, diphenylpropionate derivatives and pharmacologically acceptable salts or pharmacologically acceptable esters thereof as active ingredients, Gestational diabetes (pregnancy-induced hypertension), polycystic ovary syndrome, malignancy, autoimmune disease, allergic disease, immunodeficiency syndrome, inflammatory disease, neurosis, neurodegenerative disease, infection, cancer (eg, gastric cancer , Lung cancer, breast cancer, colorectal cancer, prostate cancer, pancreatic cancer, liver cancer), leukemia, sarcoma (for example: liposarcoma) and other therapeutic drugs and / or preventive drugs (preferably therapeutic drugs and / or preventive drugs for diabetes). Furthermore, the present invention relates to a preventive or therapeutic agent for the above-mentioned diseases containing the above-mentioned compound as an active ingredient, and a preventive or therapeutic composition for the above-mentioned disease containing the above-mentioned compound as an active ingredient, and is intended to produce a medicine for preventing or treating the above-mentioned diseases The use of the above-mentioned compound or the administration of a pharmacologically effective amount of the above-mentioned compound to a warm-blooded animal (preferably a human) is used as a method for preventing or treating the above-mentioned diseases. 200408628 It is known that sulfonylurea compounds such as insulin, tributamide, and glipizide are used in the treatment of diabetes and hyperglycemia, and thiazolinidinedione derivatives are used in the treatment of insulin-independent diabetes. However, these compounds have disadvantages such as incomplete activity and causing side effects. Therefore, it is clinically expected that a potent and safe therapeutic and preventive agent for such diseases. In addition, a compound having a partial common structure (benzimidazolyl or imidazopyridyl) with the phenylpropionic acid derivative of the present invention and exhibiting a blood glucose lowering action is disclosed in International Publication No. 99/18081 (Japanese Patent Application Laid-Open No. 11- _ 1 9 3 2 7 6), US Patent Registration No. 5 8 8 6 0 1 4 (Japanese Patent Registration No. 3 2 4 9 4 90), International Publication No. 00/61581 (Japanese Patent Application Laid-Open No. 00-61581) 2000-351779), Japanese Patent Publication No. 2000-1-9 7 9 54, International Publication No. 00/5 9 8 8 9 (Japanese Patent Publication No. 2000-1-9 7 9 5 )Wait. However, the main compounds disclosed in these publications are different from the compounds of the present invention in that the main compounds without a carboxyl group must have a thiazolinidine dione skeleton, or even if they have a carboxyl group, which must have an α-position substituent. [Summary of the Invention] The present inventors deliberately investigated the development of therapeutic and / or preventive drugs such as diabetes with excellent activity and safety, and found that novel phenylpropionic acid derivatives have excellent PPAR r activation and insulin improvement Resistance effect, lowering blood glucose effect, lowering lipid effect, anti-inflammatory effect, inhibiting colonization of cancer cells, can improve hyperlipidemia, hyperglycemia, obesity, insufficient glucose tolerance, insulin resistance, non-glucose deficiency, insulin Resistance, 200408628 cachexia, dry addiction, diabetic flare, arteriosclerosis, hypertension, pancreatitis, polycystic ovary syndrome, fatty liver, gestational diabetes, cancer, etc., and completed the present invention. That is, the present invention provides hyperlipidemia, hyperglycemia, obesity, impaired glucose tolerance (IGT) status, and insulin resistance and non-glucose tolerance (115115 丨 11) ^ 5 丨 3131 ^ 11011- IGT: NGT) status, hypertension, Teng Yan, cachexia, fatty liver, diabetic flare (such as omentum, nephropathy, neurosis, etc.), arteriosclerosis, gestational diabetes mellitus: _ GDM), diseases caused by insulin resistance in polycystic ovary syndrome (PCOS), inflammatory diseases (such as osteoarthritis, pain, inflammatory bowel disease, etc.), acne, sunburn, dryness, wetness Rash, allergic disease, asthma, GI ulcer, cardiovascular disease (such as blood deficiency heart disease, etc.), tumor damage caused by tumor atherosclerosis and blood deficiency disease (such as brain damage caused by stroke), autologous Immune diseases (such as systemic lupus erythematosus, chronic rheumatoid arthritis, S j oegre η syndrome, systemic dysdermatosis, mixed combined tissue disease, Hashimoto Disease, ulcerative colitis, idiopathic A ddis ο η disease, male infertility, G ο dpasture syndrome, acute glomerulonephritis, myasthenia gravis, multiple tendinitis, multiple sclerosis, autoimmune Hemolytic anemia, idiopathic thrombocytopenic purpura, Bechet's disease, CREST syndrome, etc.), cancer (eg, gastric cancer, lung cancer, breast cancer, colorectal cancer, prostate cancer, pancreatic cancer, liver cancer), leukemia, sarcoma (Eg, liposarcoma) and phenylpropionic acid derivatives and its 200408628 pharmacologically acceptable salts and pharmacologically acceptable esters which are effective as therapeutic and preventive drugs. The present invention is a compound represented by the following general formula (I) or a pharmacologically acceptable salt or ester thereof

[Wherein X is CH or N, R] is a C1-6 alkyl group (the alkyl group may be optionally substituted with 1 to 5 substituents of the substituent group α), a C 3-丨 cycloalkyl group, C2-6 alkenyl (the alkenyl may be substituted with 1-5 substituents selected from the substituent group α), C6-10 aryl (the aryl may have 1-5 substitutions selected from the substituent group ^ Group substitution), C 7-1 6 aralkyl (the aralkyl group may be substituted with 1-5 substituents selected from the substituent group α) or contain the same or different 1-3 selected from nitrogen, oxygen and sulfur 4- to 10-membered heterocyclic group of a heteroatom (the heterocyclic group may be substituted with 1-5 substituents selected from the substituent group α), R2 is a C7-16 aryl group (the aralkyl group may have Selected from i-5 substituents of the substituent group ^), C9-16 arylalkenyl (the arylalkenyl group may be substituted with 1-5 substituents selected from the substituent group α) or contains a group selected from nitrogen 5.10-membered heteroaromatic cycloalkyl of the same or different 3 heteroatoms of oxygen and sulfur (the heteroaromatic cycloalkyl may be substituted with 1-5 substituents selected from the substituent group α), R3 Is hydrogen, C1-6 alkyl or C6-10 aryl (the aryl may be substituted with 1-5 substituents selected from the substituent group ^) m is 1 or 2, n is an integer of 1~3. (Substituent group α)

Cl_6 alkyl, C1-6 hydroxyalkyl, ci-6 haloalkyl, C1-6 alkylthio 200408628 'C1-6 alkoxy, Cl-6 haloalkoxy, C2-6 alkenyl, C2-6 Alkynyl, C 1-6 alkylsulfonamido, amine, C 1-6 alkylamino, C 1-6 dialkylamino, C 1-6 hydroxyalkylamino, C 3-1 0 cycloalkylamino , C 1-6 alkyl, C 3 -10 cycloalkylamino, C3-10 dicycloalkylamino, C6-10 arylamino, C1-6 alkylsulfonamido, C 6-10 arylsulfonamido Group, C 1-1 1 aliphatic amidoamine group, C7-11 arylcarbonylamino group, C1-6 alkylamine carbonyl group, C6-10 arylamine carbonyl group, C 1-6 alkoxycarbonyl group, C7-16 aralkylamine carbonyl group , C7-16 aralkyloxy, 4- to 10-membered heterocyclic group containing 1-3 same or different heteroatoms selected from nitrogen, oxygen, and sulfur, C6-10 aryl, C9-16 arylalkenyl, Carboxy, carbamoyl, hydroxy, cyano, nitro, halogen]. In the present invention, "C1-6 alkyl" is a C1 ~ 6 straight or branched alkyl group, for example: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, second Butyl, third butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, n-hexyl, isohexyl, 4-methylpentyl, 3-methyl Pentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1, 2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, heptyl, 1-methylhexyl, 2-methylhexyl , 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1-propylbutyl, 4,4-dimethylpentyl, octyl, 1-methylheptyl, 2-methyl Heptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 1-propylpentyl, 2-ethylhexyl or 5,5-dimethyl Kihexyl and others. 111, ^, and the substituent group 0 are preferably (: 1 to 3 alkyl groups, and most preferably methyl groups. In the present invention, "C3-10 cycloalkyl group" is a fused 3 to 10 member -10 -200408628 and cyclic hydrocarbon groups, such as: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, adamantyl, etc. R1 and the substituent group α should preferably be 3 to 7 members A saturated cyclic hydrocarbon group is more preferably a cyclopentyl group, a cyclohexyl group, or a cycloheptyl group. In the present invention, the "C3-l0 cycloalkylamino group" is a group in which the above-mentioned "C3-10 cycloalkyl group" is combined with an amine group. For example: cyclopropylamino group, cyclobutylamine group, cyclopentylamine group, cyclohexylamino group, cycloheptylamine group, norbornylamine group, adamantylamine group, etc. In the substituent group α, a cyclohexylamine group is preferred. In the present invention, "C3-10 dicycloalkylamino" is a substituent having two identical or different "C3-10 cycloalkyl" groups on the amine group, for example: bicyclo_propylamino, bicyclobutan Amino group, dicyclopentylamino group, dicyclohexylamino group, dicycloheptylamino group, dinormidine amino group, diadamantylamine group, etc. The substituent group α is preferably a dicyclohexylamine group. In the present invention "C1-6 alkyl C3-10 cycloalkylamino" In the amine group, there are the above-mentioned "C3-10 cycloalkyl" and the above-mentioned "C1-6 alkyl" substituted groups. For example: N, N-cyclopropylmethylamino, N, N-cyclobutylmethylamino, ^^ Cyclopentylmethylamino, Ν, Ν -cyclohexylmethylamino, Ν, Ν -cycloheptylmethylamino, Ν, Ν-norbornylmethylamino, Ν, Ν-adamantylmethylamino, Ν, N ·· cyclopropylethylamino, N, N-cyclobutylethylamino, N, N-cyclopentylethylamino, N, N -cyclohexylethylamino, etc. The substituent group α is preferably Ν, Ν-cyclohexylmethylamino group. In the present invention, "C1-6 alkylthio group" is a group in which the above-mentioned "C1-6 alkyl group" is combined with a sulfur atom, for example: methylthio group, ethylthio group, In the 'substituent group α' such as tributylthio group, a methylthio group is preferred. In the present invention, the "C1-6 alkylamino group" is a group in which the aforementioned "ci-6 alkyl group" is bonded to an amine group of 11-200408628, For example: methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, second butylamine, third butylamine, n-pentylamine, isoamylamine, 2-methylbutylamino, neopentylamino, 1-ethylpropylamino, n-hexylamino, isohexylamine, 4 -Methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 1-methylpentylamino, 3,3-dimethylbutylamino, 2,2-dimethylbutylamine Amine, dimethylbutylamino, it dimethylbutylamino, 1,3-dimethylbutylamine, 2,3-dimethylbutylamine, 2-ethylbutylamine, heptylamine Methyl, 1-methylhexylamino, 2-methylhexylamino, methylhexylamino, 4-methylhexylamino, 5.methylhexylamino, propylpropylamino, 4-dimethylpentylamino, octylamino, i-methylheptylamino, 2-methylheptylamino, 3-methylheptylamino, 4-methylheptylamino, methylheptylamino , Methylheptylamino, 1-propylpentylamino, 2-ethylhexylamino, or 5,5-dimethylhexylamino, etc., and isopropylamine is preferred in the substituent group α. In the present invention, a "C1-6 dialkylamino group" is a substituent group having two identical or different above-mentioned "C1-6 alkyl groups" on an amine group, for example, ν, N-dimethylamino group, N, N-diethylamino, N, N-di-n-propylamino, N, N-diisopropylamino, N, N-di-n-butylamino, N, N_diisobutylamino, N, N _Di-diamino group, butylamino group, N, N-di-third butylamino group, ν, N-di-n-pentylamino group, Ν, N-diisoamylamino group, n: 2-methylbutylamino group , N, N_di neopentylamino, N, N-di1-ethylpropylamino, N, N • di-n-hexylamino, N, N · ~ isohexylamino, N, N_di-4- Methylpentylamino, N, N- = 3-methylpentylamino, N, N-di-2-methylpentylamino, ν, N_di1-methylpentylamino, ν, ν-a The heptylamine group, N, N • dioctylamino group, N, N • ethylmethylamino group, N, N-isopropylmethylamino group and the like, and the substituent group α is preferably a dimethylamino group. -12 · 200408628 In the present invention, "" Cl-6 halofluorenyl "is the above-mentioned" ci-6; (: halogen atom in the end group is substituted, for example: trifluoromethyl, trichloromethyl, mono · ~ m methyl, dichloromethyl, dibromomethyl, fluoromethyl, 2,2,2-trifluoroethyl, 2, 2, 2-trichloroethyl, 2-bromoethyl, 2-chloro Ethyl, 2-fluoroethyl, 2-iodoethyl, 3-chloropropyl, 4-fluorobutyl, 6-iodohexyl, 2''monoethyl, etc., preferably trifluoromethyl in the substituent group α In the present invention, the "C1-6 meridian group" refers to the above-mentioned "ci-6 fluorenyl group substituted by j hydroxyl group, for example: methylol, hydroxyethyl, hydroxypropyl, xyl , Hydroxyhexyl and the like, a substituent group 0: is preferably a methylol group. In the present invention, "" C b 6 hydroxyalkylamino "is a group in which the amine group is substituted in the" c 丨 _6 alkyl group ", For example: methylolamine, hydroxyethylamine, propylamine, butylamine, hydroxyhexylamine, etc., and the substituent group α is preferably ethylamine. In the present invention, "C1-6 "Methenyl" is the above-mentioned "cu alkynyl" combined with sulfonyl, such as ... Base, n-propanesulfanyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, second butylsulfanyl, third butylsulfonyl, n-pentylsulfonyl, isopentylsulfonyl, Methyl butanesulfonyl, neopentylsulfonyl, n-hexanesulfonyl, 4-methylpentylsulfonyl, 3-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3,3-di Methylbutanesulfonyl, 2,2 · dimethylbutanesulfonyl, υ-dimethylbutanesulfonyl, i, 2-dimethylbutanesulfonyl, 1,3-dimethylbutanesulfonyl Amidino, 2, 3-dimethylbutanesulfonyl, etc. The amine substituent in the substituent group α is preferably a C1-4 straight or branched chain alkylsulfonyl, most preferably methylsulfonyl. In the present invention, the "C1-6 alkoxy group" is a group in which the above-mentioned "C1-6 alkyl group" and -13-200408628 oxygen atom are combined, for example, a methoxy group, an ethoxy group, an n-propoxy group, and an isopropoxy group. , N-butoxy, isobutoxy, second butoxy, third butoxy, n-pentyloxy, isoamyloxy, 2-methylbutoxy, neopentyloxy, n-hexyloxy, 4-methylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 3,3-dimethylbutoxy, 2,2-dimethyl Butyl, u-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,3 · dimethylbutoxy, etc. The chain or branched alkoxy group and the substituent group are preferably methoxy groups. In the present invention, "" C1-6 haloalkoxy "is a group in which the above-mentioned" Cl-6 haloalkyl group "is bound to an oxygen atom. , Such as · trifluoromethoxy, trichloromethoxy, monomethoxy, monomethoxy, dibromomethoxy, fluoro (methoxy, 2,2,2-dichloroethoxy , 2,2,2-trifluoroethoxy, 2-bromoethoxy, 2-chloroethoxy, 2-fluoroethoxy, 2,2-dibromoethoxy, etc., in the substituent group α Preferably it is trifluoromethoxy or difluoromethoxy. In the present invention, "C2-6 alkenyl" is a C2 ~ 6 straight or branched alkyl group, for example, vinyl, 1-propenyl, 2-propenyl (or allyl), 1-methyl- 2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propanyl_, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1- Butanyl, 2-butanyl, 1-methyl-2-butanyl, 1-methyl-1-butanyl, methyl · 2-butanyl, 1-ethyl-2-butanyl Base, 3-butanyl, 1-methylbutenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, h-pentyl, 2-pentenyl, 1 -Methyl-2-pentenyl, 2-methyl-2-pentenyl '3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4 -Pentyl, 1-methylpentyl, 2-methyl-4-pentanyl, 1-hexenyl, -14-200408628 2 -hexenyl, 3-hexenyl, 4-hexene , 5-hexenyl and the like. R1 and the substituted group α are preferably C3 to 5 straight-chain or branched alkenyl groups, and more preferably 2-propenyl or ethylene. In the present invention, "C2-6 alkynyl" is a C2-6 straight or branched chain alkynyl, such as: ethynyl, 2-propynyl, 1-methyl-2-propynyl, 2-methyl -2 -propynyl, 2-ethyl-2-propynyl, 2-butynyl, bmethyl-2 -butynyl, 2-methyl-2-butynyl, 1-ethyl- 2-butynyl, 3-butynyl, 1-methyl-3 -butynyl, 2-methyl-3 -butynyl, 1 -ethyl-3 -butynyl, 2-pentynyl , 1-methyl-2-pentynyl, 2-methyl-2 -pentynyl, 3-pentyl, 1-methyl-3 -pentynyl, 2-methyl-3 -pentynyl , 4-pentynyl, 1-methyl-4 -pentynyl, 2-methyl-4 -pentynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexyl Alkynyl, etc. The substituent group α is preferably a C3 to 5 linear or branched alkynyl group. In the present invention, "C6-10 aryl" is a C6-10 aromatic hydrocarbon group, such as: phenyl, indenyl, naphthyl, etc., R1,! ^ 3 and the substituent group α are preferably phenyl. In the present invention, the "C6-10 arylamine group" is a group in which the above-mentioned "C6_10 aryl group" is combined with an amine group, for example, aniline group, benzylamine group, naphthylamine group, etc., and aniline is preferred in the substituent group α. base. In the present invention, "C7-16 aralkyl" is a group in which the above "C6-10 aryl" is combined with the above "C1-6 alkyl", for example: benzyl, α-naphthylmethyl, / 3-naphthalene Methyl, indylmethyl, phenanthryl, onionmethyl, benzyl, trityl, 1-phenethyl, 2-phenethyl, 1-naphthylethyl, 2-naphthylethyl, I-phenylpropyl, 2-phenylpropyl, 3-phenylpropyl, naphthyl, 2-naphthyl-15-200408628, 3-naphthyl, 1-phenylbutyl, 2-phenylbutyl, 3-Phenylbutyl, 4-Phenylbutyl, 1-naphthylbutyl, 2-naphthylbutyl, 3-naphthylbutyl, 4-naphthylbutyl, 1-phenylpentyl, 2-phenylpentyl, 3- Phenylpentyl, 4-phenylpentyl, 5-phenylpentyl, phenapentyl, 2-naphthylpentyl, 3-naphthylpentyl, naphthylpentyl, 5-naphthylpentyl, 1-phenylhexyl, 2- Phenylhexyl, 3-phenylhexyl, 4-phenylhexyl, 5-phenylhexyl, 6-phenylhexyl, 1-naphthylhexyl, 2-naphthylhexyl, 3-naphthylhexyl, 4-naphthylhexyl, 5-naphthylhexyl, 6- Naphthylhexyl and the like. R1 and R2 are preferably "alkyl" and "aralkyl" of C1 to 4, more preferably benzyl. In the present invention, the "C7-16 aralkyloxy group" is a group in which the "C7-16 aralkyl group" is combined with an oxygen atom, for example, benzyloxy group, α-naphthylmethoxy group, / 3 -naphthylmethoxy group , Indylmethoxy, phenanthrylmethoxy, onionmethoxy, diphenylmethoxy, triphenylmethoxy, 1-phenethoxy, 2-phenethoxy, phenaethoxy, 2- Naphthylethoxy, 1-phenylpropoxy, 2-phenylpropoxy, 3-phenylpropoxy, 1-naphthylpropoxy, 2-naphthylpropoxy, 3-naphthylpropoxy, 1-benzene Butoxy, 2-phenylbutoxy, 3-phenylbutoxy, 4-phenylbutoxy, 1-naphthylbutoxy, 2-naphthylbutoxy, 3-naphthylbutoxy, 4-naphthalene Oxy, phenpentyloxy, 2-phenpentyloxy, 3-phenylpentyloxy, 4-phenylpentyloxy, 5-phenylpentyloxy, 1-naphthylpentyloxy, 2-naphthylpentyloxy, 3-naphthylpentyloxy, 4-naphthylpentyloxy, 5-naphthylpentyloxy, 1-phenylhexyloxy, 2-phenylhexyloxy, 3-phenylhexyloxy, 4-phenylhexyloxy, 5 -Phenhexyloxy, 6-phenhexyloxy, I.naphthylhexyloxy, 2-naphthylhexyloxy, 3-naphthylhexyloxy, 4-naphthylhexyloxy, 5-naphthylhexyloxy, 6- Nehexyloxy and the like. The substituent group ^ is preferably a ethoxy group. In the present invention, the "" C9-16 arylalkenyl group "is a group in which the above-mentioned rC6-l0 aryl group" is combined with the above-mentioned "C3-6 alkenyl group", and r2 and the substituent group α are preferably -16 '200408628 "alkenyl group "" Aryl "of C2 ~ 4, more preferably 3-phenyl-propenyl, 3-phenyl-2 -methyl-2 -propenyl, 3-phenyl-2-ethyl-2 -Propenyl, 4-phenyl-2-butenyl. In the present invention, "a 4- to 10-membered heterocyclic group containing the same or different 1 to 3 heteroatoms selected from nitrogen, oxygen, and sulfur" is 4 to 1 containing 1 to 3 sulfur atoms, oxygen atoms, or nitrogen atoms. A membered heterocyclic group, such as the corresponding part of furyl, thienyl, lauryl, azepinyl, pyrazolyl, imidazolyl, oxazolyl, piperidinyl, venyl, tetrahydropyranyl, or Completely reduced radicals, etc. Furthermore, the above "4- to 10-membered heterocyclic group" may be fused with other rings, such as: isobenzofuranyl, tryptenyl, fluorenyl, phenanthryl, indyl, isoindolyl, Indolyl, indazolyl, purinyl, quinolinyl, isoquinolinyl, quinolinyl, sulfonyl, pyridyl, quinolinyl, quinazolinyl, carbazolyl, oxolinyl, Acridinyl, isoindolyl and the like. R 1 and the substituent group α are preferably 4 to 10-membered heterocyclic groups containing 1 or more nitrogen atoms, which may contain oxygen atoms or sulfur atoms, such as pyrrolyl, azepinyl, pyrazolyl, imidazolyl, Oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, tetrazyl, thiadiazolyl, pyridyl, daphyl, pyrimidinyl, Aromatic heterocyclic groups such as pyridyl and morpholinyl, thiomorpholinyl, pyrrolidyl, pyrrolidyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, piperidinyl, piperidinyl The corresponding partially or completely reduced groups such as a well group and a tetrahydropyranyl group are preferably pyrrolidinyl, piperidinyl, piperidinyl, morpholinyl, and tetrahydropyranyl. In the present invention, "a 4- to 10-membered heteroaromatic cycloalkyl group containing the same or different 1-3 heteroatoms selected from nitrogen, oxygen, and sulfur" is a group containing 1 to 3 sulfur atoms, oxygen atoms, or nitrogen atoms. The above-mentioned "4- to 10-membered aromatic heterocyclic group" is combined with the above-mentioned -17-200408628 "C1-6 courtyard group", and R2 is preferably "4--10" membered to Cl ~ 4 of "4-10 membered heterocyclic group" "Aromatic cycloalkyl", also preferably 2-pyrimidinylmethyl, 2-pyridylethyl, 3-Diodinated methyl, 4-Diodinated methyl, 2-quinolinylmethyl, 2-thiophene And 2-thienylethyl. In the present invention, "C1-6 alkylsulfonyl" is a group in which the above "ci-6 alkyl" is combined with sulfonyl, such as: methanesulfonyl, ethanesulfonyl, n-propylsulfonyl, isopropyl Propanesulfonyl, n-Butylsulfonyl, Isobutylsulfonyl, Second Butylsulfonyl, Third Butylsulfonyl, N-pentylsulfonyl, Isopentylsulfonyl, 2-Methylbutanesulfonyl Base, neopentylsulfonyl, n-hexanesulfonyl, 4-methylpentylsulfonyl, trimethyl 3-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3,3-dimethylbutanesulfonyl Fluorenyl, 2,2-dimethylbutanesulfonyl, 1,1-dimethylbutanesulfonyl, dimethylbutanesulfonyl, 1,3-monomethylbutanesulfonyl, 2 , C-1-6 linear or branched alkanesulfonyl and the like such as 3-dimethylbutanesulfonyl and the like. The substituent group α is preferably a C1-4 straight-chain or branched alkanesulfonyl group, and more preferably a mesosulfonyl group. In the present invention, "C1-6 sulfonamido" is the group in which the above-mentioned "C1-6 sulfoamido" is combined with an amine group, for example: methanesulfonylamine, ethyl amine, and n-propylamine Base, isopropylsulfonylamine, n-butylamine, butylamine φ fluorene, second butylsulfonylamine, third butylsulfonylamine, n-pentylsulfonylamine, isopentylsulfonyl Amidino, 2-methylbutanesulfonamido, neopentylamine, n-hexanesulfonamido, 4-methylpentanesulfonamido, 3-methylpentanesulfonamido, 2-methyl Pentamsulfenylamino, 3,3-dimethylbutansulfenylamino, 2 · dimethylbutanesulfonylamino, 1,1-dimethylbutanesulfonylamino, 1,1,2 C1-6 linear or branched alkanesulfonylamino groups, such as dimethyl butanamine, 1,3-monomethylbutanamine, 2,3-dimethylbutanesulfonylamino, etc. The substituent group ^ is preferably -18-200408628 C 1 ~ 4 straight or branched chain alkylsulfonamido group, and more preferably methanesulfonamido group. In the present invention, "C6-10 arylsulfonamido" is a group in which the above-mentioned "C6-10 aryl" is combined with sulfonamido, such as: benzenesulfonamido, α-naphthalenesulfonamido, / 3-naphthalenesulfonamido, 2-methylbenzenesulfenamido, 3-methylbenzenesulfenamido, 4-methylbenzenesulfenamido, 2-ethylbenzenesulfenamido, 3- Ethylbenzenesulfonamido, 4-ethylbenzenesulfonamido, 2,4,6-trimethylbenzenesulfonamido, 3,4, 5-trimethylbenzenesulfonamido, 2- N-propylbenzenesulfonamido, 4-n-propylbenzenesulfenamido, 2-isopropylbenzenesulfenamido, 4-isopropylbenzenesulfenamido, 2-butylbenzenesulfenamido , 4-Butylsulfenylsulfenylamino group, 2-methoxybenzsulfenylsulfonamide group, 3-methoxybenzylsulfonamide group, 4-methoxybenzylsulfonamide group, 2-ethoxybenzenesulfonamide group , 3 -ethoxybenzenesulfonamido, 4-ethoxybenzenesulfenamido, 2-n-propyloxybenzenesulfenamido, 3-n-propoxybenzenesulfenamido, 4-n-propoxybenzyl Sulfamethyl, 2-isopropyloxybenzenesulfonamido, 3-isopropyloxybenzenesulfonamido, 4-isopropyloxybenzenesulfonamido, 2-n-butoxybenzenesulfonamido, 3 -N-Butoxybenzenesulfonamide, 4- Butoxybenzenesulfonamido, 2-trifluorotoluenesulfonamido, 3-trifluorotoluenesulfonamido, 4-trifluorotoluenesulfonamido, 2-pentafluoroethylbenzenesulfonamido, 3 -Pentafluoroethylbenzenesulfonamido, 4-pentafluoroethylbenzenesulfonamido®, 2-(2-chloroethyl) benzenesulfonamido, 3-(2-chloroethyl) benzenesulfonamide Group, 4- (2-chloroethyl) benzenesulfonamido group, 2- (2-bromoethyl) benzenesulfonamido group, 3- (2-bromoethyl) benzenesulfonamido group, 4-( 2-bromoethyl) benzenesulfonamido, 2-methoxycarbonylbenzenesulfonamido, 3-methoxycarbonylbenzenesulfonamido, 4-methoxycarbonylbenzenesulfonamido, 2-ethoxycarbonyl Benzenesulfonylamine, 3 · ethoxycarbonylbenzenesulfonylamine, 4-ethoxycarbonylbenzenesulfonylamine, 2-aminomethylsulfonylbenzenesulfonylamine, 3-aminomethylsulfonylbenzenesulfonamide 4-methylaminomethylsulfenyl-19-200408628 fee group, 2-methylaminomethylbenzylbenzene sulfonamide, 3-methylaminomethylbenzylbenzene sulfonamide, 4-methylamine methylsulfonium Benzylsulfonamido, 2-dimethylamine benzylsulfonamido, 3-dimethylamine benzylsulfonamido, 4-dimethylamine benzsulfenamido, 2 -Nifedisulfazone Group, 4-nitrobenzenesulfonamido, 2-chlorobenzenesulfonamido, 3-chlorobenzenesulfonamido, 4-chlorobenzenesulfonamido, 2-fluorobenzenesulfonamido, 3-fluoro Benzenesulfonamide, 4-fluorobenzenesulfonamide, 2,6-dichlorobenzenesulfonamide, 2, 6-fluorobenzenesulfonamide, 2-bromobenzenesulfonamide, 3-bromo Benzylsulfonamido, 4-bromobenzenesulfonamido, 4-cyanobenzenesulfenamido, 4-phenylbenzenesulfenamido and the like. Among the amino group substituents of the substituent group α, a benzylsulfonamido group is preferable. In the present invention, the "C 1-1 1 aliphatic amido group" is a C 1-10 aliphatic hydrocarbon group or a group in which hydrogen is bonded to a carbonyl amino group, for example: formamidine, acetamido, propyl Amido, butyramido, isobutyramido, pentamido, pentamidine, pentamido, isoamylamino, octylamino, nonanylamino, decylcarbonyl Women's group, 3-methylnonylcarbonylamino group, 8-methylnonylaminoamine group, 3-ethyloctylcarbonylamino group, 3,7-dimethyloctylcarbonylamino group, alkylcarbonylamino group, and chloroacetamidine Halogenated alkylcarbonylamino groups such as amino, dichloroacetamido, trichloroacetamido, trifluoroacetamido, lower alkoxyalkylcarbonylamino groups such as methoxyacetamido, (E) -2 -Unsaturated alkylcarbonylamino groups such as methyl-2-butenylamino and the like. Among the amino group substituents of the substituent group α, a C 1-6 aliphatic amido group is preferred. In the present invention, the "C7-11 arylcarbonylamino group" is a group in which the above-mentioned "ci-10aryl group" and a carbonylamino group are combined, for example, a benzamidine group, an α-naphthylamidine group, / S- Arylcarbonylamino groups such as naphthylamino group, halogenated arylcarbonylamino groups such as 2-bromobenzylamino group, 4-chlorobenzylamino group, 2,4,6-trimethylbenzylamino group, 4-toluidine group Low alkylated arylcarbonylamino groups such as alkyl, low alkylated aryl groups such as 4-p-methoxybenzylamine, etc.-20- 200408628 Carboxamide, 4-nitrobenzylamidoamine, 2-nitrobenzylamidoamine, etc. Aromatic amidoamines such as low alkoxycarbonylated arylcarbonylamino groups such as 2-arylmethylamino, 2- (methoxycarbonyl) benzylamino, and 4-arylbenzylamino groups such as 4-phenylbenzylamino Base etc. The substituent group α is preferably a benzamidine group. In the present invention, "C1-6 alkoxycarbonyl" is a group in which the above-mentioned "cl-6 alkoxy" is combined with a carbonyl group, for example: methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n- Butoxycarbonyl, isobutoxycarbonyl, second butoxycarbonyl, third butoxycarbonyl, n-pentyloxycarbonyl, isoamyloxycarbonyl, 2-methylbutoxycarbonyl, neopentyloxycarbonyl, n-hexyloxycarbonyl, 4- Methylpentyloxycarbonyl, 3-methylpentyloxycarbonyl, 2-methylpentyloxycarbonyl, 3,3-dimethylbutoxycarbonyl, 2,2-dimethylbutoxycarbonyl, 1,1-bis Methylbutoxycarbonyl, it dimethylbutoxycarbonyl, 1,3-dimethylbutoxycarbonyl, 2,3-dimethylbutoxycarbonyl, etc. C1-6 straight or branched chain oxygen radicals, etc., The substituent group ^ is preferably a third butoxy group or a methoxy group, and more preferably a third butoxy group. In the present invention, the "C1-6 alkylamine carbonyl group" is a group in which the "ci-6 alkylamine group" and a carbonyl group are combined, for example: methylamine carbonyl, ethylamine carbonyl, n-propylamine carbonyl, isopropylamine carbonyl, n-butylamine Carbonyl, isobutylamine carbonyl, second butylamine® carbonyl, tertiary butylamine carbonyl, n-pentylamine carbonyl, isopentylamine carbonyl, 2-methylbutylamine carbonyl, neopentylamine carbonyl, 1-ethylpropylamine carbonyl, N-hexylamine carbonyl, isohexylamine, 4-methylpentylamine, 3-methylpentylamine, 2-methylpentylamine carbonyl, 1-methylpentylamine carbonyl, 3,3-dimethyl Butylamine carbonyl, 2,2-dimethylbutylamine carbonyl, 1,1-dimethylbutylamine carbonyl, 1,2-dimethylbutylamine carbonyl, 1,3-dimethylbutylamine carbonyl, 2, 3-dimethylbutylamine carbonyl, 2-ethylbutylamine carbonyl, heptylamine carbonyl, 1-methylhexylamine carbonyl, 2-methylhexylamine carbonyl 21-200408628, methylhexylamine carbonyl, 4_ Methylhexylamine carbonyl, 5-methylhexylamine carbonyl, 1-propylbutylamine carbonyl, 4,4-dimethylpentylamine carbonyl, octylamine carbonyl, 1-methylheptylamine carbonyl, 2-methylheptylamine Aminocarbonyl, 3-methylheptylamine carbonyl, 4-methylheptylamine carbonyl , 5-methylheptylamine carbonyl, 6-methylheptylamine carbonyl, 1-propylpentylamine carbonyl, 2-ethylhexylamine carbonyl or 5, 5-dimethylhexylamine carbonyl, etc. in the substituent group α Preferably it is isopropylamine carbonyl. In the present invention, “C6-10 arylamine carbonyl group” is a group in which the “(: 6-10 arylamine group) is combined with a carbonyl group, for example, aniline carbonyl, indenyl carbonyl, naphthylamine carbonyl, etc., and the substituent group α is preferably Is an aniline carbonyl group. _ In the present invention, the "C7-16 aralkylamine carbonyl group" is a group in which the above-mentioned "C7-16 aralkyl group" is bonded to an carbonyl group by an amine group, for example: benzylamine carbonyl group, naphthylmethylamine carbonyl group, / 3-naphthylmethylamine carbonyl, indenylamine carbonyl, phenanthramine carbonyl, allylamine carbonyl, dibenzylamine carbonyl, tritylamine carbonyl, 1-phenethylamine carbonyl, 2-phenethylamine carbonyl, 1- Naphthylethylamine carbonyl, 2-naphthylethylamine carbonyl, 1-amphetamine carbonyl, 2-amphetamine carbonyl, 3-amphetamine carbonyl, 1-naphthylamine carbonyl, 2-naphthylamine carbonyl, 3-naphthylamine carbonyl, 1-phenbutylamine Carbonyl, 2-Phentermine carbonyl, 3-Phentermine carbonyl, 4-Phentermine carbonyl, 1-naphthylamine carbonyl, 2-naphthylamine carbonyl, 3-naphthylamine carbonyl, 4-naphthylamine Carbonyl, 1-phenylpentylamine carbonyl, 2-phenylpentylamine carbonyl, 3-phenylpentylamine carbonyl, 4-phenylpentylamine carbonyl, 5-phenylpentylamine carbonyl, 1-naphthylpentylamine carbonyl, 2-naphthylpentylamine carbonyl , 3- Amylamine carbonyl, 4-naphthylpentylamine carbonyl, 5-naphthylpentylamine carbonyl, 1-phenylhexylamine carbonyl, 2-phenylhexylamine carbonyl, 3-phenylhexylamine carbonyl, 4-phenylhexylamine carbonyl, 5-phenylhexyl Aminocarbonyl, 6-Phenylhexylaminecarbonyl, 1-naphthylhexylaminecarbonyl, 2-naphthylhexylaminecarbonyl, 3-naphthylhexylaminecarbonyl, 4-naphthylhexylaminecarbonyl, 5-naphthylhexylaminecarbonyl, 6-naphthylhexylamine Carbonyl, etc. -22- 200408628 The benzylamine carbonyl group is preferred in the substituent group α. In the present invention, the "halogen atom" is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and the fluorine atom or Chlorine atom. The phenylpropionic acid derivative of the general formula (I) in the present invention can be used to obtain an acid addition salt from a basic group according to a conventional method. Such salts are, for example, hydrofluoric acid, hydrochloric acid, hydrobromic acid, and hydroiodic acid. Isohydrohalides; inorganic acid salts such as nitrates, perchlorates, sulfates, and phosphates; low-alkane sulfonates such as methanesulfonate, trifluoromethanesulfonate, and ethanesulfonate; benzenesulfonic acid Aromatic sulfonates such as salt, p-toluenesulfonate; Amino acid salts such as glutamic acid, aspartic acid; acetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, benzene A , Amyglic acid, ascorbic acid, lactic acid, gluconic acid, citric acid and other organic acid salts, etc. It is preferably a hydrohalide, most preferably a hydrochloride. Furthermore, when the phenylpropionic acid is derived from the general formula (I) above When the substance contains a base, a metal salt can be obtained according to a conventional method. The salt is, for example, an alkali metal salt such as lithium, sodium, and potassium; an alkaline earth metal salt such as calcium, barium, and magnesium; an aluminum salt, etc. It is preferably an alkali metal salt. The phenylpropionic acid derivative having the above general formula (I) can be obtained by a pharmacologically acceptable ester according to a conventional method. As long as these esters are the same as the phenylpropionic acid derivative of the general formula (i) above, they can be used in medicine and pharmacologically acceptable. The esters of the phenylpropionic acid derivatives of the general formula (I) in the present invention are, for example, C1-6 courtyard (the courtyard may be substituted based on Sansao sand courtyard), [7-16 aromatic courtyard C1-6 alkyl substituted with C1-6 alkanoyloxy, C1-5 alkyl substituted with ci-6 alkoxycarbonyloxy, ci-5 alkyl substituted with C5-7 cycloalkoxycarbonyloxy, C6 A C1-5 alkyl group substituted by a -10 aryloxycarbonyloxy group and a 5-substituted group may be a 2-oxo-1,3-dendorocene group having a C1-6 fluorenyl group and the like. -23- 200408628 C1-6 alkyl is preferably C1-4 straight or branched chain alkyl, more preferably methyl, ethyl, propyl, isopropyl, butyl or isobutyl, most preferably methyl Or ethyl. C 5-7 cycloalkyl is a 5- to 7-membered saturated cyclic hydrocarbon group, such as cyclopentyl, cyclohexyl, cycloheptyl, etc., and is preferably cyclohexyl. C6-10 aryl is, for example, phenyl, naphthyl, etc., and is preferably phenyl. C7-16 Fangyuanji should be a festival base. Specific examples of preferred ester residues are, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, third butyl, benzyl, ethoxymethyl, 1- (ethyl (Oxy) ethyl, propionyloxymethyl, 1- (propanyloxy) ethyl, butyryloxymethyl, 1- (butyryloxy) ethyl, isobutyryloxymethyl, 1- ( Isobutyryloxy) ethyl, pentamyloxymethyl, 1- (pentyloxy) ethyl, isoamyloxymethyl, 1- (isopentyloxy) ethyl, pivalamyloxymethyl , 1- (t-pentamyloxy) ethyl, methoxycarbonyloxymethyl, 1- (methoxycarbonyloxy) ethyl, ethoxycarbonyloxymethyl, 1 · (ethoxycarbonyloxy) ethyl , Propoxycarbonyloxymethyl, 1- (propoxycarbonyloxy) ethyl, isopropoxycarbonyloxymethyl, (isopropoxycarbonyloxy) ethyl, butoxycarbonyloxymethyl, b (butoxy (Carbonyloxy) ethyl ruthyl, isobutoxycarbonyloxymethyl, i-(isobutoxycarbonyloxy) ethyl, third butoxycarbonyloxymethyl, 1- (second butoxycarbonyloxy) ethyl Methyl, cyclopentylcarbonyloxymethyl, 1- (cyclopentylcarbonyloxy) ethyl, cyclohexylcarbonyloxymethyl, (cyclohexylcarbonyloxy) ethyl, cyclopentylcarbonyloxymethyl, cyclopentyloxycarbonyl Oxy) ethyl , Cyclohexyloxycarbonyloxymethyl, (cyclohexyloxycarbonyloxy) ethyl, benzamidineoxymethyl, 1- (fluorenyloxy) ethyl, phenoxycarbonyloxymethyl, i · (phenoxycarbonyl (Oxy)) ethyl, (5-methyloxy, seleno-4_yl) methyl or 2_-24-200408628 trimethylsilylethyl. The phenylpropionic acid derivative of the above general formula (I) may have various isomers. For example, in the phenylpropionic acid derivative of the general formula (I), the R 2 moiety is a cis-isomer and a trans-isomer due to the geometric isomers. And R1, R2 and R3 have optical isomers due to the presence of asymmetric carbon atoms. In the above general formula (I), equal and non-equivalent isomer mixtures are represented by a single formula. Therefore, the present invention also includes isomers and mixtures of isomers in any ratio. Furthermore, when the phenylpropionic acid derivative of the above general formula (1), its salt or ester forms a vehicle (such as a hydrate), it is also included in the present invention. Furthermore, the present invention also includes a phenylpropionic acid derivative of the above general formula (1), a salt or an ester-converting compound thereof (e.g., amidine derivatives, etc., and prodrugs) that can be metabolized in vivo. The phenylpropionic acid derivative of the above general formula (I), a salt or an ester thereof of the present invention can be used in combination with other drugs. The drugs used in combination include, for example, sulfonylurea, an α-glucosidase inhibitor, an aldose reductase inhibitor, an antidiabetic agent such as a biguanide, and a diuretic. The above sulfonylurea is an agent that can promote insulin secretion, and is not particularly limited, such as: metinine, acetohexamide, tolazamide, chlorpropamide, and the like. The aforementioned α-glucosidase inhibitor is an agent that can inhibit digestive enzymes, and delay the digestion of starch and sucrose, and is not limited, for example: a c a r b o s e, boglybose, miglytol, and the like. The above-mentioned aldose reductase inhibitor is not limited as long as it can inhibit -25- 200408628 diabetes dysentery by inhibiting the rate-limiting enzyme of the first step of the polyol pathway, for example: Lestard, Elba Lulestad, Inmilestad, Zelenstad, etc. The above-mentioned biguanide is an agent that can promote anaerobic glycolysis, stubborn insulin effect, inhibit glucose absorption from the intestinal tract, inhibit liver glucose new synthesis, inhibit fatty acid oxidation and other effects, such as phenformin , Metformin, bumpin, etc. The above-mentioned diuretics are drugs that can increase the amount of urinary excretion, such as: acetazolamide, azosemide, amiloride, isosodihydrosorbide (iS0S0rbide), diuretic acid , Kanley acid gentry, chlortalidone, cyclopenthiazide, spironolactone, torasemide, triamterene, trichlormethiazide, hydrochlorothiazide, hydroflumethiazide, piretanide, bumetanide, furosemide, pentylhydrochlorothiazide, penthymefurazone, metoprolazefriaide Miloride and others. In the general formula (I), X is preferably CH. R1 is preferably a C1-6 alkyl group, a C6-10 aryl group (the aryl group may be substituted with 1-5 substituents selected from the substituent group α), or a C7-16 aralkyl group (the aralkyl group may have Selected from 1-5 substituents of the substituent group α), more preferably methyl, or phenyl (the phenyl group may be substituted with 1-5 substituents selected from the substituent group α), particularly preferably methyl. R2 is preferably a C7-16 aralkyl group (the aralkyl group may be substituted with 1 to 5 substituents selected from the substituent group α-26-200408628), a c 9 _ 丨 6 aralkyl group (the aralkyl group may 5-7-membered heteroaromatic cycloalkyl having 1 ~ 3 heteroatoms selected from nitrogen, oxygen, and sulfur which are the same or different from the substituent group 0: (the heteroaromatic cycloalkyl may be optionally selected) Self-substituent group 0: one substituent is substituted) 'is more preferably a C7-16 aralkyl group (the aralkyl group may be substituted with 1-3 substituents selected from the substituent group 0), and more preferably benzyl (The benzyl group may be substituted with 5 to 5 substituents selected from the substituent group α), and particularly preferably benzyl (the benzyl group may be substituted with 1-5 methoxy or halogen atoms). R3 is preferably C1-6 alkyl, more preferably methyl. Call m preferably 2. η should be 1. In the present invention, specific examples of the phenylpropionic acid derivative, its salt or ester of the general formula (1) are the following exemplified compounds. However, the present invention is not limited to the compounds exemplified below. In the following Tables 1 and 2, "Me" is methyl, "Et" is ethyl, "nPr" is n-propyl, "yin!" Is isopropyl, "nBu" is n-butyl, and "ιΒιι" "" Is third butyl, "iu" is isobutyl, "nPn" is n-pentyl, "nHex" is n-hexyl, "cHex" is cyclohexyl, "cPn" is cyclopentyl, and "cHp" is Cycloheptyl, "MeO" is methoxy, "

"EtO" is ethoxy, "Ph" is phenyl, "diMe-Ph" is xylyl, "diCl-Ph" is dichlorophenyl, "diMeO-Ph" is dimethoxyphenyl, and "Pfp" Is pentafluorophenyl, `` styryl '' is phenethyl, `` Naph '' is naphthyl, `` Pyr '' is ladenyl, `` Piperidinyl '' is piperidinyl, `` Quinolyl '' is quinolinyl, and `` Thienyl '' is -27 · 200408628 Thienyl, "cinnamyl" is cinnamyl, "vinyl" is ethyl, "Fur" is furyl, "Thp" is tetrahydropyranyl, "Thtp" is tetrahydrothiopyranyl "Mor" is morpholinyl, "Piz" is piperidinyl, "Pyrd" is pyrrolidinyl, "All" is allyl, "S02" is sulfonyl, and "Boc" is Tributoxycarbonyl.

-28- 200408628 Table 1 No. R1 R " R0 mn Μ Me PhCH2 Me 2 1 1-2 Me 2-Me-PhCH2 Me 2 1 1-3 Me 3-Me-PhCH2 Me 2 1 1-4 Me 4-Me -PhCH2 Me 2 1 1-5 Me 2-Et-PhCH2 Me 2 1 1-6 Me 3-Et-PhCH2 Me. 2 1 1-7 Me 4-Et-PhCH2 Me 2 1 1-8 Me 2-1Pr- PhCH2 Me 2 1 1-9 Me 3-1Pr-PhCH2 Me 2 1 1-10 Me WPi-PhCHs Me 2 1 1-11 Me 2-lBu-PhCH2 Me 2 1 M2 Me 3-lBu-PhCH2 Me 2 1 M3 Me 4-tBu-PhCH2 Me 2 1 1-14 Me 2-MeO-PhCH2 Me 2 1 1-15 Me 3-MeO-PhCH2 Me 2 1 1-16 Me 4-MeO-PhCH2 Me 2 1 1-17 Me 2- EtO-PhCH2 Me 2 1 1-18 Me 3-EtO-PhCH2 Me 2 1 1-19 Me 4-EtO-PhCH2 Me 2 1 1-20 Me 4-CF30-PhCH2 Me 2 1 1-21 Me 4-CF2OPhCH2 Me 2 1 1-22 Me 2-PhCH20-PhCH2 Me 2 1 1-23 Me 3-PhCH20-PhCH2 Me 2 1 1-24 Me 4-PhCH20-PhCH2 Me 2 1 1-25 Me 2-F-PhCH2 Me 2 1 1-26 Me 3-F-PhCH2 Me 2 1 1-27 Me 4-F-PhCH2 Me 2 1 1-28 Me 2-Cl-PhCH2 Me 2 1 1-29 Me 3-Cl-PhCH2 Me 2 1 1- 30 Me 4-Cl-PhCH2 Me 2 1 1-31 Me 2-Br-PhCH2 Me 2 1 1-32 Me 3-Br-PhCH2 Me 2 1 1-33 Me 4-Br-PhCH2 Me 2 1 1-34 Me 2-I-PhCH2 Me 2 1 1-35 Me 3-I-PhCH2 Me 2 1 1-36 Me 4-I-PhCH2 Me 2 1 1-37 Me 2-OH-PhCH2 Me 2 1 1-38 Me 3-OH-PhCH2 Me 2 1 1-39 Me 4-OH-PhCH2 Me 2 1 1-40 Me 2- CN-PhCH2 Me 2 1 1-41 Me 3-CN-PhCH2 Me 2 1 1-42 Me 4-CN-PhCH2 Me 2 1 1-43 Me 2-NOrPhCH2 Me 2 1 1-44 Me 3-N02-PhCH2 Me 2 1 1-45 Me 4-N02-PhCH2 Me 2 1 1-46 Me 2-CHF2-PhCH2 Me 2 1 1-47 Me 3-CHF2-PhCH2 Me 2 1 -29- 200408628 1-48 Me 4-CHF2- PhCH2 Me 2 1 1-49 Me 2-CF3-PhCH2 Me 2 1 1-50 Me 3-CF3-PhCH2 Me 2 1 1-51 Me 4-CF3-PhCH2 Me 2 1 1-52 Me 2-vinyl-PhCH2 Me 2 1 1-53 Me 3-vinyl-PhCH2 Me 2 1 1-54 Me 4-vinyl-PhCH2 Me 2 1 1-55 Me 2-NHrPhCH2 Me 2 1 1-56 Me 3-NHrPhCH2 Me 2 1 1 -57 Me 4-NH2-PhCH2 Me 2 1 1-58 Me 2-MeNH-PhCH2 Me 2 1 1-59 Me 3-MeNH-PhCH2 Me 2 1 1-60 Me 4-MeNH-PhCH2 Me 2 1 1-61 Me 2-Me2N-PhCH2 Me 2 1 1-62 Me 3-Me2N-PhCH2 Me 2 1 1-63 Me 4-Me2N-PhCH2 Me 2 1 1-64 Me 2-COOH-PhCH2 Me 2 1 1-65 Me 3 -COOH-PhCH2 Me 2 1 1-66 Me 4-COOH-PhCH2 Me 2 1 1-67 Me 2-CONH2-PhCH2 Me 2 1 1-68 Me 3-CONH2-PhCH2 Me 2 1 1-69 Me 4-CONH2 -PhCH2 Me 2 1 1-70 Me 2-CONH Me-PhCH2 Me 2 1 1-71 Me 3-CONHMe-PhCH2 Me 2 1 1-72 Me 4-CONHMe-PhCH2 Me 2 1 1-73 Me 2-COOMe-PhCH2 Me 2 1 1-74 Me 3-COOMe- PhCH2 Me 2 1 1-75 Me 4-COOMe-PhCH2 Me 2 1 1-76 Me 2-MeS02NH-PhCH2 Me 2 1 1-77 Me 3-MeS02NH-PhCH2 Me 2 1 1-78 Me 4-MeS02NH-PhCH2 Me 2 1 1-79 Me 2-CH3CONH-PhCH2 Me 2 1 1-80 Me 3-CH3CONH-PhCH2 Me 2 1 1-81 Me 4-CH3CONH-PhCH2 Me 2 1 1-82 Me 2-PhCONH-PhCH2 Me 2 1 1-83 Me 3-PhCONH-PhCH2 Me 2 1 1-84 Me 4-PhCONH-PhCH2 Me 2 1 1-85 Me 2-MeS02-PhCH2 Me 2 1 1-86 Me 3-MeS02-PhCH2 Me 2 1 1- 87 Me 4-MeS02-PhCH2 Me 2 1 1-88 Me 2-MeS-PhCH2 Me 2 1 1-89 Me 3-MeS-PhCH2 Me 2 1 1-90 Me 4-MeS-PhCH2 Me 2 1 1-91 Me 2-Ph-PhCH2 Me 2 1 1-92 Me 3-Ph-PhCH2 Me 2 1 1-93 Me 4-Ph-PhCH2 Me 2 1 1-94 Me 2-styryl-PhCH2 Me 2 1 1-95 Me 3-styryl-PhCH2 Me 2 1 1-96 Me 4-styryl-PhCH2 Me 2 1 -30 · 200408628 1-97 Me 2,6-diCl-PhCH2 Me 2 1 1-98 Me 2,4- οϋ (: μΡ1ιαΗ2 Me 2 1 1-99 Me 3,4-diCl-PhCH2 Me 2 1 MOO Me 3,5-diMeO-PhCH2 Me 2 1 1-101 Me Ph (CH2) 2 Me 2 1 1-1 02 Me Ph (CH2) 3 Me 2 1 M03 Me Cinnamonyl Me 2 1 1-104 Me Naph-CH2 Me 2 1 1-105 Me 3-PyrCH2 Me 2 1 1-106 Me 4-PyrCH2 Me 2 1 1- 107 Me 2-quinolinyl "CH2 Me 2 1 1-108 Me 5-C1-2-thienyl CH2 Me 2 1 1-109 Me 2-Cl-5-Pyr-CH2 Me 2 1 1-110 Me 5- CH2〇H-2-Pyr-CH2 Me 2 1 1-111 Me PhCH = CHCH2 Me 2 1 1-112 Me PhCH2 Me 1 1 1-113 Me 4-F-PhCH2 Me 1 1 1-114 Me 4-Cl- PhCH2 Me 1 1 1-115 Me 4 Small PhCH2 Me 1 1 1-116 Me 4-Me-PhCH2 Me 1 1 1-117 Me 4-MeO-PhCH2 Me 1 1 1-118 Me PhCH2 Me 2 2 M19 Me 4- F-PhCH2 Me 2 2 1-120 Me 4-Cl-PhCH2 Me 2 2 1 -121 Me 4-I-PhCH2 Me 2 2 1 -122 Me 4-Me-PhCH2 Me 2 2 1-123 Me 4-MeO- PhCH2 Me 2 2 1-124 Me PhCH2 Me 2 3 1-125 Me 4-F-PhCH2 Me 2 3 1-126 Me 4-Cl-PhCH2 Me 2 3 1-127 Me 4-I-PhCH2 Me 2 3 1- 128 Me 4-Me-PhCH2 Me 2 3 1-129 Me 4-MeO-PhCH2 Me 2 3 1-130 Et PhCH2 Me 2 1 1-131 Et 4-F-PhCH2 Me 2 1 1-132 Et 4-Cl- PhCH2 Me 2 1 1-133 Et 4-I-PhCH2 Me 2 1 1-134 Et 4-Me-PhCH2 Me 2 1 1-135 Et 4-MeO-PhCH2 Me 2 1 1-136 Ψν PhCH2 Me 2 1 1- 137] Pr 4-F-PhCH2 Me 2 1 1-138] Pr 4-Cl-PhCH2 Me 2 1 1-139 l? R 4-I-PhCH2 Me 2 1 1-140! Pr 4-Me-PhCH2 Me 2 1 1-141 JPr 4-MeO-PhCH2 Me 2 1 1-142 nBu PhCH2 Me 2 1 1-143 nBu 4-F-PhCH2 Me 2 1 1-144 nBu 4-Cl-PhCH2 Me 2 1 1-145 nBu 4-I-PhCH2 Me 2 1

-31- 200408628 1-146 nBu 4-Me-PhCH2 Me 2 1 1-147 nBu 4-MeO-PhCH2 Me 2 1 1-148 'Bu PhCH2 Me 2 1 1-149 lBu 4-F-PhCH2 Me 2 1 1 -150 lBu 4-Cl-PhCH2 Me 2 1 1-151 lBu 4-I-PhCH2 Me 2 1 1-152 lBu 4-Me-PhCH2 Me 2 1 1-153 lBu 4-MeO-PhCH2 Me 2 1 1-154 Ph PhCH2 Me 2 1 1-155 Ph 4-F-PhCH2 Me 2 1 M56 Ph 4-Cl-PhCH2 Me 2 1 1-157 Ph 4-I-PhCH2 Me 2 1 1-158 Ph 4-Me-PhCH2 Me 2 1 1-159 Ph 4-MeO-PhCH2 Me 2 1 1-160 4-NH2-Ph PhCH2 Me 2 1 1-161 4-NH2-Ph 4-F-PhCH2 Me 2 1 1-162 4-NH2-Ph A -Cl ^ hCRj Me 2 1 1-163 4-NHrPh 4-I-PhCH2 Me 2 1 1-164 4-NH2-Ph 4-Me-PhCH2 Me 2 1 1-165 4-NH2-Ph 4-MeO-PhCH2 Me 2 1 1-166 4-MeS02NH-Ph PhCH2 Me 2 1 1-167 4-MeS02NH-Ph 4-F-PhCH2 Me 2 1 1-168 4-MeS02NH-Ph 4-α_Ρίι (: Η2 Me 2 1 1- 169 4-MeS02NH-Ph 4-I-PhCH2 Me 2 1 M79 4-MeS02NH-Ph 4-Me-PhCH2 Me 2 1 M71 4-MeS02NH-Ph 4-MeO-PhCH2 Me 2 1 1-172 3-] PrNH- Ph PhCH2 Me 2 1 1-173 3-】 PrNH-Ph 4-F-PhCH2 Me 2 1 1-174 3-! PrNH-Ph 4-Cl-PhCH2 Me 2 1 1-175 S ^ PrNH-Ph 4-I -PhCH2 Me 2 1 1-176 3 ″ PrNH-Ph 4-Me-PhCH2 Me 2 1 1-177 3-1PrNH-Ph 4-MeO-PhCH2 Me 2 1 1-178 4-NH2-3,5-diMe-Ph PhCH2 Me 2 1 1-179 4-NH2-3,5-diMe-Ph Ph (CH2) 2 Me 2 1 1-180 4 > NH2-3,5-diMe-Ph 4-F-PhCH2 Me 2 1 1-181 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Me 2 1 1-182 4-NH2-3,5-diMe-Ph 4-I-PhCH2 Me 2 1 1-183 4-NH2-3,5-diMe-Ph 4-Br-PhCH2 Me 2 1 1-184 4- NH2-3,5-diMe-Ph 4-Me-PhCH2 Me 2 1 1-185 4-NHr3,5-diMe-Ph 4-MeO-PhCH2 Me 2 1 1-186 4-OH-3,5-diMe- Ph PhCH2 Me 2 1 1-187 4-OH-3,5-diMe-Ph 4-F-PhCH2 Me 2 1 1-188 4-OH-3,5 > diMe-Ph 4-Cl-PhCH2 Me 2 1 1 -189 4-OH-3,5-diMe-Ph 4 small PhCH2 Me 2 1 1-190 4-OH-3,5-diMe-Ph 4-Me-PhCH2 Me 2 1 1-191 4-OH-3, 5-diMe-Ph 4-MeO-PhCH2 Me 2 1 1-192 4-Cl-Ph PhCH2 Me 2 1 1-193 4-CN-Ph PhCH2 Me 2 1 1-194 4-N02-Ph PhCH2 Me 2 1 M95 4-CFs-Ph PhCH2 Me 2 1 -32- 200408628 1-196 4-MeO-Ph PhCH2 Me 2 1 1-197 4-Ph-Ph PhCH2 Me 2 1 1-198 4-Et2N-Ph PhCH2 Me 2 1 1 -199 4-piperidinyl-Ph PhCH2 Me 2 1 1-200 4-cHexNH-Ph PhCH2 Me 2 1 1-201 4-cHex2N-Ph PhCH2 Me 2 1 1-202 4-PhS02-Ph PhCH2 Me 2 1 1 -203 4-CH3CONH-Ph PhCH2 Me 2 1 1-204 4-PhCONH-Ph PhCH2 Me 2 1 1-205 4-COOH-Ph PhCH2 Me 2 1 1-206 4-CONH2-Ph PhCH2 Me 2 1 1-207 4-COOMe-Ph PhCH2 Me 2 1 1-208 4-PhNH-Ph PhCH2 Me 2 1 1-209 4-CONHPhCH2-Ph PhCH2 Me 2 1 1-210 4-CONHMe-Ph PhCH2 Me 2 1 1-211 4-CONHPh-Ph PhCH2 Me 2 1 1- 212 4-cHex (Me) N-Ph PhCH2 Me 2 1 1-213 3-NH2-Ph PhCH2 Me 2 1 1-214 4-NH2-Ph nBu Me 2 1 1-215 3-MeS02NH-Ph PhCH2 Me 2 1 1-216 4-1PrNH-Ph PhCH2 Me 2 1 1-217 PhCH2 PhCH2 Me 2 1 1-218 PhCH2 4-Cl-PhCH2 Me 2 1 1-219 Ph (CH2) 2 PhCH2 Me 2 1 1-220 2-PyrCH2 PhCH2 Me 2 1 1-221 4-PyrCH2 PhCH2 Me 2 1 1-222 Me PhCH2 Et 2 1 1-223 Me 4-Cl-PhCH2 Et 2 1 1-224 Me 4-I-PhCH2 Et 2 1 1-225 Me 4-MeO-PhCH2 Et 2 1 1-226 Me PhCH2 nPr 2 1 1-227 Me 4-Cl-PhCH2 nPr 2 1 1-228 Me 4-I-PhCH2 nPr 2 1 1-229 Me 4-MeO-PhCH2 nPr 2 1 1-230 Me PhCH2 Tr 2 1 1-231 Me 4-Cl-PhCH2 ipr 2 1 1-232 Me 4-I-PhCH2 JPr 2 1 1-233 Me 4-MeO-PhCH2 lPr 2 1 1-234 Me PhCH2 nBu 2 1 1-235 Me 4-Cl-PhCH2 nBu 2 1 1-236 Me 4-I-PhCH2 nBu 2 1 1-237 Me 4-MeOPhCH2 nBu 2 1 1-2 38 Me PhCH2 lBu 2 1 1-239 Me 4-Cl-PhCH2 lBu 2 1 1-240 Me 4-I-PhCH2 lBu 2 1 1-241 Me 4-MeO-PhCH2 lBu 2 1 1-242 Me PhCH2! Bu 2 1 1-243 Me 4-Cl-PhCH2】 Bu 2 1 1-244 Me 4-I-PhCH2 2 1 1-245 Me 4-MeO-PhCH2! Bu 2 1 -33- 200408628 1-246 Me PhCH2 nPn 2 1 1-247 Me 4-Cl-PhCH2 nPn 2 1 1-248 Me 4-I-PhCH2 nPn 2 1 1-249 Me 4-MeO-PhCH2 nPn 2 1 1-250 Me PhCH2 nHex 2 1 1-251 Me 4- Cl-PhCH2 nHex 2 1 1-252 Me 4-I-PhCH2 nHex 2 1 1-253 Me 4-MeO-PhCH2 nHex 2 1 1-254 Me PhCH2 Et 2 2 1-255 Me 4-Cl-PhCH2 Et 2 2 1-256 Me 4-I-PhCH2 Et 2 2 1-257 Me 4-MeO-PhCH2 Et 2 2 1-258 S ^ PrNH-Ph PhCH2 Et 2 1 1-259 S ^ PrNH-Ph 4-Cl-PhCH2 Et 2 1 1-260 S ^ PrNH-Ph 4-MeO-PhCH2 Et 2 1 1-261 4-NH2-3,5-diMe-Ph PhCH2 Et 2 1 1-262 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Et 2 1 1-263 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 Et 2 1 1-264 S ^ PrNH-Ph PhCH2 nPr 2 1 1-265 B ^ PrNH-Ph 4-Cl-PhCH2 nPr 2 1 1-266 S ^ PrNH-Ph 4-MeO-PhCH2 nPr 2 1 1-267 4-NH2-3,5-diMe-Ph PhCH2 nPr 2 1 1-268 4-NH2-3 , 5-diMe-Ph 4-Cl-PhCH2 nPr 2 1 1-269 4-NH2-3,5-diMe -Ph 4-MeO-PhCH2 nPr 2 1 1-270 S ^ PrNH-Ph PhCH2 JPr 2 1 1-271 3JPrNH-Ph 4-Cl-PhCH2! Pr 2 1 1-272 S ^ PrNH-Ph 4-MeO-PhCH2 】 Pr 2 1 1-273 4-NH2-3,5-diMe-Ph PhCH2 Ti * 2 1 1-274 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Ψτ 2 1 1-275 4- NH2-3,5-diMe-Ph 4-MeO-PhCH2! Ργ 2 1 1-276 S ^ PrNH-Ph PhCH2 nBu 2 1 1-277 S ^ PrNH-Ph 4-Cl-PhCH2 nBu 2 1 1-278 S ^ PrNH-Ph 4-MeO-PhCH2 nBu 2 1 1-279 4-NH2-3,5-diMe-Ph PhCH2 nBu 2 1 1-280 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 nBu 2 1 1-281 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 nBu 2 1 1-282 S ^ PrNH-Ph PhCH2 " Bu 2 1 1-283 3''PrNH-Ph 4-Cl- PhCH2! Bu 2 1 1-284 S ^ PrNH-Ph 4-MeO-PhCH2 JBu 2 1 1-285 4-NH2-3,5-diMe-Ph PhCH2】 Bu 2 1 1-286 4-NH2-3,5 -diMe-Ph 4-Cl-PhCH2 JBu 2 1 1-287 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 " Bu 2 1 1-288 S ^ PrNH-Ph PhCH2 lBu 2 1 1- 289 B ^ PrNH-Ph 4-Cl-PhCH2 lBu 2 1 1-290 S ^ PrNH-Ph 4-MeO-PhCH2 lBu 2 1 1-291 4-NHr3,5-diMe-Ph PhCH2 lBu 2 1 1-292 4 -NHr3,5-diMe-Ph 4-Cl-PhCH2 lBu 2 1 1-293 4-NHr3,5-diMe-Ph 4-MeO-PhCH2 lBu 2 1 1-294 3''PrNH-Ph PhCH2 nPn 2 1 1-295 S ^ PrNH-Ph 4-Cl-PhCH2 nPn 2 1 -34- 200408628 1-296 3 ″ PrNH-Ph 4-MeO-PhCH2 nPn 2 1 1-297 4-NHr3,5-diMe-Ph PhCH2 nPn 2 1 1-298 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 nPn 2 1 1-299 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 nPn 2 1 1-300 S ^ PrNH-Ph PhCH2 nHex 2 1 1-301 S ^ PrNH-Ph 4-Cl-PhCH2 nHex 2 1 1-302 3-】 PrNH-Ph 4-MeO-PhCH2 nHex 2 1 1-303 4-NH2-3 , 5-diMe-Ph PhCH2 nHex 2 1 1-304 4-NHr3,5-diMe-Ph 4-Cl-PhCH2 nHex 2 1 1-305 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 nHex 2 1 1-306 3``PrNH-Ph PhCH2 Et 2 2 1-307 S ^ PrNH-Ph 4-Cl-PhCH2 Et 2 2 1-308 S ^ PrNH-Ph 4-MeO-PhCII2 Et 2 2 1-309 4 -NH2-3,5-diMe-Ph PhCH2 Et 2 2 1-310 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Et 2 2 1-311 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 Et 2 2 1-312 3-】 PrNH-Ph PhCH2 Et 2 3 1-313 3-! PrNH-Ph 4-Cl-PhCH2 Et 2 3 1-314 S ^ PrNH-Ph 4-MeO- PhCH2 Et 2 3 1-315 4-NH2-3,5-diMe-Ph PhCH2 Et 2 3 1-316 4-NHr3,5-diMe-Ph 4-Cl-PhCH2 Et 2 3 1-317 4-NH2-3 , 5-diMe-Ph 4-MeO-PhCH2 Et 2 3 1-318 3 ″ PrNH-Ph PhCH2 Et 1 3 1-319 3-! PrNH-Ph 4-Cl-PhCH2 Et 1 3 1-320 3-1PrN H-Ph 4-MeO-PhCH2 Et 1 3 1-321 4-NH2-3,5-diMe-Ph PhCH2 Et 1 3 1-322 4-NHr3,5-diMe-Ph 4-Cl-PhCH2 Et 1 3 1 -323 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 Et 1 3 1-324 Me PhCH2 Me 1 3 1-325 Me 4-F-PhCH2 Me 1 3 1-326 Me 4-Cl-PhCH2 Me 1 3 1-327 Me 4-I-PhCH2 Me 1 3 1-328 Me 4-Me-PhCH2 Me 1 3 1-329 Me 4-MeO-PhCH2 Me 1 3 1-330 Me PhCH2 H 2 1 1-331 Me 4-Cl-PhCH2 H 2 1 1-332 Me 4-I-PhCH2 H 2 1 1-333 Me 4-MeO-PhCH2 H 2 1 1-334 Me PhCH2 Ph 2 1 1-335 Me 4-Cl-PhCH2 Ph 2 1 1-336 Me 4-Ι-ΡΙιΟ: Η2 Ph 2 1 1-337 Me 4-MeO-PhCH2 Ph 2 1 1-338 Me PhCH2 Naph 2 1 1-339 Me 4-Cl-PhCH2 Naph 2 1 1 -340 Me 4-I-PhCH2 Naph 2 1 1-341 Me 4-MeO-PhCH2 Naph 2 1 1-342 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Me 2 2 1-343 4- NH2-3,5-diMe-Ph PhCH2 Me 2 2 1-344 4-NHr3,5-diMe-Ph Ph (CH2) 2 Me 2 2 1-345 4-NHr3,5-diMe-Ph 4-F-PhCH2 Me 2 2 -35- 200408628 1-346 4-NH2-3,5-diMe-Ph 4-I-PhCH2 Me 2 2 1-347 4-NHr3,5-diMe-Ph 4-Br-PhCH2 Me 2 2 1 -348 4-NH2-3,5-diMe-Ph 4-Me-PhCH2 Me 2 2 1-349 4-NHr3,5-diMe-Ph 4-MeO-PhCH2 Me 2 2 1-350 Me Pfp Me 2 1 1-351 Me 2-Me-5-thienyl-CH2 Me 2 1 1-352 Me 3-Br-5-thienyl-CH2 Me 2 1 1-353 Me 2-Br- 5-thienyl-CH2 Me 2 1 1-354 Me 2-C1-5-thienyl-CH2 Me 2 1 1-355 Me 3-Br-Fur-CH2 Me 2 1 1-356 Me 2-Br-Fur- CH2 Me 2 1 1-357 HO-CH2CH2 (Cl-PhCHs Me 2 1 1-358 3- (HO-CH2CH2-NH) -Ph 4-Cl-PhCH2 Me 2 1 1-359 Me2N-CH2CH2 4-α-P1ι (: Η2 Me 2 1 1-360 4-piperidinyl 4-Cl-PhCH2 Me 2 1 1-361 4- (1-Me-piperidinyl) 4-Cl-PhCH2 Me 2 1 1-362 3- ( 1-Me-Chrysene D-Methyl) 4-Cl-PhCH2 Me 2 1 1-363 4- (l-MeS02-piperidinyl) 4-Cl-PhCH2 Me 2 1 1-364 4- (1-Boc- Piperidinyl) 4-Cl-PhCH2 Me 2 1 1-365 1-piperidinyl-ch2ch2 4_Cl-PhCH2 Me 2 1 1-366 4-Mor-CH2CH2 4-Cl-PhCH2 Me 2 1 1-367 4-Mor -Ph 4 ^ CbFhCE2 Me 2 1 1-368 4- (4-Me-Piz) -Ph 4-Cl-PhCH2 Me 2 1 1-369 3- (l-Me-Pyrd) 4-Cl-PhCH2 Me 2 1 1-370 Thp 4-Cl-PhCH2 Me 2 1 1-371 4-Thtp 4-Cl-PhCH2 Me 2 1 1-372 cPn 4-Cl-PhCH2 Me 2 1 1-373 cHex 4-Cl-PhCH2 Me 2 1 1-374 cHp 4-Cl-PhCH2 Me 2 1 1-375 All 4-Cl-PhCH2 Me 2 1 1-376 Ph 4-Cl-PhCH2 Me 2 2 1-377 3 -NHrPh 4-Cl-PhCH2 Me 2 2 1-378 4-NH2-Ph 4-Cl-PhCH2 Me 2 2 1-379 3-NH2-PhCH2 4-Cl-PhCH2 Me 2 2 1-380 Thp 4-α- Ρίί: Η2 Me 2 2 1-381 cPn 4-Cl-PhCH2 Me 2 2 1-382 cHex 4-Cl-PhCH2 Me 2 2 1-383 cHp 4-Cl-PhCH2 Me 2 2 1-384 All 4-Cl- PhCH2 Me 2 2 1-385 3- (HO-CH2CH2-NH) -Ph 4-Cl-PhCH2 Me 2 2 1-386 4-Mor-Ph 4-Cl-PhCH2 Me 2 2 1-387 Me 2-C1- 5-thienyl-CH2 Me 2 2

-36- 200408628

C〇〇H Table 2 No.R1 Rz mn 2-1 Me PhCH2 Me 2 1 2-2 Me 2-Me-PhCH2 Me 2 1 2-3 Me 3-Me-PhCH2 Me 2 1 2-4 Me 4-Me -PhCH2 Me 2 1 2-5 Me 2-Et-PhCH2 Me 2 1 2-6 Me 3-Et-PhCH2 Me 2 1 2-7 Me 4-Et-PhCH2 Me 2 1 2-8 Me 2-1Pr-PhCH2 Me 2 1 2-9 Me S ^ Pr-PhCHs Me 2 1 2-10 Me 4-1Pr-PhCH2 Me 2 1 2-11 Me 2-ιΒιι-Ρ1ι (: Η2 Me 2 1 2-12 Me 3-tBu- PhCH2 Me 2 1 2-13 Me 4 ″ Βιι-Ρ1ι (: Η2 Me 2 1 2-14 Me 2-MeO-PhCH2 Me 2 1 2-15 Me 3-MeO-PhCH2 Me 2 1 2-16 Me 4-MeO -PhCH2 Me 2 1 2-17 Me 2-EtO-PhCH2 Me 2 1 2-18 Me 3-EtO-PhCH2 Me 2 1 2-19 Me 4-EtO-PhCH2 Me 2 1 2-20 Me 4-CF30-PhCH2 Me 2 1 2-21 Me 4-CF20-PhCH2 Me 2 1 2-22 Me 2-PhCH20-PhCH2 Me 2 1 2-23 Me 3-PhCH20-PhCH2 Me 2 1 2-24 Me 4-PhCH20-PhCH2 Me 2 1 2-25 Me 2-F-PhCH2 Me 2 1 2-26 Me 3-F-PhCH2 Me 2 1 2-27 Me 4-F-PhCH2 Me 2 1 2-28 Me 2-Cl-PhCH2 Me 2 1 2 -29 Me 3-Cl-PhCH2 Me 2 1 2-30 Me 4-Cl-PhCH2 Me 2 1 2-31 Me 2-Br-PhCH2 Me 2 1 2-32 Me 3-Br-PhCH2 Me 2 1 2-33 Me 4-Br-PhCH2 Me 2 1 • 37- 200408628 2-34 Me 2-I-PhCH2 Me 2 1 2-35 Me 34-PhCH2 Me 2 1 2-36 Me 4-I-PhCH2 Me 2 1 2-37 Me 2-OH-PhCH2 Me 2 1 2-38 Me 3-OH-PhCH2 Me 2 1 2-39 Me 4-OH-PhCH2 Me 2 1 2-40 Me 2-CN-PhCH2 Me 2 1 2-41 Me 3-CN-PhCH2 Me 2 1 2-42 Me 4-CN-PhCH2 Me 2 1 2-43 Me 2- NOrPhCH2 Me 2 1 2-44 Me 3-N02-PhCH2 Me 2 1 245 Me 4-N02-PhCH2 Me 2 1 2-46 Me 2 > CHF2-PhCH2 Me 2 I 2-47 Me 3-CHF2-PhCH2 Me 2 1 2-48 Me 4-CHF2-PhCH2 Me 2 1 2-49 Me 2-CF3-PhCH2 Me 2 1 2-50 Me 3-CF3-PhCH2 Me 2 1 2-51 Me 4-CF3-PhCH2 Me 2 1 2- 52 Me 2-vinyl-PhCH2 Me 2 1 2-53 Me 3-vinyl-PhCH2 Me 2 1 2-54 Me 4-vinyl-PhCH2 Me 2 1 2-55 Me 2-NH2-PhCH2 Me 2 1 2-56 Me 3-NH2-PhCH2 Me 2 1 2-57 Me 4-NH2-PhCH2 Me 2 1 2-58 Me 2-MeNH-PhCH2 Me 2 1 2-59 Me 3-MeNH-PhCH2 Me 2 1 2-60 Me 4- MeNH-PhCH2 Me 2 1 2-61 Me 2-Me2N-PhCH2 Me 2 1 2-62 Me 3-Me2N-PhCH2 Me 2 1 2-63 Me 4-Me2N-PhCH2 Me 2 1 2-64 Me 2-COOH- PhCH2 Me 2 1 2-65 Me 3-COOH-PhCH2 Me 2 1 2-66 Me 4-COOH-PhCH2 Me 2 1 2-67 Me 2-CONH2-PhCH2 Me 2 1 2-68 Me 3-CONH2-PhCH2 Me 2 1 2-69 Me 4-CONH2-PhCH2 Me 2 1 2-70 M e 2-CONHMe-PhCH2 Me 2 1 2-71 Me 3-CONHMe-PhCH2 Me 2 1 2-72 Me 4-CONHMe-PhCH2 Me 2 1 2-73 Me 2-COOMe-PhCH2 Me 2 1 2-74 Me 3 -COOMe-PhCH2 Me 2 1 2-75 Me 4-COOMe-PhCH2 Me 2 1 2-76 Me 2-MeS02NH-PhCH2 Me 2 1 2-77 Me 3-MeS02NH-PhCH2 Me 2 1 2-78 Me 4-MeS02NH -PhCH2 Me 2 1 2-79 Me 2-CH3CONH-PhCH2 Me 2 1 2-80 Me 3-CH3CONH-PhCH2 Me 2 1 2-81 Me 4-CH3CONH-PhCH2 Me 2 1 2-82 Me 2-PhCONH-PhCH2 Me 2 1 2-83 Me 3-PhCONH-PhCH2 Me 2 1 -38- 200408628 2-84 Me 4-PhCONH-PhCH2 Me 2 1 2-85 Me 2-MeS02-PhCH2 Me 2 1 2-86 Me 3-MeSOrPhCH2 Me 2 1 2-87 Me 4-MeS02-PhCH2 Me 2 1 2-88 Me 2-MeS-PhCH2 Me 2 1 2-89 Me 3-MeS-PhCH2 Me 2 1 2-90 Me 4-MeS-PhCH2 Me 2 1 2-91 Me 2-Ph-PhCH2 Me 2 1 2-92 Me 3-Ph-PhCH2 Me 2 1 2-93 Me 4-Ph-PhCH2 Me 2 1 2-94 Me 2-styryl-PhCH2 Me 2 1 2-95 Me 3-styryl-PhCH2 Me 2 1 2-96 Me 4-styryl-PhCH2 Me 2 1 2-97 Me 2,6-diCl-PhCH2 Me 2 1 2-98 Me 2,4 -diCl-PhCH2 Me 2 1 2-99 Me 3,4-diCl-PhCH2 Me 2 1 2-100 Me 3,5-diMeO-PhCH2 Me 2 1 2-101 Me Ph (CH2) 2 Me 2 1 2-102 Me Ph (CH2) 3 Me 2 1 2-103 Me Cinnamonyl Me 2 1 2-104 Me Naphthyl ch2 Me 2 1 2-105 Me 3-PyrCH2 Me 2 1 2-106 Me 4-PyrCH2 Me 2 1 2 -107 Me 2-quinolinyl CH2 Me 2 1 2-108 Me 5-C1-2-thienyl CH2 Me 2 1 2-109 Me 2-Cl-5-Pyr-CH2 Me 2 1 2-110 Me 5- CH2OH-2-Pyr-CH2 Me 2 1 2-111 Me PhCH = CHCH2 Me 2 1 2-112 Me PhCH2 Me 1 1 2-113 Me 4-F-PhCH2 Me 1 1 2-114 Me 4-Cl-PhCH2 Me 1 1 2-115 Me 4-I-PhCH2 Me 1 1 2-116 Me 4-Me-PhCH2 Me 1 1 2-117 Me 4-MeO-PhCH2 Me 1 1 2-118 Me PhCH2 Me 2 2 2-119 Me 4-F-PhCH2 Me 2 2 2-120 Me 4-Cl-PhCH2 Me 2 2 2-121 Me 4-I-PhCH2 Me 2 2 2-122 Me 4-Me-PhCH2 Me 2 2 2-123 Me 4- MeO-PhCH2 Me 2 2 2-124 Me PhCH2 Me 2 3 2-125 Me 4-F-PhCH2 Me 2 3 2-126 Me 4-Cl-PhCH2 Me 2 3 2-127 Me 4-I-PhCH2 Me 2 3 2-128 Me 4-Me-PhCH2 Me 2 3 2-129 Me 4-MeO-PhCH2 Me 2 3 2-130 Et PhCH2 Me 2 1 2-131 Et 4-F-PhCH2 Me 2 1 2-132 Et 4- Cl-PhCH2 Me 2 1 -39- 200408628 2-133 Et 4-I-PhCH2 Me 2 1 2-134 Et 4-Me-PhCH2 Me 2 1 2-135 Et 4-MeO-PhCH2 Me 2 1 2-136 on PhCH2 Me 2 1 2-137】 Pr 4-F-PhC H2 Me 2 1 2-138! Pr 4-Cl-PhCH2 Me 2 1 2-139! Pr 4-I-PhCH2 Me 2 1 2-140 JPr 4-Me-PhCH2 Me 2 1 2-141 4-MeO-PhCH2 Me 2 1 2-142 Bu PhCH2 Me 2 1 2-143 Bu 4-F-PhCH2 Me 2 1 2-144 Bu 4-Cl-PhCH2 Me 2 1 2-145 Bu 4-I-PhCH2 Me 2 1 2-146 Bu 4-Me-PhCH2 Me 2 1 2-147 Bu 4-MeO-PhCH2 Me 2 1 2-148 lBu PhCH2 Me 2 1 2-149 lBu 4-F-PhCH2 Me 2 1 2-150 'Bu 4-Cl- PhCH2 Me 2 1 2-151 'Bu 4-I-PhCH2 Me 2 1 2-152' Bu 4-Me-PhCH2 Me 2 1 2-153 'Bu 4-MeO-PhCH2 Me 2 1 2-154 Ph PhCH2 Me 2 1 2-155 Ph 4-F-PhCH2 Me 2 1 2-156 Ph 4-Cl-PhCH2 Me 2 1 2-157 Ph 4-I-PhCH2 Me 2 1 2-158 Ph 4-Me-PhCH2 Me 2 1 2 -159 Ph 4-MeO-PhCH2 Me 2 1 2-160 4-NH2-Ph PhCH2 Me 2 1 2-161 4-NHi-Ph 4-F-PhCH2 Me 2 1 2-162 4-NHi-Ph 4-Cl -PhCH2 Me 2 1 2-163 4-NH2-Ph 4-I-PhCH2 Me 2 1 2-164 4-NH2-Ph 4-Me-PhCH2 Me 2 1 2-165 4-NH2-Ph 4-MeO-PhCH2 Me 2 1 2-166 4-MeS02NH-Ph PhCH2 Me 2 1 2-167 4-MeS02NH-Ph 4-F-PhCH2 Me 2 1 2-168 4-MeS02NH-Ph 4-Cl-PhCH2 Me 2 1 2-169 4-MeS02NH-Ph 4-I-PhCH2 Me 2 1 2-179 4-MeS02NH-Ph 4-Me-PhCH2 Me 2 1 2-171 4-MeS02NH-Ph 4-MeO-PhCH2 Me 2 1 2-172 S ^ PrNH-Ph PhCH2 Me 2 1 2-173 3``PrNH-Ph 4-F-PhCH2 Me 2 1 2-174 S ^ PrNH -Ph 4-Cl-PhCH2 Me 2 1 2-175 S ^ PrNH-Ph 4-I-PhCH2 Me 2 1 2-176 S ^ PrNH-Ph 4-Me-PhCH2 Me 2 1 2-177 S ^ PrNH-Ph 4-MeO-PhCH2 Me 2 1 2-178 4-NHr3,5-diMe-Ph PhCH2 Me 2 1 2-179 4-NH2-3,5-diMe-Ph Ph (CH2) 2 Me 2 1 2-180 4 -NH2-3,5-diMe-Ph 4-F-PhCH2 Me 2 1 2-181 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Me 2 1 2-182 4-NH2-3,5 -diMe-Ph 4-I-PhCH2 Me 2 1 -40- 200408628 2-183 4-NH2-3,5-diMe-Ph 4-Br-PhCH2 Me 2 l 2-184 4-NH2-3,5-diMe -Ph 4-Me-PhCH2 Me 2 l 2-185 4-NHr3,5-diMe-Ph 4-MeO-PhCH2 Me 2 l 2-186 4-0H-3,5-diMe-Ph PhCH2 Me 2 l 2- 187 4-OH-355-diMe-Ph 4-F-PhCH2 Me 2 l 2-188 4-OH-3,5-diMe-Ph 4-Cl-PhCH2 Me 2 l 2-189 4-OH-3,5 -diMe-Ph 4-I-PhCH2 Me 2 l 2-190 4-OH-3,5-diMe-Ph 4-Me-PhCH2 Me 2 l 2-191 4-OH-3,5-diMe-Ph 4- MeO-PhCH2 Me 2 l 2-192 4-Cl-Ph PhCH2 Me 2 l 2-193 4-CN-Ph PhCH2 Me 2 l 2-194 4-N02_Ph PhCH2 Me 2 l / Λ 1 z-iyj 4-CFs- Ph PhCH2 Me 2 1 2-196 4-MeO-Ph PhCH2 Me 2 1 2-197 4-P h-Ph PhCH2 Me 2 1 2-198 4-Et2N-Ph PhCH2 Me 2 1 2-199 4-Piperidinyl-Ph PhCH2 Me 2 1 2-200 4-cHexNH-Ph PhCH2 Me 2 1 2-201 4-cHex2N- Ph PhCH2 Me 2 1 2-202 4-PhS02-Ph PhCH2 Me 2 1 2-203 4-CH3CONH-Ph PhCH2 Me 2 1 2-204 4-PhCONH-Ph PhCH2 Me 2 1 2-205 4-COOH-Ph PhCH2 Me 2 1 2-206 4-CONH2-Ph PhCH2 Me 2 1 2-207 4-COOMe-Ph PhCH2 Me 2 1 2-208 4-PhNH-Ph PhCH2 Me 2 1 2-209 4-CONHPhCH2-Ph PhCH2 Me 2 1 2-210 4-CONHMe-Ph PhCH2 Me 2 1 2-2 ll 4-CONHPh-Ph PhCH2 Me 2 1 2-212 4-cHex (Me) N-Ph PhCH2 Me 2 1 2-213 3-NH2-Ph PhCH2 Me 2 1 2-214 4-NH2-Ph Bu Me 2 1 2-215 3-MeS02NH-Ph PhCH2 Me 2 1 2-216 4-1PrNH-Ph PhCH2 Me 2 1 2-217 PhCH2 PhCH2 Me 2 1 2- 218 PhCH2 4-Cl-PhCH2 Me 2 1 2-219 Ph (CH2) 2 PhCH2 Me 2 1 2-220 2-PyrCH2 PhCH2 Me 2 1 2-221 4-PyrCH2 PhCH2 Me 2 1 2-222 Me PhCH2 Et 2 1 2-223 Me 4-Cl-PhCH2 Et 2 1 2-224 Me 4-I-PhCH2 Et 2 1 2-225 Me 4-MeO-PhCH2 Et 2 1 2-226 Me PhCH2 nPr 2 1 2-227 Me 4- Cl-PhCH2 nPr 2 1 2-228 Me 4-I-PhCH2 nPr 2 1 2-229 Me 4-MeO-PhCH2 nPr 2 1 2-230 Me PhC H2! Pr 2 1 2-231 Me 4-Cl-PhCH2! Pr 2 1 2-232 Me 4-I-PhCH2 JPr 2 1 -41-200408628 2-233 Me 4-MeO-PhCH2 JPr 2 1 2-234 Me PhCH2 nBu 2 1 2-235 Me 4-Cl-PhCH2 nBu 2 1 2-236 Me 4-Ι-ΡΚΉ2 nBu 2 1 2-237 Me 4-MeO-PhCH2 nBu 2 1 2-238 Me PhCH2 lBu 2 1 2- 239 Me 4-Cl-PhCH2 lBu 2 1 2-240 Me 4-I-PhCH2 lBu 2 1 2-241 Me 4-MeO-PhCH2 lBu 2 1 2-242 Me PhCH2 lBu 2 1 2-243 Me 4-Cl- PhCH2 lBu 2 1 2-244 Me 4-I-PhCH2 2 1 2-245 Me 4-MeO-PhCH2! Bu 2 1 2-246 Me PhCH2 nPn 2 1 2-247 Me 4-Cl-PhCH2 nPn 2 1 2- 248 Me 4-I-PhCH2 nPn 2 1 2-249 Me 4-MeO-PhCH2 nPn 2 1 2-250 Me PhCH2 nHex 2 1 2-251 Me 4-Cl-PhCH2 nHex 2 1 2-252 Me 4-I- PhCH2 nHex 2 1 2-253 Me 4-MeO-PhCH2 nHex 2 1 2-254 Me PhCH2 Et 2 2 2-255 Me 4-Cl-PhCH2 Et 2 2 2-256 Me 4-I-PhCH2 Et 2 2 2- 257 Me 4-MeO-PhCH2 Et 2 2 2-258 S ^ PrNH-Ph PhCH2 Et 2 1 2-259 3 ″ PγΝΗ-Ph 4-Cl-PhCH2 Et 2 1 2-260 3 ″ PrNH-Ph 4-MeO- PhCH2 Et 2 1 2-261 4-NH2-3,5-diMe-Ph PhCH2 Et 2 1 2-262 4-NHr3,5-diMe-Ph 4-Cl-PhCH2 Et 2 1 2-263 4_NHr3,5-diMe -Ph 4-MeO- PhCH2 Et 2 1 2-264 S ^ PrNH-Ph PhCH2 nPr 2 1 2-265 3 ″ PrNH-Ph 4-Cl-PhCH2 nPr 2 1 2-266 3 ″ PrNH-Ph 4-MeO-PhCH2 nPr 2 1 2- 267 4 > NH2-3,5-diMe-Ph PhCH2 nPr 2 1 2-268 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 nPr 2 1 2-269 4-NH2-3,5-diMe -Ph 4-MeO-PhCH2 nPr 2 1 2-270 S ^ PrNH-Ph PhCH2! Pr 2 1 2-271 S ^ PrNH-Ph 4-Cl-PhCH2! Pr 2 1 2-272 3 ″ PrNH-Ph 4- MeO-PhCH2! Pr 2 1 2-273 4-NH2-3,5-diMe-Ph PhCH2 JPr 2 1 2-274 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2! Pr 2 1 2- 275 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2! Pr 2 1 2-276 S ^ PrNH-Ph PhCH2 nBu 2 1 2-277 S ^ PrNH-Ph 4-Cl-PhCH2 nBu 2 1 2 -278 S ^ PrNH-Ph 4-MeO-PhCH2 nBu 2 1 2-279 4-NHr3,5-diMe-Ph PhCH2 nBu 2 1 2-280 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 nBu 2 1 2-281 4-NHr3,5-diMe-Ph 4-MeO-PhCH2 nBu 2 1 2-282 S ^ PrNH-Ph PhCH2 2 1 • 42- 200408628 2-283 3-! PrNH-Ph 4-Cl -PhCH2 2 1 2-284 S ^ PrNH-Ph 4-MeO-PhCH2 JBu 2 1 2-285 4-NHr3,5-diMe-Ph PhCH2 2 1 2-286 4-NHr3,5-diMe-Ph 4-Cl -PhCH2! Bu 2 1 2-287 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2! Bu 2 1 2-288 S ^ PrNH-Ph PhCH2 lBu 2 1 2-289 S ^ PrNH -Ph 4-Cl-PhCH2 'Bu 2 1 2-290 S ^ PrNH-Ph 4-MeO-PhCH2' Bu 2 1 2-291 4-NHr3,5-diMe-Ph PhCH2 lBu 2 1 2-292 4-NHr3 , 5-diMe-Ph 4-Cl-PhCH2 lBu 2 1 2-293 4-NHr3,5-diMe-Ph 4-MeO-PhCH2 'Bu 2 1 2-294 S ^ PrNH-Ph PhCH2 nPn 2 1 2-295 S ^ PrNH-Ph 4-Cl-PhCH2 nPn 2 1 2-296 S ^ PrNH-Ph 4-MeO-PhCH2 nPn 2 1 2-297 4-NH2-3,5-diMe-Ph PhCH2 nPn 2 1 2-298 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 nPn 2 1 2-299 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 nPn 2 1 2-300 S ^ PrNH-Ph PhCH2 nHex 2 1 2-301 S ^ PrNH-Ph 4-Cl-PhCH2 nHex 2 1 2-302 S ^ PrNH-Ph 4-MeO-PhCH2 nHex 2 1 2-303 4-NH2-3,5-diMe-Ph PhCH2 nHex 2 1 2-304 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 nHex 2 1 2-305 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 nHex 2 1 2-306 3''PrNH-Ph PhCH2 Et 2 2 2-307 S ^ PrNH-Ph 4-Cl-PhCH2 Et 2 2 2-308 S ^ PrNH-Ph 4-MeO-PhCH2 Et 2 2 2-309 4-NHr3,5- diMe-Ph PhCH2 Et 2 2 2-310 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Et 2 2 2-311 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 Et 2 2 2-312 B ^ PrNH-Ph PhCH2 Et 2 3 2-313 S ^ PrNH-Ph 4-Cl-PhCH2 Et 2 3 2-314 S ^ PrNH-Ph 4-MeO-PhCH2 Et 2 3 2-315 4- NHr3,5-d iMe-Ph PhCH2 Et 2 3 2-316 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Et 2 3 2-317 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 Et 2 3 2-318 S ^ PrNH-Ph PhCH2 Et 1 3 2-319 S ^ PrNH-Ph 4-Cl-PhCH2 Et 1 3 2-320 S ^ PrNH-Ph 4-MeO-PhCH2 Et 1 3 2-321 4- NHr3,5-diMe-Ph PhCH2 Et 1 3 2-322 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Et 1 3 2-323 4-NH2 > 3,5-diMe-Ph 4-MeO -PhCH2 Et 1 3 2-324 Me PhCH2 Me 1 3 2-325 Me 4-F > PhCH2 Me 1 3 2-326 Me 4-Cl-PhCH2 Me 1 3 2-327 Me 4-I-PhCH2 Me 1 3 2 -328 Me 4-Me-PhCH2 Me 1 3 2-329 Me 4-MeO-PhCH2 Me 1 3 2-330 Me PhCH2 H 2 1 2-331 Me 4-Cl-PhCH2 H 2 1 2-332 Me 4-I -PhCH2 H 2 1 -43- 200408628 2-333 Me 4-MeO-PhCH2 H 2 1 2-334 Me PhCH2 Ph 2 1 2-335 Me 4-Cl-PhCH2 Ph 2 1 2-336 Me 4-I-PhCH2 Ph 2 1 2-337 Me 4-MeO-PhCH2 Ph 2 1 2-338 Me PhCH2 Naph 2 1 2-339 Me 4-Cl-PhCH2 Naph 2 1 2-340 Me 4-Ι-Ρ1ί (: Η2 Naph 2 1 2-341 Me 4-MeO-PhCH2 Naph 2 1 2-342 4-NH2-3,5-diMe-Ph 4-Cl-PhCH2 Me 2 2 2-343 4-NH2-3,5-diMe-Ph PhCH2 Me 2 2 2-344 4-NH2-3,5-diMe-Ph Ph (CH2) 2 Me 2 2 2-345 4-NH2-3,5-diMe-Ph 4-F-Ph CH2 Me 2 2 2-346 4-NH2-3,5-diMe-Ph 4-I-Ph CH2 Me 2 2 2-347 4-NH2-3,5-diMe-Ph 4-Br-PhCH2 Me 2 2 2- 348 4-NH2 ~ 3,5-diMe-Ph 4-Me-PhCH2 Me 2 2 2-349 4-NH2-3,5-diMe-Ph 4-MeO-PhCH2 Me 2 2 2-350 Me Pfp Me 2 1 2-351 Me 2-Me-5-thienyl-CH2 Me 2 1 2-352 Me 3-Br-5-thienyl-CH2 Me 2 1 2-353 Me 2-Br-5-thienyl-CH2 Me 2 1 2-354 Me 2-C1-5-thienyl-CH2 Me 2 1 2-355 Me 3-Br-Fur-CH2 Me 2 1 2-356 Me 2-Br-Fur-CH2 Me 2 1 2-357 HO -CH2CH2 4-Cl-PhCH2 Me 2 1 2-358 3- (HO-CH2CH2-NH) -Ph 4-Cl-PhCH2 Me 2 1 2-359 Me2N-CH2CH2 4-Cl-PhCH2 Me 2 1 2-360 4 -Piperidinyl 4-Cl-PhCH2 Me 2 1 2-361 4- (1-Me-piperidinyl) 4-Cl-PhCH2 Me 2 1 2-362 3- (l-Me-piperidinyl) 4- Cl-PhCH2 Me 2 1 2-363 4- (l-MeSOr piperidinyl) 4-Cl-PhCH2 Me 2 1 2-364 4- (1-Boc-piperidinyl) 4-Cl-PhCH2 Me 2 1 2 -365 1-piperidinyl-ch2ch2 4-Cl-PhCH2 Me 2 1 2-366 4-Mor-CH2CH2 tCl-PhCH? Me 2 1 2-367 4-Mor-Ph 4-Cl-PhCH2 Me 2 1 2- 368 4- (4-Me-Piz) -Ph 4-Cl-PhCH2 Me 2 1 2-369 3- (l-Me-Pyrd) 4-Cl-PhCH2 Me 2 1 2-370 Thp 4-Cl-PhCH2 Me 2 1 2-371 4-Thtp 4-α-Ρ1ι <: Η2 Me 2 1 2-372 cPn Me 2 1 2-373 cHex 4-Cl-PhCH2 Me 2 1 2-374 cHp 4-Cl-PhCH2 Me 2 1 2-375 All 4-Cl- PhCH2 Me 2 1 2-376 Ph 4-Cl-PhCH2 Me 2 2 2-377 3-NH2-Ph 4-α-P1ι (: Η2 Me 2 2 2-378 4-NHrPh 4-α-P1ι (: Η2 Me 2 2 2-379 3-NH2-PhCH2 4-Cl-PhCH2 Me 2 2 2-380 Thp 4-Cl-PhCH2 Me 2 2 -44- 200408628 2-381 cPn 4-Cl-PhCH2 Me 2 2 2-382 cHex 4-Cl-PhCH2 Me 2 2 2-383 cHp 4-Cl-PhCH2 Me 2 2 2-384 All ICl-PhCHa Me 2 2 2-385 3- (HO-CH2CH2-NH) -Ph 4-Cl-PhCH2 Me 2 2 2-386 4-Mor-Ph 4-CV? HCU2 Me 2 2 2-387 Me 2-C1-5-thienyl-CH2 Me 2 2 In the above table, 1-1, 1-4, 1-7, 1-10, 1-13, 1-14, 1-15, 1-16, 1-19, 1-20, 1-21, 1-24, 1-27, 1-30, 1- 33, 1-36, 1-49, 1-50, 1-51, 1-54,

1-66, 1-81, 1-87, 1-90, 1-93, 1-97, 1-98, 1-99, 1-101, 1-102, 1-105, 1-106, 1- 107, 1-108, 1-109, 1-110, 1-111, 1-120, 1-124, 1-120, 1-162, 1-165, 1-168, 1-171, 1-174, 1- 177, 1-178, 1-181, 1-185, 1-342, 1-350, 1- 351, 1-352, 1-353 > 1-3 5 5, 1-3 5 6, 1 -3 5 7, 1 -358, 1-359, 1-360, 1-361, 1-362, 1-363, 1-364, 1-365, 1-366, 1-367, 1-368, 1 -369, 1-370, 1-371, 1-376, 1-377, 1-378, 1-379, 1-380, 1-381, 1-382, 1-383, 1-384, 1-385 , 1-387, 2-30 or 2-156, more preferably 3-[4-[6-(4-amino-3,5-dimethyl-phenoxy) -1-methyl-115 -Benzimidazol-2-ylmethoxy] -2- (4-methoxy-benzyloxy) -phenyl] -propionic acid, 3- [2- (4-methoxybenzyloxy) -4 -(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] propionic acid, 3-[4-[6- (4-amino-3, 5-dimethyl-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2-(4-chloro-benzyloxy) -phenyl ] -Propionic acid, 3- [2- (4-iodobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl- 45-200408628] -propionic acid, 3- [2- (4-molyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazole-2-ylmethoxy)- Phenyl] -propionic acid, 3- [4--[6-(3-isopropylamino-phenoxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] -2- (4 -Methoxy-fluorenyloxy) -benzyl] -propionic acid, 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- ( 4-methylbenzyloxy) -phenyl] -propionic acid, 3- [4- [6- (3-isopropylamino-phenoxy) -1-methyl-1H-benzimidazol-2-yl [Methoxy] -2-(4-chloro-benzyloxy) -phenyl] -propionic acid, 3-[2- (4-chlorobenzyloxy) -4- {1-methyl-6- (3 -Morpholinyl-4 -ylphenoxy) -1H -benzimidazol-2-ylmethoxy} -phenyl-propionic acid, 3- [4- {2- [6- (4-amino group- 3,5-dimethyl-phenoxy) -1-methyl-111-benzimidazol-2-yl] -ethoxy} -2- (4-chloro-fluorenyloxy) -phenyl]- Propionic acid, 3-{2- (4-chloro-fluorenyloxy) -4- [2- (6-cyclopentyloxy-1-methyl-1H-benzimidazol-2-yl)- Ethoxy] -phenyl} -propionic acid, 3- [4- [2- (6-allyloxy) -1-methyl-1H-benzimidazol-2-yl] -ethoxy]- 2- (4-Chloro-benzyloxy) -phenyl] -propionic acid or a pharmacologically acceptable salt or ester thereof, particularly preferably 3-[4-[6-(4-amino-3,5 -monomethyl -Phenoxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] -2- (4-methoxy · benzyloxy) -phenyl] -propionic acid, 3-[2 -(4-methoxybenzyloxy) -4- (6-methoxy-1-methyl-111-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid, 3- [4 -[6- (4-amino-3,5-dimethyl-phenoxy) -1-methyl-111-benzimidazol-2-ylmethoxy] -2- (4-chloro-benzyl (Oxy) -phenyl] -propionic acid, or a pharmacologically acceptable salt or ester thereof. In the present invention, the compound of the general formula (I) described below can be produced by the following method using a known compound of 200408628 as a starting material.

, M and η are as defined above.

-47- 200408628 A project [French Aa2 project; COOP1 first ^^ ΓΓΟΟΟΟΡ1 Η〇ύ, ΟΗ p20y (0 (Π) 'COOP1 first Aa3 third trip fj " > ^ n ^ COOP1 third Aa4 project ρ2〇Λ ^ 〇ρ3 --H (y (Hi) (iv)

Ηγν

• J3C COOP1 (vi) A project b method

HCT v, OH (VI ») CH0 Ab1 project Ab2 project

p50-V, 0H (viii)

COOP " P5〇 ^^ 〇H (ix) 3J〇C (Ab3 Project / w ^ wCOOP. P5〇〆 (iia) -48- 200408628 B Project A Method (x) N〇2 N-P7 Ba1 Project

. Mo Yan sugar. . (xiv) R (xv) Project Ba6 is cheap. . , R3 (xvi) Ba7 project

200408628 Project B Method

+ ,. You (Vi) ί_1 Part Bb1?

iCOOP1 In the above project and in the following description, ρ1,? 4, and ρ6 are the same or different, and each is an ester residue such as C1-6 alkyl (preferably methyl or ethyl), C7-19 aryl (preferably benzyl); P2, P3, and P5 are Same or different, each is a phenol protecting group such as C1-6 alkoxymethyl (preferably methoxymethyl), C7-16 aroyl (preferably benzyl); P7 is C1-6 alkoxycarbonyl (preferably Tertiary butoxycarbonyl), C7-16 aralkyloxycarbonyl (preferably benzyloxycarbonyl), and other protecting groups; L1 is a leaving group such as a halogen atom (preferably a chlorine atom). The manufacturing process of the compound (I) of the present invention is the following two processes. (1) Process A is a process for manufacturing the intermediates (i v) and (v i) on the right side of the compound (I). (2) Project B is to condense the intermediate [(iv) or (vi)] obtained from Project A with the intermediate [U Π i) or U vii)] on the left side of compound (I) to produce the compound of the present invention ( I) project, depending on the relative compound (I) can choose method a, b. Each process will be described below. -50- 200408628 (Project A) (Method A a) (Project A a 1) This project is a process for producing a phenol-based protected compound (ii), which makes the phenolic hydroxyl group of the known substance J (i) into an alkali In the presence, protection is achieved by appropriate protection groups. The solvent used is not limited as long as it does not hinder the reaction and can dissolve the raw materials. 'It is preferably ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, and dimethoxyethane. Methylamine, N, N-dimethylformamidine, N, N-dimethylresomide, N-methyl-2-pyrrolidone, N-methylpyrididone, hexamethylphosphonium triamine, etc. Amine, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, dichlorobenzene, acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone Ketones, such as cyclohexanone, are particularly preferably halogenated hydrocarbons or amidines, most preferably dichloromethane or N, N-dimethylformamide. The alkali used is not particularly limited, and is preferably alkali metal carbonates such as sodium carbonate, potassium carbonate, and lithium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate, potassium hydrogen carbonate, and lithium hydrogen carbonate; lithium hydride , Sodium hydride, potassium hydride and other alkali genus belong to hydrides; sodium hydroxide, potassium hydroxide, barium hydroxide, lithium hydroxide and other alkali metal hydroxides and other inorganic bases; sodium methoxide, sodium ethoxide, Alkali metal alkoxides such as potassium methyl oxide, potassium ethoxide, potassium tert-butoxide, lithium methoxide; N-methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, Cyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picolin, 4- (N, N-dimethylamino) pyridine, 2,6-bis (third butyl)- 4-methylpyridine, quinoline, N, N-dimethylaniline, N, N-di-51- 200408628 ethylaniline, 1,5-diazinebicyclo [4.3.0] non-5 · ene (DBn ), ^ Diazine bicyclic [2.2.2] octane (DABCO), 1, 8, dicyanobicyclo [5.4.0] undecyl-7-ene (DBU) and other organic bases, or butyl lithium, Lithium diisopropylamide, bis (trimethylsilane) ) Amides organic lithium metal based test. More preferred are alkali metal carbonates or organic bases, and most preferred is diisopropylethionate or potassium carbonate. The reagents used are generally used for the introduction of phenol-based protecting groups. * There is no good test. It is preferred to use aralkyl halides such as benzyl bromide and benzyl chloride, and methyl methoxide such as methoxymethyl chloride. 〇 The reaction temperature is 0 t ~ 50 ° C, preferably room temperature. The reaction time is from 0.5 to 96 hours, preferably from 1 to 24 hours. (Project A a 2) This project is a process for manufacturing a phenol-based protected compound (iii), which can be achieved according to the method of Project Aal. (Project A a 3) This project is a process for producing a compound (iv) whose phenol-based protecting group is deprotected, and the protective group of compound (i i i) is selectively deprotected. Depending on the type of protective group to be removed, it can be carried out according to a generally known method (C is implemented as follows. When the hydroxy protecting group is an aralkyl group or an aralkyloxycarbonyl group, it can be used in a solvent and contacted with a reducing agent (preferably It is removed under contact with catalyst at room temperature or removed by using an oxidant. The solvent used for contact reduction is not limited as long as it does not participate in the reaction, such as alcohols such as methanol, ethanol, isopropanol, ether, Ethers such as tetrahydrofuran and Ershu-52-200408628 alkanes, aromatic hydrocarbons such as toluene, benzene, xylene, aliphatic hydrocarbons such as hexane and cyclohexane, esters such as ethyl acetate and propyl acetate, formazan Amines such as amines, dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, hexamethylphosphonium triamine, fatty acids such as formic acid, acetic acid, water, or Mixed solvents are more suitable for alcohols, esters, and fatty acids. The catalyst used is usually used by users who are in contact with reduction reactions, and is not limited. It is preferably palladium-carbon, palladium hydroxide-carbon, palladium rhenium, Ruanlai nickel, Platinum oxide, platinum rhenium, rhodium-alumina, triphenylphosphine-rhodium chloride, palladium- Barium acid. The pressure is not limited, usually 1 to 10 atmospheres. _ Reaction temperature and reaction time may vary depending on the types of raw materials, solvents and catalysts, etc., usually 0 ° C ~ 100 ° c (preferably 20 ° c ~ 70) ° c), reaction time is 5 minutes to 48 hours (preferably 1 hour to 24 hours). When the hydroxy protecting group is alkoxymethyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydro When thiofuranyl or substituted ethyl, it is usually removed by treatment in a solvent with an acid. The acid used is not generally limited to Bronsted or Lewis acid, preferably hydrogen chloride; hydrochloric acid, sulfuric acid, nitric acid, etc. Inorganic acids; Or organic acids such as acetic acid, trifluoroethaneic acid, methanesulfonic acid, p-toluenesulfonic acid, etc .; Bronsted acid; Strong acidic cation exchange resins such as Lewis acid such as boron trifluoride, Dowex50W. The solvent is not limited as long as it does not hinder the reaction and it can dissolve the raw materials. It is preferably aliphatic hydrocarbons such as hexane, heptane, petroleum spirit, petroleum ether, etc .; aromatic hydrocarbons such as benzene, toluene, xylene; Halogenated hydrocarbons such as methyl chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene Ester such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, diethyl carbonate; ether-53-200408628, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol Ethers such as dimethyl ether; methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tertiary butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, cyclohexanol , Methyl lysin and other alcohols; acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone, cyclohexanone and other ketones; water, or this mixed solvent, more preferably halogenated hydrocarbons , Esters or ethers. The reaction temperature and reaction time may vary depending on the raw materials, solvents, and types and concentrations of the acids used, usually between -10 ° c ~ 100 ° C (preferably -5 ° c ~ 60 ° c). 5 minutes to 48 hours (preferably 30 minutes to 10 hours). (Project A a 4) This project is a process in which a phenolic hydroxyl group of compound (iv) is introduced into an alkanoic acid unit to produce compound (v), and compound (iv) is treated in an inactive solvent in the presence of a base to treat This is achieved by halogenating alkanoates. Halogenated alkanoates are, for example, ethyl bromoacetate, third butyl bromoacetate, ethyl 4-bromobutyrate, and ethyl 4-bromovalerate. The solvent used is not limited as long as it does not hinder the reaction and can dissolve the raw materials. It is preferably aromatic hydrocarbons such as benzene, toluene, and xylene; ether, diisopropyl ether, tetrahydrofuran, dioxane, and dimethoxy Ethers such as ethane and diethylene glycol dimethyl ether; ketones such as acetone and methyl ethyl ketone; amidines such as dimethyl sulfene and the like. More preferably, it is acetone. The alkali used is not particularly limited, such as: alkali metal carbonates such as carbonate carbonate, sodium carbonate, potassium carbonate, lithium carbonate, etc., alkali metal hydrogen carbonates such as sodium hydrogen carbonate, hydrogen carbonate, lithium hydrogen carbonate, etc. ; Alkali metal hydrides such as lithium hydride, sodium hydride, potassium hydride; sodium hydroxide, potassium hydroxide, barium hydroxide -54- 200408628, alkali metals such as lithium hydroxide and other inorganic bases, N-formaldehyde Morpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picolin, 4-(N , N-dimethylamino) pyridine, 2,6-bis (third butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, n, N-diethylaniline, 1 , 5-diazinebicyclo [4 · 3 · 0] non-5-ene (DBN), 1,4-diazinebicyclo [2 · 2 · 2] octane (DABCO), 1,8-diazinebicyclo [ 5.4.0] Undecyl-7-ene (DBU) and other organic bases. More preferred are alkali metal carbonates and organic alkalis, and particularly preferred is carbonate shavings. # Reaction temperature is 0 ° C ~ 100 ° C, preferably room temperature ~ 50 ° C. The reaction time is 1 hour to 48 hours, preferably 2 hours to 24 hours. (Project A a 5) This project is a process for manufacturing an intermediate (v i), and the monoester of the diester compound (v) is selectively hydrolyzed to obtain a carboxylic acid. The removal of the acid protecting group varies depending on the type, and can be carried out according to a method well known in the general art as follows. The carboxylic acid protecting group can be removed by treatment with an acid or a base when a lower alkyl group or an aryl group is used. Acids can be used, such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, and alkali. There are no restrictions on those that have no effect on other parts of the compound. It is preferably alkali metal carbonates such as sodium carbonate, potassium carbonate, sodium hydroxide, lithium hydroxide, An alkali metal hydroxide such as potassium hydroxide or a concentrated ammonium water-methanol solution. The solvents used are those used in hydrolysis reactions, and there are no restrictions on those that do not hinder the reaction. They are water or alcohols such as methanol, ethanol, n-propanol or tetrahydrofuran, -55- 200408628 Yishuyuan, or organic Mixed solvent of solvent and water. The reaction temperature may vary depending on the raw material compounds, solvents, and reagents used. There are no particular restrictions on who can inhibit side reactions, but it is usually 10 ° C to 50 ° C, and preferably room temperature. The reaction time is 1 hour to 48 hours, and preferably 3 hours to 24 hours. (A b method) This method is for producing a compound in which m is 2 among compounds (i i). (Project A b 1) This project is a process for manufacturing a phenol-based protected compound (viii), which can be achieved by the method of Project A a 1. (Project A b 2) This project is a process for producing a compound (i X), which can be achieved by reacting the aldehyde group of the compound (v i i i) with a henameis reagent. The anamonite reagent used is an alkyl dialkylphosphoacetate such as ethyl diethylphosphate. The solvent used is not limited as long as it does not hinder the reaction and can dissolve the raw materials. It is preferably aromatic hydrocarbons such as benzene, toluene, xylene; methylene chloride, chloroform, carbon tetrachloride, dichloroethane, Halogenated hydrocarbons such as chlorobenzene and dichlorobenzene; ethers such as diethyl ether, diisopropyl ether, and tetrahydrofuran; nitriles such as acetonitrile and isobutyronitrile; formamidine, dimethylformamide, dimethylacetamide, Ammonium amines such as hexamethylphosphonium triamine; sub-maples such as dimethylarsine, cyclobutane, etc., more preferably tetrahydrofuran. The base to be used is not limited to the conventional one used in the Horner Elmens reaction, and is preferably alkali metal carbonates such as sodium carbonate, potassium carbonate, lithium carbonate; alkali metal carbonates such as sodium bicarbonate, potassium bicarbonate, and lithium bicarbonate Hydrogen salts; alkali metal hydrides such as lithium hydride, sodium hydride-56-200408628, and potassium hydride; inorganic alkalis such as alkali hydroxides such as sodium hydroxide, sodium hydroxide, barium hydroxide, and lithium hydroxide; Alkali metal alkoxides such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, lithium methoxide; N-methylmorpholine, triethylamine, tripropylamine, tributylamine, Isopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picolin, 4- (N, N-dimethylamino) pyridine, 2,6-di (Third butyl) -4-methylpyridine, quinoline, N, N-dimethylaniline, 1? -Diethylaniline, 1,5-diazinebicyclo [4.3.0] non-5-ene (DBN), 1,4-diazinebicyclo [2.2.2] octane (DABCO), i, 8- _diazinebicyclo [5 · 4 · 0] undec-7-ene (DBU) and other organic bases , Or butyllithium, lithium diisopropylamide, bis (trimethylsilyl) Yl) Amides such as lithium metal test machine class. More preferred are inorganic bases, and most preferred is sodium hydride. The reaction temperature is from room temperature to 100 ° C, and preferably from 50 C to 80 ° C. The reaction time varies depending on the reaction temperature, the starting compound or the type of solvent used, but it is usually 6 hours to 48 hours, and preferably 12 hours to 24 hours. (Project A b 3) This project is to reduce the compound (i X) double bond to produce the compound (iia). The project is to make the compound (ix) in an inactive solvent and contact it in the presence of hydrogen and a catalyst. Achieved by reduction. The catalysts used are those that are usually used in contact reduction reactions, such as palladium-carbon, palladium-rhenium, palladium hydroxide-carbon, Raney nickel, platinum oxide, platinum-rhenium, rhodium-alumina, triphenylphosphine-chlorine Rhodium, palladium-barium sulfate, etc., preferably palladium hydroxide-carbon. As long as the solvent used does not impede the reaction and it can dissolve the raw materials, there is no special limit of -57- 200408628. It is preferably alcohols such as methanol, ethanol, ethers such as tetrahydrofuran and dioxane, fatty acids such as acetic acid, and ethyl acetate. Ester, more preferably ethyl acetate. The reaction temperature is 2 (TC ~ 50t :, preferably room temperature. The reaction time is 6 hours ~ 48 hours, preferably 12 hours ~ 24 hours. The order of each process of method A is not limited, and it is manufactured (vi ), They can be carried out in combination. For example, A b 1 project, then A a 2 project, A b 2 project, A b 3 project, A a 3 project, A a 4 project, A a 5 project (B process) (B a process) (B a 1 process) This process is a process for producing a compound (xi), in which a known compound (x) is subjected to an alcohol R 1-〇 Η in the presence of a base. The nucleophilic substitution reaction is achieved. The solvent used is not limited as long as it does not hinder the reaction and can dissolve the raw materials. It is preferably diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, dioxane, etc. Ethers such as ethylene glycol dimethyl ether; formamidine, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-formamidine Pyrrolidone, hexamethylphosphonium triamine, and other amines and the like. More preferably, it is N, N-dimethylformamide. The base used is not particularly limited, and it is preferably carbonic acid or carbonic acid. sodium Alkali metal carbonates such as potassium carbonate and lithium carbonate; alkali metal bicarbonates such as sodium hydrogen carbonate, potassium bicarbonate, and lithium hydrogen carbonate; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; sodium hydroxide, Inorganic bases such as potassium hydroxide, barium hydroxide, lithium hydroxide and other alkali metal hydroxides, N-methylmorpholine, tri-58- 200408628 ethylamine, tripropylamine, tributylamine, diisopropylethylamine , Dicyclohexylamine, N-methylpiperidine, pyridine, 4-pyrrolidinopyridine, picolin, 4- (N, N-dimethylamino) pyridine, 2,6-bis (third butyl) ) -4-methylpyridine, quinoline, N, N-dimethylaniline, n, N-diethylaniline, 1,5-diazinebicyclo [4.3.0] non-5-ene (〇8 至, 1,4-Diazine bicyclic [2.2.2] octane (DABCO), 1,8-Diazine bicyclic [5 · 4 · 0] ~ 1 --- 7-ene (DBU) and other organic bases. More It is preferably an inorganic base, particularly sodium hydride. The reaction temperature is 50 ° C ~ 150 ° C, preferably 80. (: ~ 120 ° C. The reaction time is 0 · 5 hours ~ 24 hours, preferably 1 hour. ~ 1 2 hours. _ (B a 2 project) This project is for the production of aniline compounds (X ii) Engineering, the reduction of the nitro group of compound (xi) in an inert solvent in the presence of a catalyst is achieved. The solvent used is not limited as long as it does not hinder the reaction and can dissolve the raw materials. Other alcohols, ethers such as tetrahydrofuran and dioxane, fatty acids such as acetic acid, esters such as ethyl acetate, or a mixed solvent thereof, more preferably tetrahydrofuran or ethanol. The catalyst used is usually used for the amine reduction reaction of nitro. There are no special restrictions, such as: palladium-carbon, palladium hydroxide-carbon, nickel chloride, hafnium chloride, sodium borohydride, etc., and most preferably palladium-carbon. The reaction can be carried out under hydrogen if necessary. The reaction temperature is from 20 ° C to 50 ° C (the boiling point of the solvent used), preferably room temperature. The reduction time is 6 hours to 48 hours, and preferably 3 hours to 24 hours. (Project B a 3) -59- 200408628 This project is a process for manufacturing an imidazole derivative compound (χ i i i), which is achieved by cyclizing the compound (X i i) in the presence of an acid. Compound (xiii) can be produced according to the method described in International Publication No. 99/18081 (Japanese Patent Application Laid-Open Nos. 1 1 to 1 9 3 2 76). (Project B a 4) This project is a process for producing compound (X iv). The compound (xiii) and the intermediate (iv) obtained from Project A are condensed in the presence of a condensing agent to achieve the solvent used. The reaction is unhindered, and there are no restrictions on those who can dissolve the raw materials. It is preferably ethers such as ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, aromatic hydrocarbons such as benzene, toluene, and xylene. , More preferably toluene or tetrahydrofuran. The condensing agent used is an agent generally used to condense phenol with an alcohol to form an ether bond, and is not particularly limited. For example, diazide dicarboxylic acid such as diethyl azide dicarboxylate-triphenylphosphine, etc. Condensing agents such as oligoalkyl esters-triphenylphosphines, azidodicarbonyldipiperidine-tributylphosphine, and the like are present in the presence of condensation agents. It is suitable for azide dicarbonyl dipiperidine-tributylphosphine and other azide dicarbonyldiamine-triane ® phosphines. The reaction temperature is -10C ~ 60 ° C, preferably room temperature. The reaction time is 30 minutes to 24 hours, preferably 2 hours to 20 hours. (Project B a 5) This project is a process for producing a compound (XV) by deprotecting a phenol-based protecting group, and the compound (xiv) can be achieved according to the method of Project Aa3. (Project B a 6) -60- 200408628 This project is a process for producing compound (xii) by introducing R2 group, which can make compound (X i) and known compound R, halide and reagent, according to project A a 1 Approach. (Project B a 7) This project is a process for producing the target compound (5), and the compound (X v i) is achieved according to the method of Project Aa5. The obtained target compound (I) can be prepared as an acid addition salt by a conventional method when a basic group is present, and is preferably a hydrochloride. (B b method) _ Compound (xvii) can be registered under US Patent No. 5886014 (Japanese Patent No. 3249490) or International Publication No. 99/18081 (Japanese Patent Laid-Open No. 1 1-1 9 3 2 7 6) Documented method to manufacture. (Project B b 1) This process is a process for producing a compound (X v), which is achieved by condensing an amine compound (xiv) with a carboxylic acid compound (Vi) in an inert solvent. The reaction can be carried out according to a conventional method for synthesis of phthalein. That is, the carboxylic acid is reacted with an activating agent in an inert solvent, activated, or simultaneously activated with an amine compound. If necessary, a base may be added to promote the reaction. The solvent used is not particularly limited, such as: halogenated hydrocarbons such as dichloromethane, chloroform, ethers such as diethyl ether, tetrahydrofuran, amines such as dimethylformamide, dimethylacetamide, Aromatic hydrocarbons such as benzene, toluene, xylene, esters such as ethyl acetate, or mixed solvents thereof, more preferably ethers, amidines, and halogenated hydrocarbons, and particularly preferably tetrahydrofuran, dichloromethane, and dioxane Or -61- 200408628 dimethylformamide. The active agents used are, for example, diimidazole compounds such as 1,1, -oxadibenzimidazole, N, N'-carbonyldiimidazole, and succinic acid such as N, N, -dibutyldiimide dicarbonate. Acid compounds; N, N, -bis (2-oxo-3-oxazolyl) Phosphophosphonium chloride compounds such as phosphatidyl chloride; N, N'-dibutyldiphosphonium imine oxalate (DSO), N, N'-diphthalimide oxalate (DPO), N, N'-bis (norctenyl butadiamidoimino) oxalate (BNO), 1,1 '- Bis (benzotriazolyl) oxalate (BBTO), 1,1'_bis (6-chlorobenzotriazolyl) oxalate (BCTO), 1,1, -bis (6-trifluoromethyl) Oxazine compounds such as benzotriazolyl) oxalate (BTBO); N -ethyl-5 -benzeneisoamidine-3 '-sulfonate and other N -lower alkyl-5 -aryl Esotriazole-3'-sulfonic acid salts; Phosphonocyanines such as diethylphosphonium cyanide (DEPC); 1-ethyl-3- (3-dimethylaminepropyl) carbodiimide (WSC) Carbodiimide-N-hydroxybutanediamine, N, N'-dicyclohexylcarbodiimide (DCC), carbodiimide-N-hydroxybutanediamine, etc. Imines Di-2 -pyridine diselenyl-triphenylphosphine and other diheteroaryl diselenyl-triarylphosphines; dipyridine disulfide-triphenylphosphine and other disulfide-triarylphosphines ·, p-nifezenesulfon triazole and other aromatic compounds Sulfatriazoles: 2-chloro-1 -methylpyridine iodide and other 2-halo-1 -lower alkylpyridine halides; diphenylphosphonium azide (DPPA) and other diarylphosphonium azides Type; low alkyl carbonate halides such as ethyl chlorocarbonate and isobutyl chlorocarbonate; phosphoric acid cyclic anhydrides such as 1-propionic phosphoric acid cyclic anhydride (T3P). Phosphorocyanines such as diethylphosphonium cyanide (DEPC) should be used. The reaction temperature of the active esterification reaction is -10 ° C to room temperature, the reaction temperature of the active ester compound and amine is room temperature, and the total reaction time of the two reactions is 30 minutes -62- 200408628 to 10 hours. The base used is not particularly limited, such as: N.methylmorpholine, triethylamine, tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, and N-methylpiperidine , Pyridine, 4-pyrrolidinopyridine, picolin, 4- (N, N-dimethylamino) pyridine, 2,6-bis (third butyl) -4-methylpyridine, quinoline, Ν , N-dimethylaniline, N, N-diethylaniline, ι, 5-diazinebicyclo [4 · 3 · 0] non-5-ene (DBN), 1,4-diazinebicyclo [2.2 .2] Organic bases such as octane (DABCO), 1,8-diazinebicyclo [5.4.0] undec-7-ene (DBU). More preferred are 4- (N, N-dimethylamino) pyridine, pyridine, diisopropylethylamine, and triethylamine. This project is achieved by treating a carboxylic acid compound (ν i) with a halogenating agent in an inert solvent to obtain a hafnium halide, and reacting the obtained hafnium halide with an amine compound (X i ν). The solvent used for the halogenation reaction is not limited as long as it does not hinder the reaction and can dissolve the raw materials. For example, ethers such as diethyl ether, tetrahydrofuran, and dioxane, dimethylformamide, dimethylacetamide, and hexamethylene Phosphonium amines such as diphosphonium triamine, halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, nitriles such as acetonitrile, propionitrile, and esters such as ethyl formate and ethyl acetate, preferably The mixed solvent is more preferably a halogenated hydrocarbon or an ether, and particularly preferably dichloromethane or tetrahydrofuran. The halogenating agent used is not particularly limited to those commonly used in the reaction of carboxylic acids with halogens, such as sulfenyl chloride, sulfenyl bromide, sulfinyl iodine and the like, sulfonyl chloride, sulfonium bromide, Sulfonium halides such as sulfonium iodine, phosphorus trichlorides, phosphorus tribromide, phosphorus trihalides such as phosphorus triiodide, phosphorus pentachlorides, phosphorus pentabromide, phosphorus pentahalides and other oxygen pentahalides Phosphorus oxyhalides such as phosphorus chloride, phosphorus oxybromide, and phosphorus iodide, grass chlorides, and other grass halides such as grass chlor bromide, grass chloro bromide, and the like are preferred. -63- 200408628 The reaction temperature is 0 ° c ~ under heating (using the boiling point of the solvent), preferably from room temperature to under heating (using the boiling point of the solvent). The reaction time is 10 minutes to 24 hours, preferably 1 hour to 5 hours. After the reaction is completed, it is concentrated, dried, and then reacted with the amine compound (x i v). The solvent used for the reaction between the halogen and the amine compound (X iv) is not limited as long as it does not hinder the reaction and can dissolve the raw materials. For example, ethers such as diethyl ether, tetrahydrofuran, and dioxane, dimethylformamide, Ammonium amines such as dimethylacetamide, hexamethylphosphonium triamine, esters such as ethyl formate, ethyl acetate, fluorenes such as dimethylarsine, or mixed solvents thereof, more preferably tetrahydrofuran, N, N-Dimethylmethylformamide or dimethylformamide. For the reaction between the halide and the amine compound (X i v), organic bases such as triethylamine and pyridine can be added as needed. (Project B b 2) This project is a process for cyclizing compound (xv) to manufacture (xiv), which can be achieved by the method of project B a 3. The obtained target compound (I) can be prepared as an acid addition salt by a conventional method when a basic group is present, and is preferably a hydrochloride. It is suggested that the target compounds can be obtained from the reaction mixture after the completion of the above-mentioned engineering reactions. For example, the reaction mixture is suitably neutralized. Furthermore, when insoluble matter is present, the insoluble matter is filtered off, and an immiscible organic solvent such as water and ethyl acetate is added. After washing with water, the organic layer containing the target compound is separated. It is obtained by drying the anhydrous magnesium sulfate and other solvents. The obtained target substance can be used according to ordinary methods, such as recrystallization, re-sinking, or usual, conventional methods for separation and purification of organic compounds, such as: adsorption column layer-64-200408628 analysis, partition column chromatography, etc. The method, ion exchange chromatography, or a suitable combination of cis-phase and reverse-phase column chromatography of silica gel or alkylated silica gel, is separated and purified by dissolving with a dissolving agent as appropriate. The phenylpropionic acid derivative of the above general formula (I) of the present invention may have various pharmacologically acceptable salts and esters thereof in various administration forms. The form of administration is not limited, and it depends on various formulations, other conditions such as the age of the patient, gender, and the degree of the disease. For example, lozenges, nine doses, powders, granules, syrups, liquids, suspensions, emulsions, granules and capsules are administered orally. When injecting, it can be administered intravenously alone or mixed with conventional rehydration fluids such as glucose and amino acids. It can also be administered intramuscularly, intradermally, subcutaneously or intraperitoneally as needed. Suppositories can be administered intrarectally. Should be administered orally. These various preparations can be prepared by mixing excipients, binding agents, disintegrating agents, slip agents, dissolving agents, flavoring agents, coating agents and other auxiliary agents known in the pharmaceutical preparation technology according to a conventional method. For the formation of tablets, well-known carriers can be used, such as lactose, sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid and other excipients, water, ethanol, propanol, Monosyrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and other binding agents, dried starch, sodium alginate, agar powder, layered body Disintegrating agents such as powder, sodium bicarbonate, calcium carbonate, polyoxyethylene fatty acid esters, sodium lauryl sulfate, glyceryl monostearate, starch, lactose, sugar, stearin, cocoa butter Collapse inhibitors such as hydrolyzed oil, absorption enhancers such as 4th ammonium base, sodium dodecyl sulfate, humectants such as glycerin, starch, starch, lactose, kaolin, bulk-65- 200408628 moist soil, colloidal silicon Sorbents such as acids, refined talc, lubricants such as stearates, ground borate, and polyethylene glycol. Furthermore, the lozenges can be applied with conventional skins, such as sugar-coated lozenges, gelatin-coated lozenges, enteric coated lozenges, double-coated lozenges, and multi-layer lozenges, if necessary. The carrier used for the nine-dose formation can be used by conventional users, such as glucose, lactose, starch, cocoa butter, hardened vegetable oil, kaolin, talc and other excipients, gum arabic, tragacanth, gelatin, ethanol and other binding agents, layered agar And other disintegrating tinctures. The carrier used for suppository formation can be conventional, such as polyethylene glycol, cocoa butter, higher alcohols, higher alcohol esters, gelatin, semi-synthetic glycerol, and the like. In the preparation of injections, sterilized liquids and suspensions should be used and isotonic with blood. The diluents used in the formation of such liquids, emulsions and suspensions are customary, such as water, ethanol, propylene glycol, ethoxylation Isostearyl alcohol, polyoxyisostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, the pharmaceutical preparation may contain a sufficient amount of table salt, glucose, or glycerin necessary for preparing an isotonic solution, and conventional dissolution aids, buffers, analgesics, and the like may be added. If necessary, it may contain other medicines such as coloring agents, preservatives, flavors, flavors, sweeteners, and the like. The amount of the active ingredient compound contained in the above-mentioned pharmaceutical preparation can be appropriately selected within a specific range. Usually, the total composition contains 1 to 70% by weight, preferably 1 to 30% by weight. The dosage may vary depending on symptoms, age, weight, administration method and dosage form, etc. Generally, the lower limit for adults is 0.001 mg (preferably 0.01 mg, 200408628 is 0.1 mg), and the upper limit is 2.000 mg (preferably 200 mg) , More preferably 20 mg), can be administered in fractions of a second.

-67- 200408628 [Embodiment] The present invention will be described in more detail by way of examples, reference examples, test examples, and formulation examples, but the scope of the present invention is not limited thereto. (Example 1) 3- [2-benzyloxy-4- (6-methoxy-1-methyl-1H-benzimidazole-2-ylmethoxy) -phenyl] -propionic acid Salt (Exemplified Compound No. 1-1) (la) 2 -Dimethyl-4-methoxymethoxybenzaldehyde Dissolve 2,4-dihydroxybenzaldehyde (1 g, 7.24 mmol) in dichloromethane ( 70 ml), N, N-diisopropylethylamine (3.03 ml, 17.37 mmol) and chloromethyl methyl ether (0.66 ml, 8.68 mmol) were added and stirred at room temperature for 90 minutes. After the reaction solution was concentrated, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1) to obtain the target compound (1.03 g, yield 78%). H-NMR (400MHz, CDC13): (5 ppm 4 8 (3 Η, s), 5. 2 2 (2 H, s), 6.60 (1 H, d, 2.2 Hz), 6.65 (1 H, dd , J = 8. 2,, 2.2 H z), 7.45 Η, d, J = = 8. 1 H z), 9. 7 4 (1 H, s), 11.36 (1 H, s) MS (El) m / z: 182 (M) + 〇 (lb) 3-(2-Ethyl-4-methoxymethoxyphenyl) ethyl acrylate The 2-hydroxy group produced in Example (la) 4-methoxymethoxybenzaldehyde (1.03 g, 5.66 mol) dissolved in tetrahydrofuran ml), -68-200408628 diethyl phosphodiacetate (1.35 ml, 6.79 mmol), carbon shavings (2.76 g, 8.49 mmol), and stirred at 70 t for 4 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1) to obtain the target compound (868 mg, yield 61%). 1 H-NMR (400 MHZ, CDC 1 3): 5 p pm 1.34 (3 H, t, J = 7. 3 H z), 3.4 7 (3H, s), 4.27 (2 H, q , J =: 7.3Hz), 5.16 (2 H, s), 6 · 5 (1 H, d, J = 16 .1 H z) 6.52 (1 H, br), 6.55 (1 H, d, J = 2.1 Hz), 6.61 (1 H, dd, J = 8.7, 2.1 Hz), 7.39 (1 H, d, J = 8. · 7Ηζ), 7.93 (1 H, d, J = 1 6.1 H z) 〇 (1 C) 3- (2-hydroxy-4 -methoxymethoxyphenyl) -ethyl propionate The 3-(2-hydroxy-4- Methoxymethoxyphenyl) ethyl acrylate (868 mg, 3.44 mmol) was dissolved in ethyl acetate (20 ml), and a catalytic amount of palladium hydroxide was added, followed by stirring at room temperature for 10 minutes under hydrogen. After removing the catalyst through diatomaceous earth, the filtrate was concentrated under reduced pressure to obtain the target compound (874 mg, 100%). H-NMR (400 MHz, CDC13): 5 ppm 1.23 (3H, t, J = 7. 3 Hz), 2.65 -2. 6 8 (2 H, m), 2.81- 2.84 (2H, m) , 3.46 (3 H, s), 4.14 (2H, q, J =: 7.3 Hz), 5.12 (2H, s), 6.56 (1 H, dd, J = 2.1, 8.0 Hz), 6.61 (1 H, d, J = 2.1 Hz), 6.97 (1 H, dd, J = 8. 0 H z), 7.38 (1H, s) 〇-69- 200408628 MS (El) m / z: 2 5 4 (M) +. (Id) 3-(2-Benzyloxy-4 -methoxymethoxyphenyl) -ethyl propionate The 3-(2-hydroxy-4-methoxymethoxyphenyl) produced in Example (lc) ) -Ethyl propionate (874 mg, 3.44 mmol) dissolved in n, N-dimethylformamide (30 ml), potassium carbonate (1.42 g, 10.32 mmol), benzyl bromide (0.62 Millimoles, 5.16 millimoles), and stirred overnight at room temperature. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed successively with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: Kiyain / ethyl acetate = 3/1) to obtain the target compound (1.23 g, yield 100%). . 1 Η -N MR (400MHz, CDC] 1 3) ·· 5 ρ ρ m 1. 2 2 (3 Η, t, J = 7. 3 H z), 2 • 59 (2 Η, t, J = 7 '7 H z), 2. 9 3 (2 Η, t, J = 7. 7 H z) 3. 4 6 (3 H, s), 4 .10 (2 Η, q, J = 7. 3 H z), 5.06 (2 Η, s), 5.13 (2 H, s), 6. 5 7 (1 H, dd, J = 2.1, 8 • 0 Η ζ), 6.63 (1 H, d, J = 2 1 H z), 7 • 06 (: 1 H, d 9 J = 8.0 Hz), 7.3 0-7.4 4 (5 Η, m). MS (El) m / z: 3 3 4 (M) +. (1 e) 3-(2-benzyloxy-4-hydroxyphenyl) -ethyl propionate The 3-(2-benzyloxy-4-methoxymethoxyphenyl) produced in Example (Id) ) -Ethyl propionate (1.23 g, 3.56 mmol) was dissolved in ethanol (10 ml), p-toluenesulfonic acid (100 mg) was added, and the mixture was heated and stirred at 60 ° C for 3 hours. Triethylamine was added to the reaction solution, and after concentration, the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2/1) to obtain the target compound (1.09 g). (Yield 100%). ] Η-NMK (400MHz, CDCI3) 5 ppm 1.21 (3 Η, t, J = 7. 3 Η ζ), 2.59 (2 Η, d, J = 7. 7 Η ζ), 2.91 (2 Η, d , J = 7.7Hz), 4.10 (2 Η, q, J = 7. 3 Η ζ), 4.86 (1 Η, br), 5.05 (2 Η, s), 6.33 (1 Η, dd, J = 2. 1, 8 .0 Η ζ), 6.44 (1 η, d, J = 2.1 Η ζ), 7.00 (1 Η, d, J = 8. 0 Η ζ), 7.30-7.43 (5 Η, m) MS (El) m / ζ: 3 0 0 (M) +. (If) 3- [2-Benzyloxy-4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester will be implemented 3-(2-benzyloxy-4 -hydroxyphenyl) -ethyl propionate (1.09 g, 3.62 mmol) produced in Example (1 e) and 2-hydroxymethyl produced in Reference Example (lb) 6-methoxy-1-methyl-1H · benzimidazole (697 mg, 3.62 mmol) was dissolved in toluene (30 ml), and tributylphosphine (1.13 ml, 4.53 mmol) was added and 1 , 1 '-(Jiqi-mineral-based) diamidine (1.14 g, 4.53 mmol), and stirred at room temperature overnight. The reaction solution was purified by silica gel column chromatography (eluent ·· hexane / ethyl acetate = 1/1) to obtain the target compound (1.50 g, yield 87.7%). 1 Η-NMR (400 Μ Η z, CDC 1 3): δ ppm 1.20 (3 Η, t, J = 7. 3 Η ζ), 2.57 (2 Η, t, J = 7. 7 Η ζ) , 2.91 (2Η, t, J = 7. 7 Η ζ), 3.80 (3 Η, s), 3.88 (3 Η, s), 4.08 (2Η, q, J = 7. 3 Η ζ), 5.04 (2 Η, s), -71- 200408628 5.29 (2H, s), 6.61 (1H, dd, J = 2.1, 8 · 0Ηζ), 6.66 (1H, d, J = 8.0Hz), 6.78 (1 H, d, J = 2.1Hz), 6.91 (1H, dd, J = 2.1, 8.0Hz), 7.07 (1H, d, J = 8.0Hz), 7.29-7.43 (5H, m), 7.64 (1H, d, J = 8.7Hz) 〇IR (KB r): 1721, 1614, 1507, 1243, 1212, 1172, 1120, 1041, 820 cm " 1 MS (FAB) m / z: 4 7 5 (M + H) + HR- MS (FAB) m / z: c28H3105N2 (M + H) + Calculated 値: 475.2233; Found 値: 475.2233. Analysis of C28H30.055N2, calculated 値: c, 7087; h, 6.37; 〇, 5.90; continuous measurement of 値: c, 70.81; Η, 6.15; N, 5.88. (lg) 3- [2-Benzyloxy-4_ (6-methoxy-1_methyl-111_benzimidazol-2-ylmethoxy) -phenyl] -propionic acid )-[2-Benzyloxy-4- (6-methoxy-1-methyl-1H-benzimidazolylmethoxy) -phenyl] -propionic acid ethyl ester (1.5 g, 3.152 mmol) was dissolved in a mixed solution of ethanol (7 ml) and tetrahydrofuran (7 ml), and 1 n aqueous sodium hydroxide solution (6.3 ml, 6.30 mmol) was added, and the mixture was stirred at room temperature overnight. After the reaction solution was concentrated, 1N hydrochloric acid and ethyl acetate were added and stirred. The crystals were collected by filtration and washed with water and ether. Dry under reduced pressure to obtain the target compound (640 mg, 4 5%). 1 Η-NMR (400 MHZ, DMS 0-d6): δ ρ ρ m 2.44 (2Η, t, J = 7.7Hz), 2.74 (2Η, t, J = 7.7 Η z), -72- 200408628 3.80 (3 Η, s), 3.82 (3 Η, s), 5.11 (2 Η, s), 5,31 (2 Η, s), 6.65 (1 Η, dd, J = 2.2 , 8. 2 Η ζ), 6.80-6.8 4 (2 Η, m), 7.07 (1 Η, d, J = 8. 2 Η ζ), 7.12 (1 Η, d, J = 2.4 Η ζ ), 7.0 6-7.4 6 (5 Η, m), 7.51 (1 Η, d, J = 8.8 Η ζ), 12.06 (1 Η, br). MS (FAB) m / ζ: 4 4 7 (Μ + Η) + HR-MS (FAB) m / ζ: C26H2705N2 (M + H) + Calculated 値: 4 4 7.1 9 2 0; Measured 値: 4 4 7.1 9 1 1.

(Example 2) 3-{2-benzyloxy-4- [3- (6-methoxy-1-methyl-1H-benzimidazol-2-yl) -propoxy] -phenyl} -Propionate (exemplified compound number 1-1 24) (2a) 3- {2-benzyloxy-4- [3- (6-methoxy-1-methyl-111-benzene

Benzimidazol-2-yl) -propoxy] -phenyl} -propionic acid ethyl ester 3-(2-Benzyloxy-4-hydroxyphenyl) -propionic acid ethyl ester prepared in Example (le) was used. (500 mg, 1.665 mmol), 3- (6-methoxy-1-methyl-1H.benzimidazol-2-yl) -propan-1-ol (366 mg, 1.665 mmoles), tributylphosphine (0.41 ml, 2.498 mmoles), 1,1 '-(azidodicarbonyl) dipiperidine (629 mg, 2. 498 mmoles) and toluene (1 7 ml), and reacted and worked up according to the method of Example (1 f) to obtain the target compound (472 mg, yield 56.6%). MS (FAB) m / z: 5 0 3 (M + H) + 〇 (2b) 3_ {2_benzyloxy_4_ [3_ (6_methoxy_1-methyl_111-benzene-73- 200408628 benzimidazole-2 -yl) -propoxy] -phenyl} -propionate hydrochloride 3-{2 -benzyloxy-4- [3- (6-methyl Oxy-1-methyl-1H-benzimidazol-2-yl) -propoxy] -phenyl} -propionic acid ethyl ester (260 mg, 0.517 mmol), 1N sodium hydroxide (1 ml, 1 millimolar), ethanol (2 ml) and tetrahydrofuran (1 ml). The reaction and post-treatment were carried out according to the method of Example (1 g) to obtain the target compound (169 mg, 64%). 1 Η-NMR (400 MHZ, DMS Ο-d 6): 5 ρ ρ m 2.25-2.31 (2 Η, m), 2.43 (2 Η, t, J = 7.6 Η ζ), 2.72 (2 Η, t, J = 7.6 Η ζ), 3.29 (2 Η, t, J = 7.1 Η ζ), 3.85 (3 Η, s), 3.90 (3 Η, s), 4.07 (2 Η, t, J = 5.7 Η ζ), 4.91 (2 Η, s), 6.21 (1 Η, d, J = 2.1. Η ζ), 6.35 (1 Η, dd, J = 2.3, 8.4 Η ζ), 7.02 (1 Η, d, J = 8. 2 Η ζ), 7.15 (1 Η, dd, J = 2.3, 9.0 Η ζ), 7.30-7.40 (5 Η, m), 7.51 (1 Η, d, J = 2.1 Η ζ), 7.67 (1 Η, d, J = 9. 0 Η ζ), 12.04 (1 Η,

IR (Κ Β r): 2 9 4 6, 1 7 1 7, 1 6 1 6, 1 5 0 3, 1 2 5 8, 1227, 1175, 1154 cm · 1 MS (FAB) m / z: 4 7 5 (M + H) + HR-MS (FAB) m / z: C28H3105N2 (M + H) + Calculated 値 · 4 7 5.2 2 3 3; Measured 値 · 4 7 5 · 2 2 3 1 (Example 3) 3- (4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy-74-200408628) -2- (2-difluoromethyl (Oxy) -phenyl] -propionate (exemplified compound numbers 1-4 9) (3a) 3-[4-methoxymethoxy-2- (2-trifluoromethylbenzyloxy)- Phenyl] -ethyl propionate using 3- (2-Ethyl-4-methoxymethoxyphenyl) -ethyl propionate (500 mg, 1.966 mmol), carbonic acid produced in Example (lc) Gen (815 mg, 5.889 mmol), 2-trifluoromethylbenzyl bromide (705 mg, 2.949 mmol) and N, N-dimethylformamide (20 ml), according to the example (1 d ) Method for reaction and post-treatment, the target compound (8 12 mg, 100%) can be obtained. MS (E I) m / z: 412 (M) +. (3b) 3- [4-Hydroxy-2- (2-trifluoromethylbenzyloxy) -phenyl] -propionic acid ethyl ester The 3- [4-methoxymethoxy produced in Example (3a) was used. Ethyl-2- (2-trifluoromethylbenzyloxy) -phenyl] -propionic acid ethyl ester (812 mg, 1.959 mmol), p-toluenesulfonic acid (82 mg) and ethanol (20 ml), The reaction and post-treatment were performed according to the method of Example (1e) to obtain the target compound (721 mg, 100%). MS (EI) m / z: 3 6 8 (M) +. (3c) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (2-trifluoromethylbenzyloxy) -phenyl ] -Ethyl propionate The 3- [4-hydroxy-2- (2-trifluoromethylbenzyloxy) -phenyl] -propionic acid ethyl ester (721 mg, 1.959 mmol) produced in Example (3b) was used. Mol) -75 · 200408628, 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (377 mg, 1.959 mmol), tributylphosphine (0.61 ml, 2.449 mmol) Ear), 1,1, _ (azidodicarbonyl) dipiperidine (617 mg, 2.449 mmol) and toluene (20 ml). The target compound was obtained (981 mg, yield 93%). MS (FAB) m / z: 5 4 2 (M + H) + 〇 (3d) 3-[4- (6 -methoxy-1) -Methyl-1H-benzimidazol-2-ylmethoxy) -2- (2-trifluoromethylbenzyloxy) -phenyl] -propionate was prepared using Example (3c) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (2-trifluoromethylbenzyloxy) -phenyl] -propyl Ethyl Ester (981 mg, 1.815 mmol), 1N Hydroxide Sodium (3.6 ml, 3.6 mmol), ethanol (5 ml) and tetrahydrofuran (5 ml) were reacted and worked up according to the method of Example (1 g) to obtain the target compound (6 7 6 mg, 6 8 % ). 1 Η-NMR (400 MHz, DMS Ο-d 6): δ ppm 2.42 (2 Η, t, J = 7.6 Η z), 2.73 (2 H, t, J = 7.6 H z) , 3.86 (3H, s), 3.92 (3H, s), 5.25 (2 H, s), 5.53 (2 H, s), 6.73 (1 H, dd, J = 2.3, 8.3 H z) , 6.85 (1 H, d, J = 2. 3 H z), 7.03 (1 H, dd, J = 2. 3, 8.9 Hz), 7.13 (1 H, d, J = 8. 3 H z), 7.36 (1H, d, J = 2 · 1 H z), 7. 5 8-7. 6 4 (2 H, m), 7.71-7.75 (1H, m), 7.7 8-7.8 2 (2 H, m ), 12.00 (1H, br). -76- 200408628 IR (KB r): 1711, 1611, 1504, 1315, 1296, 1261, 1218, 1170, 1120, 1095 cm-] MS (FAB) m / z: 5 1 5 (M + H) + HR -MS (FAB) m / z: c27h26〇5N2F3 (M + H) + calculated 値: 5 1 5 · 1 7 9 4; measured 实 ·· 5 i 5. I 7 8 5. (Example 4) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(4-trifluoromethylbenzyloxy)- Phenyl] -propionic acid (Exemplified compound numbers 1-5 1) · (4a) 3-[4-methoxymethoxy-2- (4-trifluoromethylbenzyloxy) -phenyl] -propionic acid As the ethyl ester, ethyl 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889 mmol) produced in Example (lc) was used. Mol), 4-trifluoromethylbenzyl bromide (705 mg, 2.949 mmol) and N, N-dimethylformamide (20 ml), the reaction was carried out according to the method of Example (1 d) After treatment, the target compound (811 mg) can be obtained. Lu MS (E I) m / z: 412 (M) +. (4b) 3- [4-Hydroxy-2- (4-trifluoromethylbenzyloxy) -phenyl] -propionic acid ethyl ester The 3- [4-methoxymethoxy produced in Example (4a) was used. Ethyl-2- (4-trifluoromethylbenzyloxy) -phenyl] -propionic acid ethyl ester (815 mg, 1.966 mmol), p-toluenesulfonic acid (81 mg) and ethanol (20 ml), The reaction and post-treatment were performed according to the method of Example (1e), and the target compound -77-200408628 (723 mg, 100%) was prepared. M S (E I) m / ζ: 3 6 8 (M) +. (4c) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-trifluoromethylbenzyloxy) -phenyl ] -Ethyl propionate The 3- [4-hydroxy-2- (4-trifluoromethylbenzyloxy) -phenyl] -propionic acid ethyl ester produced in Example (4b) was used (723 mg, 1.967 mmol Mol), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (378 mg, 1.982 mmol), tributylphosphine (0.62 ml, 2.459 mmol) , 1,1, _ (azidodicarbonyl) dipiperidine (620 mg, 2.459 mmol) and toluene (20 ml), and the reaction and post-treatment were carried out according to the method of Example (1 f). The title compound (934 mg, 88% yield) was obtained. MS (FAB) m / z: 5 4 3 (M + H) +. (4d) 3-[4- (6-methoxy-1 · methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-trifluoromethylbenzyloxyphenyl]- Example of propionate salt (3- (4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) manufactured by 40) 2- (4- Trifluoromethylbenzyloxy) -phenyl] -ethyl propionate (934 mg, 1.728 mmol), 1N sodium hydroxide (3.5 ml, 3.5 mmol), ethanol (5 ml), and tetrahydrofuran ( 5 ml), followed by reaction and post-treatment according to the method of Example (1 g), to obtain the target compound (526 mg, 59%). 1 Η-NMR (4 0 MHZ, DMS 〇- d 6): 5 ρ ρ m -78- 200408628 2.46 (2H, t, J = 7. 6 Η z), 2.78 (2 H, t, J = 7.6 H z), 3. 7 9 (3 Η , S), 3.82 (3 Η, s), 5. 2 4 (2H, s)? 5. 3 1 (2 Η, s;), 6.67 (1 Η, dd, J = 2, .2, 8.3Hz ), 6. 8 1 (1 Η, d, J = 2.2 Η ζ), 6.83 (1 Η, dd, J = 2.3, 8.8 Η ζ), 7. 0 9 (1 Η , D, J = 8. 3 Η ζ), 7 · 12 (1 Η, d, J = 2.3 Η ζ), 7. 5 1 (1 Η, d, J = 8. 8 Η ζ), 7.67 (2 Η, d, J = 8. 2 Η ζ):, 7.76 (2 Η, d, J = 8. 2 Hz), 12.06 (l Η, s) IR (κ Β r): 1 7 3 4, 1 6 1 4, 1 5 0 6, 1 324, 1258, 1 2 15, 1192, 1161, 1120, 1 066 cm'1 M; S (FAB ) m / ζ: 5 15 (Μ + Η) + HR-MS (FAB) m /: C 2 7 Η 2 ι 5 0 5 Ν 2 F 3 (Μ + Η) + calculation 値: 5 15.17 9 4; Measured erbium: 5 1 5. 1 7 9 7 ° (Example 5) 3-[2-(2-methoxythenyloxy) -4- (6 -methoxy-1 -methyl-1 fluorene -benzene Benzimidazole-2 -ylmethoxy) -phenyl] -propionate (Exemplified Compound No. 1-14) (5 a) 3-[2-(: 2-Methoxybenzyloxy) -4- Methoxymethoxy-phenyl] -ethyl propionate The 3- (2-hydroxy-4 · • methoxymethoxyphenyl) -ethyl propionate (50) produced in Example (1c) was used. 0 mg, 1.9 '66 mmoles), potassium carbonate (815 mg, 5.8 89 mmoles), 2-methoxybenzyl bromide (59 3 mg, 2.9 4 9 Millimoles) and Ν, Ν-dimethylformamide (20 ml), according to the actual The reaction and post-treatment can be carried out in the method of Example (1d) to obtain the target compound.

-79- 200408628 (705 mg, 96% yield). MS (EI) m / z: 3 7 4 (M) +. (5b) 3- [4-Hydroxy-2- (2-methoxybenzyloxy) -phenyl] -propionic acid ethyl ester The 3- [2- (2-methoxybenzyl) produced in Example (5a) was used. (Oxy) -4-methoxymethoxy-phenyl] -propionic acid ethyl ester (705 mg, 1.882 mmol), p-toluenesulfonic acid (70 mg) and ethanol (20 ml), according to the examples ( The method of 1e) is followed by reaction and post-treatment to obtain the target compound (583 mg, yield 94%). _ MS (E I) m / z: 3 3 0 (M) +. (5c) 3-[2- (2-methoxybenzyloxy) -4-(6-methoxy-l-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl]- Ethyl propionate was prepared using 3- (4-hydroxy-2-(2-methoxybenzyloxy) -phenyl] -propionic acid ethyl ester prepared in Example (5b) (583 mg, 1.765 mmol). , 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (339 mg, 1.765 mmol), tributylphosphine (0.55 ml, 2.206 mmol), 1,1 ' -(Azido-dicarbon-based) dipiperidine (556 mg, 2.206 mmol) and toluene (20 ml), which were reacted and worked up according to the method of Example (1 f) to obtain the target compound ( 7 3 9 mg, yield 83%). MS (FAB) m / z: 5 0 5 (M + H) + o (5d) 3-[2-(2-methoxybenzyloxy) -4-(6-methoxy-i-methyl · 1H-benzimidazol-2-ylmethoxy) -phenyl] -propionate hydrochloride 3-[2-(2-methoxybenzyloxy) _4_ (6- Methoxy-1-methyl-1H -benzimidazol-2-ylmethoxy) -phenyl • 80-200408628] -ethyl propionate (739 mg, 1.466 mmol), sodium hydroxide IN (3 ml, 3 mmol), ethanol (5 ml) and tetrahydrofuran (5 ml). The reaction and post-treatment were carried out according to the method of Example (1 g) to obtain the target compound (59 9 mg, 8 4 %). 1 Η-NMR (400 MHz, DMSO-d6): ά ppm 2.44 (2 H, t, J = 7.6 H z), 2.71 (2 H, t, J = 7.6 H z), 3.82 (3 H, s), 3.85 (3 H, s), 3.88 (3H, s), 5.07 (2 H, s), 5.44 (2 H, s), 6.67 (1 H, dd,

J = 2.2, 8.3 Hz), 6.83 (1H, d, J = 2.2Hz), 6.95 (2H, t, J = 7.3Hz), 7.0 4-7.0 9 (2 H, m), 7.27 (1 H, d, J = 1.0 Hz), 7.31-7.35 (1H, m), 7.41 (1H, dd, J = 1. 0, 7. 3 Hz) , 7.58 (1 H, d, J = 8.8 H z), 12.01-12.06 (1H, br). I R (K B r): 1 7 2 9, 1710, 1610, 1591, 1 5 0 3, 1463, 1439, 1286, 1247, 1218, 1170, 1122, 1208 cm * 1

MS (FAB) m / z: 4 7 7 (M + H) + HR-MS (FAB) m / z: C27H2906N2 (M + H) + Calculated 値: 477.2026; Measured 値: 477.2031. (Example 6) 3- [2- (4-methoxybenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazole-2-ylmethoxy) -phenyl ] -Propionate (Exemplified Compound No. 1-1 6) (6a) 3-[2-(4-Methoxybenzyloxy) -4 -methoxymethoxy-phenyl]--81- 200408628 For ethyl propionate, 3- (2-hydroxy-4-methoxymethoxyphenyl) -ethyl propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889 mmol), 4-methoxybenzyl chloride (0.4 ml, 2.949 mmol) and N, N-dimethylformamide (20 ml), according to the method of Example (1 d) By reaction and post-treatment, the target compound (625 mg, yield 85%) can be obtained. MS (EI) m / z: 3 7 4 (M) + 〇 (6b) 3- [4-hydroxy-2- (4-methoxybenzyloxy) -phenyl] -ethinyl propionate (6a) 3- [2- (4-Methoxybenzyloxy) -4-methoxymethoxy-phenyl] -propionic acid ethyl ester (625 mg, 1.669 mmol), p-toluene The sulfonic acid (63 mg) and ethanol (20 ml) were reacted and worked up according to the method of Example (1e) to obtain the target compound (205 mg, yield 37%). MS (EI) m / z: 3 3 0 (M) + 〇 (6c) 3-[2-(4-methoxybenzyloxy) -4-(6-methoxy-1-methyl- -1H -Benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester The 3- [4-hydroxy-2- (4-methoxybenzyloxy) -benzene produced in Example (6b) was used. [Yl] -ethyl propionate (205 mg, 0.621 mmol), 2-hydroxymethyl "6-methoxy_; [-methyl-1H-benzimidazole (119 mg, 0.621 mmol), Tributylphosphine (0.19 mL, 0.776 mmol), 1,1 '-(azidodicarbonyl) dipiperidine (196 mg, 0.776 mmol) and toluene (10 mL), according to the examples ( The method of 1 f) was used for reaction-82-200408628 and post-treatment to obtain the target compound (211 mg, yield 67%). MS (FAB) m / z: 5 0 5 (M + H) + 〇 (6 d) 3-[2-(4-methoxybenzyloxy) -4-(6-methoxy-l-methyl -

1H-benzimidazol-2-ylmethoxy) -phenyl] -propionate hydrochloride 3-[2-(4-methoxybenzyloxy) -4-produced in Example (6c) (6-Methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (211 mg, 0.419 mmol), sodium hydroxide IN (0.9 ml, 0.9 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml). The reaction and post-treatment were carried out according to the method of Example (1 g) to obtain the target compound (51 mg, 24%). ). 1 Η-NMR (400 MHZ, DMS 0-d6): δ ppm 2.42 (2 2, t, J = 7.6 Η ζ), 2.71 (2Η, t, J = 7.6 Η ζ ), 3.75 (3 Η, s), 3.83 (3 Η, s), 3.84 (3 Η, s), 5.03 (2 Η, s), 5.37 (2 Η, s), 6.64 (1 Η, dd, J = 2. 2, 8. 3 Η ζ), 6.82 (1 Η, d, J = 2.2Hz), 6.89 (1Η, dd, J = 2. 2, 8. 8 Η ζ), 6.93 (2 Η, d ,

J = 8. 6 Η ζ), 7.06 (1 Η, d, J = 8. 3 Η ζ), 7.20 (1 Η, d, J = 1. 9 Η ζ), 7.37 (2Η, d, J = 8 6 Η ζ), 7.55 (1 Η, d, J = 8.8 Η ζ), 12.04 (1 Η, br). IR (Κ Β r): 1711, 1612, 1513, 1 5 0 4, 1 4 6 7, 1288, 1249, 1217, 1171, 1030 cm-1 MS (FAB) m / ζ: 4 7 7 (Μ + Η ) + Η R-MS (FAB) m / z: C27H2906N2 (M + H) + calculated 値: 477.2026; found 实: 477.2017. -83- 200408628 (Example 7) 3-[4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) 2- (3-trifluoromethylbenzyloxy ) ~ Phenyl] -propionic acid (Exemplified compound number 1-50) (7a) 3-[4-methoxymethoxy-2- (4-trifluoromethylbenzyloxy) · phenyl] -propionic acid ethyl As the ester, ethyl 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889 mmol) produced in Example (lc) was used. Ear), 3-trifluoromethylbenzyl bromide (705 mg_, 2.949 mmol) and N, N-dimethylformamide (20 ml), the reaction was carried out according to the method of Example (1 d), and after After treatment, the target compound was obtained (694 mg, yield 85%). MS (EI) m / z: 412 (M) + 〇 (7b) 3- [4-hydroxy-2- (3-trifluoromethylbenzyloxy) -phenyl] -propionic acid ethyl ester Example (7a ) -Ethyl 3- [4-methoxymethoxy-2- (3-trifluoromethylbenzyloxy) -phenyl] -propionate (694 mg, 1.675 mmol · ear), p-toluene The sulfonic acid (70 mg) and ethanol (20 ml) were reacted and worked up according to the method of Example (1e) to obtain the target compound (616 mg, 100%). MS (EI) m / z: 3 6 8 (M) +. (7c) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (3-trifluoromethylbenzyloxy) -phenyl] -Ethyl propionate The 3- [4-hydroxy-2- (3-trifluoromethylbenzyl-84-200408628oxy) -phenyl] -propionic acid ethyl ester (616 mg, 1.675 mmol), 2-hydroxymethyl-6-methoxy-1-methyl-benzimidazole (321 mg, 1.675 mmol), dibutyl scale (0.52 pens; liter, 2.094 mmol) Moore), 1,1,-(azidodicarbonyl) dipiperidine (528 mg, 2.094 mmol) and toluene (20 ml), the reaction and post-treatment were carried out according to the method of Example (1f), The target compound was obtained (770 mg, yield 85%). MS (FAB) m / z: 5 4 3 (M + H) +. (7d) 3- [4- (6 · methoxy-1-methyl-1H-benzimidazole_2 · ylmethoxy) -2- (3-trifluoromethylbenzyloxyphenyl] -propyl The hydrochloride was prepared using 3- (4- (6-methoxy-1-methyl-1Η-benzimidazole-2-ylmethoxy) -2- (3-tri Flumebenzyloxy) -phenyl] -ethyl propionate (770 mg, 1.419 mmol), 1N sodium hydroxide (2.9 ml, 2.9 mmol), ethanol (6 ml), and tetrahydrofuran (6 ml ), According to the method of Example (1 e) and reaction and post-treatment, the target compound (425 mg, 54%) can be obtained. 1 Η-NMR (4 0 MHZ, DMS 0-d 6 ): 5 ρ ρ m 2.47 (2 Η, t, J = 7.6 Η ζ), 2.79 (2 Η, t, J = 7.6 Η ζ), 3.88 (3 Η, s), 3.96 (3 Η , s), 5.27 (2 Η, s), 5.59 (2 Η, s), 6.72 (1 Η, dd, J = 2.2, 8 · 2Ηζ), 6.88 (1 Η, d, J = 2.2 Η ζ), 7.12 (1Η, dd, J = 2.1, 9 .0 Η ζ), 7.15 (1 Η, d, J = 8.4 Η ζ), 7.46 (1 Η, d, J = 1.9Hz), 7.63-7.71 (3Η, m), 7.78 (1 Η, d, J = 7. 5 Η ζ), 7.83 (1 Η, s) -85- 200408628 IR (KBr): 1717, 1612, 1 5 0 3, 1 3 3 2, 1 2 6 2, 1225, 1177, 1167, 1122, 1040 cm'1 MS (FAB) m / z: 515 (M + H) + HR-MS (FAB) m / z: C27H2605N2F3 (M + H) + Calculated 値: 5 1 5. 1 7 9 4; Measured 値: 5 1 5 · 1 7 7 6. (Example 8) 3-[2-(3-methoxybenzyloxy) -4-(6-methoxy-1-methyl_1H-benzimidazol-2-ylmethoxy) -phenyl] -propyl Hydrochloride (Exemplified Compound No. 1-1 5) (8a) 3-[2- (3-methoxybenzyloxy) -4 -methoxymethoxy-phenyl] -ethyl propionate (10-Ethyl 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889 mmol), 3-Methoxybenzyl bromide (0.42 ml, 2.949 mmol) and N, N-dimethylformamide (20 ml) can be prepared and reacted according to the method of Example (1 d) to obtain Target compound (615 mg, yield 84%). MS (E I) m / z: 3 7 4 (M) +. (8b) 3- [4-Hydroxy-2- (3-methoxybenzyloxy) -phenyl] -propionic acid ethyl ester The 3- [2- (3-methoxybenzyl) produced in Example (8a) was used (Oxy) -4-methoxymethoxy-phenyl] -propionic acid ethyl ester (615 mg, 1.642 mmol), p-toluenesulfonic acid (62 mg) and ethanol (20 ml), according to the examples ( 1 e) The reaction and post-treatment can be carried out to obtain the target compound (• 86- 200408628 542 mg, 100%). MS (El) m / z: 3 3 0 (M) +. (8c) 3- [2- (3-methoxybenzyloxy) -4- (6-methoxy-i-methyl-1H-benzimidylmethoxy) -phenyl] -propionic acid As the ethyl ester, 3- [4-hydroxy-2-(4-methoxybenzyloxy) -phenyl] -propionic acid ethyl ester (542 mg, 1.642 mmol) produced in Example (8b), 2 was used. -Hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (316 mg, 1.642 mmol), tributylphosphine (0.51 ml, 2.053 mmol),: 1,1'_ (Azidedicarbonyl) dipiperidine (517 mg, 2.053 mmol) and toluene (20 ml) were reacted and worked up according to the method of Example (1 f) to obtain the target compound (6 8 8 Mg, yield 83%). MS (FAB) m / z: 5 0 5 (M + H) +. (8d) 3- [2- (3-methoxybenzyloxy) -4 · (6-methoxy-l-methyl-lH-benzimidazol-2-ylmethoxy) -phenyl]- The propionate was prepared using 3- (2 · (3-methoxybenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazole-2) produced in Example (8c). -Ylmethoxy) -phenyl] -ethyl propionate (688 mg, 1.365 mmol), sodium hydroxide (2.8 ml, 2.8 mmol), ethanol (6 ml), and tetrahydrofuran (6 ml ), According to the method of Example (1 g) and reaction and post-treatment, the target compound (3 8 3 mg, 57%) can be obtained. 1 Η-NMR (400 MHZ, DMS Ο-d 6): 5 ρ ρ m 2.45 (2 Η, t, J = 7.6 Η ζ), 2.75 (2 Η, t, J = 7. 6 Η ζ), 3.75 (3Η, s), 3.80 (3 Η, s), 3.82 (3Η, s), 5.09 (2Η, s), 5.31 (2Η, s), 6.65 (1Η, dd,- 87- 200408628 J = 2 · 2, 8 (1 Η, d, 7.01 (2 J = 8 · 2 Η z) (1 H, m), (1 H, br) IR (KB r; 1457, 12 1159, 10: MS (FAB HR-MS (: 値: 4 7 7. 2 (Example 9 3-[4-(6) -2- (3-10 2) (9 a) 3-[Ethyl Acetate use implementation) -Ethyl propionate 8 1 5 mg, liter '2 · 9 7 3 according to the example compound (7 5 4 • 2Hz), 6.80 (1H, d, J = 2.2Hz), 6.83 J = 2.5, 8.8Hz), 6.87-6.89 (1H, m), H, d, J = 7. 3 H z), 7.07 (1H, d,), 7.12 (1H, d, J = 2.2Hz), 7.28-7.31 7.51 (1H, d, J = 8.8Hz), 12.02-12.11 o): 1720, 1611, 1590, 1502, 1488, 97, 1269, 1252, 1219, 1184, 1166, 3 4cm · 1 φ) m / z: All (M + H) + FAB) m / z: C27H2906N2 (M + H) + Calculate 0 2 6; *, Test: 4 7 7.2 0 3 0.) > -Methoxy-1_methyl-1H · Benzimidene _2 -methylmethoxy Phenylpropoxy) -phenyl] -propionic acid (Exemplified compound number Iα-methoxymethoxy-2- (3-phenylpropoxy) -phenyl] · Propionate Example (lc) 3 -(2-hydroxy-4-methoxymethoxyphenyl ester (500 mg, 1.966 mmol), potassium carbonate (5.889 mmol), bromo-3-phenylpropane (0.45 mmol) And N, N-dimethylformamide (20 ml), (1 d) for reaction and post-treatment to obtain the desired halogram (100% yield). -88-200408628 MS (El) m / z: 3 7 2 (M) +. (9b) 3- [4-Hydroxy-2- (3-phenylpropoxy) -phenyl] -propionic acid ethyl ester The 3- [4-methoxymethoxy-2 produced in Example (9a) was used. -(3-Phenyloxy) -phenyl] -propionic acid ethyl ester (754 mg, 1.966 mmol), p-toluenesulfonic acid (75 mg) and ethanol (20 ml), according to Example (1 e ) Method of reaction and post-treatment 'can produce the target compound (645 mg, 100%). MS (EI) m / z: 3 2 8 (M) + 〇 (9c) 3-[4- (6-methoxy-1-methyl-1H-benzoyl) ) -2- (3-Phenyloxy) -phenyl] -propionic acid ethyl ester The 3- [4-hydroxy-2- (3-phenylpropoxy) · phenyl group produced in Example (9b) was used. ] -Ethyl propionate (645 mg, 2.026 mmol), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (378 mg, 2.026 mmol), tributane Phosphine (0.63 ml, 2.532 mmol), 1,1 '-(azidodicarbonyl) dipiperidine (638 mg, 2.532 mmol) and toluene (20 ml) were performed according to the method of Example (if) By reaction and post-treatment, the target compound (885 mg, yield 90%) can be obtained. MS (FAB) m / z: 5 0 3 (Μ + Η) + 〇 (9d) 3-[4- (6 -methoxy-1-methyl-1Η-benzimidazol-2-ylmethoxy) ) -2- (3-Phenyloxy) -phenyl] -propionic acid The 3- [4- (6-methoxy-l-methyl-lH-benzimidazole) produced in Example (9c) was used. 2-ylmethoxy) -2- (3-phenylpropoxy) -phenyl] -propionic acid ethyl ester (885 mg, 1.761 mmol), 1N sodium hydroxide (3.5 ml, 3.5 Millimolar), ethanol (8 ml) and tetrahydrofuran-89-200408628 (8 ml), the reaction and post-treatment were performed according to the method of Example (1 g), and the target compound (64 3 mg, 77 ). 1H-NMR (400MHz, DMSO-d6): (5 ppm 1.9 8-2.0 5 (2 H, m), 2.45 (2H, t, J = 7.7Hz), 2.7 2-2.7 7 (4 H, m), 3.80 (3H, s), 3.82 (3 H, s), 3.96 (2 H, t, J = 6.1Hz), 5.31 (2 H, s), 6.61 (1 H, dd, J = 2.3, 8.3 Hz), 6.68 (1H, d,

J = 2.2 Hz), 6.83 (1H, dd, J = 2.2, 8.8Hz), 7.05 (1H, d, J = 8.3Hz), 7.12 (1H, d , J = 2. 3 H z), 7.16-7.30 (5 H, m), 7.50 (1 H, d, J = 8. 8 H z), 12.05 (1H, s) ° IR (KBr): 1 7 0 7, 1613, 1 5 9 0, 1 5 0 5, 1 4 8 8, 1 2 8 5, 1 2 5 9, 12 17, 1192, 1 1 7 1, 1 0 3 0 cm · 1 MS (FAB ) m / z: 4 7 5 (M + H) + HR-MS (FAB) m / z: C28H3105N2 (M + H) + Calculation 値: 4 7 5.2 2 3 3; Measured 値 ·· 4 7 5.2 2 3 8 °

(Example 1) 3- [2- (4- (Third-butylbenzyloxy))-4- (6-methoxy-l-methyl-1H-benzimidazole-2-ylmethoxybenzene Group] -propionate (Exemplified compound number 1-1 3) (10a) 3-[2-(4-tert-butylbenzyloxy) -4 -methoxymethoxy-phenyl] -propyl As the ethyl acetate, ethyl 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionate (500 mg, 1.966 mmol), potassium carbonate (-90-200408628) produced in Example (lc) was used. 815 mg, 5.889 mmol), 4-tert-butylbenzyl (ml, 2.949 mmol) and N, N-dimethylformamide (2, according to the method of Example (1 d)) After post-treatment, compounds can be obtained (795 mg, yield 100%). MS (EI) m / z: 4 0 0 (M) +. (1 0 b) 3-[2- (4-tert-butylbenzyloxy) ) -4-hydroxy-benzene 3 ethyl ester 3-[2-(4 -third) -4 -methoxymethoxy-phenyl] -propionic acid ethyl ester produced in Example (10a) (795 mg millimolar), p-toluenesulfonic acid (80 mg) and ethanol (20 were reacted and worked up according to the method of Example (1e), and a compound (707 mg, 100%) was prepared. MS ( E I) m / z: 3 5 6 (M) +. (10c) 3-[2- (4- tert-butylbenzyloxy) -4- (6-methoxy-1H -benzimidazole-2- Methoxy) -phenyl] -P 3-[2-(4 · third) -4 -hydroxy-phenyl] -propionic acid ethyl ester (707 mg, 1.98), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole, 1.985 mmoles, tributylphosphine (0.62 ml, 2 J ears), 1, 1 ' -(Azidodicarbonyl) dipiperidine (625 mg millimolar) and toluene (20 ml), according to the reaction and post-treatment of Example (1 f), the target compound (8.89 mg, i I (0.54 ml) to obtain the target B] -Butylbenzyl propionate (1.985 ml), to give the target, ethyl-1 -methyl tosylate butyryloxy 5 mmol (3 8 2 mmol 8 1 mmol, 2.481 method for g yield 8 4% 200408628 (1 0 d) 3-[2- (4- tert-butylbenzyloxy) -4- (6 -methoxy-1-methyl-1H- Benzimidazol-2-ylmethoxyphenyl] -propionate

Using 3 · [2- (4-_third-butylbenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazole-2 · ylmethoxy) produced in Example (10c) ) -Phenyl] -ethyl propionate (889 mg, 1.676 mmol), sodium hydroxide (3.4 ml, 3.4 mmol), ethanol (4 ml) and tetrahydrofuran (4 ml), in accordance with The method of Example (1 g) was used for reaction and post-treatment to obtain the target compound (771 mg, 85%). 1 Η-NMR (400 Μ Η ζ, DMSO-d6): (5 ppm 1.28 (9 Η, s)), 2.46 (2Η, t, J = 7.6 Η ζ), 2.76 (2 Η, t, J = 7.6 Η ζ), 3.89 (3 Η, s), 3.99 (3 Η, s), 5.12 (2 Η, s), 5.64 (2 Η, s), 6.71 (1 Η, dd J = 2 2, 8. 3 Η ζ), 6.90 (1 Η, d, J = 2.2 Η ζ), 7.13

(1 Η, d, J = 8. 3 ζ), 7.15 (1 Η, dd, J = 2.2, 8.9 Η ζ), 7.3 7-7.4 2 (4 Η, m), 7.50 (1 Η, d, J = 2 · 2 Ηζ), 7.71 (1Η, d, J = 8.9Hz). IR (Κ Β r): 2 9 6 2, 1 7 1 6, 1613, 1 2 6 3, 1 2 2 9, 1171, 1155 cm · 1 MS (FAB) m / ζ: 5 0 3 (Μ + Η ) + HR-MS (FAB) m / z: C30H35O5N2 (M + H) + Calculated 値: 5 Ο 3 · 2 5 4 6; Measured 値: 5 0 3. 2 5 8 1 〇 (Example 1 1) 3 -[2-(2, 4-dichlorobenzyloxy) -4- (6-methoxy-1-methyl-1Η · -92- 200408628 benzimidazol-2-ylmethoxy) -phenyl ] -Propionate (Exemplified Compound Nos. 1-9 8) (11 &) 3- [2- (2,4-dichlorobenzyloxy) -4-methoxymethoxy, phenyl] -propyl As the ethyl acetate, ethyl 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889) produced in Example (lc) was used. Mmol), 2,4-dichlorobenzyl chloride (0.41 ml, 2.949 mmol) and N, N-dimethylformamide (20 ml), the reaction was carried out according to the method of Example (1 d) After treatment, the target compound (783 mg, yield 96%) can be obtained. MS (E I) m / z: 412 (M) +. (1 1 b) 3-[2-(2,4-dichlorobenzyloxy) -4 · hydroxy-phenyl] -propionic acid ethyl ester 3-[2- (2 , 4-dichlorobenzyloxy) -4 -methoxymethoxy-phenyl] -propionic acid ethyl ester (781 mg, 1.89 mmol), p-toluenesulfonic acid (80 mg) and ethanol ( 20 ml), and reacted and worked up according to the method of Example (1e) to obtain the target compound (697 mg, 100%). MS (EI) m / z: 3 6 8 (M) +. (11〇) 3- [2- (2,4-dichlorobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -benzene Ethyl] · ethyl propionate using 3- [2- (2,4-dichlorobenzyloxy) -4-hydroxy-phenyl] -propionic acid ethyl ester (1.89 mmol) produced in Example (11b) ), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (363 mg, 1.89 mmol-93-200408628), dibutyl ^ (0.59 ml 2.363 mmol) ), 丨 '丨,-(Azide dimine-based) diazepam (595 mg, 2.363 mmol) and toluene (20 pen liters), react according to the method of Example (1 f) and After treatment, the target compound (944 mg, yield 92%) can be obtained. MS (FAB) m / z: 5 4 3 (M + H) + 〇 (11 (1) 3- [2- (2,4-dichlorofluorenyloxy) -4- (6-methoxy-1 -Methyl-1H-benzimidyl-d-methoxy) -phenyl] -propionate

-HTL

3-[2-(2, 4-dichlorobenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazole-2-ylmethyl) produced in Example (lie) (Oxy) -phenyl] -ethyl propionate (9.44 mg, 1.7 3 7 mmol), 1 N sodium hydroxide (3.5 ml ^ 3.5 mmol), ethanol (4 ml ) And tetrahydrofuran (4 ml), according to the method of Example (lg) and post-treatment to obtain the target compound (8 8 3 mg, 93%) 0 1 Η -N 1 S4 R (4 CI 0 Μ Η) : z, DMSO- d 6): (5 P pm 2. 4 4 (2 H, t, J = 7.6 Hz), 2 · 7 5 (2 H, t, J = 7.6 Η ζ), 3 8 8 (3 Η, s) ,: (.98 (3 H, s), 5 · 18 (2 Η [, s), 5. 6 2 (2 Η, S), 6 • 74 (1 H, dd, J = 2.2, 8. 3 Η ζ), 6. 8 9 (1 Η, d, J:: = 2.2. 2 H z), 7. 1 1-7. 16 (2 Η, Π1), 7 4 7- 7.49 (2H, m), 3 · 0 5-Ί 1.7 (3 (3 Η, m), 12. 0 5 -12.11 (1 H, br). IR (: κ Β r): 2 9 3 1, 1720, 16 1 2, 1 5 0 2, 1 2 6 2, 1 2 2 5, 117 6 cm · 1

MS (FAB) m / z: 515 (Μ + Η) -94- 200408628 HR-MS (FAB) m / z: C26H2505N2C1 (M + H) + Calculated 値: 515.1141; Measured 値: 5 1 5. 1 1 3 1. (Example 1 2) 3- [2- (3,4-dichlorobenzyloxy) -4- (6-methoxy-1-methyl-111-benzimidazole-2-ylmethoxybenzyl Group] -propionate (exemplified compound number 1-9 9) (1 2 a) 3-[2- (3, 4-dichlorobenzyloxy) -4 -methoxymethoxy-phenyl] -Ethyl propionate Using 3- (2-hydroxy-4-methoxymethoxyphenyl) -ethyl propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg) produced in Example (lc) , 5.889 mmol), 3,4-dichlorobenzyl bromide (0.41 ml, 2.949 mmol) and N, N -dimethylformamide (20 ml), according to the method of Example (1 d) The target compound (781 mg, yield 96%) can be obtained by reaction and post-treatment. MS (EI) m / z: 4 12 (M) + o (121 >) 3- [2- (3,4- Dichlorobenzyloxy) -4- mesityl-phenyl] -propionamidine ethyl ester 3-[2- (3, 4-dichlorobenzyloxy) -4 -methyl produced in Example (12a) Oxymethoxy-phenyl] -propionic acid ethyl ester (781 mg, 1.89 mmol), p-toluenesulfonic acid (80 mg) and ethanol (20 ml) were reacted according to the method of Example (1e). And post-processing can be made Compound (697 mg, 100%). MS (EI) m / z: 3 6 8 (M) + 〇 (1 2 c) 3-[2- (3,4-monofluoromethyl) -4- ( 6-methoxy-1-methyl-95- 200408628 yl-1H-benzimidazole-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3_ [2- (3, 4-dichlorobenzyloxy) -4-ethyl-phenyl-phenyl] -propanoate (697 mg, 1.89 mmol), 2-Methyl-6-methoxyq-methyl Benzimidazole (363 mg, 1.89 mmol), tributylphosphine (0.59 ml, 2.363 mmol), 1,1 '· (azidodicarbonyl) dipiperidine (595 mg, 2.363 mmol) Moore) and toluene (20 ml), and the reaction and post-treatment according to the method of Example (1 f) to obtain the target compound (861 mg, yield 84%). MS (FAB) m / z: 543 (M + H) +. (12 (1) 3- [2- (2,4-dichlorobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazolyl (Methoxy) -phenyl] -propanoic acid hydrochloride 3-[2-(3, 4-dichlorobenzyloxy) -4- (6 -methoxy-1) produced in Example (12c) -Methyl-benzimid-2-ylmethoxy) _phenyl] -ethyl propionate (861 mmol , 1.584 mmoles), 1N sodium hydroxide (3.2 ml, 3.2 mmoles), ethanol (4 ml) and tetrahydrofuran (4 ml). The target compound can be obtained (912 mg, 100%). 1 Η-NMR (400 MHz, DMS 〇-d 6): 5 ppm 2.46 (2H, t, J = 7.6Hz), 2.77 (2H, t, j = 7.6Hz), 3.88 (3 H, s) , 3.97 (3H, s), 5.i 8 (2H, s), 5.61 (2H, s), 6.73 (1H, dd, J = 2.4 to 8.4Hz), 6.86 (1H, d, J = 2 .4 H z), 7. 1 0-7. 1 5 (2H, m), 7.4 4-7.4 7 (2 H, m), 7.6 4-7.6 9 (2 H 7 7 q -96- 200408628 ( 1H, d, J = 1.5 H z) 5 12.12-12.15 (1H, br). IR (KBr): 1720, 1612, 1503, 1262, 1224, 1178 cm · 1 MS (FAB) m / z: 515 (M + H) + HR-MS (FAB) m / z: C26H2505N2C1 (M + H) + Calculated 値: 5 1 5 · 1 1 4 1; Measured 値: 5 1 5. 1 1 2 5. (Example 1 3) 3- [2- (2,6-dichlorobenzyloxy) -4- (6-methoxy-1-methyl-^-benzimidazol-2-ylmethoxyphenyl]- Propionate (Exemplified Compound Xin No. 1-9 7) (13 &) 3- [2- (2,6-dichlorobenzyloxy) -4-methoxymethoxy-phenyl] -propionic acid As the ethyl ester, ethyl 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionate (500 mg, ΐ · 966 mmol), potassium carbonate (815 mg, 5.889 Mol), 3,4-dichlorobenzyl chloride (576 mg, 2.949 mmol) and N, N-dimethylformamide (20 ml), the reaction was carried out according to the method of Example (1 d) and After treatment, the target compound (811 mg, yield 99%) can be obtained.

Ms (E I) m / z: 4 12 (M) +. U3b) 3-[2- (2, 6-dichlorobenzyloxy) -4-hydroxy-phenyl] -propionic acid ethyl ester 3-[2- (2, 6- Dichlorobenzyloxy) -4 -methoxymethoxyphenyl] -propionic acid ethyl ester (Hi mg, κ 962 halo), p-toluenesulfonic acid (82 mg) and ethanol (20 ml), -97- 200408628 The reaction and post-treatment were performed according to the method of Example (10) to obtain the target compound (724 mg, 100%). MS (E I) m / ζ: 3 6 8 (M) +. ) 3- [2- (2,6-dichlorobenzyloxy) -4- (6-methoxymethyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -ethyl propionate As the ester, ethyl 3- [2- (2,6-dichlorobenzyloxy) -hydroxy-phenyl] -propionate (724 mg, 1.962 mmol), 2-hydroxyl produced in Example (13b) was used. Methyl-6-methoxy-1-methyl-1H-benzimidazole (377 mg, 1.962 mmol), tributylphosphine (0.61 ml, 2.452 mmol), 1,1 '-(stack Nitrodicarbonyl) dipiperidine (618 mg, 2.452 mmol) and toluene (20 ml) were reacted and worked up according to the method of Example (1 f) to obtain the intended compound. (860 mg, yield 81%) ° MS (FAB) m / z: 5 4 3 (M + H) +. (1 3 d) 3-[2- (2, 6 -dichlorobenzyloxy)- 4. · (6-Methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] · propionate The 3-[2 produced in Example (13C) -(2, 6-dichlorobenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester ( 860 mg, 1.583 mmol), 1N sodium hydroxide (3.2 ml, 3.2 mmol), ethanol (4 ml) and tetrahydrofuran (4 ml). The reaction and post-treatment were carried out according to the method of Example (1 g) The target compound (820 mg, 95%) can be prepared. 1 Η-NMR (400 MHZ, DMS 0-d 6): δ ppm -98- 3 8 (2 Η, d, J = 7.6 Η ζ), 2, .6 3 (2 Η 9 d, 7.6 Η ζ), 3.90 (3 Η, s) 4 • 03 (3 Η, s), 5. 2 7 Η, s ), 5 .7 2 (2 Η, s), 6, • 7 7 (1 Η, dd 9 J = 2.2, 4 Η: ζ), 7 · 0 8 (1 Η, d, J = 2. 2 Hz), 7 • 13 (1 Η, d, 8. 4Ηζ), 7.18 (1 Η, dd, J = 2.2, 9. 0 Η ζ), 7.4 6-5 0 (1 Η, m), 7.54 (1 Η d, J = 2.2 Η ζ), 7. 5 8-6 9 (2 Η, m), 7 • 74 (1 Η, d J = 9. OH ζ) ° (Κ Β r): 16 9 6, 1 6 10, 1 5 0 2, 1 4 3 7, 12 2 7, 200408628 1216, 1196, 1177cm-1 9 MS (FAB) m / z : 515 (M + H) + HR-MS (FAB) m / z: C26H2505N2C1 (M + H) + Calculated 値: 5 1 5 · 1 1 4 1; Measured 値: 515.1120 ° (Example 1 4) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-phenethoxy-phenyl] -propionate (Exemplified Compound No. 1 -10 1) (14a) 3-(4-methoxymethoxy-2-phenethoxy-phenyl) -ethyl propionate ^ 3-(2-hydroxy- 4-methoxymethoxyphenyl) -ethyl propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889 mmol), 2-bromoethylbenzene (0.4 ml, 2.949 mmol) And N, N-dimethylformamide (20 ml), and reacted and worked up according to the method of Example (1 d) to obtain the target compound (338 mg, yield 48%). MS (EI) m / z: 3 5 8 (M) +. -99- 200408628 (14b) 3-(4-hydroxy-2-phenethoxy-phenyl) -dicarboxylic acid ethyl ester 3-(4-methoxymethoxy · 2) produced in Example (14a) -Phenethoxy-phenyl) -ethyl propionate (338 mg, 0.943 mmol), p-toluenesulfonic acid (40 mg) and ethanol (10 ml), according to Example (je) The reaction and post-treatment were carried out in this way to obtain the target compound (29.1 mg, 98%). MS (EI) m / z: 314 (M) +. (14c) 3- [4- (6-Methoxy-1-methyl-1H-benzimidyl DZ_2-ylmethoxy) -2-phenethoxy-phenyl] -propionate 3- (4-hydroxy-2-phenethoxy-phenyl) -propionic acid ethyl ester (291 mg, 0.925 mmol), 2-hydroxymethyl-6-produced in Example (14b) Methoxy-1-methyl-1fluorene-benzimidazole (178 mg, 0.925 mmol), tributylphosphine (0.29 ml, 1.156 mmol), 1,1 '-(azidodicarbonyl ) Dipiperidine (291 mg, 1.156 mmol) and toluene (10 ml). The reaction and post-treatment were carried out according to the method of Example (1 f) to obtain the target compound (38 2 mg, yield 8). 5%). MS (FAB) m / z: 4 8 9 (M + H) +. (14d) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-phenethoxy-phenyl] -propionate Using 3- (4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-phenylethoxy-phenyl] produced in Example (14c) · Ethyl propionate (382 mg, 0.782 mmol), 1N sodium hydroxide (1.6 ml, 1.6 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml), according to Example (1 g) The method was reacted and post-processed to obtain 200,408,628 to obtain the target compound (31 1 mg, 81%). 1 Η-NMR (400 MHz, DMS Ο-d 6): 5 ppm 2.32 (2 H, d, J = 7. 7 H z), 2.67 (2 H, d, J = 7.7 H z) , 3.05 (2H, d, J =: 6.4 Hz), 3.88 (3H, s), 3.97 (3H, s), 4.19 (2H, d, J = 6.4 Hz), 5.6 (2 H, s), 6.65 (1H, dd, J = 2.2, 8 .2 H z), 6.78 (1 H, d, J = 2.2 Hz), 7.07 (1H, d, J = 8. 2 H z), 7.14 (1 H, dd, J = 2.2, 8.9 H z), 7.19-7.23 (1 H,

m), 7.2 7-7.3 4 (4 H, m), 7.48 (1H, d, J = 2. 2 H z), 7.69 (1 H, d, J = 8.9 H z), 11.98- 12.05 ( 1 H, br) ° IR (KB r): 2 9 2 8, 1 7 2 0, 1 6 1 1, 1 5 0 2, 1 2 6 2, 1226, 1177 cm · 1 MS (FAB) m / z : 461 (M + H) + 〇HR-MS (FAB) m / z: C27H2905N2 (M + H) + Calculated 値: 4 6 1.2 0 7 6; Measured 値: 4 6 1 · 2 0 7 9

(Example 1 5) 3-[2- (4-ethylbenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -benzene Group] -propionate (exemplified compound number 1-7), and 3- [2- (2-ethylbenzyloxy) -4- (6-methoxy-bmethyl-1H-benzo) Imidazol-2-ylmethoxyphenyl] -propionate (Exemplified Compound Nos. 1-5) mixture (15a) 3-[2- (4-ethylbenzyloxy) -4 -methoxymethyl Example of using a mixture of ethyloxyphenyl] -ethyl propionate and 3- [2- (2-ethylbenzyloxy) -4-methoxymethoxyphenyl-101-200408628] -ethyl propionate (lc ) Ethyl 3-(2-hydroxy-4-methoxymethoxyphenyl) · propionate (500 mg, 1.966 mmol), Potassium carbonate (815 mg, 5.889 mmol), 4-B Mixture of benzyl bromide and 2-ethylbenzyl bromide (65 1 mg, 2. 949 mmol) and N, N-dimethylformamide (20 ml), according to Example (1 d) The reaction and post-treatment were carried out to obtain the target compound (621 mg, yield 78%). MS (EI) m / z: 3 7 2 (M) +. (15b) 3-[2-(4- Ethylbenzyloxy) · 4-hydroxyphenyl]- The mixture of ethyl acetate and _ 3-[2-(2-ethylbenzyloxy) -4 -hydroxyphenyl] -propionic acid ethyl ester was prepared using 3-[2- (4- Ethylbenzyloxy) -4 -methoxymethoxyphenyl] -propionic acid ethyl ester and 3- [2- (2-ethylbenzyloxy) -4 -methoxymethoxymethoxyphenyl] -propionic acid The mixture of ethyl ester (621 mg, 1.535 mmol), p-toluenesulfonic acid (62 mg) and ethanol (20 ml) were reacted and worked up according to the method of Example (1e) to obtain the target compound. (504 mg, 100%). _ MS (EI) m / z: 3 2 8 (M) +. (15c) 3-[2-(4-ethylpreoxy) -4 · (6-methoxy 1-methyl-1 -methyl-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester and 3- [2- (2-ethylbenzyloxy) -4-(6- The mixture of methoxy-1-methyl-1fluorene-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester was prepared using 3-[2-(4- Ethyl benzyloxy)--102- 200408628 4-ethyl 4-hydroxyphenyl] -propionate and 3- [2- (2-ethylbenzyloxy) -4 -hydroxyphenyl] -propionate Mixture (504 mg, 1.535 mmol), 2- Hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (295 mg, 1.535 mmol), tributylphosphine (0.48 ml, 1.919 mmol), 1, 1, (azido Dicarbonyl) dipiperidine (484 mg, 1.919 mmol) and toluene (20 ml) were reacted and worked up according to the method of Example (1 f) to obtain the target compound (732 mg, product Rate 95%) MS (FAB) m / z: 503 (M + H) +. (I5d) 3-[2- (4-ethylbenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl]- Propionate and 3-[2- (2-ethylbenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazole_2_ylmethoxy) -benzene The mixture of phenyl] -propionate was prepared using 3- (2- (4-ethylbenzyloxy) -4- (6-methoxy-1-methyl-1H-) produced in Example (15c). Benzimidazol-2-ylmethoxy) · phenyl] · ethyl acetate and 3- [2- (2-ethylbenzyloxy) -4- (6-methoxy · 1-methyl- 1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester mixture (732 mg, 1.456 millimoles), 1N sodium hydroxide (2.9 halo; l, 2.9 pens;旲 ear), ethanol (3 halo; liter) and tetrahydrofuran (3 ml), the reaction and post-treatment were carried out according to the method of Example (1 g) to obtain the target compound (585 mg, 76%). ^ H-NMR (400MHz, DMSO-dg): 5 ppm 1.15_1 · 21 (3H, m), 2.4 · 2 · 77 (6H, m), 3.89 200408628 (3 Η, s), 3.99 ( 1.8 Η, s), 4.00 (1.2 Η, s), 5.11 (1.2 Η, s), 5.13 (0.8 Η, s), 5.64 (1.2 Η, s), 5.66 ( 0.8 Η, s), 6.6 9-6.7 4 (1 Η, m), 6.88-6.96 (1 Η? M), 7.11-7.45 (6 Η, m), 7.50 (1 Η, d, J = 2 1 Η ζ), 7.70 (1 Η, d, J = 8.9 Hz). IR (ΚΒγ): 1 7 2 3, 1611, 1 5 0 2, 1 2 6 2, 1 2 2 5, 1174 cm-1 MS (FAB) m / ζ: 4 7 5 (Μ + Η) + HR- MS (FAB) m / z: C28H3105N2 (M + H) + Calculated 値: 4 7 5.2 2 3 3; Measured 47: 475.2215. (Example 16) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(3-phenylallyloxy) -benzene Group] -propionate (exemplified compound number 1-1 1 1) (16a) 3-[4-methoxymethoxy-2- (3-phenylallyloxy) -phenyl] -propionic acid As the ethyl ester, ethyl 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionate (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889) produced in Example (1c) was used. Millimoles), cinnamidine bromide (581 mg, 2.949 millimoles) and Ν, Ν-dimethylformamide (20 ml). The reaction and post-treatment were carried out according to the method of Example (1d). The title compound was obtained (709 mg, yield 97%). MS (E I) m / ζ: 3 7 0 (M) +. (1 6b) 3-[4-Hydroxy-2- (3-phenallyloxy) -phenyl] -ethyl-104-200408628 ester 3- [4 -A produced in Example (16a) Oxymethoxy- (3-phenallyloxy) -phenyl] -propionic acid ethyl ester (709 mg, i.914 mmol), p-toluenesulfonic acid (71 mg) and ethanol (20 ml), The reaction and post-treatment were performed according to the method of Example (1e) to obtain the target compound (354 mg, 57%). MS (EI) m / z: 3 2 6 (M) + o (16c) 3-[4- (6 -methoxy-1-methyl-1H -benzimidyl D--2-ylmethoxy) ) -2- (3-Phenylpropoxy) -phenyl] -propionic acid ethyl ester The 3- [4-hydroxy-2- (3-phenallyloxy) produced in Example (16b) is used -Phenyl] -ethyl propionate (354 mg, 1.085 mmol), 2-Methyl-6-methoxy-1-methyl-1H-benzozine (209 mg, 1.085 halo; Wu ear), dibutyl scales (0.34 halo; liter, 1.356 millimoles), 1,1'_ (azidodicarbonyl) dipiperidine (342 mg, 1.356 millimoles) and toluene (1 0 Ml), and the reaction and post-treatment were carried out according to the method of Example (1f) to obtain the target compound (428 mg, yield 79%). MS (FAB) m / z: 501 (M + H) +. (16d) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(3-phenallyloxy) -phenyl] -The propionate salt was prepared using 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (3 -Phenallyloxy) -phenyl] -ethyl propionate (428 mg, 0.855 mmol), 1N sodium hydroxide (1.7 ml, 1.7 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml), the reaction was carried out in accordance with the method of Example (1 g) and after-105 · 200408628, and the target compound (35.3 mg, 81%) was obtained. 1 Η-NMR (400 MHZ, DMS 〇-d6): δ ppm 2.46 (2Η, t, J = 7.6 Ηz), 2.79 (2H, t, J = 7.6Hz), 3.88 (3 H, s), 3.98 (3H, s), 4.78 (2 H, d, J = 5. 2 H z), 5.63 (2 H, s), 6.50-6.5 6 (1 H, m) , 6.70 (1H, dd, J = 2.2, 8.4Hz), 6.79 (1 H, d, J = 16. 0 H z), 6.86 (1H, d, J = 2.2 Hz), 7.12 -7.15 (2 H, m), 7.2 5-7.2 9 (1 H, m), 7.3 3-7.3 7 (2 H, m), 7.4 7-7.4 9 (3 H, m), 7.69 (1 H, d, J = 8.9 H z) o IR (KBr): 1 7 2 5, 1 6 1 1, 1 5 9 2, 1 5 0 2, 1 4 4 7, 1261, 1225, 1175 cm · 1 MS (FAB) m / z: 4 7 3 (M + H) + HR-MS (FAB) m / z: C28H2905N2 (M + H) + Calculated 値: 4 7 3.2 0 7 6; Measured 値: 4 7 3 · 2 0 8 4. (Example 17) 3- [2- (4-carboxybenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazole-2-ylmethoxy) -phenyl ] -Propionate (Exemplified Compound No. 1-66) (1 7 a) 3-[2- (4-methoxymethoxypreoxy) -4 -methoxymethoxy-phenyl] -propionic acid As the ethyl ester, 3- (2-hydroxy-4-methoxymethoxyphenyl) -propionic acid ethyl ester (500 mg, 1.96 mmol), potassium carbonate produced in Example (lc) was used. (815 mg, 5. 8 9 mmol), 4-methoxycarbonylbenzyl chloride (676 mg-106-200408628, 2.949 mmol) and N, N-dimethylformamide (20 ml) The reaction and post-treatment were carried out according to the method of Example (1d) to obtain the target compound (745 mg, yield 94%). MS (E I) m / z: 4 0 2 (M) +. (17b) 3- [4-Hydroxy-2- (4-methoxycarbonylbenzyloxy) -phenyl] -propionic acid ethyl ester The 3- [2- (4-methyloxy) produced in Example (17a) was used Carbonylbenzyloxy) -4 -methoxymethoxy-phenyl] -propionic acid ethyl ester (745 mg, 1.851 mmol), p-toluenesulfonic acid (75 mg) and ethanol (19 ml) according to implementation The method of Example (1e) was reacted and worked up to obtain the target compound (663 mg, 100%). MS (E I) m / z: 3 5 8 (M) +. (17c) 3- [2- (4-Methoxybenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -Ethyl propionate The 3- [4-hydroxy-2- (4-methoxycarbonylbenzyloxy) -phenyl] -propionic acid ethyl ester (663 mg, 1.851 mmol) produced in Example (17b) was used. ), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (356 mg, 1.851 mmol), tributylphosphine (0.58 ml, 2.314 mmol), 1, 1 (_Azidedicarbonyl) dipiperidine (583 mg, 2.314 mmol) and toluene (19 ml), according to the method of Example (1 f) @ θ & The target compound was obtained (850 mg, yield 86%). MS (FAB) m / z: 5 3 3 (M + H) +. (1 7 d) 3-[2- (4-carboxybenzyloxy) -4- (6-methoxy-1-methyl- -107- 200408628 1H -benzimidone-2-ylmethoxy Group) _phenyl] · bis-acid salt 3-[2- (4- (methoxy) benzyloxy) -4- (6-methoxy-1-methyl) produced in Example (17c) -Benzimidazole_2 • ylmethoxy) · phenyl] -propionic acid ethyl ester (422 mg, 0.792 mmol), sodium hydroxide (3.2 mL, 3.2 mmol), ethanol (3 ml) and tetrahydrofuran (3 ml) were reacted and worked up according to the method of Example (丨 g) to obtain the target compound (300 mg, 73%). 1 Η-NMR (400MHz, DMSO-d6): δ ppm 2.48 (2 Η, t, J = 7. 5 Η ζ), 2.80 (2 Η, t, J = 7. 5 Η ζ), · 3 · 88 (3Η, s), 3.97 (3Η, s), 5.26 (2Η, s), 5.61 (2 Η, s), 6.72 (1Η, dd, J = 2. 3, 8 .4 Η ζ), 6.86 (1 Η, d, J = 2.3 Η ζ), 7.11-7.15 (2 Η, m), 7.45 (1 Η, d, J = 2. 1 Η ζ), 7.57 (2 Η, d, J = 8. 2 Η ζ), 7.68 (1 Η, d, J = 8.9 Η ζ), 7.95 (2 Η, d, J = 8. 2 Η ζ). IR (ΚΒγ): 2 9 3 4, 1 7 0 4, 1611, 1 5 0 3, 1 2 6 2, 1225, 1175cm-1 Φ MS (FAB) m / ζ: 491 (Μ + Η) + HR-MS (FAB) m / ζ : C27H2707N2 (Μ + Η) + calculated 値: 4 9 1 · 1 8 1 8; measured 实: 4 9 1.1 8 3 0. (Example 1 8) 3- [2- (4-Isopropylbenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazole · 2-ylmethoxy) -benzene Group] -propionate (exemplified compound number 1-10), and 3- [2- (2-isopropylbenzyloxyH (6-methoxy-108-200408628) -1-methyl-1H -Benzimidazole · 2-ylmethoxy) -phenyl] -propionate (Exemplified Compound No. 1-8) (18a) 3-[2-(4-isopropylbenzyloxy) -4 -methoxymethoxy-phenyl] -ethyl propionate and 3- [2- (2-isopropylbenzyloxy) -4 -methoxymethoxy-phenyl] -propionic acid ethyl ester The mixture was prepared using Example (3- (2-hydroxy-4-methoxymethoxyphenyl) -ethyl propionate (500 mg, 1.966 mmol) manufactured by 10, potassium carbonate (815 mg, 5.889 mmol) Mol), a mixture of 4-isopropylbenzyl chloride and 2-isopropylbenzyl chloride (553 mg, 2.949 mmol) and N, N-dimethylformamide (20 ml), according to the examples (1 d) The reaction and post-treatment were carried out to obtain the target compound (574 mg, yield 76%). MS (EI) m / z: 3 8 6 (M) +. (18b) 3-[2 -(4-isopropyl Example of a mixture of oxy) -4 · hydroxy-phenyl] -ethyl propionate and 3- [2- (2-isopropylbenzyloxy) -4-hydroxy-phenyl] -propionic acid ethyl ester (18a) 3- [2- (2- (4-isopropylbenzyloxy) -4-methoxymethoxy-phenyl] -propionic acid ethyl ester and 3- [2- (2-isopropyl) Benzyloxy) mixture of 4-methoxymethoxy-phenyl] -propionic acid ethyl ester (574 mg, 1.485 mmol), p-toluenesulfonic acid (57 mg) and ethanol (15 ml), The reaction and post-treatment according to the method of Example (1e) were performed to obtain the target compound (508 mg, 100%). MS (E I) m / ζ: 3 4 2 (M) +. (1 8 c) 3-[2- (4-Isopropylbenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid Ethyl-109- 200408628 and 3-[2- (2-isopropylpropyloxy) -4- (6-methoxy-I-methyl-1H-benzimidazol-2-ylmethoxy) -Phenyl] -ethyl propionate was used in the mixture of 3- [2- (4- (isopropylbenzyloxy) -4-hydroxy-phenyl] -propionic acid ethyl ester and 3 prepared in Example (18b)). -[2-(2-isopropylbenzyloxy) -4 -hydroxy-phenyl -Mixture of ethyl propionate (508 mg, 1.485 mmol), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (285 mg, 1.485 mmol) , Tributylphosphine (0.46 ml, 1.856 mmol), 1,1,-(azidodicarbonyl) dipiperidine (468 mg, 1.856 mmol) and toluene (15 ml), according to Example (1 f ) Method to carry out the reaction and post-treatment to obtain the target compound (763 mg, yield 99%). MS (FAB) m / z: 517 (M + H) + 〇 (18d) 3- (2- (4-isopropylbenzyloxy) -4- (6-methoxy-1-methyl-1H -Benzimidazol-2-ylmethoxy) -phenyl] -propionate and 3- [2- (2-isopropylbenzyloxy) -4- (6-methoxy-1- A mixture of methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionate hydrochloride was prepared using 3- [2- (4-isopropylbenzyloxy) produced in Example (18c). Phenyl) -4- (6 · methoxy-1-methyl-1H-benzimidazole · 2-ylmethoxy) -phenyl] · propionic acid ethyl ester and 3, [2- (2 -iso Propylbenzyloxy) -4-(6 · methoxy-1-methyl_1H-benzimidazol-2-ylmethoxy) _phenyl] -propionic acid ethyl ester mixture (763 mg, 1.477 Millimolar), 1N sodium hydroxide (3ml, 3mmol), ethanol (3ml), and tetrahydrofuran 110- (3ml), the reaction was performed according to the method of Example (1g), and after After treatment, the target compound (61 1 mg, 79%) < D 1 H-NMR (400MHz, DMS 0 ·: (5 ppm 1.1 9-1.22 (6 ，, m), 2.39- 2.4 8 (2 Η, m), 2.6 8-2.7 7 (2Η, m), 2 · 83-2.93 (1 Η, m), 3.88 (3 Η, s), 3.98 {2,1 〖Η, s), 3. 9 9 (〇 · 3 H, s), 5.11 (1.8 Η, s), 5. 1 3 (0.2 Η, s), 5 · 6 1 (1.8 H, s), 5. 6 4 (0.2 Η, s), 6.68-6. 7 3 (1 H, m), 6.88 (〇. 9 Η , S), 6.9 B (0.1 Η, s), 7.11.-7.48 (7 H, m), 7.6 (9 1, d, J = 8. .9 Η ζ). IR (KB r): 2 9 6 0, 1 7 1 2, 16 11, 1502, 1 2 6 2, 12 2 ί 4, 117 4, 8 2 1 cm'1 MS (FAB) m / z: 4 8 9 (Μ + Η) + HR-MS (FAB) m / ζ: C 2 9 Η 3 3 0 5 Ν 2 (M + H) + Calculated 値: 489.2389; Measured 9: 4 8 9 .240 ι 9 〇 ( Example 1 9) 3-[2-(3,5 -dimethoxybenzyloxy) -4-(6 -methoxy-1 -methyl-1 fluorene -benzimidazole-2 -ylmethoxy ) -Phenyl] -propionate (exemplified compound number 1-100) 200408628 (1 9a) 3-[2- (3, 5-dimethoxybenzyloxy) -4 -methoxymethoxy- Phenyl] -ethyl propionate 3-(2-hydroxy-4-methoxymethoxyphenyl) -ethyl propionate (500 mg, 1.966 mmol) prepared in Example (lc) was used ), Potassium carbonate (815 mg, 5.889 mmol), 3,5 · dimethoxybenzyl bromide (718 -111- 200408628 mg, 2.949 mmol), and n, N-dimethylformamide (20 ml) 'The reaction and post-treatment were carried out according to the method of Example (1 d) to obtain the target compound (659 mg, yield 83%). MS (E I) m / z: 4 0 4 (M) +. (19b) 3- [2- (3, 5-dimethoxybenzyloxy) -4-hydroxy-phenyl] -propionic acid ethyl ester 3-[2- (3, 5-Dimethoxybenzyloxy) -4 · methoxymethoxy-phenyl] -propionic acid ethyl ester (659 mg, 1.629 mmol), p-toluenesulfonic acid (66 mg) and ethanol (17 ml ), According to the method of Example (1e), the reaction and post-treatment are performed to obtain the target compound (587 mg, 100%). MS (EI) m / z: 3 6 0 (M) + 〇 (19c) 3-[2-(3, 5-dimethoxybenzyloxy): 4- (6-methoxy-l-methyl -1H -benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[2- (3, 5-dimethoxybenzyloxy)- 4-hydroxy-phenyl] -propionic acid ethyl ester (587 mg, 1.629 mmol), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (313 mg, 1.629 mmol Mol), tributylphosphine (0.51 ml, 2.036 mmol), 1,1 '-(azidodicarbonyl) dipiperidine (513 mg, 2.036 mmol) and toluene (17 ml), according to The reaction and post-treatment in the method of Example (if) can obtain the target compound (7 1 3 mg, yield 8 2%). MS (FAB) m / z: 5 3 5 (M + H) +. • 112 · 200408628 (19 (1) 3- [2- (3,5-Dimethoxybenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-yl (Methoxy) -phenyl] -propionate

Using 3- [2- (3, 5-dimethoxybenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-yl) produced in Example (19c) (Methoxy) -phenyl] -ethyl propionate (713 mg, 1.334 mmol), 1N sodium hydroxide (2.7 ml, 2.7 mmol), ethanol (3 ml), and tetrahydrofuran ( 3 ml), followed by reaction and post-treatment according to the method of Example (1 g), to obtain the target compound (731 mg, 100%). H-NMR (400MHz, DMSO-d6) · δ ppm 2.48 (2H, t, J = 7.6 H z), 2.79 (2 H, t, J = 7.6 H z), 3.74 (6H, s ), 3.88 (3 H, s), 2.97 (3 H, s), 5.10 (2 H, S), 5.60 (2 H, s), 6.4 4 (1 H, t, J = 2.1 Hz), 6.62 (2H, d, J = 2.1Hz), 6.71 (1H, dd, J = 2.2, 8.2Hz), 6.85 (1H, d, J = 2.2Hz), 7.13 ( 1 H, dd, J = 2.2, 8. 2 H z), 7.14 (1 H, d, J = 8. 2 Hz), 7.46 (1 H, d, J = 2.2 H z), 7.68 (1 H,

d, J = 8.9 H z). IR (KB r): 1718, 1 6 0 8, 1 5 9 6, 1 5 0 3, 1 4 5 9, 1430, 1262, 1225, 1204, 1180, 1157 cm'1 MS (FAB) m / z: 5 0 7 (M + H) + HR-MS (FAB) m / z: C28H3107N2 (M + H) + Calculated 値: 5 0 7. 2 1 3 1; Measured 値: 5 0 7.2 1 2 9 (Example 20) -113- 200408628 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-trifluoromethoxy Benzyloxy) -phenyl] -propionate (Exemplified Compound Numbers 1-2 0) (20a) 3-[4-methoxymethoxy-2- (4-trifluoromethoxybenzyloxy) -Phenyl] -ethyl propionate 3-(2-hydroxy-4-methoxymethoxyphenyl) -ethyl propionate (500 mg, 1.966 mmol), carbonic acid produced in Example (lc) was used. Potassium (815 mg, 5.889 mmol), 4-trifluoromethoxybenzyl bromide (752 mg, 2.949 mmol) and N, N-dimethylformamide (20 ml), according to Example (1 d) The reaction and post-treatment are carried out to obtain the target compound (830 mg, yield 98%). MS (EI) m / z: 4 2 8 (M) + o (2 0 b) 3-[4-hydroxy-2- (4-trifluoromethoxybenzyloxy) -phenyl] -propionic acid ethyl ester Using 3- [4-methoxymethoxy-2- (4-trifluoromethoxybenzyloxy) -phenyl] -propionic acid ethyl ester (830 mg, 1.937 mmol) produced in Example (20a) Moore), p-toluenesulfonic acid (83 mg) and ethanol (20 ml) were reacted and worked up according to the method of Example (1e) to obtain the target compound (744 mg, 100%). MS (E I) m / z: 3 8 4 (M) +. (20c) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-trifluoromethoxybenzyloxy) -phenyl ] -Ethyl propionate The 3- [4-hydroxy-2- (4-trifluoromethyl-114- 200408628 oxybenzyloxy) -phenyl] -ethyl propionate (744 Mg, 1.937 mmol), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (372 mg, 1.937 mmol), tributylphosphine (0.6 ml, 2.421 Mol), 1,1, _ (azidodicarbonyl) dipiperidine (610 mg, 2.421 milli-ears) and toluene (20 ml). The reaction and post-treatment were carried out according to the method of Example (If). The title compound (1.04 g, 96% yield) was obtained. MS (FAB) m / z: 559 (M + H) +. (2〇d) 3-[4-(6-methoxy-1-methyl-1H-benzimidazole-2 -ylmethoxy) -2-(4-trifluoromethoxybenzyloxy)- Phenyl] -propionate was prepared using 3- (4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2 produced in Example (20c). -(4-trifluoromethoxybenzyloxy) -phenyl] -propionic acid ethyl ester ([034 g, 1.851 mmol), 1N sodium hydroxide (3.7 ml, 3.7 mmol), ethanol (4 Ml) and tetrahydrofuran (4 ml) 'according to the method of Example (1 g) and post-treatment to obtain the target compound (899 mg, 88%) ° 1H-NMR (400MHz, DMSO-d6) : 5 ppm 2.46 (2H, t, J = 7.6 H z), 2.77 (2 H, t, J = 7.6 Hz), 3.87 (3H, s), 3.94 (3H, s), 5.19 (2H, s ), 5.55 (2H, s), 6.71 (1H, dd, J = 2.2, 8.3Hz), 6.86 (1 H, d, J = 2.2 Hz), 7.07 (1H, dd, J = 2.2, 8.8 Hz), 7.13 (1H, d, J = 8. 3 Hz), 7.38-7.60 (3H, m), 7.59 (2H, d, J = 8.6Hz), 7.65 (1H, d, -115- 200408628 J = 8. 8 Η z), 12.06-12.09 (1 Η, br). IR (KBr): 1715, 1613, 1 5 0 5, 1 2 6 2, 1221, 1198, 117 1 cm * 1 MS (FAB) m / z: 531 (M + H) + HR-MS (FAB) m / z: C27H2606N2F3 (M + H) + Calculated 値: 5 3 1.1 7 4 3; Measured 値: 5 3 1.1 7 4 7. (Example 2 1) 3- [4- (6-methoxy-i-methyl-1H_benzimidazolylmethoxy) -2- (4-vinylbenzyloxy) -phenyl] -propyl Hydrochloride (Exemplified Compound Nos. 1-5 4) (21a) 3- [4-methoxymethoxy-2- (4-vinylbenzyloxy) -phenyl] -propionic acid ethyl ester Usage Examples ( 1 c) 3-(2-hydroxy-4-methoxymethoxyphenyl) -propionic acid ethyl ester (500 mg, 1.966 mmol), potassium carbonate (815 mg, 5.889 mmol), 4 -Vinyl benzyl chloride (0.42 ml, 2.949 mmol) and N, N-dimethylformamide (20 ml). The reaction and post-treatment were carried out according to the method of Example (1 d). The title compound was obtained (728 mg, 99% yield). MS (E I) m / z: 3 7 0 (M) +. (21b) 3- [4-Hydroxy-2- (4-vinylbenzyloxy) -phenyl] -propionic acid ethyl ester The 3- [4-methoxymethoxy-2 produced in Example (2la) was used. -(4-vinylbenzyloxy) -phenyl] -propionic acid ethyl ester (728 mg, 1.965 mmol), p-toluenesulfonic acid (73 mg) and ethanol (20 ml) in accordance with -116- 200408628 The method of Example (1e) was reacted and worked up to obtain the target compound (641 mg, 100%). MS (EI) m / z: 3 2 6 (M) + 〇 (2 1 c) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) ) -2- (4-Ethylbenzyloxy) -phenyl] -propionic acid ethyl ester The 3- [4-ethynyl-2- (4-ethenylbenzyloxy) -benzene produced in Example (21b) was used. Yl] -ethyl propionate (641 mg, 1.965 mmol), 2-hydroxymethyl-6-methoxy-1-methyl-1H-benzimidazole (378 mg, 1.965 mmol), three Butylphosphine (0.62 ml, 2.456 mmol), 1,1 '_ (azidodicarbonyl) dipiperidine (619 mg, 2.456 mmol) and toluene (20 ml), according to Example (1 f) The reaction and post-treatment were performed in this way to obtain the target compound (947 mg, yield 96%). MS (FAB) m / z: 501 (M + H) +. (2 1 d) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-vinylbenzyloxy) -phenyl] -The propionate salt was produced using the 3- (4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(4 -Vinylbenzyloxy) -phenyl] -ethyl propionate (947 mg, 1.892 mmol), 1N sodium hydroxide (3.8 ml, 3.8 mmol), ethanol (4 ml) and tetrahydrofuran (4 ml ), According to the method of Example (1 g), the reaction and post-treatment can be performed to obtain the target compound (809 mg, 85%). 1H-NMR (400MHz, DMSO-d6): 5 ppm 2.46 (2 Η, t, J = 7.6 Η z), 2.77 (2 H, t, J = 7.6 H z), 3.88 (3 H, s), 3.97 (3 H, s), 5.15 (2 H, s), • 117- 5. 2 7 (1 Η, d, J = 1 1.1Hz), 5., 60 (2H, s), 5.84 (1 Η, d, J: = 17.6 Hz), 6.69-6. 7 7 (2H, m), 6.87 (1 Η, d, J: = 2. 3Hz), 7.10-7.1 3 (2H, m), 7.42- 7. 4 9 (5 H, m), 7.68 (1 H, d, J =: 8.9Hz), 1 2.10- 200408628 12.14 (1 Η, br). IR (KB r): 17 2 1, 1611, 1 5 0 2, 1291, 1261, 1223, 1173, 8 2 8 cm " 1 MS (FAB) m / z: 4 7 3 (M + H) + HR-MS (FAB) m / z: C28H2905N2 (M + H) + Calculated 値: 4 7 3.2 0 7 6; Measured 値: 473.2084. (Example 2 2) 3- [2- (biphenyl-4-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxybenzene Group] -propionate (exemplified compound number 1-9 3) (22a) 4-benzyloxy-2 -methoxymethoxybenzaldehyde Alkyl 2,4-dihydroxybenzaldehyde (20 g, 0.14 mo Ear) dissolved in dichloromethane (200 ml), added N, N-diisopropylethylamine (55 ml, 0.319 mole) and benzyl bromide (18.8 ml, 0.158 mole), and stirred at room temperature for 4 days After the reaction solution was concentrated, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. (Eluent: hexane / ethyl acetate = 5/1), 4-benzyloxy-2-hydroxybenzaldehyde (22.3 g, yield 68%) can be obtained. The obtained 4-benzyloxy-2- Hydroxybenzaldehyde (22.3 g, 0.0979 mol) was dissolved in dichloromethane (150 ml) -118-200408628, and N, N-diisopropylethylamine (51.2 ml, 0.147 mol) and chloroform Methyl ether (22.3 ml, 0.293 mol), stirred overnight at room temperature After the reaction solution was concentrated, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography. (Eluent: hexane / ethyl acetate = 5/1), the target compound (26.65 g, yield 99%) can be obtained. 1 Η-NMR (4 0 0 MHZ, CDC 1 3): 5ppm 3.51 (3 Η, s), 5.11 (2 Η, s), 5.26 (2 Η, s), 6.68 (1 Η, dd, J = 2.2, 8.7 H z), 6.80 (1H, d, J = 2. 2 H z), 7.3 3-7.4 4 (5 H, m), 7.82 (1 H, d, J = 8. 7 H z), 10.33 (1H, s) ° MS (El) m / z: 2 7 2 (M) +. (22b) Ethyl 3-(4-benzyloxy-2-methoxymethoxyphenyl) acrylate dissolves diethylphosphoacetic acid diester (21.95 g, 0.0979 mol). To tetrahydrofuran (100 ml), add sodium hydride (60%, 3.92 g, 0.09 7.9 mol) at zero degrees, and stir at room temperature for 1 hour. Add 4-benzylbenzene produced in Example (22a) Tetrahydrofuran (loo ml) of oxy-2-methoxymethoxybenzaldehyde (26.65 g, 0.0979 mol), heated below For 4 hours. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 5/1) to obtain the target compound (32.17 g, yield 9 6%). -119- 200408628 AH-NMR (400 MHz, CDC13): 5 ppm 1.33 (3H, t, J = 7. 3 H z), 3.49 (3H, s), 4.25 (2H, q, J = 7. 3 H z), 5.07 (2 H, s), 5.22 (2 H, s), 6.39 (1H, d, J = 16.5Hz), 6.63 (1H, dd, J = 2 2 8.7Hz), 6.81 (1 H, d, J = 2.2 Hz), 7.31-7.47 (6 H, m), 7.95 (1 H, d, J = 16.5Hz) MS (FAB) m / z: 3 4 3 (M + H) +. (22c) 3- (4-hydroxy-2-methoxymethoxyphenyl) -ethyl propionate The 3- (4-benzyloxymethoxymethoxyphenyl) acrylic acid ethyl ester produced in Example (22b) The ester (32.17 g, 0.094 mole) was dissolved in ethyl acetate (200 ml), and a catalytic amount of palladium hydroxide was added, followed by stirring at hydrogen and room temperature for 1 day. After the catalyst was filtered through diatomaceous earth, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2/1) to obtain the target compound (22.8 g, product Rate 95%). 1 Η-NMR (400 MHZ, CDC 1 3): δ ρ ρ m 1.24 (3 Η, t, J = 7. 3 Η ζ), 2.56 (2 Η, t, J = 8. 0 Η ζ), 2. 8 7 (2H, t, J = 8. 0 H z), 3 · 4 7 (3 Η, s), 4, .12 (2 Η, q, J = 7.3 H z) , 4.76 (1 Η, s), 5.17 (2 Η, s), 6. 3 9 (1 Η, dd, J = 2.2, 8.0Hz), 6 • 62 (1 Η, d, J : 2. 2 H z), 6.9 9 (1 H, d, J = 8 • 0 H z). M s (El) m /: B: 254 (M) + < (2 2d) 3- [2 -methoxymethoxy-4- (6-methoxy-1 -methyl-1 fluorene-benzimidazole-2-ylmethoxy) -phenyl] -propionic acid ethyl ester Example ( 22c) 3- (4-hydroxy-2-methoxymethoxyphenyl 200408628) -ethyl propionate (15.13 g, 0.0095 mole) and 2-hydroxymethyl-6-methoxy -1-Methyl-1H-benzimidazole (ιι · 44 g, 0.0595 mole) was dissolved in toluene (500 ml), and tributylphosphine (18.5 ml, 0.0744 mole) was added and 1,1 '-(azido Dicarbonyl) dipiperidine (18.74 g, 0.074 mol), and stirred at room temperature overnight. The reaction solution was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/2) to obtain g of the compound (23.26 g 'yield 9 1%) o 1 Η -N MR ( 4 0 0 ΜΗζ, CD Cl3): δ P pm 1.2 2 (3 Η, t, J = 7. 3 Η ζ), 2.5 5 (2 H, t, J = 8. 0 Hz), 2. 8 7 (2 Η, t, J = 8. OH z), 3.46 (3 H, s), 3.83 (3 Η, s), 3.88 (3 Η, s), 4.1 1 (2 H, t, J = 7.3 Hz), 5.17 (2 Η, s), 5.3.1 (2 H, s), 6 • 66 (1 H, dd, J = 2.2, 8.8 Η ζ), 6.79 (1 H, d, J = 2.2 Hz), 6.82 (1 Η, d, J = 2.2 Η ζ) 6.91 (1 H, dd, J = 2.2, 8.8 Η ζ), 7.06 (1 Η, d, J = 8.8 Η z), 7.64 (1 H, d, J = 8.8 Η ζ). MS (FAB) m / z: 429 (M + H) +. (22e) 3- [2-Hydroxy-4- (6-methoxyj-methyl_1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester Example ( 22d) 3- [2-methoxymethoxy-4 · (6 · methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid produced Ethyl acetate (23.36 g, 0.0543 mol) was dissolved in ethanol (100 ml), 4N hydrochloric acid-1,4-dioxane solution (100 ml) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction solution was concentrated, it was neutralized with a saturated sodium bicarbonate aqueous solution -121- 200408628. It was extracted with ethyl acetate, and the organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained crystals were washed with diisopropyl ether and dried under reduced pressure to obtain the target compound (18.65 g, yield 89%). 1 Η-NMR (400 MHz, CDC 1 3): 5 ppm 1.22 (3 H, t, J = 7. 3 H z), 2.65 (2 H, t, J = 6.6 H z), 2.84 (2H, t, J = 6.6Hz), 3.79 (3H, s), 3.87 (3H, s), 4.13 (2 H, q, J = 7. 3 H z), 5.23 (2 H, s), 6.53 (1 H, dd, J = 2.2, 8.0 Hz), 6.63 (1H, d, J = 2.2 Hz), 6 · 7 7 (1 H, d, J = 2.2 H z), 6 · 8 9 (1 H, dd, J = 2.2, 8.8 Hz), 6.97 (1 H, d, J = 8. 〇 H z), 7.59 (1 H, d, J = 8. 8 H z ), 8.63 (1H, br). (22f) 3- [2- (biphenyl-4-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl ] -Ethyl propionate 3-[2 -hydroxy-4-(6 -methoxy-1-methyl-1H -benzimidazol-2-ylmethoxy) produced in Example (2 2 e) ) -Phenyl] -ethyl propionate (400 mg, 1.041 mmol) was dissolved in N, N-dimethylformamide (10 ml), potassium carbonate (431 mg, 3.123 mmol) was added and 4 -Benzyl bromide (386 mg, 1.562 mmol), stirred overnight at room temperature. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in this order, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1) to obtain the target compound (478 mg, yield 83% 200408628 MS (FAB) m / z: 551 (M + H) +. (22g) 3-[2- (biphenyl-4 -ylmethoxy) -4-(6-methoxy-1 -methyl-1H-benzimidazole -2-Methoxyphenyl] -propionate The 3- [2- (biphenyl-4-ylmethoxy) -4- (6-methoxy group) produced in Example (22f) -1-Methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (473 mg, 0.868 mmol) dissolved in ethanol (2 ml) and tetrahydrofuran (2 ml) The mixed solution was added with a sodium hydroxide aqueous solution (1.8 ml, 1.8 mmol) and stirred at room temperature overnight. After the reaction solution was concentrated, 1N hydrochloric acid and ethyl acetate were added and stirred. It was washed with water and ether. The target compound (446 mg, 93%) was obtained by drying under reduced pressure. 1 Η-NMR (4 0 0 MHZ, DMS Ο-d 6): 5ppm 2.49 (2 Η, t, J = 7.6 Η z), 2.79 (2 H, t, J = 7.6 Hz), 3.87 (3 H, s), 3.97 (3H, s), 5.2 2 (2H, s), 5.62 (2H, s), 6.71 (1H, dd, J = 2.2, 8.2Hz), 6.91 (1H, d, J = 2.2Hz), 7.10- 7.15 (2H, m), 7.3 5-7.3 9 (1 H, m), 7.4 5-7.4 9 (3 H, m), 7.55 (2H, d, J = 8. 1 H z), 7.6 6-7.6 9 (5 H, m) 〇IR (KB r): 1716, 1612, 1 5 0 2, 1261, 1 2 2 3, 1173 cm'1 MS (FAB) m / z: 5 2 3 (M + H) + HR-MS (FAB) m / z: C32H3105N2 (M + H) + Calculated 値: 5 2 3 · 2 2 3 3; Measured 値: 5 2 3.2 2 2 4 ° -123- 200408628 (Example 2 3) 3- [4- (6-Methoxyμ-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-styrenebenzyloxy) -phenyl] -propionic acid Salt (Exemplified compound number 1-9 6) (23a) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-benzene Ethylbenzyloxy) -phenyl] -propionic acid ethyl ester 3- (2-hydroxy-4- (6-methoxy-1-methyl-1H-benzimidazole) produced in Example (22e) 2-ylmethoxy) -phenyl] -propionic acid ethyl ester (400 mg, 1.041 mmol), potassium carbonate (431 mg, 3.123 mmol), 4-styrene benzyl bromide (427 Mg , 1.562 millimoles) and N, N -dimethylformamide (10 ml). The reaction and post-treatment were carried out according to the method of Example (22f) to obtain the target compound (4.99 mg, yield 7). 6%). MS (FAB) m / z: 5 7 7 (M + H) + o (23b) 3-[4- (6-methoxy-i-methyl-1H-benzimidazol-2-ylmethoxy) ) -2- (4-styrenebenzyloxy) -phenyl] -propionate hydrochloride The 3- [4- (6 · methoxy-1-methyl-1H) produced in Example (23a) was used. -Benzimidyl-2-phenylmethoxy) -2- (4-phenylethenyloxy) _phenyl] -propionic acid ethyl ester (459 mg, 0.796 mmol), 1N hydroxide Sodium (1.6 ml, 1.6 mmol), ethanol (2 ml), and tetrahydrofuran (2 ml) were reacted and worked up according to the method of Example (22 g) to obtain the target compound (57 mg, 1 0 0%). 1 Η-NMR (400 MHZ, DMS 〇-d 6): (5 ρ ρ m • 124- 200408628 2.4 8 (2 Η, t, J: = 7. 6 H: B), 2 · 7 8 (2 H, t, J = 7.6 Hz), 3. 8 8 (3 Η, s), 3.99 (3 H, s), 5.18 (2 H, s), 5. 6 4 (2 Η, s), 6., 71 (1 H, dd, J = 2.2, 8.3 Hz), 6.8 9 (1 Η, d, J = 2.2 Hz), 7.13-7. 16 (2 H, m), 7. 2 6-• 7.29 (3 H, m), 7.37- 7.40 (2 H, m), 7.4 5-7.5 0 (3 Η, m), 7 .59 -7.69 (4 H, m), 7 · 7 1 (l H, d,. J = 4. 7 Η z) ° IR (Κ Β r):: 17 15, 1 6 1 2, 1 5 0 3, 12 6 1, 1 2 2 7, 11 6 9, 115 3 cm -1 MS (FAB) m / z:: 5 4 9 (M + H) + HR -U [S (FAB) m / z: C 3 4 H 3 3 O 5 N 2 (M + H) + Calculated 値: 5 4 9.23 8 9; Found 値: 5 4 9., 2392 〇

(Example 24) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-methylbenzyloxy) -phenyl ] -Propionate (Exemplified Compound Nos. 1-4)

(2 4 a) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-methylbenzyloxy) -phenyl ] -Ethyl propionate 3-[2 -hydroxy-4-(6 -methoxy-methyl-1H-benzimidazole-2 -ylmethoxyphenyl) produced in Example (2 2 e) ] -Ethyl propionate (400 mg, 1.041 mmol), potassium carbonate (431 mg, 3.123 mmol), 4-methylbenzyl bromide (289 mg, 1.562 mmol) and N, N -di Methylformamide (10 ml) was reacted and worked up according to the method of Example (2 2 f) to obtain the target compound (-125 · 200408628 410 mg, yield 81%). MS (FAB) m / z: 4 8 9 (M + H) +.

(2 4 b) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-methylbenzyloxy) -phenyl ] -Propionate using 3-[4-(6 · methoxy-1 -methyl-1H -benzimidazol-2-ylmethoxy) -2 produced in Example (2 4 a) -2 -(4-methylbenzyloxy) -phenyl] -propionic acid ethyl ester (410 mg, 0.839 mmol), 1N sodium hydroxide (1.7 ml, 1.7 mmol), ethanol (2 ml ) And tetrahydrofuran (2 ml), and reacted and worked up according to the method of Example (2 2 g) to obtain the target compound (381 mg, 92%). 1 Η-N M R (4 0 0 Μ H z, D M S 〇-d 6): δ ρρ m

2. 3 0 (3 H, s), 2.4 5 (2 H, t, J = 7.6 Hz), 2.74 (2 Η, t, J = = 7.6 Hz),, 3 · 8 8 (3 H, s), 3.97 (3 H, s), 5. 1 0 (2 H, s), 5 • 60 (2H, s) 6.68 (1 H, dd, J = 2.2, 8 · 3 H z), 6. 8 6 (1 H, d, J: = 2. 2 H z), 7.1 1-7. 1 4 (2 H, m), 7 • 18 (2 H, d , J = 7. 9 H z), 7.34 (2 Η, d, J = 7.9 H z), 7.47 (l H, d, J = 2.0 Hz), 7. 6 8 (1: H, d, J = 8. 8 H z) o IR (KB r): 2 S) 2 3 ′, 1 7 2 3, 16 11, 1502, 1 4 4 6, 12 9 1, 1 2 6 2, 1 2 2 7, 1 17 1,1 12 2 cm · 1 MS (FA B) m / z: 4 6 1 (M + H) + HR -MS (FAB) m / z: C 2 7 H 2 9 0 5 N 2 (M + H) + Calculated 値 ·· 4 6 1., 2 丨 0 7 6; Measured 値:: 461.207 6 ° (Example 2 5) • 126- 200408628 3-[2-(4-chlorobenzyloxy) Group) -4- (6-methoxy-1-methyl-1H-benzimidazole-2-ylmethoxy) -phenyl] .- propionate (exemplified compound number 1-30) ( 2 5 a) 3-[2- (4-chlorobenzyloxy) -4- (6-methoxy-1 -methyl-1H-benzimidyl -2 -Methylmethoxy) -phenyl] · propionic acid ethyl ester 3-[2 -hydroxy-4-(6 -methoxy-i -methyl-1H) produced in Example (2 2 e) -Benzimidazole-2-ylmethoxy) -phenyl] -ethyl propionate (2 g, 5.203 mmol), potassium carbonate (2.157 g, 15.608 mmol), 4-chlorobenzyl chloride ( 1.26 g, 7.805 mmol) and Ν, Ν-dimethylformamide (50 ml), followed by reaction and post-treatment according to the method of Example (2 2 f), to obtain the target compound (1.28 g , Yield 48%). MS (FAB) m / z: 509 (M + H) +. (25b) 3- [2- (4-chlorobenzyloxy) -4- (6-methoxy-1-methyl-1fluorene-benzimidazol-2-ylmethoxy) -phenyl] -prop As the hydrochloride salt, 3 · [2- (4-chlorobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-yl) produced in Example (25a) was used. (Methoxy) -phenyl] -ethyl propionate (1.28 g, 2.515 mmol), 1N sodium hydroxide (5.1 ml, 5.1 pen moles), ethanol (5 ml), and tetrahydrofuran (5 ml ), According to the method of Example (2 2 g) and reaction and post-treatment, the target compound (729 mg, 94%) can be obtained. 1 H-NMR (400 MHZ, DMS 〇-d6): 5 ppm 2.45 (2H, t, J = 7.6 Hz), 2.76 (2H, t, J = 7.6 H z), 3.88 (3H, s), 3.96 (3H, s), 5.16 (2H, s), -127- 200408628 5.58 (2 Η, s), 6.70 (1 Η? dd, J = 2.2 , 8. 3 Η ζ), 6.85 (1 Η, d, J = 2. 2 Η ζ), 7.09-7.12 (2 Η, m), 7.14-7.50 (5 Η, m), 7.67 (1 Η, d , J = 8.8Hz). IR (Κ Β r): 1 7 2 4, 1 6 1 1, 1, 5 0 2, 1 2 6 3, 1 2 2 8, 1168 cm-1 MS (FAB) m / ζ: 481 (Μ + Η) + HR-MS (FAB) m / z: C26H2605N2C1 (M + H) + Calculated 値: 4 8 1. 1 5 3 0; Measured 値: 4 8 1.1 5 3 1. (Example 2 6) φ 3-[2- (4-difluoromethoxybenzyloxy) -4- (6-methoxy-l-methyl-1H-benzimidazol-2-ylmethoxy) ) -Phenyl] -propionate (exemplified compound number 1-2 1) (26a) 3-[2-(4-difluoromethoxybenzyloxy) -4-(6 -methoxy-1 -Methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[2 -hydroxy-4-(6 -methyl) produced in Example (2 2 e) Oxy-b methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -ethyl propionate (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol) ), 4-difluoromethoxybenzyl bromide (278 mg, 1.17 mmol) and N, N-dimethylformamide (8 ml), the reaction was carried out in accordance with the method of Example (2 2 f), and after After treatment, the target compound was obtained (362 mg, yield 86%). MS (FAB) m / z: 541 (M + H) +. (2 6b) 3-[2- (4-difluoromethoxybenzyloxy) -4- (6-methoxy-1- -128- 200408628 methyl-1H -benzimidazol-2-ylmethoxy (Phenyl) -phenyl] -propionate, using 3- (2- (4-difluoromethoxybenzyloxy) -4- (6-methoxy-1-methyl) produced in Example (26a) -1H-benzimidazol-2-ylmethoxy) -phenyl J-ethyl propionate (362 mg, 0.67 mmol), 1N sodium hydroxide (1.4 ml, 1.4 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml) were reacted and worked up according to the method of Example (2 2 g) to obtain the target compound (32 2 mg, 91%). 1 Η-NMR (400 MHZ, DMS Ο-d 6): δ ppm · 2.44 (2 Η, t, J = 7.6 Η ζ), 2.74 (2 Η, t, J = 7.6 Η ζ), 3.84 (3 Η, s), 3.85 (3 Η, s), 5.12 (2 Η, s), 6.67 (1 Η, dd, J = 2.2, 8. 3 Η ζ), 6.82 ( 1 Η, d, J = 2.3 Η ζ), 6.92 (1 Η, dd, J = 2.3, 8.8 Η ζ), 7.09 (1 Η, d, J = 8.3 Η ζ), 7.19 (2 Η, d, J = 8. 6 Η ζ), 7.23 (1 Η, d, J = 2. 2 Η ζ), 7.25 (1 Η, t, J = 7 4. 1 Η ζ), 7.51 (2Η, d, J = 8. 6 Η ζ), 7.57 (1 Η, d, J = 8 · 8 Η ζ), 1 2 · 0 6 (1 Η, br). _ IR (KBr): 1710, 1 6 1 3, 1 5 1 0, 1 2 5 9, 1 2 2 2, 1171, 1123, 1030, 820 cm'1 MS (FAB) m / z: 513 (M + H) + HR-MS (FAB) m / z: C27H2706N2F2 (M + H) + Calculated 値: 5 1 3.1 8 3 7; Measured 値: 5 1 3 · 1 8 3 4. (Example 2 7) 3- [2- (4-bromobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzo-129-200408628 imidazol-2-ylmethoxy ) -Phenyl] -propionate (Exemplified Compound No. 1-33) (2 7 a) 3-[2- (4-O-octyloxy) -4- (6 · methoxy-1-methyl -Yl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3- (2-hydroxy-4- (6-methoxy-1) produced in Example (22e) -Methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol), 4-Bromobenzyl bromide (293 mg, 1.17 mmol) and N, N-dimethylformamide (8 ml) were reacted and worked up according to the method of Example (22f) to obtain the target compound. (395 mg, yield 92%). MS (FAB) m / z: 5 5 3 (M + H) +. (27b) 3- [2- (4-Bromobenzyloxy) -4- (6-methoxy-1-methyl · 1H-benzimidazol-2-ylmethoxy) -phenyl] -propyl The hydrochloride was prepared using 3-[2-(4-bromobenzyloxy) -4-(6-methoxy-1-methyl-1H -benzimidazole-2) produced in Example (2 7 a). -Ylmethoxy) -phenyl] -ethyl propionate (395 mg, 0.714 mmol), sodium hydroxide (1.5 ml, 1.5 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml ) 'According to the method of Example (22 g), the reaction and post-treatment are performed to obtain the target compound (300 mg, 76%). Η-NMR (400 MHZ, DMS Ο-d6): δ 2.45 (2 Η, t, J =: 7.6 Hz), 2.75 (2 H, t, J = 7 · 6 Hz), 3.86 (3 Η, s), 3.89 (3 H, s), 5.12 (2 H, s), 5.47 (2 Η, s), 6.68 (1 H, dd, J = 2.2, 8.2 Hz),- 130- 200408628 6.82 (1 Η, d, J = 2.2 Η ζ)? 7.00 (1 Η, dd, J = 2.2, 8 · 8Η ζ), 7.11 (1 Η, d, J = 8. 2 Η ζ), 7.32 (1 Η, d, J = 2.2 Η ζ), 7.42 (2Η, d, J = 8.2Hz), 7.57-7.62 (3Η, m), 12.05-12.06 (1 Η, br). IR (Κ Β r): 1 7 2 4, 1 6 1 2, 1, 5 0 3, 1 2 9 0, 1261, 1223, 1171, 1121, 1011 cm'1 MS (FAB) m / z: 5 2 4 (M + H) + HR-MS (FAB) m / z: C 2 6 H 2 5 O 5 N 2 B r Na (M + Na) + Calculated 値: 547.0845; Measured 値: 547.0836. (Example 2 8) 3-[2- (4-iodobenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxyphenyl]- Propionate (Exemplified Compound No. 1-36) (2 8 a) 3-[2- (4-iodobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzo) Imidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[2 -hydroxy-4-(6 -methoxy-1-methyl- 1H-Benzoyl-2-oxo-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol), 4-iodobenzyl Bromide (348 mg, 1.17 mmol) and N, N-dimethylformamide (8 ml) were reacted and worked up according to the method of Example (22f) to obtain the target compound (4 2 0 Mg, yield 90%). MS (FAB) m / z: 601 (M + H) + 〇 (28b) 3- [2- (4-iodobenzyloxy) -4 · (6-methoxy 1-methyl- • 131- 200408628 1H -benzimidazol-2-ylmethoxy) -phenyl] -propionate salt 3-[2- (4- Iodobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy ) -Phenyl-propionic acid ethyl ester (420 mg, (K 6 99 mmol), 1 N sodium hydroxide (1.4 ml, 1.4 mmol), ethanol (2 ml) and Tetrahydrofuran (2 ml) was prepared according to the method of Example (2 2 g): the reaction and post-treatment were performed to obtain the target compound (366 mg, S! 7%) ο 1 Η-NMR (4 0 0 Μ : Η ζ, D Μ S 0-d 6): 5 ppm 2. 4 5 (2 Η, t, J = 7.6 Η ζ), 2. 7 6 (2 H, t, J = 7.6 Η ζ), 3. 8 8 (3 Η, s), 3.95 (3 Η, S), 5. 1 2 (2 H, s), 5. 5 7 (2 Η, s), 6.70 (1 Η, dd , J = 2.3, 8. 4 Η ζ), 6. 8 4 (1 Η, d, J = 2. 3 Η ζ), 7. 10 (1 H, dd, J = 2.1, 8. 9 Η ζ), 7. 12 (1 Η, d, J = 8. 4 H; O, 7. 27 (2 Η, d, J =: 8. 2 Η ζ), 7.43 (1 Η, d, J: = 2. 1 Η z), 7.66 (1 Η,

d, J = 8.9 H z), 7.7 3-7.7 6 (2 Η, m), 12.04-12.05 (1 Η, b r) 〇

IR (KBr): 1717, 1612, 1503, 1261, 1227, 1171, 1152, 1123, 1 0 2 3, 1 0 0 6 cm'1 MS (FAB) m / z: 5 7 3 (M + H) + HR-MS (FAB) m / z: C26H2605N2I (M + H) + Calculated 値: 5 7 3.0886; actual 湏! (値: 573.0901. (Example 2 9) 3-[2-(4-fluorobenzyloxy ) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxyphenyl] -propionate (Exemplified Compound No.-132- 200408628 1-27) ( 29a) 3- [2- (4-fluorobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid As the ethyl ester, 3-[2 -hydroxy-4-(6 -methoxy-1 · methyl-1H -benzimidazol-2-ylmethoxy) -phenyl produced in Example (2 2 e) was used. ] -Ethyl propionate (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol), 4-fluorobenzyl bromide (0.15 ml, 1.17 mmol) and N, N- Dimethylformamide (8 ml) was reacted and worked up according to the method of Example (22f) to obtain the target compound (277 mg, yield 72%). MS (FAB) m / z : 4 9 3 (M + H) +. (2 9 b) 3-[2- (4 -fluorooxygen ) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxyphenyl] -propionate, manufactured using Example (2 9 a) 3 -[2-(4-fluorobenzyloxy) -4-(6-methoxy-1 -methyl-1 hydrazone-benzimidazole-2-ylmethoxy) -phenyl) -ethyl propionate (277 mg, 0.562 mmol), 1 N sodium hydroxide (1.2 ml., 1.2 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml) according to the examples (2 2 g) by reaction and post-treatment to obtain the target compound (229 mg, 86%). 1 Η-NMR (400 MHz, DMSO-d6): (5 ppm 2. 4 4 (2Η, t, J = 7.6Hz), 2. 74 (2 Η, t, J = 7,6Hz), 3 · 8 5 (3 Η, s), 3.88 (3 Η, s), 5.11 ( 2 H, s), 5 · 4 4 (2Η, S), 6.68 (1 Η, dd, J = 2.2, 8.. 2 Η z), 6 · .83 (1 Η, d, J = 2. 2 Η ζ), 6.96 (1 H, dd,, J = 2.2, -133- 200408628 8. 8 Η z), 7.10 (1 Η, d, J = 8.2 Η ζ), 7.18-7.25 (2Η, m), 7.28 (1 Η, d, J = 2.2 Η ζ), 7.48-7.52 (2 , M), 7.59 (1 Η, d, J = 8. 8 Η ζ), 12.00-12.10 (1 Η, b r). IR (Κ Β r): 1710, 1610, 1511, 1 2 8 7, 1 2 5 9, 1222, 1172, 1157, 1122, 1029, 824 cm " 1 MS (FAB) m / ζ: 4 6 5 (Μ + Η) + HR-MS (FAB) m / z: C 2 6 H 2 5 O 5 N 2 FN a (M + N a) + Calculate 値: 4 8 7 · 1 6 4 5; Measured 値: 4 8 7.1 6 4 9 ° (Example 30) 3-[2-(4-benzyloxybenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazole-2 -Ylmethoxyphenyl] -propionate (exemplified compound number 1-2 4) (3 0 a) 3-[2-(4-benzyloxybenzyloxy)-4- (6 -methoxy -L-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester produced using the 3- (2-Ethyl-4- (6) produced in Example (22e) -Methoxy-1-methyl-iH-benzimidazol-2-ylmethoxy) -phenyl] -ethyl propionate (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 Millimoles), 4-benzyloxybenzyl bromide (273 mg, 1.17 millimoles) and Ν, Ν-dimethylformamide (8 ml) were performed according to the method of Example (2 2 f) Reaction and post-treatment to obtain the target compound (409 mg, yield 90% ). MS (FAB) m / ζ: 581 (Μ + Η) + 〇 (3 0 b) 3-[2-(4-benzyloxybenzyloxy) -4- (6-methoxy-1-methyl -134- 200408628 1H -benzimidazol-2-ylmethoxy) -phenyl] -propionate, which was produced using 3-[2 · (4-benzyloxybenzyloxy) produced in Example (30a) Methyl) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (409 mg, 0.704 mmol), 1N Sodium hydroxide (1.4 ml, 1.4 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml) were reacted and worked up according to the method of Example (2 2 g) to obtain the target compound (3 4 0 mg, 83%).

1 Η-NMR (400 MHZ, DMS Ο-d 6): δ ppm 2.44 (2 Η, t, J = 7.6 Η ζ), 2.73 (2 Η, t, J = 7.6 Η ζ), 3.87 (3Η, s), 3.95 (3 Η, s), 5.06 (2 Η, s), 5.10 (2 Η, s), 5.56 (2 Η, s), 6.68 (1 Η, dd, J = 2. 4, 8 .4 Η ζ), 6.86 (1 Η, d, J = 2.4 Η ζ), 7.00- 7.03 (2 Η, m), 7.07-7.1 1 (2 Η, m), 7.31 -7.46 (8 Η, m), 7.66 (1 Η, d, J = 8.8Hz). I R (ΚΒγ): 1 7 0 6, 1612, 1511, 1 5 0 3, 1 4 5 4, 1293, 1243, 1225, 1173, 1122, 1024 cm'1

MS (FAB) m / ζ: 5 5 3 (Μ + Η) + HR-MS (FAB) m / ζ: C33H3306N2 (Μ + Η) + Calculated 値: 5 5 3 · 2 3 3 9; Measured 値: 5 5 3.2 3 4 1. (Example 31) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-methylsulfanylbenzyloxy) -benzene Group] -propionate (exemplified compound number 1-9 0) (3 1 a) 3-[4-(6-methoxy-1-methyl-1H-benzimidazole-2-ylmethyl- 135-200408628oxy) -2- (4-methylsulfanebenzyloxy) -phenyl] -propionic acid ethyl ester 3-[2-hydroxy-4-(6 -Methoxy-i-methyl-1H-benzimidazole-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol Mol), 4-methylsulfanyl benzyl bromide (0.18 ml, 1.17 mmol) and N, N-dimethylformamide (8 ml), the reaction was carried out according to the method of Example (2 2 f) and After treatment, the target compound (374 mg, yield 92%) can be obtained. MS (FAB) m / z: 521 (M + H) +. · (3 1 b) 3-[4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-methylsulfanylbenzyloxy)- Phenyl] -propionate was prepared using 3- (4- (6-methoxy-1 -methyl-1H-benzimidazole-2-ylmethoxy) produced in Example (3 1 a). -2- (4-methylsulfane benzyloxy) -phenyl-propionic acid ethyl ester (3 74 mg, 0.718 mmol: ear), IN sodium hydroxide (1.5 ml, 1.5 mmol) ), Ethanol (2 ml) and tetrahydrofuran (2 ml), the reaction and post-treatment can be carried out according to the method of Example (22 g), to obtain the target compound (38 mg, 90%:) °! H -NMR (4 0 Μ Η z, DMS 0-d 丨 6): δ ρ pm 2.4 5 (2 Η, t, J = 7.6 Η ζ)? 2 • 47 (3 H, s), 2.75 ( 3 Η 9 t, J = 7.6 .6 Η z), 3.88 (3 Η, s), 3.9 7 (3 H, s), 5. 1 1 (2 Η, s), 5.60 (2 Η, s ), 6 · 6 9 (1 H, dd, J = 2.4, 8. 3 Η ζ), 6.86 (1 Η, d, J = 2.4 H z), 7 .11- 7. 1 3 ( 2 Η, m), 7.26 (2 Η, d, J = i 5. 2 Η z), 7.40 -136- 20040 8628 (2 Η, d, J = 8. 2 Η ζ), 7.46 (1 Η, d, J = 2.1 Η ζ), 7.68 (1 Η, d, J = 8.9 Hz). IR (ΚΒγ): 1 7 2 5, 1 7 0 7, 1611, 1 5 0 2, 1441, 1295, 1261, 1226, 1174, 1123, 1093 cm'1 MS (FAB) m / z: 4 9 3 ( Μ + Η) + Η R-Μ S (FAB) m / z: C27H2905N2S (M + H) + Calculated 値: 4 9 3.1 7 9 7; Measured 値: 4 9 3. 1 8 2 6. (Example 3 2) 3-[2-(4-Methanesulfonylbenzyloxy) -4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy)- Phenyl] -propionate (Exemplified Compound Nos. 1-8 7) (3 2 a) 3-[2- (4-Methanesulfonylbenzyloxy) -4- (6-methoxy-1- Methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[2 -hydroxy-4-(6 -methoxy) produced in Example (2 2 e) Methyl-1-methyl-1H -benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol) , 4-methanesulfenylbenzyl bromide (240 mg, 1.17 mmol) and N, N-dimethylformamide (8 ml), the reaction and post-treatment were performed according to the method of Example (2 2 f), The target compound was obtained (371 mg, yield 86%). MS (FAB) m / ζ: 5 5 3 (Μ + Η) +. (32b) 3-[2- (4-Methanesulfonylbenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -Propionate salt-137- 200408628 3-[4-(6 -methoxy-1 -methyl-1H -benzimidazol-2-ylmethoxy) produced using Example (3 2 a) ) -2- (4-methylsulfane benzyloxy) -phenyl] · propionic acid ethyl ester (371 mg, 0.671 mmol), 1N sodium hydroxide (1.4 ml, 1.4 mmol), ethanol ( 3 ml) and tetrahydrofuran (3 ml), and the reaction and post-treatment were carried out according to the method of Example (2 2 g) to obtain a giant compound (349 mg, 94%). 1 Η-NMR (4 0 Μ [Hz, DMS 0-d 6): 5 ppm 2. 4 8 (2 Η, t, J = 7.6 Hz), 2. 8 1 (2 H, t, J = 7 6 Ηζ), 3. 2 3 (3 Η, s), 3. 8 8 (3 Η, s), '5.96 (3 Η, s), 5. 3. 0 (2 Η, s), 5.5 9 (2 Η, S) '6 .7 3 (1 Η, dd, J = 2.2, 8. 2 Η: ζ), 6.8 7 (1 Η, d, J = = 2.2. 2 Η ζ), 7.12 (1 Η, dd, J = 2.2, 8.9 Η ζ), 7.15 (1 Η, d, J = 8. 2 Η ζ), 7, .4 6 (1 Η, d, J =: 2. 2 H ζ), 7.68 (1 Η, d, J = 8.9 Η ζ) 9 7.7 3 (2 Η, d, J =: 8. 3 Η ζ), 7.96 (2 Η, d , J = 8. 3 Η ζ) 〇IR (Κ Β r): 1 6 13, 1 5 0 3, 12 9 6, 1262, 1 2 2 9, 11 82, 1147, 1 12 9, 1091 cm -1 Μ; S (F Α Β) m > f ζ: 5 2 5 (Μ + Η) + HR-MS (FAB) m / ζ: C 2 7 Η 2 9 0 7 N 2 S (Μ + Η) + Calculated fluorene: 525.1695 • 'Measured fluorene: 5 2 5.1 7 2 8 0 (Example 3 3) 3-[4-(6 -methoxy-1 -methyl-1 fluorene -benzimidazole-2-ylmethyl) (Oxy) -2- (Naphthalene-2 -ylmethoxy) -phenyl) -propionate (exemplified compound number 1-104) -138- 200408628 (3 3 a) 3-[4- (6 -methoxy -L-methyl-1H-benzimidazol-2-ylmethoxy) -2- (danaphth-2-ylmethoxyphenyl] -propionic acid ethyl ester produced using Example (22e) 3- [2-Hydroxy-4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol Ear), potassium carbonate (324 mg, 2.341 mmol), 2-naphthyl benzyl bromide (270 mg, 1.17 mmol), and N, N -dimethylformamide (8 ml), as per implementation The reaction (2 2 f) and reaction and post-treatment can be used to prepare the target compound (281 mg, yield 69%). · MS (FAB) m / z: 5 2 5 (M + H) +. (33b) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy)-2- (dannaphthalene-2 -ylmethoxy) -phenyl ] -Propionate Use 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (produced in Example (33a)) Naphthalene-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (281 mg, 0.536 mmol), 1N sodium hydroxide (1 ml, 1 mmol), ethanol (1 ml), and Tetrahydrolufuran (1 ml) was reacted and worked up according to the method of Example (2 2 g) to obtain the target compound (268 mg, 94%). 1 Η-NR (4 0 0 MHZ, DMS Ο-d 6): (5 ρ ρ m 2.49 (2 Η, t, J = 7. 6 Η ζ), 2.82 (2Η, t, J = 7 6 Η ζ), 3.88 (3 Η, s), 3.97 (3 Η, s), 5.34 (2 Η, s), 5.61 (2 Η, s), 6.71 (1 Η, dd, 2.4, 8.4 Η ζ), 6.94 (1 Η, d, J = 2.4Hz), 7.12 (1 Η, dd, J = 2.4, -139- 8.9Hz), 7.15 (1 H, d, J = 8. 4 H z) , 7.46 (1 H, d, J = 2.4Hz), 7.51-7.5 5 (2 H, m), 7.58-7. 6 0 (1 H, m), 7.68 (1 H, d, J = 8.9 Hz), 7.9 0-7. 9 6 (3 H, m), 8.00 (1H, s). IR (KB r): 1725, 1 6 11, 1 5 0 2, 12 9 2 1 2 6 2 , 200408628 1225, 1176, 829 cm'1 MS (FAB) m / z: 4 9 7 (M + H) + HR-MS (FAB) m / z: C30H29O5N2 (M + H) + Calculate: 4 9 7 · 2 Ο 7 6; Actual measurement: 4 9 7.2 0 6 7. (Example 3 4) 3-[2- (4-ethoxybenzyloxy) -4- (6-methoxy-1- Methyl · 1Η-benzimidazol-2-ylmethoxy) -phenyl] -propionate (exemplified compound number 1 _ 1 9) (34a) 3- [2-(4 -ethoxybenzyloxy ) -4-(6-methoxy-1-methyl -1H -benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester [3-hydroxy-2- (6-methoxy-1- Methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol), 4 -Ethoxybenzyl chloride (399 mg, 1.17 mmol) and N, N-dimethylformamide (8 ml). The reaction and post-treatment were carried out according to the method of Example (22f) to obtain the target compound. (401 mg, 99% yield). MS (FAB) m / z: 519 (M + H) +. (3 4b) 3-[2-(4-ethoxybenzyloxy) -4-(6-methoxy-1-methyl- -140- 200408628 1H -benzimidazol-2-ylmethoxy) -Phenyl] -propionate was prepared using 3-[2-(4-ethoxybenzyloxy) _ 4-(6-methoxy-1-methyl-1H- Benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (401 mg, 0.773 mmol), 1N sodium hydroxide (1.6 ml, 1.6 mmol), ethanol (2 Ml) and tetrahydrofuran (2 ml), and the reaction and post-treatment were carried out according to the method of Example (22 g) to obtain the target compound (349 mg, 87%). ] H-NMR (400MHz, DMSO-d6): 5 PP m 1 · 3 2 (3 H, t, J = 7 · 3 H z), 2 · 4 3 (2 H, t, J = 7 · 6 H z), · 2.72 (2H, t, J = 7.6 H z), 3.87 (3 H, s), 3.93 (3H, s), 4.01 (2 H, q, J = 7.3 H z), 5.04 (2H, s), 5.53 (2H, s), 6.67 (1H, dd, J = 2.2, 8.0Hz), 6.85 (1H, d, J = 2.2Hz), 6.91 (2H, d , J = 8.8 H z), 7.05 (1 H, dd, J = 2.2, 8. 8 H z), 7.09 (1 H, d, J = 8. 0 H z), 7.36 (2H, d, J = 8.8 H z), 7.38 (1 H, d, J = 2.2 H z), 7.64 (1H, d, J = 8 · 8 H z), 1 2 · 0 6 (1 H , Br). ® IR (KB r): 1713, 1612, 1512, 1 5 0 3, 1291, 1246, 1229, 1172, 1118, 822 cm * 1 MS (FAB) m / z: 491 (M + H) + HR-MS (FAB) m / z: C28H3106N2 (M + H) + Calculated 値: 4 9 1 · 2 1 8 2; Measured 値: 4 9 1.2 2 0 5 ° (Example 3 5) 3-[2- (4- Ethylamine benzyloxy) -4- (6-methoxy-1-methyl-1H- -141- 200408628 benzimidin-2-ylmethoxy) -phenyl] · propionic acid (exemplified Compound No. 1-81) (3 5 a) 3-[2- (4- (acetamidobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-yl (Methoxy) -phenyl] -propionic acid ethyl ester The 3- [2-hydroxy (6-methoxy-1-methyl-1H-benzimidazole-2-ylmethyl) produced in Example (22e) was used. (Oxy) -phenyl] -ethyl propionate (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol), 4-acetamidine benzyl chloride (215 mg, mmol) Ear) and Ν, Ν-dimethylformamide (8 ml), the reaction and post-treatment were carried out according to the method of Example (2 2 f), to obtain the target compound (318 mg, yield 77%). MS (FAB) m / z: 5 3 2 (M + H) +. (3 5 b) 3-[2- (4- (Ethylamine) oxy) -4- (6-methoxy-l-methyl-1H-benzimidazol-2-ylmethoxy) -benzene Group] -propionic acid 3-[2- (4- (acetamidobenzyloxy) -4-(6-methoxymethyl-1H • benzimidazole — I-methyl) produced in Example (35a) (Oxy) _ phenyl] -ethyl propionate (318 mg, 0.598 mmol), iN sodium hydroxide (1.2 ml, 1.2 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml), according to The method of Example (22 g) was used for reaction and post-treatment to obtain the target compound (218 mg, 72%). Η-NMR (400 MHZ, DMS Ο-d6): 5 ρ ρ m 2.04 (3 Η, s), 2.44 (2 Η, t, J = 7.3 Η ζ), 2.73 (2Η, t, J = 7 · 3 Η ζ), 3. 8 4 (3 Η, s), 3.86 (3 Η, s), 5.04 (2 Η, s), 5.41 (2 Η, s), 6 • 65 (1 Η, dd, • 142 · J = 2 • 2, 8.0 Hz), 6.82 (1 Η 9 d, J = 2.2 Hz), 6 .9 4 (1 Η, dd, J = = 2.2, 8 · 8 Η ζ), 7.08 (1 Η d, J = 8.8 Η z), 7.24 (1 H, d, J = 2, .2 Η ζ), 7.37 (2H, d, J = 8.8 H z ), 7.56-7.5 9 (3 Η, m), 9.99 (1 Η, s), 12.0 4 (1 H,, br) ° IR (KB r): 1686, 160 9, 1 5: 3 6, 15 15 , 15 〇4, 14 0 9, 1 2 6 0, 1 2 18, 117 1 cm _ 1 MS (FAB) m / z: 5 0 4 (M + Η) + HR-MS (FAB) m / z: C 2 8 Η 3 0 0 6 Ν 3 (IV [+ Η) + calculated 値: 5 0 4. 2 13 5; found: 5 0 4. 2] [4 6 〇 (Example 3 6) 3- [ 4- [6- (4.-Amino-3,5-dimethyl-phenoxy) -1 -methyl_1 fluorene-benzimidazole-2 -ylmethoxy] -2 -. (4-methoxy-benzyloxy) -phenyl] -propionic acid (Exemplified Compound No. 1-1 8 5) (36a) 3- [4-[6_ (4_ Amine. 3,5_ Dimethyl Phenoxy) · 1-methyl-1H-benzimidazol-2-ylmethoxy] -2-methoxymethoxy-phenyl] -ethyl propionate 200408628 Manufactured in Reference Example 3 Of [6- (4-amino-3, 5-dimethyl-phenoxy) -b methyl-1H-benzimidazol-2-yl] -methanol (0.84 g), 3- (4-hydroxy -2-methoxymethoxy-phenyl) -propionic acid ethyl ester (0.60 g), 1,1 '-(azidodicarbonyl) dipiperidine (0.71 g) dissolved in anhydrous toluene (40 ml ) 'Add tri-n-butylphosphine (0.70 ml) and stir at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/2) to obtain the target compound (1.17 g). -143- 200408628 1 Η-NMR (4 0 0 Μ Η z, CDC 1 3): δ ppm 1.22 (3 Η, t, J = 7. 3 Η z), 2.13 (6 H, s), 2.51 (2 H, t, J = 8.1 Hz), 2.83 (2 H, t, J = 8.1 Hz), 3.42 (3 H, s), 3.72 (3 H, s), 4.08 (2H, m), 5.13 (2H, s), 5.25 (2H, s), 6.61 (1H, d, J = 2. 9 Hz), 6.63 (1H, d, J = 2. 2 Hz), 6.64 (2 H, s ), 6.79 (1 H, dd, J = 2.2, 8.8 H z), 6.92 (1H, dd, J = 2.9, 8.8 H z), 7.01 (1 H, d, J = 8. 8 H z), 7.61 (1 H, d, J = 8 · 8 H z). ⑩ (3 6 b) 3-[4-[6-(4_amino_3,5 -dimethylphenoxy) _1_methyl-1H -benzimidazol-2-ylmethoxy] -2 -(4-methoxy-benzyloxy) -phenyl] -propionic acid ethyl ester 3-[4-[6-(4 -amino-3,5- Dimethyl-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2-methoxymethoxy-phenyl] -propionic acid ethyl ester (1.17 g) was dissolved in Ethanol (20 ml), 4N hydrochloric acid-1,4-dioxane (20 ml) was added, and the mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and the resulting residue was extracted with ethyl acetate, washed with a saturated sodium bicarbonate aqueous solution, saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue (0.98 g) was dissolved in anhydrous N, N-dimethylformamide (30 ml), and potassium carbonate (0.83 g) and 4-methoxybenzyl chloride ( 0.41 ml), stirred at room temperature for 2.5 hours, and then stirred at 6 (TC for 1 hour. The solvent was evaporated under reduced pressure. The resulting residue was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (-144- 200408628 谷 Liquid · Kein / ethyl acetate = 1/3) to obtain the target compound (0.93 g) 1 Η-NMR (4 〇 0 Μ H z, CDC 1 3): ^ ρ ρ mi · 15 (3Η, t, J = 7.3Hz), 2.06 (6Η, s), 2.45 (2Η, t, J = 7.8Hz), 2.78 (2 Η, t, J = 7.8 Η z), 3.65 (3H, s), 3.70 (3 H, s), 4.02 (2 H, q, J = 7.8 H z), 4.86 (2H, s), 5.19 (2H, s), 6.49 (1H, dd, J = 2.2, 8.1Hz), 6.56 (1H, d, J = 2.2Hz), 6.58

(2H, s), 6.73 (1H, d, J = 2.2 Hz), 6.79 (2H, d, J = 8. 8 Hz), 6 · 8 6 (1 H, dd, J = 2 · 2, 8 · 8 H z), 6 · 9 5 (1H, d, J = 8. 1 H z), 7.23 (2H, d, J = 8. 8 H z), 7.55 (1 H, d, J = 8.8 H z), 7.91 (1 H, s). (36c) 3-[4-[6-(4-amino-3,5 · dimethyl · phenoxy) · ι · methyl-1Η-benzimidazole-2-ylmethoxy] -2 -(4-methoxy-benzyloxy) -phenyl] -propionic acid

The 3-[4-[6-(4-amino-3,5-dimethyl-phenoxy) -1-methyl-1H -benzimidazole-2 produced in Example (3 6 b) -Ylmethoxy] -2- (4-methoxy-benzyloxy) -phenyl] -propionic acid ethyl ester (0.93 g) and potassium hydroxide (0.43 g) were dissolved in methanol (20 ml) and water (10 ml), 1,4-dioxane (8 ml), and stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the obtained residue was extracted with water and acidified with hydrochloric acid. Ethyl acetate was added to the obtained suspension, and the mixture was washed with ultrasonic waves, and then collected by Shen Dian. The obtained Shen Dian was re-sinked from ethanol / ethyl acetate to obtain the target compound (0.8 g). 1 Η-NMR (400 MHz, CDC 1 3): δ ppm -145- 200408628 2.31 (6H, s), 2.44 (2 Η, t, J = 7.6 Η z), 2.73 (2H, t, J = 7.6 Hz), 3.76 (3H, s), 3.91 (3H, s), 5.06 (2H, s), 5.56 (2H, s), 6.68 (1H, dd, J = 2.2, 8.2.2 Hz), 6.79 (2H, s), 6.86 (1H, d, J = 2.2Hz), 6.94 (2H, d, J = 8.8Hz) , 7.10-7.14 (2H, m), 7.38 (2 H, d, J = 8.8 H z), 7.54 (1H, d, J = 2.0 Hz), 7.77 (2 H, d, J = 8.8Hz). (Example 3 7) 3-[4-[6-(3-Isopropylamino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2-(4- Methoxy-benzyloxyphenyl] -propionic acid (exemplified compound number 1-1 7 7) (37a) 3- [4--[6- (3-isopropylamino-phenoxy) -1-methyl -1H-benzimidazol-2-ylmethoxy] -2-methoxymethoxy-phenyl] -propionic acid ethyl ester [6-(3-isopropylamino-phenoxy) produced in Reference Example 4 Yl) -1-methyl-1H-benzimidazol-2-yl] -methanol (716 mg), 3- (4-hydroxy-2-methoxymethoxy-phenyl) -ethyl propionate (487 Mg), 1,1'_ (azidodicarbonyl) dipiperidine (580 mg), tri-n-butylphosphine (0.57 ml), anhydrous toluene (25 ml), the reaction was performed according to the method of Example (36a) After treatment, the target compound (1.1 g) was obtained. 〇 1 Η-NMR (400 MHz, CDC 1 3): δ p pm 1.18 (6H, d, J = 6.6Hz), 1.26 (3 H, t , J = 7. 3 H z), 2.66 (2H, t, J = 7. 7 H z), 2.88 (2 H, t, -146- 200408628 J = 7. 7 Η z), 3.46 (3 Η, s), 3.5 3-3.6 0 (1 Η, m), 3.80 (3 Η , s), 4.09-4.15 (2 Η, m), 5.18 (2 Η, s), 5.31 (2 Η, s), 6.23 (1 Η, d, J = 2.2 Η z), 6.28 (1H, dd, J = 2.2, 8.1 Hz), 6.31 (1H, dd, J = 2.2, 8.1 Hz), 6.67 (1H, dd, J = 2.9, 8.8 H z), 6.83 (1 H, d, J = 2. 9 H z), 6.99-7.10 (4 H, m), 7.69 (1 H, d, J = 8.8 Hz).

(3 7 b) 3-[4- [6-(3- Isopropylamino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-methyl Oxy-benzyloxy) -phenyl] -ethyl propionate

3-[4-[6-(3 -isopropylamino-phenoxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] produced in Example (3 7 a)- 2-methoxymethoxy-phenyl] -propionic acid ethyl ester (1.1 g), 4N hydrochloric acid-1,4-dioxane (10 ml), ethanol (10 ml), 4-methoxybenzyl chloride (0 · 29 ml), sodium hydride (55%, 79 mg), anhydrous N, N · dimethylformamide (20 ml), the reaction and post-treatment were carried out according to the method of Example (3 6 b), The target compound (960 mg) can be obtained. 1 Η-NMR (400 MHZ, CDC 1 3): δ pp m 1.14 (6H, d, J = 5.9 Hz), 1.22 (3H, t, J = 7.3 Hz), 2.51 (2H, t, J = 7.9 H z), 2.84 (2 H, t, J = 7.9 H z), 3.4 8-3.5 6 (1 H, m), 3.74 (3 H, s) , 3.7 7 (3 H, s), 4.08 (2 H, q, J = 7. 3 H z), 4.93 (2 H, s), 5.27 (2 H, s), 6.18 (1 H, d, J = 2. 2 H z), 6.24 (1 H, dd, J = 2.2, 8.1 Hz), 6.27 (1 H, dd, -147- 200408628 J = 2.2, 8.1 Hz), 6.66 (1 H , dd, J = 2.2, 8.1 Hz), 6.84 (1 H, d, J = 2. 9 H z), 6.85 (2 H, d, J = 8. 1 H z), 6.9 5-7.0 6 (4 H, m), 7.29 (1 H, d, J = 8.1 Hz), 7.65 (1H, d, J = 8.8 Hz). (3 7 c) 3-[4--[6- (3-isopropylamino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-methyl Oxy-benzyloxy) -phenyl] -propionic acid

3-[4-[6-(3-isopropylamino-phenoxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] produced in Example (3 7 b)- 2- (4-methoxy-benzyloxyphenyl] -ethyl propionate (960 mg), potassium hydroxide (432 mg), ethanol (10 ml), water (5 ml), 1,4-

Dioxane (5 ml) 5 According to the method of Example (3 6 c): The reaction and post-treatment were performed to obtain the target compound (3 86 mmol: g) 0 1 Η-N MR (4 0 0 MH z, CD Cl 3) · δ PP m 1.07 (6 Η 9 d, J = 6.5] Hz), 2. 4 2 (2 H t, J = 7.3 Η z), 2. 7 1 (2 H 9 t, J = 7.3 Hz), 3.4 .2 -3., 47 (1 Η, m), 3.7 5 (3 H, s), 3. 7 9 (3 H s), 5., 03 (2 Η, s), 5. .35 (2 H, s), 5.5 .0 (1 H, d, J = 7.3 Hz), 6.08 (1 H, dd J = 2. 2:,, : 8. 8 H [z), 6. 1 2 (1] H, d, J = 2.2 H z), 6. 2 6 (1 H, dd, J = 2 • 2, 8. 1 H: z), 6.64 (1 Η, dd, J = 8, .8, 2.2 Hz), 6. 8 2 (1 H d, J = 2.2 Hz), 6. 9 0 (1 H, dd , J = 2.2, 8. 8 H: z), 6 • 93 (2 Η, d, J = 8. 1 H: z), 7. 0 l (1 H, d, J = 8. 1 H z), 7.06 (1 H, d, J = 8.8 H z), 7 • 28 (1 H, d, -148- 200408628 J = 2. 2 Η z)? 7.37 (2H, d, J = 8 1 H z), 7.63 (1 H, d, J = 8 · 8 H z) ° (actually Example 3 8) 3-[4-[6- (4-Methanesulfonamido-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4- Chloro-benzyloxy) · phenyl] -propionic acid (Exemplified compound numbers 1-1 6 8)

(38a) 3-[4- [6. (4-Amino-phenoxy) methyl_1H. Benzimidazol-2-ylmethoxy] -2 -methoxymethoxy-phenyl]- Ethyl propionate [6-(4-amino-phenoxy) -1 -methyl-1H-benzimidazol-2-yl] -methanol (857 mg), 3-( 4-Hydroxy-2-methoxymethoxy-phenyl) -propionic acid ethyl ester (675 mg), 1,1 '-(azidodicarbonyl) dipiperidine (801 mg), tri-n-butylphosphine (0.79 Ml), anhydrous toluene (35 ml), and reacted and worked up according to the method of Example (36a) to obtain the target compound (1.4 g). 1 Η-N M R (4 0 0 MHZ, C D C 1 3): δ ppm

0.93 (3 Η, t, J = 7. 3 Η ζ), 2.55 (2 Η, t, J = 7. 7 Η ζ), 2.87 (2 Η, t, J = 7. 7 Η ζ), 3.46 ( 3 Η, s), 3.76 (3 Η, s), 4.08-4.14 (2 Η, m), 5.17 (2 Η, s), 5.29 (2 Η, s), 6.49 (2 Η, brs), 6.64 -6.6 7 (1 Η, m), 6.68 (2 Η, dd, J = 2.2, 6.6 Η ζ), 6.81 (1 Η, d, J = 2. 2 Η ζ), 6.84 (1 Η, d , J = 2.2Hz), 6.87 (2 Η, dd, J = 2.2, 6 · 6Ηζ), 6.96 (1 Η, dd, J = 2.2, 8 · 8Ηζ), 7.05 (1 Η, d, J = 8.1 Hz), 7.65 (1Η, d, -149-200408628 J = 8 · 8 Η z). (3 8 b) 3-[4-[6-(4-amino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-chloro- Benzyloxy) -phenyl] -propionic acid ethyl ester 3-[4-[6-(4-Amino-phenoxy) d-methyl-1H-benzimidazole] produced in Example (38a) 2-ylmethoxy] -2-methoxymethoxy-phenyl] -propionic acid ethyl ester (1.4 g), 4N hydrochloric acid 1,4-dioxane (15 ml), ethanol (15 ml) , 4-chlorobenzyl chloride (216 mg), sodium hydride (55%, 49 mg), anhydrous N, N-dimethylformamide (15 ml), according to Example (3 6 b)) Reaction and post-treatment. 4-chlorobenzylation was performed at room temperature. The target compound (475 mg) was obtained. 'H-NMR (400 MHz, CDC13): (5 ppm 1.15 (3 H, t, J = 7. 3 H z), 2.50 (2 H, t, J = 7. 7 H z), 2.84 (2 H, t, J = 7. 7 H z), 3.70 (3H, s), 4.04 (2 H, q, J = 7. 3 H z), 4.95 (2 H, s), 5.25 (2 H, s),

6.56 (1H, dd, J = 2.2, 8.1Hz), 6.59 (1H, d, J = 2.2Hz), 6.6 2-6.6 5 (2H, m), 6.79 (1H, d , J = 2.2 Hz), 6.81-6.85 (2H, m), 6.92 (1 H, dd, J = 2.2, 8.8 Hz), 7.02 (1 H, d, J = 8. 1 H z), 7.22- 7.31 (4H, m), 7.60 (1 H, d, J = 8.8Hz). (3 8 c) 3-[4- [6- (4- (Methanesulfonylamino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4 -Chloro-benzyloxy) -phenyl] -propionic acid-150- 200408628

3-[4-[6-(4-amino-phenoxy)-! _ Methyl-1H-benzimidazole · 2-methylmethoxy] -2 produced in Example (3 8 b) -2 -(4-Chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (200 mg) was dissolved in anhydrous dichloromethane (20 ml). Pyridine (0.146 ml) and methanesulfonyl chloride ( 〇4 6 ml), and stirred at room temperature for 6 hours. The solvent was distilled off under reduced pressure, and the residue was extracted with ethyl acetate, washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and ethanol (6 ml), potassium hydroxide (84 mg), water (3 ml), and 1,4-diBfane (3 ml) were added to the residue, and the mixture was stirred at room temperature overnight. After adding water to the reaction mixture and acidifying it with 1 N hydrochloric acid, a small amount of ethyl acetate was added, and Shen Dian was filtered to obtain the desired compound (94 mg). ^ -NMR (400MHz, CDC13): δ ppm 2.46 (2 Η, t, J = 7. 7 Η ζ), 2.76 (2 Η, t, J = 7. 7 Η ζ), 2.97 (3Η, s), 3.90 (3 Η, s), 5.15 (2 Η, s), 5.55 (2 Η, s), 6.70 (1 Η, dd, J = 2. 2, 8.1Ηζ), 6.83 (1 Η, d, J = 2 2 Η ζ), 7.03 (2 Η, d,

J = 8. 8 Ηζ), 7.12 (1 Η, d, J = 8. 1 Η ζ), 7.14 (1 Η, d, J = 2. 2 Η ζ), 7.24 (2 Η, d, J = 8 8 Η ζ), 7.44- 7.52 (5 Η, m), 7.75 (1 Η, d, J = 8. 8 Η ζ), 9.66 (1 Η, s). (Example 3 9) 3. [4- [6- (4-Amino-phenoxy) -1-methyl-1fluorene-benzimidazole-2-ylmethoxy] -2-(4- Chloro-benzyloxy) -phenyl] -propionic acid (exemplified compound number 1-1 6 2) '151- 200408628 3-[4-[6-(4-amino group- Phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (257 mg), hydrogen Potassium oxide (109 mg), ethanol (10 ml), and water (5 ml) were reacted and worked up according to the method of Example (36 c) to obtain the target compound (104 mg). 1 Η-NMR (400 MHz, CDC 1 3): δ ppm 2.46 (2H, t, J = 7. 3 H z), 2.77 (2 H, t, J = 7. 3 H z), 3.91 ( 3 H, s), 5.16 (2H, s), 5.56 (2H, s), 6.70 (1 H, dd, J = 2.2, 8.1Hz), 6.84 (1H, d, J = 2.2 Hz ), 7.12 (2H, d, J = 8.8 Hz), 7.11-7.14 (1 H, m), 7.17 (1H, dd, J = 2.2, 8.8Hz), 7.38 (2 H, d, J = 8.8 Hz), 7.44-7.51 (4 H, m), 7.60 (1H, d, J = 2.2 Hz), 7.79 (1 H, d, J = 8.8 Hz) (Examples 4 0) 3-[4- [6-(4-Methanesulfonylamino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-methyl Oxy-benzyloxy) -phenyl] -propionic acid (Exemplified compound numbers 1-1 7 1) (4 0 a) 3-[4- [6- (4_amino-phenoxy) · 1_ Methyl_1H_benzimidazol-2-ylmethoxy] -2- (4-methoxy-benzyloxyphenyl] -propionic acid ethyl ester 3-manufactured using Example (3 8 a) [4-[6-(4-Amino-phenoxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] -2-methoxymethoxy-phenyl] -propionic acid Ethyl ester (1.31 g), 4N hydrochloride-1,4-dioxane • 152- 200408628 (15 ml), ethanol (15 ml), 4-methoxybenzyl chloride (0.14 ml), sodium hydride (55%, 38 mg), anhydrous Ν, Ν -dimethylformamidine Amine (20 ml) was reacted and worked up according to the method of Example (36 b) to obtain the target compound (468 mg). 1 Η-NMR (4 0 Μ Η ζ, CDC 1 3 ): (5 ρ ρ m 1.12 (3 Η, t, J = 7. 3 Η ζ), 2.47 (2 Η, t, J = 7. 7 Η ζ), 2.80 (2 Η, t, J = 7. 7 Η ζ), 3.67 (3 Η, s), 3.73 (3Η, s), 4.00 (2 Η, q, J = 7. 3 Η ζ), 4.89 (2 Η, s), 5.22 (2 Η, s ), 6.51 (1 Η, dd, J = 2.2, 8 · 1Ηζ), 6.58 (1 Η, d, J = 2.2 Η ζ), 6.61 (2 Η, d, J = 8.8Hz), 6.76 (2 Η, d, J = 8.8 Η ζ), 6.78-6.83 (3 Η, m), 6.89 (1 Η, dd, J = 2.2, 8.8 Η ζ), 6.97 (1 Η, d, J = 8. 1 Η ζ), 7.25 (2 Η, d, J = 8. 1 Η ζ), 7.58 (1 Η, d, J = 8. 8 Η ζ) 〇 (40b) 3-[4- [ 6- (4-Methanesulfonylamino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy ] -2- (4-methoxy-benzyloxy) -phenyl] -propionic acid 3-[4-[6 · (4-amino-phenoxy)- 1-Methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-methoxy-benzyloxy) -phenyl] -propionic acid ethyl ester (234 mg), methanesulfonyl chloride (0.031 ml), pyridine (0.097 ml), anhydrous dichloromethane (20 ml), potassium hydroxide (112 mg), ethanol (10 ml), water (5 ml), according to the method of Example (38c) The reaction and post-treatment were performed to obtain the target compound (128 mg). 200408628 H-NMR (400 MHz, CDC13): (5 ppm 2.. 4 1 (2 H, t, J = 7. 7 H z), 2. 7 1 (2 H, t, J = 7. 7 H z), 2 '.9 4 (3 H, s), 3. 7 5 (3 H, s), 3.80 (3 H, s), 5, .0 3 (2 H, s), 5 • 35 (2 H, s), 6.64 (1 H, dd, J = 2 • 2, 8. 8.1 H z), 6 • 81 (1 H, d, J = 2. 2 H z), 6. 9 1 -6 .9 9 (5 H, m), 7 • 05 (1 H, d, J = 8.8 H z), 7 • 20 (2H, J = 8.8 H z), 7.30 (1 H, d, J = 2.2 Hz), 7.37 (2 H, d, J = 8. 1 Hz), 7.65 (1H, d, J = 8.8Hz).

(Example 4 1) 3-[4-[6- (4-Amino-phenoxy) methyl-1H-benzimidazole-2-ylmethoxy] -2- (4-methoxy- Benzyloxy) -phenyl] -propionic acid (Exemplified compound numbers 1-1 6 5)

3 · [4-[6-(4-amino-phenoxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] produced in Example (4 0 a)- 2- (4-methoxy-benzyloxy) -phenyl] -propionic acid ethyl ester (234 mg), potassium hydroxide (112 mg), ethanol (6 ml), water (3 ml), 1,4 -Dinoxane (4 ml), which was reacted and worked up according to the method of Example (36 c) to obtain the target compound (174 mg). 1 H-NMR (400 MHz, CDC 1 3): 5 ppm 2.42 (2H, t, J = 7. 7 Hz), 2.71 (2H, t, J = 7. 7 Hz), 3.74 (3 H, s), 3.7 5 (3 H, s), 5.02 (2 H, s), 5.33 (2H, s), 6. 5 9 (2 H, d, J = 8. 8 H z) , 6.63 (1 H, dd, J = 2.2, 8.1 Hz), 6.76 (2 H, d, J = 8.8 H z), 6.80 (1H, d, J = 2. 2 H z), 6.83 (1 H, -154- 200408628 dd, J = 2.2, 8. 8 H z), 6.93 (2 H, d, J = 8. 8 H z), 7.05 (1 H, d, J = 8. 1 H z), 7.05 (1 H, d, J = 2.2 Hz), 7.37 (2 H, d, J = 8. 8 H z), 7.57 (1 H, d, J = 8 · 8 H z ). (Example 4 2) 3- [4- [6- (4-Amino-3,5-dimethyl-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy ] -2- (4-chloro-benzyloxy) -phenyl] -propionic acid (Exemplified compound number 1-1 8 1) (42a) 3-[4- [6- (4-aminoamino-3, 5 -Dimethyl-phenoxy)-1-methyl-1H -benzimidazol-2-ylmethoxy] -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester [6- (4-Amino-3,5-dimethyl-phenoxy) -1-methyl-1H-benzimidazol-2-yl] -methanol (319 mg) produced in Reference Example 3, 3- [4-Ethyl-2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (300 mg), 1,1 '_ (azidodicarbonyl) dipiperidine (272 mg ), Tri-n-butylphosphine (0.27 ml), anhydrous toluene (20 ml), and the reaction and post-treatment were carried out according to the method of Example (36a) to obtain the target compound (402 mg). 1 Η-NMR (400 MHZ, CDC 1 3): δ ppm 1.26 (3 Η, t, J = 7. 3 Η ζ), 2.17 (6 Η, s), 2.55 (2 Η, t, J = 7.7 ζ ζ), 2.89 (2 Η, t, J = 7.7 Η ζ), 3.75 (3 Η, s), 4.12 (2 Η, q, J = 7.3 Η ζ), 5.01 (2 Η, s), 5.31 (2 Η, s), 6.61 (1 Η, dd, J = 2. 2, 8.. 1 Η ζ), 6.64 (1 Η, brs), 6.69 (2 Η, s) , 6.83 (1 Η, d, -155- 200408628 J = 2.2 Η z), 6.98 (1 Η, dd, J = 2.2? 8.8 H z), 7.07 (1H, d, J = 8 1 H z), 7.31-7.86 (4 H, m), 7.65 (1H, d, J = 8.8 Hz). (4 2 b) 3-[4-[6-(4-amino-3, 5-dimethyl-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-Chloro-benzyloxy) -phenyl] -propanoic acid 3-[4-[6-(4 -amino-3,5-dimethyl) produced in Example (4 2 a) -Phenoxy) -1-methyl-111-benzimidazol-2-ylmethoxy] -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (401 mg) , Potassium hydroxide (183 mg), ethanol (10 ml), water (5 ml), 1,4-dioxane (4 ml), the reaction was performed according to the method of Example (36 c), and after After treatment, the target compound (297 mg) can be obtained. ! H-NMR (400 MHz, CDC13): δ pp m 2.07 (6 Η, s), 2.43 (2 Η, t, J = 7. 7 Η z), 2.74 (2 H, t, J = 7. 7 H z), 3.74 (3 H, s), 5.11 (2 H, s), 5.32 (2H, s), 6.58 (2 H, s), 6.65 (1 H, dd, J = 2.2, 8.1 Hz), 6.78 (1 H, d, J = 2.2 H z), 6.82 (1H, dd, J = 2.2, 8.8 Hz), 7.05 (1H, d, J = 2.2 H z), 7.07 (1 H, d, J = 8.8 H z), 7.43-7.49 (4 H, m), 7.55 (1 H, d, J = 8.8 Hz). (Example 4 3) 3- [4- (6-Benzyloxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-chloro-benzyloxy) -benzene Group] -propionic acid (Exemplified compound number 1-218) -156- 200408628 (43a) 3-[4 -Third-butoxycarbonylmethoxy-2- (4-chloro-benzyloxy) _phenyl]- Ethyl propionate Ethyl 3- [4-isopropyl-2- (4-chloro-benzyloxy) _phenyl] -propanoate (970 mg) was dissolved in acetone (30 ml), and bromoacetic acid was added to the Butyl ester (0.75 ml) and carbonate shavings (1.4 g) were stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure. The obtained residue was extracted with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the target compound (1.6 g).

1 Η-NMR (400 MHz, CDC 1 3): 5 ppm 1.17 (3H, t, J = 7.3Hz), 1.44 (9H, s), 2.53 (2H, t, J = 7. 7 H z), 2.87 (2 H, t, J = 7 · 7 Hz), 4.05 (2H, q, J = 7. 3 H z), 4.42 (2H, s), 4.97 (2 H, s), 6.30 (1H , Dd, J = 2.9, 8.8Hz), 6.49 (1H, d, J = 2. 9 H z), 7.02 (1 H, d, J = 8. 8 H z), 7.22 (2H, s), 7.31 (2 H, s). (4 3 b) 3-[4- (6-Benzyloxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-chloro-benzyloxy) -phenyl ] -Ethyl propionate The 3- [4-tertiary-butoxycarbonylmethoxy-2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester produced in Example (43a) ( (800 mg) was dissolved in 1,4-dioxane (5 ml), 4N hydrochloric acid-1,4-dioxane (15 ml) was added, and the mixture was stirred at room temperature overnight. The solvent was distilled off under reduced pressure. The obtained residue was dissolved in anhydrous tetrahydrofuran (20 ml), and (2-amino-5-benzyloxyphenyl) -methylcarbamic acid third butyl ester (Japanese Patent Laid-Open No. 2001-87372) (222 mg) was added. ), Diethyl cyanophanoate (0.12 halo; liter) and triethylamine (o.ii ml-157-200408628), and stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and the residue was extracted with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2: 1) to obtain an intermediate (300 mg). 4N hydrochloric acid-1,4-dioxane (20 ml) was added to the intermediate and stirred at room temperature overnight. The solvent was distilled off under reduced pressure, and the residue was washed with ethyl acetate, ethanol, ether, and hexane to obtain the target compound (164 mg). 1 Η · NMR (400 MHz, CDC 1 3): δ ppm 1.11 (3 Η, t, J = 7. 3 Η ζ), 2.50 (2 Η, m), 2.77 (2 Η, t, J = 8. 1 Η ζ), 3.88 (3 Η, s), 3.99 (2 Η, q, J = 7. 3 Η ζ), 5.13 (2 Η, s), 5.19 (2 Η, s), 5.48 (2 Η; s), 6.67 (1 Η, dd, J = 2.2, 8.8 Η ζ), 6.81 (1 Η, m), 7.10 (1 Η, d, J = 8.8 Η ζ), 7.31 -7.35 (1 Η, m), 7.39 (2 Η, d, J = 7. 3 Η ζ), 7.42-7.43 (1 Η, m), 7.4 4-7.4 9 (5 Η, m), 7.48 (2 Η, d, J = 7. 3 Η ζ), 7.62 (1 Η, d, J = 8.8 Hz, (4 3 c) 3-[4_ (6 -benzyloxy-1-methyl-1H -benzo) Imidazol-2-ylmethoxy) -2- (4-chloro-thenyloxy) -phenyl] -propionic acid The 3- [4- (6-benzyloxy-l) produced in Example (43b) -Methyl-1H-benzimidazol-2-ylmethoxy) -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (164 mg), ethanol (6 ml), Water (3 ml), potassium hydroxide (74 mg), and 1,4-dioxane (4 ml) were stirred at room temperature for 6 hours. The solvent was distilled off under reduced pressure, and the residue was extracted with water. Acetic acid was used to acidify and filter Shen Dian to obtain the target compound (134 mg). -158- 200408628 H-NMR (400MHz, CDCI3): ppm 2.43 (2 H, t, J = 7.3 H z), 2.74 (2 H, t, J == 7 · 3 hz), 3.80 (3H, s), 5.12 (2 H, s), 5.17 (2H, s), 5.32 (2 H, s), 6.66 (1 H , dd, J = 2.2, 8.1Hz), 6.80 (1H, d, J = 2.2 Hz), 6.92 (1H, dd, j = 2.2 8.8Hz), 7.01 (1H, d, J = 8. 1 H z), 7.26 (1H, d J = 2. 9 H z), 7.34 (2 H, d, J = 7.3 Hz), 7. 3 9. 7. 4 8 (6H, m), 7.50 (1H, d, J = 2. 9 H z), 7.53 (1 H, d,

J = 8.8 H z), 12.03 (1 H, brs). (Example 4 4) 3-[4- [6-(3-Isopropylamino-phenoxy) -1-methylbenzimidazol-2-ylmethoxy] -2- (4-chloro-benzyl (Oxy) -phenyl] -propionic acid (exemplified compound number 1-1 7 〇 (44a) 3-[4- [6-(3-isopropylamino-phenoxy) -i_methyl-1H_benzo Imidazol-2-ylmethoxy] -2-(4-chloro-benzyloxy) · phenyl] -propionic acid ethyl ester

3- [4-Third-butoxycarbonylmethoxy-2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (800 mg) produced in Example (4 3 a) was used ), 1,4-dioxane (5 ml), 4N hydrochloric acid-1,4-dioxane (15 ml), [2-amino-5- (3-isopropylamino) -phenyl] -methyl Third butyl carbamate (Japanese Patent Application No. 2001-319631) (350 mg), diethyl cyanophosphate (0.17 ml), triethylamine (0.16 ml), anhydrous tetrahydrofuran (20 ml), 4N hydrochloric acid-1, 4-Dioxane (20 ml) was reacted and worked up according to the method of Example (4 3 b) to obtain the target compound-159- 200408628 (4 2 3 mg). 1 Η-NMR (400 MHz, CDC 1 3): (5 ppm 1.14 (3H, t, J = 7. 3 H z), 1.14 (6 H, d, J = 6.0 H z), 2.50 (2 H, t, J = 7.3 Hz), 2.78 (2H, t, J = 7. 3 H z), 3.42 (1H, q, J = 6. 0 Hz), 3 · 89 (3H, s), 3.9 7-4.0 4 (2 H, m), 5.14 (2 H, s), 5.54 (2 H, s), 6.69 (1 H, dd, J = 2.2, 8.1Hz), 6.83 (1 H, d , J = 2.2 Hz), 7.04 (1H, dd, J = 2.2,

8.8Hz), 7.11 (1 H, d, J = 8.1 Hz), 7.15 (1H, dd, J = 2.2, 8. 8 Hz), 7.4 3-7.4 8 (6 H, m) , 7.69 (1 H, d, J = 8.8 H z), 7.76 (1 H, d, J = 8.8 Hz). (4 4 b) 3-[4-[6- (3-Isopropylamino-phenoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4-chloro -Benzyloxy) -phenyl] -propionic acid

3-[4-[6-(3 -isopropylamino-phenoxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] produced in Example (4 4 a)- 2- (4-Chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (423 mg), potassium hydroxide (178 mg), ethanol (8 ml), water (4 ml), 1, 4 · 2 Pinane (4 ml) was reacted and worked up according to the method of Example (4 3 c) to obtain the target compound (193 mg). 1 Η-NMR (400 MHz, CDC 1 3): (5 ppm 1.16 (6H, d, J = 6. 6 H z), 2.46 (2H, t, J = 7. 7 H z), 2.77 ( 2H, t, J = 7. 7 H z), 3.56 (1 H, m), 3.91 (3 H, s), 4.02 (1H, q, J = 6. 6 H z), -160-5. 15 (2 Η, 丨 s), 5.55 (2 Η, s), 6.7 〇 (1 Η, dd, J =: 2.2 8. 1 Η ζ), 6.84 (1 Η, d, J = 2.9 Hz), 7 .1 2 (1 Η, d J = 8.8 Η ζ), 7.16 (1 Η, d, J = 8.8 Η ζ), 7. 4 4-7 · 5 0 (8 Η, m), 7.57 (1 Η, m), 7.77 (1 Η, d, J = 8. 8 Η ζ) ° (Example 4 5) 3-[2-(4-chlorobenzyloxy) _4-(5 -methoxy · _ 3 -methyl-3 hydrazone-imidazo [4, 5 -b] D ratio 定 • • 2-methylmethoxy) -phenyl]-propionate (Example 200408628 shows compound number 2- 30) (45a) 3- [2- (4-chlorobenzyloxy), 4-hydroxy-phenyl] -propionic acid ethyl ester 3. (2-hydroxy-4) produced in Example (lc) Methoxymethoxyphenyl) -ethyl propionate (500 mg, 966 mmol), potassium carbonate (815 mg, 5.889 mmol), 4 -Chlorooctyl chloride (475 mg, 2.949 mmol) and N, N-dimethylformamide (20 ml), the reaction and post-treatment according to the method of Example (1 d) can produce the target compound (406 mg, yield 55%). M MS (EI) m / z: 378 (M) +. ▼ (45b) 3-[2- (4-chlorobenzyloxy) -4 -hydroxy-phenyl] -Ethyl propionate: Ethyl 3- [2- (4-chlorobenzyloxy) -4-methoxymethoxy-phenyl] -propionic acid ethyl ester (406 mg, 1.072 mmol) produced in Example (45a) was used. Moore), p-toluenesulfonic acid (41 mg) and ethanol (10 ml) were reacted and worked up according to the method of Example (10) to obtain the target compound (358 mg, 100%). MS (EI) m / z: 3 3 4 (M) +. -161-200408628 (45c) 3- [2- (4-chlorobenzyloxy) -4- (5-methoxy-3-methyl-3H-imidazo [4,5-b] pyridine-2- Methylmethoxy) -phenyl] -ethyl propionate The 3- [2- (4-chlorobenzyloxy) -4-hydroxy-phenyl] -propionic acid ethyl ester prepared in Example (45b) was used ( 300 mg, 0.896 mmoles), (5-methoxy-3-methyl-3H-imidazo [4,5-b] pyridin-2-yl) · methanol (173 mg, 0.896 mmoles), Tributylphosphine (0.28 ml, 1.12 mmol), 1,1 '-(azidodicarbonyl) dipiperidine (282 mg, 1.2 mmol) and toluene (10 ml), according to the examples (1 f) (The method is reacted and post-processed to obtain the target compound (371 mg, yield 81%). MS (FAB) m / z: 510 (M + H) +0 (45d) 3- [2- (4-chlorooctyloxy) -4_ (5-methoxy-3, methyl-3Ηimidazo [4,5-b] pyridin-2-ylmethoxy) -phenyl ] _ The propionate salt was prepared using 3- (2-(4 · chlorobenzyloxy) -4- (5-methoxy-3 -methyl-3H-imidazole) produced in Example (45c) [ 4,5-b] pyridine B.2-ylmethoxy) -phenyl] -propionic acid ethyl ester (371 mg, 0.72 7 millimoles), 1N sodium hydroxide (1.5 milliliters, 1.5 millimoles), ethyl acetate (2 pens), and tetrahydrofuran (2 milliliters) were reacted in accordance with the method and method of Example (1 g) and After treatment, the target compound (319 mg, 89%) can be obtained. ° 1 Η-NMR (4 0 Μ Η ζ, DMS Ο-d 6): δ pp m 2.44 (2H, t, J = 7.6 Hz), 2.75 (2H, t, J = 7.6Hz), 3.81 (3H, s), 3.94 (3H, s), 5.13 (2H, s), -162- 200408628 5.38 (2 Η, s), 6.67 (1Η, dd, J = 2.2, 8.0Hz), 6 · 7 6 (1H, d, J = 8.8 H z), 6.80 (1H, d, J = 2.2Hz), 7.09 (1H, d, J = 8.0Hz), 7.43-7.49 (4H, m), 8.00 (1H, d, J = 8.8Hz) IR (KBr): 1711, 1609, 1592, 1505, 1406, 1288, 1262, 1167, 1026 cm'1 MS (FAB) m / z: 4 8 2 (M + H) + HR-MS (FAB) m / z: C25H2505N3C1 (M + H) + calculation 値: 4 8 2. 1 4 8 3; Measured radon: 4 8 2 · 1 4 9 3 Hydrazone (Example 4 6) 3-[2- (4-chlorobenzyloxy) -4- (3-methyl-5-phenoxy-3H-imidazo [4,5-b]) -2-ylmethoxy) -phenyl] -propionate (exemplified compound number 2-1 5 6) (46a) 3-[2- (4 · chlorobenzyloxy) -4- (3- Methyl-5-phenoxy-3H-imidazo [4,5-b] pyridin-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[produced in Example (45b) 2- (4-chlorobenzyloxy) -4- ^ hydroxy-phenyl] -propionic acid ethyl ester (300 mg, 0.896 mmol), (3-methyl-5-phenoxy-3H-imidyl) [4,5-b] n than Π aden-2-yl) -methanol (229 mg, 0.896 mmol), tributylphosphine (0.28 ml, 1.12 mmol), 1,1 '- (Azidedicarbonyl) dipiperidine (282 mg, 1.12 mmol) and toluene (10 ml) were reacted and worked up according to the method of Example (lf) to obtain the target compound (358 mg , Yield 70%). -163- 200408628 MS (FAB) m / z: 5 7 2 (M + H) +0 (4 6 b) 3-[2- (4-chlorooctyloxy) -4- (3-methyl-5 -Phenoxy-3H -imidazo [4,5-b] pyridin-2-ylmethoxy) -phenyl] -propionate hydrochloride 3-[2 produced in Example (4 6 a) -(4 -chlorobenzyloxy) -4-(3-methyl-5-phenoxy-3H-amidine and [4,5-b] D ratio Π ding-2 · ylmethoxy)- Phenyl] -ethyl propionate (358 mg, 0.626 mmol), 1N sodium hydroxide (1.3 ml, 1.3 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml), according to the example (lg ) Method for reaction and post-treatment, the target compound (128 mg, 34%) can be obtained. 1 Η-NMR (400 MHZ, DMS 〇-d 6): δ ppm 2.42 (2 Η, t, J = 7.6 Η ζ), 2.74 (2 Η, t, J = 7.6 Η ζ), 3.70 (3 Η, s), 5.12 (2 Η, s), 5.38 (2 Η, s), 6.67 (1 Η, dd, J = 2. 2, 8 · 0Ηζ), 6.80 (1Η, d , J = 2.2. 2 Η ζ), 6.97 (1 Η, d, J = 8. 8 Η ζ), 7 0 9 (1 Η, d, J = 8. 0 Η ζ), 7.17-7.24 (3 Η, m), 7.4 2-7.4 9 (6 Η, m), 8.17 (1 Η, d, J = 8.8 Hz). IR (KBr): 1710, 1612, 1591, 1 5 0 6, 1 4 8 5, 1410, 1353, 1258, 1194, 1178 cm'1 MS (FAB) m / z: 5 4 4 (M + H) + HR-MS (FAB) m / z: C30H27O5N3C1 (M + H) + Calculated 値: 5 4 4.1 6 3 9; Measured 値: 5 4 4 · 1 6 1 6 (Example 4 7) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy200408628) -2- (quinolin-2-ylmethoxy ) —Phenyl] -propionate (Exemplified Compound No. 1-107) (4 7 a) 3-[4- (6 -methoxy ·: [-methyl-1H -benzimidazole- 2-ylmethoxy) -2- (quinolin-ylmethoxy) _phenyl] -propionic acid ethyl ester produced using 3- (2-hydroxy_4 · (6-methyl Oxy-1 · methyl-1H -benzimidazole_2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol) ), 2-chloromethylquinoline (250 mg, 1.17 mmol) and N, N-dimethylformamide (8 ml), which can be prepared and reacted according to the method of Example (22f) to obtain The target compound (327 mg, yield 80%). MS (FAB) m / z: 5 2 6 (M + H) +. (4 7 b) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (quinolin-2-ylmethoxy)- Phenyl] -propionate was used as the 3- [4- (6-methoxy-1-methyl-1H-benzyl wow-2-ylmethoxy)-produced in Example (47a). 2- (Π 奎琳 -2 · methoxymethoxy) -phenyl] -propionic acid ethyl ester (327 mg, 0.622 mmol), 1N sodium hydroxide (1.2 ml, 1.2 mmol), ethanol ( 2 ml) and tetrahydrofuran (2 ml), and reacted and worked up according to the method of Example (22 g) to obtain the target compound (247 mg, 72%). 1 Η-NMR (400 MHZ, DMS 0-d6): δ ρ ρ τη 2.55 (2 Η, t, J = 7.6 Η ζ), 2.87 (2 Η, t, J = 7. 6 Η ζ), 3.89 (3 Η, s), 3.99 (3 Η, s), 5.50 (2 Η, s), -165 · 5.66 (2 Η, s), 6 • 75 (1 H, dd, J = 2.2, 8.0 Hz), 6.95 (1 Η, d, J =: 2.2 Hz), 7. 1 5-7.1 9 (2 H, m), 7.52 (1 Η, d, J =: 2.2 Hz) , 7.6 5-7.7 0 (2 H? M), 7.76 (1 Η, d, J =: 8.8 Hz), 7.8 2-7.8 6 (1 H, m), 200408628 8.0 4-8.0 9 (2 Η , m), 8.53 (1 Η, d, J = 8.8 Hz). I R (KBr): 1723, 1612, 1599, 1503, 1295, 1261, 1225, 1175, 829 cm · 1 MS (FAB) m / z: 4 9 8 (M + H) +. (Example 4 8) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(pyridine-3-ylmethoxy)- Phenyl] -propionate (Exemplified Compound No. 1-105) (4 8 a) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-yl (Methoxy) -2- (bipyridin-3-ylmethoxy) -phenyl] -propionic acid ethyl acetate 3-[2 -hydroxy-4-( 6-methoxy-1-methyl-1H-benzimidazole-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 Mmol), 3- (chloromethyl) pyridine (192 mg, 1.17 mmol) and N, N -dimethylformamide (8 ml), the reaction was carried out according to the method of Example (2 2 f) After treatment, the target compound (248 mg, yield 67%) can be obtained. MS (FAB) m / z: 4 7 6 (M + H) +. (4 8 b) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(pyridine-3 -ylmethoxy) -benzene Group] -propanoic acid-166-200408628 salt 3 · [4- (6-methoxy-1-methyl-1Η-benzimidazol-2-ylmethoxy) produced in Example (48a) ) -2- (pyridine-3-ylmethoxy) -phenyl] -propionic acid ethyl ester (248 mg, 0.522 mmol), 1N sodium hydroxide (1 ml, 1 mmol), ethanol ( 2 ml) and tetrahydrofuran (2 ml). The reaction and post-treatment were carried out according to the method of Example (2 2 g) to obtain the target compound (181 mg, 67%). 1 Η-NMR (400 MHZ, DMS 〇-d 6): δ ppm 2.45 (2 Η, t, J = 7.6 Η ζ), 2.79 (2 Η, t, J = 7.6 Η ζ), 3.89 (3 Η, s), 4.02 (3 Η, s), 5.39 (2 Η, s), 5.69 (2 Η, s), 6.77 (1 Η, dd, J = 2.2, 8. 8 Η ζ), 6.97 (1 Η, d, J = 2.2 Η ζ), 7.16 (1 Η, d, J = 8. Ο Ο ζ), 7.18 (1 Η, dd, J = 2.2, 8. 8 Η ζ), 7.54 (1Η, d, J = 2.2 Η ζ), 7.7 3 (1 Η, d, J = 9. 5 Η ζ), 7.96 (1 Η, dd, J = 5.1, 8.0 Η ζ), 8.51 (1 Η, d, J = 8.〇 Η ζ), 8.8 2-8.8 4 (1 Η, m), 8.99 (1 Η, d, J = 1 · 5 Η ζ) . I R (κΒγ): 1719, 1612, 1 5 4 0, 1 5 0 2, 1 4 4 3, 1299, 1262, 1178 cm-1 MS (FAB) m / z: 4 4 8 (M + H) +. (Example 4 9) 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(pyridine-4-ylmethoxy)- Phenyl] -propionate (Exemplified Compound No. 1-10) -167- 200408628 (49a) 3- [4- (6-methoxy-1 * methyl-1H-benzimidazole-2 -Ylmethoxy) -2- (pyridin-4-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[2 -hydroxy-4-(6 -Methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.78 mmol), potassium carbonate (324 mg, 2.341 mmol Mol), 4- (bromomethyl) pyridine (296 mg, 1.17 mmol) and N, N-dimethylformamide (8 ml), the reaction was carried out according to the method of Example (2 2 f) and After work-up, the target compound (303 mg, yield 82%) can be obtained.搴 MS (FAB) m / z: 4 7 6 (M + H) +. (49b) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-(pyridine-3-ylmethoxy) -phenyl] -Propionate using 3-[4-(6 -methoxy-1 -methyl-1H -benzimidazol-2-ylmethoxy) -2-produced in Example (49a) (Pyridine-4 -ylmethoxy) -phenyl] -propionic acid ethyl ester (303 mg, 0.637 mmol), 1N sodium hydroxide (1.3 ml, 1.3 mmol), ethanol (2 ml) 1 And tetrahydrofuran (2 ml), followed by reaction and post-treatment according to the method of Example (2 2 g), to obtain the target compound (23 3 mg, 70%). 1 Η-NMR (400 MHz, DMS Ο-d 6): 5 ppm 2.52 (2 H, t, J = 7.6 H z), 2.87 (2H, t, J = 7.6 H z), 3.89 (3H, s), 4.00 (3H, s), 5.54 (2H, s), 5.66 (2H, s), 6.78 (1H, dd, J = 2.2, 8.8Hz), 6.90 (1 H, d, J = 2.2 Hz), 7.16 (1H, dd, J = 2.2, -168- 200408628 8. 8 Η z), 7.19 (1 Η, d, J = 8.8 Η ζ), 7.50 (1 Η, d, J = 2.2 Η ζ), 7.70 (1 Η, d, J = 8.8 Η ζ), 8.01 (2 Η, d, J = 6.6 Η ζ ), 8.89 (2 Η, d, J = 6.6Hz). IR (Κ Β r): 1 7 2 3, 1 6 3 8, 1 6 0 9, 1 5 0 3, 1 4 4 0, 1298, 1261, 1223, 1178 cm · 1 MS (FAB) m / ζ: 4 4 8 (M + H) + 〇 (Example 50)

3-〔2-(5 -Chlorophene-2. -Ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionate (exemplified compound number 1- 1〇8) (50a) 3- [2- (5-chlorothien-2-ylmethoxy) -4-(6-methoxy-methyl-1H-benzimidazol-2-ylmethoxy) ) -Phenyl] -ethyl propionate using 3- (2-hydroxy-4-(6-methoxy-1-methyl-1H-benzimidazol-2-yl) produced in Example 2 (2-20) (Methoxy) -phenyl] -ethyl propionate (600 mg, 1. 562 mmol), potassium carbonate (647 mg, 4. 682 mmol), 2-chloro-5-chloromethylthiophene (1 g, 5. 986 mmol) and N, N-dimethylformamide (15 ml), the reaction and post-treatment were carried out according to the method of Example (2 2 f), to obtain the target compound (711 mg, yield 88 %). MS (FAB) m / ζ: 515 (Μ + Η) + 〇 (50 0 b) 3-[2-(5-chlorothien-2-ylmethoxy) -4-(6-methoxy-1 -Methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionate hydrochloride-169- 200408628 3-[2- (5- Chlorothiophene-2-ylmethoxy) -4- (6-methoxy-methylbenzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (711 mg, 丨 · 381 mmol Mol), 1N sodium hydroxide (2.8 ml, 2.8 mmol), ethanol (3 ml) and tetrahydrofuran (3 ml), the reaction and post-treatment were carried out according to the method of example (2 2 g) , The target compound can be obtained (63 2 mg, 89%). 1 Η-N M R (400MHz, D M S Ο-d 6): 5 p p m 2. 43 (2 H, t, J = 7.  6 H z), 2. 71 (2 H, t, J = 7.  6 H z), 3. 87 (3 H, s), 3. 93 (3H, s), 5. 29 (2 H, s), 5. 54 (2 H, s), 6. 70 (1 H, d d, J = 2.  2, 8. 0Hz), 6. 91 (1 H, d, J = 2.  2 H z), 7. 02 (1 H, d, J = 3. 6Hz), 7. 05 (1 H, dd, J = 2.  2, 8.  8 H z), 7. 09- 7. 12 (2 H, m), 7. 38 (1 H, d, J = 2.  2 H z), 7. 64 (1 H, d, J = 8. 8Hz). IR (KBr): 1716, 1611, 1 5 0 2, 1 4 5 3, 1 2 9 0, 1261, 1216, 1170, 1121, 1021 cm · 1 MS (FAB) m / z: 4 8 7 (M + H) + 〇 (Example 5 1) 3-[2- (6-chloropyridin-3-ylmethoxy) -4- (6-methoxy-1-methyl-1H · benzimidazole-2 -Ylmethoxy) -phenyl] -propionate hydrochloride (exemplified compound number 1-10) (5 1 a) 3-[2- (6. Clopyridine-3 · ylmethoxy) -4- (6 · methoxy.  1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester-170- 200408628 3- [2-hydroxy-4- ( 6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0. 78 millimoles), potassium carbonate (324 mg, 2. 341 mmol), 2-chloro-5-chloromethylpyridine (190 mg, 1. 17 millimoles) and N, N-dimethylformamide (8 ml). The reaction and post-treatment were carried out according to the method of Example (2 2 f) to obtain the target compound (453 mg, yield 100%). ). MS (FAB) m / z: 510 (M + H) +. (51b) 3-[2- (6-chloropyridin-3-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -Phenyl] -propionate using 3 · [2-(6 -chloropyridin-3 -ylmethoxy) -4-(6 -methoxy-1) produced in Example (5 1 a) -Methyl-benzoyl D--2-ylmethoxy) -phenyl] -ethyl propionate (453 mg, 0.1 888 mmol), 1N sodium hydroxide (1.8 ml, 1. 8 millimolar), ethanol (2 ml) and tetrahydrofuran (2 ml) 'were reacted and worked up in accordance with the method of Example (22 g) to obtain the target compound (38 mg, 75%). 1 Η-N M R (4 0 Μ Η ζ, D Μ S 〇-d 6): 5 ppm 2. 44 (2 Η, t, J = 7.  6 Η ζ), 2. 75 (2 Η, t, J = 7.  6 Η ζ), 3. 86 (3 Η, s), 3. 91 (3Η, s), 5. 20 (2 Η, s), 5. 50 (2 Η, s), 6. 71 (1 Η, dd, 2. 9, 8.  0Η ζ), 6. 87 (1 Η, d, J = 2. 9Hz), 7. 02 (1 Η, dd, J = 2. 2, 8. 8Hz), 7. 12 (1 Η, d, J = 8. 〇Hz), 7. 34 (1Η, d, J = 2. 2Hz), 7. 56 (1 Η, d, J = 8. 〇Hz), 7. 62 (1H, -171- 200408628 d, J = 8.  8 Η z), 7. 95 (1H, d d, J = 2.  2, 8. 0Hz), 8. 53 (1 H, d, J = 2. 2Hz). IR (KB r): 1718, 1611, 1 5 9 1, 1 5 0 3, 1 4 6 0, 1290, 1260, 1220, 1173, 1105, 1024, 823 cm- 1 MS (FAB) m / z: 4 8 2 (M + H) +. (Example 5 2) 3- [2- (6-Methyl-D): [; Π 疋 -3 -ylmethoxy) -4 · (6-methoxy-bmethyl-1Η-benzo Imidazol-2-ylmethoxy) -phenyl] -propionate (Exemplified Compound No. 1-1 1〇) (52a) 3- [2- (6-hydroxymethylpyridin-3-ylmethoxy) Ethyl) -4- (6-methoxy-1-methyl-1H-benzimidazole · 2-ylmethoxy) -phenyl] -propionic acid ethyl ester produced using Example (2 2 e) 3- [2-hydroxy-4-(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0. 78 millimoles), potassium carbonate (324 mg, 2. 341 mmol), (5-chloromethylpyridin-2-yl) -methanol (237 mg, 1. 17 millimoles) and Ν, Ν-dimethylformamide (8 ml). The reaction and post-treatment were carried out according to the method of Example (2 2 f) to obtain the target compound (444 mg, yield 100% ). MS (FAB) m / z: 5 0 6 (M + H) +. (5 2 b) 3-[2- (6-hydroxymethylpyridin-3-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazole-2-ylmethyl (Oxy) -phenyl] -propionate hydrochloride-172- 200408628 3-[2-(6 -hydroxymethylpyridine-3 -ylmethoxy) -4 produced in Example (5 2 a) -(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (444 mg, 0.1 879 millimolar), 1N sodium hydroxide (1. 8 ml, 1. 8 millimoles), ethanol (2 ml), and tetrahydrofuran (2 ml). The reaction and post-treatment were carried out according to the method of Example (22 g) to obtain the target compound (270 mg, 55%). 1 Η-N M R (400 MHZ, D M S 〇 d 6): δ ppm 2. 51 (2 Η, t, J = 7.  3 Η ζ), 2. 82 (2 Η, t, J = 7.  3 Η ζ), 3. 89 (3Η, s), 4. 01 (3Η, s), 4. 68 (2 Η, s), 5. 33 (2 Η, s), 5. 68 (2Η, s), 6. 75 (1 Η, dd, J = 2.  2, 8. 0Ηζ), 6. 90 (1 Η, d, J = 2.  2 Η ζ), 7. 16- 7. 21 (2 Η, m), 7. 55 (1 Η, d, J = 2.  2 Η ζ), 7. 57 (1 Η, d, J = 8.  0 Η ζ), 7. 58 (1 Η, d, J = 8.  0 Η ζ), 7. 72 (1 Η, d, J = 8.  8 Η ζ), 8. 05 (1 Η, t, J = 8.  0 Η ζ) ο IR (ΚΒ r): 1719, 1 6 2 6, 1 6 1 4, 1 5 0 2, 1 4 4 0, 1300, 1262, 1225, 1180, 1094 cm'1 MS (FAB) m / z: 4 7 8 (M + H) +. (Example 5 3) 3-{2- (4-chloro-benzyloxy) -4- [2- (6-methoxy-1-methyl-1H-benzimidazol-2-yl) -ethyl Oxy] -phenyl} -propionate (exemplified compound number 1-1 2 0) (53a) 3- [3-(4-chloro-benzyloxy) -4- (2-ethoxycarbonylethyl) Group) -phenoxy] -propionic acid-173-200408628 3-[2-(4-chlorobenzyloxy) -4 -hydroxy-phenyl] -propionic acid ethyl prepared in Example (4 5 b) Esters (1 g, 3. 0 mmol) was dissolved in N, N-dimethylformamide (30 ml), sodium hydride (60%, 120 mg) was added under ice cooling, and the mixture was stirred at room temperature for 30 minutes before adding Pyricyclidine-2 -one (0.375 ml, 6 mmol) and stirred for 3 hours. 1 N hydrochloric acid was added to the reaction mixture to make p Η 3, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine in that order, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 5/1 to 1/1) to obtain the target compound (7 6 9 mg, yield 6 3 %). MS (FAB) m / z: 4 0 6 (M) +. (53b) 3-{2-(4-chloro-benzyloxy) -4- [2- (6-methoxy-1 · methyl-1Η-benzimidazol-2-yl) -ethoxy} • Phenyl} -ethyl propionate The 3 · [3-(4-chloro-benzyloxy) -4-(2-ethoxycarbonylethyl) -phenoxy group produced in Example (5 3 a) 〕 -Propionic acid (760 mg, 1. 9 mmol) was dissolved in dichloromethane (10 ml), grass grass chloride (0. 182 ml, 2. 1 mmol) and n, N-dimethylformamide (catalyst amount), and stirred at room temperature for 1 hour. After the reaction solution was concentrated, the residue was dissolved in dichloromethane (15 ml), and the (2-amino-5 -methoxy-phenyl) -methanamic acid produced in Reference Example (a) was added Butyl ester (480 mg, 1.9 mmol) was stirred at room temperature for 1 hour. The reaction solution was concentrated, and water was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and 4 N hydrochloric acid-1,4--174- 200408628 dioxane (30 ml) was added to the residue and stirred overnight, and then stirred at 60 ° C for 1 hour. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed successively with a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1 to 1/1) to obtain the target compound (400 mg, yield 40%). MS (FAB) m / z: 5 2 3 (M + H) +. (5 3 c) 3-{2-(4-chloro-benzyloxy) -4- [2- (6-methoxy-1-methyl-1H -benzimidazol-2-yl) -ethoxy Group} -phenyl} -propionate hydrochloride The 3- (2- (4-chloro-benzyloxy) -4- [2- (6-methoxy-1) produced in Example (53b) -Methyl-1H-benzimidazol-2-yl) -ethoxy] -phenyl} -propionic acid ethyl ester (100 mg, 0.1 19 millimoles) dissolved in a mixed solution of ethanol (2 ml) and 1,4-dioxane (1 ml), and a 1N aqueous sodium hydroxide solution (0. 4 ml, 0.4 mmol), and stirred at room temperature for 5 hours. After the reaction solution was concentrated, 1N hydrochloric acid was added and stirred. The crystals were collected by filtration and washed with water and ethyl acetate. The target compound (81 mg, 87%) can be obtained by drying under reduced pressure. MS (FAB) m / z: 4 9 5 (Μ + Η) + HR-MS (FAB) m / z: C27H28C105N2 (M + H) + Calculated 値: 4 9 5. 1 6 8 7; Measured 値: 4 9 5. 1 7 2 5 ° (Example 5 4) 3-{4-{2-[6-(3-amino-phenoxy) -1-methyl-1H -benzimidyl D--2-yl] -Ethoxy} -2- (4-chloro-benzyloxy) -phenyl} -propionic acid-175- 200408628 2 hydrochloride (exemplified compound number 1-377) (54a) 3- {4.  {2-[6-(3 · amino · phenoxy) _1. Methyl_1H_ benzimidazol-2-yl] -ethoxy} -2- (4-chloro-benzyloxy) -phenyl} -propionic acid ethyl ester produced using Example 3 (5 3 a) 3 -[3-(4- Chloro-benzyloxy) -4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (830 mg, 2. 04 mmol), dichloromethane (10 ml), chloramphenicol (0. 196 ml, 2. 24 millimoles), N, N -dimethylformamide (catalyst amount), [2-amino-5- (3-tert-butoxycarbonylamino-phenoxy) -phenyl]- Dilutributyl methamate (876 mg, 2. 04 millimoles), dichloromethane (10 ml) and 4 N hydrochloric acid-1,4-dioxane (30 ml). The reaction and post-treatment can be performed according to the method of Example (53b). Target compound (480 mg, 39%). MS (FAB) m / z: 6 0 (M + H) +. (54b) 3-{4-{2-[6- (3-Amino-phenoxy) -1-methyl-1H-benzimidazol-2-yl] -ethoxy} -2- (4 -Chloro-benzyloxy) -phenyl} -propanoic acid 2 hydrochloride_ 3-{4-{2-[6-(3-amino-phenoxy ) -1-methyl-1H-benzimidazol-2-yl] -ethoxy} -2- (4-chloro-benzyloxy) -phenyl} -propionic acid ethyl ester (480 mg, 0.8 Millimoles), ethanol (8 ml), 1,4-dioxane (4 ml) and 1N aqueous sodium hydroxide solution (1.  6 ml, 1.  6 millimoles), and the reaction and post-treatment were carried out according to the method of Example (53c) to obtain the target compound (360 mg, 79%). -176- 200408628 MS (FAB) m / z: 5 7 2 (M + H) + HR-MS (FAB) m / z: C32H31C105N3 (M + H ”Calculation: 5 7 2. 1 9 5 2; Real 'M 値: 5 7 2. 1 9 7 4 〇 (Example 5 5) 3-{4-{2- [6-(4-Amino-phenoxy) -1-methyl-1H -benzimidamido-2-yl]- Ethoxy} -2- (4-chloro-benzyloxy) -phenyl} -propionic acid 2 hydrochloride (exemplified compound number 1-3 7 8) (5 5 a) 3-{4-{2- [6-(4-Amino-phenoxy) -1-methyl-ijj · benzimidazol-2-yl] -ethoxy} -2- (4-chloro-benzyloxy) -phenyl} -Ethyl propionate using 3- [3- (4-chloro-benzyloxy) · 4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (833 Mg, 2β〇5 mmol), dichloromethane (10 ml), chloramphenicol (0. 197 ml, 2. 25 mmol), N, N -dimethylformamide (catalyst amount), [2-amino-5- (4-tert-butoxycarbonylamino-phenoxy) -phenyl]- Tertiary butyl methamate (880 mg, 2. 05 millimoles), dichloromethane (10 ml) and 4 N hydrochloric acid 1,4-dioxane (30 ml). The reaction and post-treatment were carried out according to the method of Example (53b). The target compound was obtained (370 mg, 30%). MS (FAB) m / z: 6 0 0 (M + H) + 〇 (55b) 3- {4-{2-[6.  (4-Amino-phenoxy) -1-methyl-1H_benzimidazol-2-yl] -ethoxy} -2- (4-chloro-benzyloxy) -phenyl} -propionic acid 2 The hydrochloride was produced using the 3-{4 · {2-[6-(4 -amino- 200408628 phenoxy) -1-methyl-1H -benzimidazole-2- produced in Example (5 5 a). Group] -ethoxy} -2- (4-chloro-benzyloxy) -phenyl} -propionic acid ethyl ester (370 mg, 0.62 mmol), ethanol (6 ml), 1,4- Dioxane (3 ml) and in sodium hydroxide aqueous solution (1.2 ml, 1.2 mmol) were reacted and worked up according to the method of Example (53c) to obtain the target compound ( 2 10 mg, 59%). MS (FAB) m / z: 5 7 2 (Μ + Η) + HR-MS (FAB) m / z: C32H31C105N3 (M + H) + calculation: 572. 1952: Found 値: 572.  1985 ° · (Example 5 6) 3-{2-(4-chloro-benzyloxy) -4- [6- (2-hydroxy-ethoxy) -i-methyl-1H -benzimidazole- 2-ylmethoxy] -phenyl} -propionate hydrochloride (exemplified compound number 1-3 5 7) (56a) acetic acid 2-[3-(third butoxycarbonyl-methylamino)-4- Nitro-phenoxy] -ethyl ester will be 2-ethoxyethanol (1. 2 ml) was dissolved in tetrahydrofuran (10 ml), and sodium hydride (55%, 50 mg) was added under ice-cooling, and stirred for 30 minutes. To the reaction mixture was added (5-chloro-2-nitrophenyl) -methylcarbamic acid tert-butyl ester (3 g), and the mixture was stirred at 90 ° C for 20 minutes, and then N, N -dimethylformamidine was added. Amine (20 ml) and stirred for 2.5 hours. The reaction mixture was added with water 'and extracted with ethyl acetate. The organic layer was concentrated, and the residue was dissolved in dichloromethane (20 ml), acetic anhydride (2 ml) and pyridine (3 ml) were added, and the mixture was stirred at 80 ° C for 2 hours. Dilute hydrochloric acid was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was washed with water and saturated brine in that order, and then dried over anhydrous -178-200408628 sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1 0/1 to 3/1) to obtain the target compound (2.  4 g, yield 65%). MS (FAB) m / z: 3 5 5 (M + H) + o (56b) acetic acid 2- [4-amino-3- (third butoxycarbonyl-methylamino) -phenoxy] -ethyl Ester The 2- [3- (third-butoxycarbonyl-methylamino) -4-nitro-phenoxy] -ethyl acetate (2.4 g) produced in Example (56a) was dissolved in ethanol ( 25 ml), 10% palladium-carbon was added, and the mixture was stirred vigorously under hydrogen at room temperature for 2.5 hours. The catalyst was filtered through diatomaceous earth and the solvent was distilled off under reduced pressure to obtain the target compound (2.1 g, 95%). MS (FAB) m / z: 3 2 5 (M + H) +. (5 6 c) 3-[4- {[4- (2- (Ethoxymethyl-ethoxy) -2- (third butoxycarbonyl-methylamino) -anilinemethyl]]-methoxy } 2- (4-Chloro-benzyloxy) -phenyl] -propionic acid ethyl ester The 2- [4-amino-3- (third butoxycarbonyl-methyl) Amine) -phenoxy] -ethyl ester (551 mg), 3- [3- (4-chloro-benzyloxy) -4- (2-ethoxycarbonylethyl) produced by Example Lu (53a) ) -Phenoxy] -propionic acid (800 mg) and diethyl cyanophosphate (0.31 ml) were dissolved in tetrahydrofuran (20 ml), triethylamine (0.28 ml) was added, and the mixture was stirred at room temperature for 4 hours. · 5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine in this order, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 5/1 to 3/1 -179- 200408628) to obtain the target compound (820 mg, yield 69%). MS (FAB) m / z: 6 9 8 (M) +. (5 6 d) 3-[4- [6- (2- (Ethyloxy-ethoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -2- (4- Chloro-benzyloxy) phenyl] -propionic acid ethyl ester The 3- [4- {[4-(2-ethylacetoxy-ethoxy) -2- ( Tributoxycarbonyl-methylamino) -anilinemethyl] -methoxy} -2-(4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (81 mg) dissolved in 4 N Hydrochloric acid-1,4-dioxane (20 ml) was stirred at room temperature overnight. It was concentrated under reduced pressure, and the obtained residue was washed with ethyl acetate to obtain the target compound (180 mg, yield 27%). MS (FAB) m / z: 581 (M + H) +. (5 6 e) 3-{2-(4-chloro-benzyloxy) -4- [6-(2-hydroxy-ethoxy) -1-methyl-1H -benzimidazole-2-ylmethyl Oxy} -phenyl} -propionate hydrochloride The 3- [4- [6-(2-ethylacetoxy-ethoxy) -1-methyl-1H-produced in Example (56d) Benzimidazol-2-ylmethoxy] -2- (4-chloro-benzyloxyphenyl] -propionic acid ethyl ester (180 mg) was dissolved in ethanol (4 ml), 1,4-dioxane ( 2 ml) solution, 1 N aqueous sodium hydroxide solution (0.61 ml) was added, and the mixture was stirred at room temperature for 4 hours. The solution was concentrated under reduced pressure, the residue was added with acetic acid water, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. It was dried under concentration. Concentrated, 4 N hydrochloric acid-1,4-dioxane was added, and Shen Dian was collected by filtration, and the target compound (107 mg, yield 68%) was obtained by drying. MS (FAB) m / z: 511 ( Μ + Η) + -180 · 200408628 HR-MS (FAB) m / z: C27H28C106N2 (M + H) + Calculated 値: 5 1 1. 1 6 3 6; actual measurement: 5 1 1. 1 6 2 8 ° (Example 5 7) 3-{2- (4-chloro-benzyloxy) -4- [6- (2-dimethylamino-ethoxy) -1-methyl-1H -Benzimidazole-2-ylmethoxy] -phenyl} ... propionic acid 2 hydrochloride (exemplified compound number 1-3 5 9) (57a) [5-(2-dimethylamino-ethoxy ) -2 -Nitrophenyl] -methylcarbamic acid tert-butyl ester 2-dimethylamine ethanol (1. 26 ml) was dissolved in tetrahydrofuran (10 ml ginseng), and sodium hydride (55%, 50 mg) was added under ice cooling and stirred for 30 minutes. To the reaction mixture was added (5-chloro-2-nitrophenyl) -methanecarbamic acid third butyl ester (3 g), and stirred at 80 ° C for 3. 5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate == 1/1 ~ ethyl acetate ~ ethyl acetate / methanol = 1 0/1) to obtain Target compound (2. 7 g, yield 76%). _ MS (FAB) m / z: 3 4 0 (M + H) +. (57b) [2-Amino-5- (2-dimethylamino-ethoxy) -phenyl] -methylcarbamic acid tert-butyl ester produced using Example (5 7 a) [5-( 2-dimethylamino-ethoxy) -2-nitrophenyl] -methylcarbamic acid tert-butyl ester (2.7 g), ethanol (25 ml) and 10% palladium-carbon, according to the examples (5 6 b) The reaction and post-treatment can be carried out to obtain the target compound (2.4 g, 97%). -181 · 200408628 MS (FAB) m / z: 3 1 〇 (M + H) + ° (57c) 3-[4- {[2 · (Third Butoxycarbonyl · Methylamino) · 4 · (2_ Dimethylamino-ethoxy) -anilinomethyl] -methoxy} 2- (4-chloro_benzyloxy) _phenyl] _ethyl propionate produced using Example (57b) [2-Amino-5- (2-dimethylamino_ethoxy) -phenyl] -methylcarbamic acid tert-butyl ester (525 mg), 3_ [3-( 4-Chloro-benzyloxy) -4_ (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (800 mg), diethyl cyanophosphate (0. 31 ml), tetrahydrofuran (20 ml) and triethylamine (0.28 ml). The reaction and post-treatment were carried out in accordance with the method of Example (56 c) to obtain the target compound (680 mg, 58%). ). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1 to ethyl acetate to ethyl acetate / methanol = 10/1). MS (FAB) m / z: 6 8 4 (M + H) +. (57d) 3.  (2-(4_ Chlorine. Benzyloxy) · 4_ 〔6-(2-dimethylamino. Ethoxy) -1-methyl-1fluorene-benzimidazol-2-ylmethoxy} -phenyl} -propionic acid ethyl ester 3-[4-{[2- (Third butoxycarbonyl-methylamino) -4- (2-dimethylamino-ethoxy) -anilinemethyl] -methoxy}-2- (4-chloro-benzyloxy)- Phenyl] -ethyl propionate (670 mg) and 4 N hydrochloride-1,4-dioxane (20 ml) were reacted and worked up in accordance with the method of Example (56d) to obtain the objective. Compound (300 mg, 54%). MS (FAB) m / z: 566 (M + H) +. -182- 200408628 (5 7 e) 3-{2- (4-chloro-benzyloxy) -4-[6-(2-dimethylamino-ethoxy) -1-methyl-1H-benzene Benzimidazol-2-ylmethoxy} -phenyl} -propionic acid 2 hydrochloride 3-{2- (4-chloro-benzyloxy) -4- [6- (2-dimethylamino-ethoxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid ethyl ester (300 mg), ethanol (8 ml) , 1,4-Dioxane (4 ml) solution and 1 N aqueous sodium hydroxide solution (2.6 ml), the reaction and post-treatment were carried out according to the method of Example (56e), and the target compound (1 0 mg, 35%). MS (FAB) m / z: 5 3 8 (Μ + Η) + HR-MS (FAB) m / z: C29H33 C105N3 (M + H) + Calculated 値: 5 3 8. 2 1 0 8; Found: 538. 2098. (Example 5 8) 3_ {2 · (4-Chloro-thenyloxy) · 4_ [1. Methyl-6- (l-methoperidine-4.  Alkoxy) -1Η-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid 2 hydrochloride (exemplified compound number 1-3 6 1) (58a) methyl-[5- (1 -Methylpiperidin-4-yloxy) -2-nitrophenyl] -carbamic acid third butyl ester 1-methylpiperidin-4-ol (1. 45 g) was dissolved in N, N-dimethylformamide (20 ml), and sodium hydride (55%, 50 mg) was added under ice-cooling and stirred for 30 minutes. To the reaction mixture was added (5-chloro-2-nitrophenyl) -methylcarbamic acid tert-butyl ester (3 g), and the mixture was stirred at 90 ° C for 3 hours. Water was added to the reaction mixture, and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order, and then dried over anhydrous sodium sulfate. The -183 · 200408628 solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1 to ethyl acetate ~ ethyl acetate / methanol = 1 0/1), The desired compound was obtained (2.9 g, 76% yield). MS (FAB) m / z: 3 6 6 (M + Η) + 〇 (58b) [2-amino-5- (1-methylpiperidin-4-yloxy) -phenyl] -methylamine The third butyl formate was used as the methyl- [5-(1 · methylidene-4-yloxy) -2 -nitrophenyl] -carbamic acid third butyl ester produced in Example (58a) ( 2. 9 g), ethanol (25 ml) and 10% palladium-carbon were reacted and worked up according to the method of Example (56 b) to obtain the target compound (2.6 g, 98%). MS (FAB) m / z: 3 3 6 (M + H) +. (5 8 c) 3-[4- {[2- (Third-butoxycarbonyl-methylamino) -4- (1-methylpiperidine-4 -yloxy) -anilinemethyl] -methyl Oxy}-2-(4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester [2-amino-5-(1 -methylpiperidine) produced in Example (5 8 b) -4 -Alkyloxy) -phenyl] -methylaminomethane acid tert-butyl ester (713 mg), 3 · [3-(4-chloro-benzyloxy) -4 produced in Example (53a) -(2-Ethoxycarbonylethyl) -phenoxy] -propionic acid (1 g), diethyl cyanophosphate (0. 3 8 7 ml), tetrahydrofuran (25 ml) and triethylamine (0. 353 ml) ′ was reacted and worked up according to the method of Example (57 c) to obtain the target compound (900 mg, 59%). MS (FAB) m / z: 710 (M + H) +. (5 8 d) 3-{2-(4-chloro · benzyloxy) _4_ [1-methyl · 6- (1-methylpiperidin-4-yloxy) -1Η-benzimidazole-2 -Ylmethoxy}--184 · 200408628 phenyl} -ethyl propionate 3-[4-{[2-(third butoxycarbonyl-methylamino) produced in Example (5 8 c)) -4- (1-methylpiperidinyloxy) _anilinemethyl] _methoxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (900 mg) And 4N hydrochloric acid-1,4-dioxane (20 ml), and reacted and worked up according to the method of Example (56 d) to obtain the target compound (750 mg, 100%). MS (FAB) m / z: 5 9 2 (M + H) +. (58e) 3-{2- (4-Chloro-benzyloxy) -4 · [1-methyl-6- (1-methyl-piperidine-4-yloxy) -1Η-benzimidazole- 2-ylmethoxy} -phenyl} -propanoic acid 2 hydrochloride The 3- (2- (4-chloro-benzyloxy) -4- [1-methyl- 6- (1-Methyl vein D 疋 -4-yloxy) -1H-benzoyl hydrazine 2- 2-methylmethoxy] -phenyl} -propionic acid ethyl ester (750 mg) was dissolved in ethanol ( 12 ml) of a solution of 1,4-dioxane (6 ml), a 1N aqueous solution of sodium hydroxide (2.7 ml) was added, and the mixture was stirred at room temperature for 5 hours, and then stirred at 60 ° C for 1 hour. The reaction mixture was concentrated, and water was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and the crystals were collected by filtration and dissolved in 4 N hydrochloric acid-1,4-1-Pf. The solvent was distilled off under reduced pressure, and the obtained residue was ethanol-ethyl acetate and then re-sinked to obtain the target compound (350 mg, 49%). MS (FAB) m / z: 5 6 4 (Μ + Η) + HR-MS (FAB) m / z: C31H35C105N3 (M + H) + Calculated 値: 5 6 4 · 2 2 6 5; Measured 値: 5 6 4.  2 2 6 9 -185- 200408628 (Example 59) 3- [4- [6- (4-Amino-3,5-dimethyl-phenoxy) -1-methyl-1H-benzumi -Ylmethoxy] -2-preoxy-phenyl] -propionic acid 2 hydrochloride (exemplified compound number 1-1 7 8) (59a) 3- (2-benzyloxy-4- {[4 -(4-tert-butoxycarbonylamino-3,5-monomethyl-phenoxy) -2- (second butoxycarbonyl-methylamino) -anilinemethyl]]-methoxy}- Phenyl) -ethyl propionate uses {4- [4-amino-3-(third butoxycarbonyl-methylamino) · phenoxy} -2, 6-dimethyl-phenyl} -amine Tert-butyl formate g), 3- [3- (4-chloro-benzyloxy) -4-(2-ethoxycarbonylethyl) -phenoxy] -propion produced in Example (53a) Acid (1g), diethyl cyanophosphate (0. 44 ml), tetrahydrofuran (30 ml) and triethylamine (0.4 ml). The reaction and post-treatment were carried out according to the method of Example (56 c), and the target compound (1.  5 grams, 78%). (59b) 3. [4_ [6-(4-amino-3,5-dimethyl-phenoxy). 1. Methyl-1H-benzimidazol-2-ylmethoxy] -2-benzyloxy-phenyl] -propionic acid ethyl ester_ 3-(2 -benzyloxy) produced using Example (5 9 a) -4 [{4-(4 · Third-butoxycarbonylamino-3, 5 -dimethyl-phenoxy) -2- (third-butoxycarbonyl-methylamino) -aniline ] -Methoxy} -phenyl) -ethyl propionate (1.5 g) and 4N hydrochloric acid-1,4-dioxane (30 ml). The reaction was carried out in accordance with the method of Example (56d). After treatment, the target compound (360 mg, 33%) can be obtained. Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1 to 1/1 to 1/3). -186- 200408628 (59 (〇3_ [4- [6 -_ (4-Amino-3,5-dimethyl-phenoxy) -1_methyl-1H -benzimidazol-2-ylmethoxy ] -2-benzyloxy-phenyl] -propanoic acid 2 hydrochloride The 3-[4-[6-(4-amino-3,5-dimethyl-benzene) produced in Example (59b) (Oxy) -1-methyl-1H -benzimidazol-2-ylmethoxy] -2-benzyloxy-phenyl] -propionic acid ethyl ester (360 mg) dissolved in ethanol (5 ml) , 4-Dioxane (2.5 ml) solution, 1N aqueous sodium hydroxide solution (1.5 ml) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, and the residue was added with acetic acid and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. Concentrated, 1N hydrochloric acid was added, and Shen Dian 'was filtered, washed with ethyl acetate, and dried to obtain the target compound (280 mg, yield 82%). (FAB) m / z: 5 5 2 (Μ + Η) + HR-MS (FAB) m / z: C33H3405N3 (M + H) + Calculated 値: 5 5 2 · 2 4 9 9; Measured 値: 5 5 2 · 2 4 6 8. (Example 60) 3 · {2- (4-chloro-benzyloxy) -4-[6- (ι · methylsulfonyl-piperidin-4-yloxy) -1-methyl-1 hydrazone Benzimidazole_2_ylmethoxy] -phenyl} _ propionate (exemplified compound number i _ 3 6 3) (60a) 4- [3-(third butoxycarbonyl · methylamino) 4-nitro-phenoxy] -piperidine-1-carboxylic acid tert-butyl ester 4-mercapto-piperidine-; 1. · carboxylic acid tert-butyl ester (2.5 g), N, N_ Monomethylformamide (20 ml), sodium hydride (55%, 550 mg), (5-chloro-2-nitrophenyl) -methylcarbamic acid tert-butyl ester (3 g), as per -187- 200408628 The method of Example (5 8 a) was used for the reaction and post-treatment to obtain the target compound (4.6 g, 97%). It was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1 〇 / 1 ~ 3/1) MS (FAB) m / z: 4 5 2 (M + H) +. (60b) 4- [4-amino-3- (third butoxycarbonyl-methylamino) ) -Phenoxy] -piperidine-1 -carboxylic acid tert-butyl ester 4- [3- (Third-butoxycarbonyl-methylamino) -4-nitro-benzene produced in Example (60a) Oxy] -piperidine-1-carboxylic acid tert-butyl ester (4. 6 g), ethanol (30 ml) and 10% palladium-carbon. The reaction and post-treatment were carried out according to the method of Example (56 b) to obtain the target compound (4 g, 93%) ° MS ( FAB) m / z: 421 (M) +. (60c) 4- (3- (2- (Third-butoxycarbonyl-methylamino) -4- {2- [3-(4-chloro-benzyloxy) -4- (2-ethoxycarbonylethyl ) -Phenoxy] -acetamido} -phenoxy) -piperidine-1-carboxylic acid tert-butyl ester 4- [4-amino- 3- ( Tert-butoxycarbonyl-methylamino) -phenoxy] -piperidine-1-carboxylic acid tert-butyl ester (1. 2 g), 3- [3- (4-chloro-benzyloxy) -4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (1. 34 g), diethyl cyanophosphate (0.52 ml), tetrahydrofuran (30 ml), and triethylamine (0.50 ml).  (47 ml), followed by reaction and post-treatment according to the method of Example (56 c), to obtain the target compound (1.4 g, 62%). (60d) 3-{2- (4-chloro-benzyloxy) -4- [1 · methyl-6- (piperidine-4 -yloxy) -1H -benzimidazol-2-ylmethoxy Group] -phenyl}-200408628 ethyl propionate The 4- (3-(2-(third butoxycarbonyl-methylamino))-4- (2-[3-( 4-chloro-benzyloxy) -4- (2-ethoxycarbonylethylphenoxy] -acetamido-phenoxy) -piperidine-1-carboxylic acid tert-butyl ester (1.4 G) Dissolved in 4 N hydrochloric acid-1,4-dioxane (30 ml), and stirred at room temperature overnight. The Shen Dian was collected by filtration, ethyl acetate-saturated sodium bicarbonate aqueous solution was added to separate layers, and the organic layer was mixed with water , Saturated saline solution was washed sequentially, and the solvent was distilled off under reduced pressure to obtain the target compound (900 mg, yield 89%). (6 0 e) 3-{2-(4-chloro-benzyloxy) -4 -[6- (1-methylsulfonyl-piperidine-4-yloxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid ethyl ester The 3- {2- (4-chloro-benzyloxy) -4- [1-methyl-6- (piperidin-4-yloxy) -1H-benzimidazole produced in Example (60d) 2-ylmethoxy] -phenyl} -propionic acid ethyl ester (400 mg), methanesulfonyl chloride (0. 064 ml) was dissolved in a solution of dichloromethane (10 ml), triethylamine (0.115 ml) was added, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1 to 1/5) to obtain the target compound (410 mg, yield 91%). MS ( FAB) m / z: 6 5 6 (M + H) +. (60f) 3-{2-(4-chloro-benzyloxy) -4- [6-(1-methylsulfonyl-piperidine-4-yloxy) -1-methyl-1H -benzo Imidazol-2-ylmethoxy] -phenyl} -propionate hydrochloride -189-200408628 3-{2- (4-chloro-benzyloxy) -4- [4] produced in Example (60e) 6- (1-Methanesulfonyl-piperidine-4-yloxy) -1-methyl-1H-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid ethyl ester (410 mg ) Dissolved in ethanol (5 ml) -1,4-dioxane (2.5 ml) solution, add 1 N aqueous sodium hydroxide solution (1.  3 ml) and stirred at room temperature overnight. The reaction mixture was concentrated, 1N hydrochloric acid was added, and Shen Dian was collected by filtration, and washed with water and ethyl acetate to obtain the target compound (280 mg, 71%). MS (FAB) m / z: 6 2 8 (M + H) +. HR-MS (FAB) m / z: C31H35C107N3S (M + H) + Calculation · Calculation: 6 2 8. 1 8 8 5; Found: 628. 1896. (Example 6 1) 3-{2- (4-chloro-benzyloxy) -4- [1-fluorenyl-6- (1-tert-butoxycarbonyl-piperidin-4-yloxy)- 1H-benzimidazol-2-ylmethoxy] -phenyl} -propionate (exemplified compound number 1-3 6 4) (6 1 a) 4-{2- [3-(4 -Ga -Benzyloxy) -4- (2-ethoxymineethyl) -phenoxymethyl] -3 -methyl-3H-benzimidazol-5-yloxy} -piperidine-1 -carboxylic acid Tributyl ester φ will contain 3-{2-(4-chloro-benzyloxy) -4_ [1-methyl-6- (piperidine-4 -yloxy) produced in Example (60 0 d) -1H -benzimidazol-2-ylmethoxy] -phenyl} -propionic acid ethyl ester (500 mg), di-tert-butyl dicarbonate (2 18 mg) in dichloromethane (10 ml) ) Solution, add ethylamine (0.  1 2 2 ml), and stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and purified by silica gel column chromatography (eluent: hexane / ethyl acetate-190-200408628 ester = 3/1) to obtain the target compound (410 mg, yield 70%). MS (FAB) m / z: 6 7 8 (M + H) +. (6 1 b) 3-{2-(4-Gas-benzyloxy) -4 · [1-methyl-6- (1-tert-butoxycarbonyl-piperidine-4 -yloxy) -1Η -Benzimidazol-2-ylmethoxy] -phenyl} -propionate hydrochloride 4-{2-[3-(4-chloro-benzyloxy) -4 produced in Example (61a) -(2-Ethoxycarbonylethyl) -phenoxymethyl] -3-methyl-3H-benzimidazole-5-yloxy} -piperidine-1-carboxylic acid tert-butyl ester (410 mg) , Ethanol (5 ml), 1,4-dioxane (2. 5 ml) and 1N aqueous sodium hydroxide solution (1.2 ml) were reacted and worked up in accordance with the method of Example (60 f) to obtain the target compound (320 mg, 81%). MS (FAB) m / z: 6 5 0 (Μ + Η) + HR-MS (FAB) m / z: C35H41C107N3 (M + H) + Calculated 値: 6 5 0. 2 6 3 3; Measured radon: 650. 2629. (Example 6 2) 3-{2-(4 · chloro-benzyloxy) · 4- [1-methyl-6- (piperidine-4 -yloxy) -1H -benzimidazole-2- Methoxy] -phenyl} -propanoic acid 2 hydrochloride (exemplified compound number 1-3 6 0) 3-{2- (4 · chloro-benzyloxy)-produced in Example (60d)- 4-[; [-Methyl-6- (piperidin-4-yloxy) -1H-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid ethyl ester (230 mg) was dissolved in 4N hydrochloric acid-1,4-dioxane (15 ml) was stirred at room temperature for 2 hours. The reaction mixture was concentrated, and Shen Dian was collected by filtration and washed with ethyl acetate to obtain the target compound (180-191-200408628 mg, 91%). MS (FAB) m / z: 5 5 0 (Μ + Η) + HR-MS (FAB) m / z: C30H33C1O5N3 (M + H) + Calculated 値: 5 5 0 · 2 1 0 9; Measured 値: 5 5 0 · 2 0 9 8. (Example 6 3) 3-{2-(4-chloro-benzyloxy) -4-[1-methyl- (6-tetrahydropyran-4-yloxy) -1H -benzimidazole- 2-ylmethoxy] -phenyl} -propionate (exemplified compound number 1-3 7 0) (63a) methyl- [2-nitro-5- (tetrahydrofluoranbiran-4- Alkoxy) -phenylcin] -carbamic acid third butyl ester using tetrahydropyran-4 · ol (0.8 ml), N, N-dimethylformamide (15 ml), sodium hydride ( 55%, 370 mg) and (5-chloro-2-nitrophenyl) -methanamic acid tert-butyl ester (2 g), which can be prepared and reacted in accordance with the method of Example (58a) to obtain Target compound (1.  9 grams, 7 7%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1 0/1 to 2/1). MS (FAB) m / z: 3 5 3 (M + H) +. (63b) [2-Amino-5- (tetrahydropyran-4-yloxy) -phenyl] -methylcarbamic acid third butyl ester using the methyl group produced in Example (6 3 a)- [2-nitro-5-(tetrahydropyran-4-yloxy) -phenyl] -carbamic acid third butyl ester (2. 0 g), ethanol (30 ml) and 10% palladium-carbon were reacted and worked up according to the method of Example (56 b) to obtain the target compound (1.5 g, 75%). MS (FAB) m / z: 3 2 3 (M + H) +. • 192- 200408628 (63c) 3- [4- {[2--(Third-butoxycarbonyl-methylamino) -4-(tetrahydropyran-4-yloxy) -anilinemethyl] -methyl Oxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester [2-amino-5-(tetrahydropyran-4) produced in Example (6 3 b) -Alkyloxy) -phenyl] -methylcarbamic acid tert-butyl ester (1 g), 3-[3-(4-Ga-fluoroxy) -4- (2- Ethoxylate ethyl) -phenoxy] -propionic acid (1. 46 g), diethyl cyanophosphate (0. 56 ml), tetrahydrofuran (30 ml), and triethylamine (0. 52 ml), and reacted and worked up according to the method of Example (56 c) to obtain the target compound (680 mg, 58%). MS (FAB) m / z: 6 9 6 (M) +. (6 3 d) 3-{2-(4-Gas-fluorenyloxy) -4- [1-methyl- (6-tetrachloropyran-4-yloxy) -1H -benzimidazole- 2-ylmethoxy] -phenyl} -propionic acid ethyl ester 3-[4-{[2-(Third-butoxy-methylamino) -4-) produced in Example (63c) Tetrahydropyran-4-yloxy) -anilinomethyl] -methoxy}-2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (1. 5 g) and 4 N hydrochloric acid-1,4-dioxane (30 ml). The reaction and post-treatment were carried out according to the method of Example (56 d) to obtain the target compound (940 mg, 7 5 %). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1). MS (FAB) m / z: 5 7 9 (M + H) + 〇 (63e) 3-{2- (4-chloro-benzyloxy) -4- [1-methyl- (6-tetrahydrofluorene) Pyran-4-yloxy) -1H-benzimidazo-2-ylmethoxy] -phenyl-193-200408628} • Propionate salt produced using Example (63d) 3- {2- (4- [1-methyl- (6-tetrahydropyran-4-yloxy) 2-ylmethoxy] -phenyl} -propionic acid ethyl ester (930 mL), 1, 4-Dioxane (7.5 ml) solution and aqueous solution (3.  2 ml), according to Example (60 f) and post-treatment, the target compound (610 mg, MS (FAB) m / z: 551 (Μ + Η) + HR-MS (FAB) m / z: C30H32C106r Calculation: 5 5 1.  1 9 4 9; Measured 値: 5 51. 1 9 5 1 (Example 6 4) 3-{2- (4 -Gas-fluorenyloxy) -4- [1-methyl-6 ~ 3 -yloxy) -1H -benzobenzoic acid 2-ylmethoxy] -hydrochloride (exemplified compound number 1-3 6 2) (64a) methyl- [5- (1-methylpiperidin-3-yloxy] -carbamic acid third butyl ester Use 1-methylpiperidine-3 -ol (0.99 ml), ammonium (15 ml), sodium hydride (55%, 3 65 5 2-nitrophenyl) -methanine Butyl ester (2 g) (5 8 a) was reacted and post-processed to obtain mesh g, 98%). (64b) [2-Amino-5-(1 -methylpiperidine-3 -ylcarbamate third butyl ester using the methyl-[5-([- Chloro-benzyloxy) -1 hafnium-benzimidazole-g), ethanol (15 1 Ν sodium hydroxide reaction 6 9%) 0 ^ 2 C 1 (Μ + Η) + ο · ( 1-methylsulfonyl_-phenyl} -propanoic acid 2-yl) -2-nitrophenyl N, N-dimethylmethyl g), (5-chloro-, compound according to the example (2.5 Gas group) · phenyl] -1-methylpiperidine-3--194- 200408628 alkoxy) -2-nitro-phenoxy] -carbamic acid third butyl ester (2.5 grams), ethanol (30 ml) and 10% palladium-carbon were reacted and worked up according to the method of Example (56b) to obtain the target compound (2.3 g, 100%). MS (FAB) m / z: 3 3 6 (M + H) +. (64c) 3_ (4.  {[2 · (Third-butoxycarbonyl-methylamino) · 4 · (1-methylpiperidin-3-yloxy) -anilinemethyl] -methoxy}-(4-chloro-benzyl [Oxyphenyl] -ethyl propionate [2-amino-5-(1-methylpiperidine-3-yloxy) -phenyl] -methylamine produced in Example (6 4 b) Tert-butyl formate (0. 95 g), 3- [3- (4-chloro-benzyloxy) -4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (1. 34 g), diethyl cyanophosphate (0.5 ml), tetrahydrofuran (25 ml) and triethylamine (0.5 47 ml), and reacted and worked up according to the method of Example (56 c) to obtain the target compound (2 g, 99%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1 to ethyl acetate to ethyl acetate / methanol = 3/1). MS (FAB) m / z: 710 (M + H) +. (6 4 d) 3-{2- (4- Gas-fluorenyloxy) -4- [1-methyl-6- (1-methylpiperidine-3 -yloxy) -1H-benzimidazole 2--2-Methoxy] _phenyl} -propionic acid ethyl ester 3-[4-{[2- (Third-butoxy-methyl-methylamino) -4- (1-methylpiperidine 4-yloxyaniline methylenyl] -methoxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (2 -195- 200408628 G) and 4 N hydrochloric acid-1,4-dioxane (30 ml), the reaction and post-treatment were carried out according to the method of Example (56 d), and the target compound (1.  36 g, 8 2%) 〇 (64e) 3_ {2- (4-chloro. Benzyl) -4-[1_ methyl. 6_ (1-methylpiperidin-3-yloxy) -1H-benzimidazole-2-ylmethoxy] -phenyl} -propanoic acid 2 hydrochloride 3 produced in Example (64d) -{2- (4-chloro-benzyloxy) -4- [1-methyl-6- (1-methylpiperidin-3-yloxy) -1H-benzimidazole-2 -ylmethoxy Phenyl] -phenyl} -ethyl propionate (700 mg) dissolved in ethanol (φ 15 ml) -1,4-dioxane (7. 5 ml) solution, 1N aqueous sodium hydroxide solution (6 ml) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated, 1N hydrochloric acid was added, and Shen Dian was collected by filtration, and washed with ethyl acetate. The resulting crystals were dissolved in 1 N sodium hydroxide, acidified with acetic acid and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. It was concentrated under reduced pressure, 1N hydrochloric acid was added, and Shen Dian was collected by filtration to obtain the target compound (270 mg, 41%). MS (FAB) m / z: 5 6 4 (Μ + Η) + · HR-MS (FAB) m / z: C31H35C105N3 (M + H) + Calculation 値: 5 6 4. 2 2 6 5; Found: 564. 2249. (Example 6 5) 3-{2- (4-chloro-benzyloxy) -4 · [1-methyl-6- (tetrahydrothiopyran-4-yloxy) -1H-benzimidazole -2-ylmethoxy] -phenyl} -propionate (exemplified compound number 1-3 7 1) (6 5 a) methyl- [2-nitro-5-(tetrahydrothiopyran -4 -yloxy) -phenyl-196-200408628] -tetrahydrothiopyran-4-ol (990 mg), N, N-dimethylformamide (1 5 Ml), sodium hydride (55%, 36.5 mg), (5-chloro-2-nitrophenyl) -methylcarbamic acid third butyl ester (2g), according to the method of Example (60a) The target compound (2.  5 g, 9 7%). MS (FAB) m / z: 3 6 9 (M + H) + 〇 (65b) [2-amino-5- (tetrahydrothiopyran-4-yloxy) -phenyl] -methanamic acid The third butyl methyl- [2-nitro-5-(tetrahydrothiopyran-4-yloxy) -phenyl] -carbamic acid third butyl ester produced in Example (65a) (2.5 grams), iron (1.9 grams), and ammonium chloride (catalyst amount) were added ethanol-water (3 ·· i), and stirred at 80 ° C for 3 hours. After the reaction mixture was cooled, insoluble matter was removed by filtration through celite, and the filtrate was concentrated. A saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the target compound (2 g > 87%). MS (FAB) m / z: 338 (M) +. (65c) 3-[4-{[2- (Third-butoxycarbonyl-methylamino) -4-(tetrahydrothiopyran-4-yloxy) -anilinemethyl]]-methoxyl 2- (4-Chloro-benzyloxy) -phenyl] -propionic acid ethyl ester [2-Amino-5- (tetrahydrothiopyran_4-yl) produced in Example (6 5b) was used (Oxy) -phenyl] -methylcarbamic acid tert-butyl ester (2 g), 3-[3-(4-chloro-benzyloxy) -4- (2-ethoxy) produced in Example (53a) Carbonyl-197- 200408628 ethyl) -phenoxy] -propionic acid (2. (78 g), diethylammonium cyanophosphate (1 ml), tetrahydrofuran (50 ml) and triethylamine (0.98 ml). The reaction and post-treatment were carried out according to the method of Example (56 c) to obtain Since spoon dagger compound (3 g, 71%). Purified by silica gel column chromatography (eluent: hexane fired / ethyl acetate = 1 0/1 to 5/1). MS (FAB) m / z: 712 (M) + 〇 (6 5 d) 3-{2-(4-chloro-benzyloxy) -4_ [1. Methyl- (tetrahydrothiopyran-4-yloxy) -1H-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid ethyl ester produced using Example (64c) 3- [4-{[2- (Third butoxycuryl-methylamino) -4- (tetrahydrothiopyran-4-yloxy) -anilinemethyl]]-methoxy} -2- ( 4-Chloro-benzyloxy) -phenyl] -propanoic acid ethyl ester (3 g) and 4N hydrochloric acid-1,4-dioxane (40 ml) were reacted according to the method of Example (56d) After treatment, the target compound (2.  3 grams, 92%). MS (FAB) m / z: 5 9 5 (M + H) +. (6 5 e) 3-{2-(4 -Gas-benzyloxy) -4- [1-methyl-6-(tetraaminothiopyran-4-yloxy) -1H -benzimidazole- 2-ylmethoxy] -phenyl} -propionate salt 3-{2- (4-chloro-benzyloxy) -4-[1-methyl-6 produced in Example (65d) -(Tetrahydrothiopyran-4-yloxy) -1H-benzimidazole-2-ylmethoxy] -phenyl} -propionic acid ethyl ester (500 mg), ethanol (15 ml), 1, 4-Dioxane (7.5 ml) and 1 N aqueous sodium hydroxide solution (6 ml) were reacted and worked up according to the method of Example (60f). 200408628 'could produce the target compound (240 mg, 50%). Wash with ethyl acetate and ethanol. MS (FAB) m / z: 5 6 7 (Μ + Η) + HR-MS (FAB) m / z: C30H32C1〇5N2C1S (M + H) + calculation 値: 5 6 7 · 1 7 2 1; measured 値: 5 6 7 · 1 7 2 7. (Example 6 6) 3-{2- (4-chloro-benzyloxy) -4- [1-methyl-6- (bumethylpyrrolidine-3-yloxy) -1H-benzimidyl Xy-2-ylmethoxy] -phenyl 丨 -propionic acid 2 hydrochloride (exemplified compound number 1-3 6 9) (66a) methyl- [5- (1-methylpyrrolidin-3 -yl (Oxy) -2-nitrophenyl] -carbamic acid third butyl ester 28 ml), n, N-dimethylformamide (15 ml), sodium hydride (55%, 3 65 mg), (5-chloro-2 -nitrophenyl) -methanamic acid third Butyl ester (2 g) was reacted and worked up according to the method of Example (5 8 a) to obtain the target compound (2.4 g, 98%). Purification by chopping gel column chromatography (eluent: Kiyain / ethyl acetate = 1/1 to ethyl acetate to ethyl acetate / methanol = 3/1). MS (FAB) m / z: 3 5 2 (M + H) + 〇 (66b) [2-amino-5- (1-methylpyrrolidinyloxy) -phenyl] -methanamic acid third Butyl ester was prepared using methyl- [5-(b methylfluorene having a slightly steeper 3- 3-oxyl group) -2 -nitrophenyl] -carbamic acid third butyl ester (2 6 a) produced in Example (2 · 5g), ethanol (30ml) and 10% palladium-carbon. The reaction and post-treatment were performed according to the method of Example (56b) to obtain the target compound (2.3g, 100%). ). -199- 200408628 MS (FAB) m / z: 3 2 2 (M + H) + 〇 (66c) 3-[4- {[2- (third butoxycarbonyl-methylamino) -4- (1 -Methylpyrrolidine-3 -yloxy) -anilinemethyl] -methoxy} -2-(4-chloro-fluorenyloxy) -phenyl] -propionic acid ethyl ester Example (6 6 b) [2-Amino-5-(1-methylpyrrolidin-3-yloxy) -phenyl] -methylcarbamic acid third butyl ester (0.7 g), Example (53a ) Produced 3- [3- (4-chloro-benzyloxy) -4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (1.03 g), diethyl cyanophosphate Ester (0. 4 ml), tetrahydrofuran (25 ml), and triethylamine (0.36 ml). The reaction and post-treatment were carried out according to the method of Example (64 c) to obtain the target compound (2 g, 99%). MS (FAB) m / z: 6 9 6 (M + H) + 〇 (66d) 3.  {2- (4 · Chloro-benzyloxy) -4- [1-Methyl · 6 · (1-Methylpyrrolidine Π 疋 -3-yloxy) -1Η-Benzimide Methoxy] -phenyl} -propionic acid ethyl ester 3-[4-{produced by Example (66c) using 3- (4-thoxybutyro-methylfee group) -4- (1-methyl卩 biol u 疋 -3-yloxy) -anilinomethyl]]-methoxy}-2- (4-gas-fluorenyloxy) -phenyl] -ethyl propionate (1 3 g) and 4N hydrochloric acid-1,4-dioxin (20 ml) was reacted and worked up according to the method of Example (56 d) to obtain the target compound (800 mg, 74%). MS (FAB) m / z: 5 7 8 (M + H) + 〇 (66e) 3-{2_ (4-chloro-benzyloxy) -4-h • methyl (1-methylpyrrolidine-3 -Yloxy) -1H-benzimidazole-2-ylmethoxy-200-200408628] -phenyl} -propanoic acid 2 hydrochloride 3-{2-(4 -Chloro-benzyloxy) -4- [1-methyl-6- (1-methylsuccinidine-3-yloxy) -1H-benzimidyl-2-phenylmethoxy] -Phenyl} -ethyl propionate (800 mg), ethanol (15 ml), 1,4-dioxane (7.5 ml) and 1 N aqueous sodium hydroxide solution (6 ml), according to the implementation The method of Example (5 9 c) was reacted and post-processed to obtain the target compound (250 mg, 33%). MS (FAB) m / z: 5 5 0 (M + H) + 〇HR-MS (FAB) m / z: C30H33C1O5N3 (M + H) + Calculated 値: 5 5 0 · 2 1 0 9; Measured 値 · 5 5 0. 2 1 0 8 ° (Example 6 7) 3-{2- (4 -Gas-benzyloxy) -4- [1-methyl-6- (2-Bamidine-l-yl-ethoxy Yl) -1H-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid 2 hydrochloride (exemplified compound number 1-3 6 5) (67a) methyl- [2-nitro-5 -(2-piperidin-1-yl-ethoxy) -phenyl] -carbamic acid third butyl ester using 2-piperidin-1-yl-ethanol (0. 51 ml), N, N-dimethylformamide (10 ml), sodium hydride (55%, 183 mg), (5-chloro-2-nitrophenyl) -methanine tert-butyl ester 1 g), according to the method of Example (5 8 a) and reaction and post-treatment, the target compound (2.  4 g, 98%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1 to ethyl acetate to ethyl acetate / methanol = 3/1). MS (FAB) m / z: 3 8 0 (M + H) +. (67b) [2-Amino-5- (2-piperidine-l-yl-ethoxy) -phenyl] -methyl-201-200408628 The third butyl carbamate was used in Example (6 7a). Production of methyl- [2-nitro-5-(2-piperidin-1-yl · ethoxy) -phenyl] -carbamic acid third butyl ester (1β2g), ethanol (20ml) And 10% palladium-carbon, which were reacted and worked up according to the method of Example (5 6 b) to obtain the target compound (1.1 g, 100%). MS (FAB) m / z: 3 5 0 (M + H) + 〇 (67c) 3-[4- {[2- (third butoxycarbonyl-methylamino) -4- (2-piperidin-1-yl-ethoxy)- Anilinemethyl] -methoxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester [2-amino-5-produced in Example (6 7 b)] (2-Piperidine-1 -yl-ethoxy) -phenyl] -methylcarbamic acid tert-butyl ester (740 mg), 3-[3-(4-chloro-benzyl) produced in Example (53a) (Oxy) -4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (998 mg), diethyl cyanophosphate (0. 39 ml), tetrahydrofuran (25 ml) and triethylamine (0. 353 ml), followed by reaction and post-treatment according to the method of Example (56 c), to obtain the target compound (800 mg, 52%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1 to ethyl acetate). MS (FAB) m / z: 7 2 4 (M + H) +. (6 7 d) 3-{2-(4-chloro-benzyloxy) -4-[1-methyl-6- (2-piperidin-1-yl-ethoxy) -1H -benzimidazole-2 -Ylmethoxy] -phenyl} -ethyl propionate 3-[4-{[2 · (third butoxycarbonyl-methylamino) -4-(2- Piperidin-1 -yl-ethoxy) -anilinemethyl]--202- 200408628 methoxy} -2-(4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (800 mg ) And 4 N hydrochloric acid · 1,4-dioxane (20 ml), and the reaction and post-treatment were carried out according to the method of Example (56 d) to obtain the target compound (660 mg, 99%). MS (FAB) m / z: 6 0 6 (M + H) +. (6 7 e) 3-{2-(4-Gas-benzyloxy) -4-[1-methyl (2-Primidin-1-yl-ethoxy) -1H -benzimidazole-2- Methylmethoxy] -phenyl} -propionic acid 2 hydrochloride 3-{2- (4-chloro-benzyloxy)-φ 4-[1-methyl-6 produced in Example (67d) -(2-piperidin-1-yl-ethoxy) -1H-benzimidazole-2-ylmethoxy] -phenyl} -propionic acid ethyl ester (660 mg), ethanol (15 ml), 1 , 4 -dioxane (7.  5 ml) and 1 N aqueous sodium hydroxide solution (4.5 ml) were reacted and worked up according to the method of Example (59c) to obtain the target compound (320 mg, 61%). MS (FAB) m / z: 5 7 8 (Μ + Η) + HR-MS (FAB) m / z: C32H36C105N3 (M + H) + Calculated 値: 5 7 8 · 2 4 2 2; Measured 値: 5 7 8 · 2 4 2 4. (Example 6 8) 3-{2- (4-chloro-benzyloxy) -4- [1-methyl-6- (2-morpholine-4.yl-ethoxy) -1H-benzene Benzimidazol-2-ylmethoxy] -phenyl} -propanoic acid 2 hydrochloride (exemplified compound number 1-3 6 6) (68a) methyl-[5-(2-morpholin-1-yl- Ethoxy) -2 -nitrophenyl] -threonyl formate uses morpholin-1-yl · ethanol (0. 55 ml), N, N-dimethyl-203 · 200408628 formamidine (10 ml), sodium hydride (55%, 183 mg), (5-chloro · 2-nitrophenyl) -methanamic acid third Butyl ester (1 g) was reacted and worked up according to the method of Example (6 6 a) to obtain the target compound (1.  1 g, 99%). MS (FAB) m / z: 3 8 2 (M + H) +. (68b) [2-Amino-5- (2-morpholin-1-yl-ethoxy) -phenyl] -methylcarbamic acid third butyl ester was used as the methyl group produced in Example (68a) -[5-(2 -morpholin-1 -yl-ethoxy) -2 -nitrophenyl] -carbamic acid third butyl ester (1. 2g), ethanol (20 ml) and 10% palladium-carbon were reacted and worked up according to the method of Example (56b) to obtain the target compound (1.1 g, 99%). MS (FAB) m / z: 3 5 2 (M + H) +. (6 8 c) 3-[4- {[2- (Third-butoxycarbonyl-methylamino) -4- (2-morpholin-1-yl-ethoxy) -anilinemethyl] -methyl Oxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester [2-amino-5-(2-morpholine-1) produced in Example (6 8 b) -Yl-ethoxyphenyl] -methylcarbamic acid tert-butyl ester (750 mg), 3-[3-(4-chloro-benzyloxy) -4- (2- Ethoxycarbonylethyl) -phenoxy] -propionic acid (1 g), diethyl cyanophosphate (0. 38 ml), tetrahydrofuran (25 ml) and triethylamine (0. 35 ml), and reacted and worked up according to the method of Example (5 7 c) to obtain the target compound (1.6 g, 100%). MS (FAB) m / z: 7 2 6 (M + H) +. (6 8 d) 3-{2-(4-chloro-benzyloxy). 4- [1-Methyl-6- (2 ·? -204- 200408628 quinolin-1-yl-ethoxy) -1H-benzimidazole-2 · ylmethoxy] monophenyl} -propionic acid ethyl ester 3-[4- {[2-(Third-butoxycarbonyl-methylamino) -4-(2 -morpholine-1 -yl-ethoxy) -aniline formamidine produced in Example (68c) Group] -methoxy}-2- (4-chloro-benzyloxy) -phenyl] · propionic acid ethyl ester (1. 6g) and 4 N hydrochloric acid-1,4-dioxane (30 ml). The reaction and post-treatment were carried out according to the method of Example (56 d) to obtain the target compound (1.1 g, 82%) ). MS (FAB) m / z: 6 0 8 (M + H) + o (6 8 e) 3-{2-(4_ chloro-benzyloxy) -4- [1-methyl · 6- (2- Morpholin-1-yl-ethoxy) -1Η-benzimidazol-2-ylmethoxy] -phenyl} -propionic acid 2 hydrochloride manufactured using Example (6 8 d) 3-{ 2- (4-chloro-benzyloxy) -4- [1-methyl-6- (2-morpholin-1-yl-ethoxy) -1H-benzimidazole-2-ylmethoxy] -Phenyl} -ethyl propionate (l. lg), ethanol (25 ml), 1,4-dioxane (13 ml) and 1 N aqueous sodium hydroxide solution (9 ml), and the reaction and post-treatment were performed according to the method of Example (59 c). The target compound (670 mg, 64%) can be obtained. Can be washed with ethyl acetate and ethanol. MS (FAB) m / z: 5 8 0 (Μ + Η) + HR-MS (FAB) m / z: C31H35C106N3 (M + H) + Calculated 値: 5 8 0 · 2 2 1 4; Measured 値: 5 8 0. 2 2 1 2. (Example 6 9) 3-[4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy-205-200408628) -2-(5-methylthiophene- 2-ylmethoxy) -phenyl] -propionate hydrochloride (exemplified compound number 1-3 5 1) (6 9 a) 3-[4- (6 -methoxy-1-methyl · 1Η -Benzimidazole-2-ylmethoxy) -2- (5-methylthiophen-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[produced in Example (22e) 2-Hydroxy-4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0.1 78 millimoles), potassium carbonate (324 mg, 2. 341 mmol), 2-chloromethyl-5-methylthiophene (1. 071 g, 7. 303 mmol) and N, N-dimethylformamide (10 ml), and the reaction and post-treatment were carried out according to the method of Example (2 2 f) to obtain the target compound (303 mg, yield 79%) ). MS (FAB) m / z: 4 9 5 (M + H) +. (6 9 b) 3-[4- (6-methoxy-l-methyl-1H-benzimidazol-2-ylmethoxy) -2- (5-methylthiophen-2-ylmethoxy Phenyl) -phenyl] -propionate hydrochloride The 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) produced in Example (69a) was used. ) -2- (5-methylthien-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (303 mg, 0. 613 millimolar), 1N sodium hydroxide (1. 3 ml, 1. 3 millimoles), ethanol (2 ml) and tetrahydrofuran (2 ml). The reaction and post-treatment were carried out according to the method of Example (22 g) to obtain the target compound (259 mg, 84%). MS (FAB) m / z: 4 6 7 (M + H) +. HR-MS (FAB) m / z: C25H2605N2S (M + H). Calculate -206- 200408628 f straight: 4 6 7. 1 6 4 1; measured 値: 4 6 7 · 1 6 4 9 (Example 70) 3- [2- (4-Bromothiophen-2-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy -Phenyl] -propionate (exemplified compound number 1-352) (7 0 a) 3-[2- (4-bromothiophen-2-ylmethoxy) -4- (6-methyl Oxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3- [2-hydroxy-4- (6) produced in Example (22e) was used · Methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (500 mg, 1. 3 millimoles), potassium carbonate (539 mg, 3. 902 mmol), 4-bromo-2-chloromethylthiophene (845 mg, 3. 995 mmol) and N, N-dimethylformamide (13 ml), and the reaction and post-treatment were carried out according to the method of Example (2 2 f) to obtain the target compound (483 mg, yield 66%) ). MS (FAB) m / z: 5 5 9 (M + H) +. (7 0 b) 3-[2-(4-bromothiophene-2 · ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy ) -Phenyl] -propionate salt 3-[2-(4-bromothiophen-2-ylmethoxy) -4-(6-methoxy-1- Methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (483 mg, 0.1 863 millimolar), 1N sodium hydroxide (1. 8 ml, 1. 8 millimolar), ethanol (2 ml) and tetrahydrofuran (2 ml), the method of Example (2 2 g) was used to carry out trans-207-200408628 and the target compound (45 mg, 8 8%). MS (FAB) m / z: 531 (M + H) + HR-MS (FAB) m / z: C24H2405N2BrS (M + H) + calculation: 531. 0589; Found 値: 531. 0599. (Example 7 1) 3- [2- (5-Bromothiophen-2-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy (Phenyl) -phenyl] -propionate (exemplified compound numbers 1-3 5 3) (7 1 a) 3-[2- (5-bromothiophen-2-ylmethoxy) -4-(6 -Methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3-[2-hydroxy-4- (6 · methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (500 mg, 1.3 mmol), potassium carbonate ( 539 mg, 3. 902 mmol), 5-bromo-2-chloromethylthiophene (1. 082 g, 5. 117 mmol) and Ν, Ν-dimethylformamide (13 ml), and reacted and worked up according to the method of Example (2 2 f) to obtain the target compound (474 mg, yield 65%) ). MS (FAB) m / z: 5 5 9 (M + H) +. (71b) 3-[2-(5-Hydroxyphen-2-ylmethoxy) -4- (6-methoxy_1-methyl-1H-benzimidazol-2-ylmethoxy) -Phenyl] -propionate was prepared using 3-[2-(5-bromothiophene-2-ylmethoxy) -4-(6-methoxy-1-methyl) produced in Example (71a). -IH-benzimidazol-2-ylmethoxy-208-200408628) -phenyl] -propionic acid ethyl ester (474 mg, 0.1 847 millimoles), 1N sodium hydroxide (1.7 milliliters, 1.7 millimoles), ethanol (2 milliliters), and tetrahydrofuran (2 milliliters). Post-treatment to obtain the target compound (427 mg, 88%) ° MS (FAB) m / z: 531 (Μ + Η) + Η R-Μ S (FAB) m / z: C 2 4 H 2 4 O 5 N 2 B r S (M + H) + Calculate 値: 5 3 1.  0 5 8 9; Actual measurement: 5 3 1. 0 5 7 6. (Example 7 2) 3-[2. (4-Bromofuran-2-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy (Phenyl) -phenyl] -propionate (exemplified compound number 1-3 5 5) (7 2 a) 3-[2- (4-bromofuran-2 -ylmethoxy) -4- (6 -Methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester 3- [2-hydroxy-4_ ( 6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (300 mg, 0. 78 millimoles), potassium carbonate (324 mg, 2. 341 mmol), 4-bromo-2-chloromethylfuran (1. 051 g, 5. 379 mmol) and N, N-dimethylformamide (8 ml), and the reaction and post-treatment were carried out according to the method of Example (2 2 f) to obtain the target compound (451 mg, yield 64%) ). MS (FAB) m / z: 544 (M + H) +. (7 2 b) 3-[2- (4-Bromofuran-2-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy ) -Phenyl] -propionic acid-209-200408628 Hydrochloride The 3- [2- (4-bromofuran-2-ylmethoxy) -4- (6-methoxy) produced in Example (72a) was used. Ethyl-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (451 mg, 0.1 83 millimolar), 1N sodium hydroxide (1. 7 ml, 1. 7 millimoles), ethanol (2 ml) and tetrahydrofuran (2 ml). The reaction and post-treatment were carried out according to the method of Example (2 2 g) to obtain the target compound (343 mg, 75%). MS (FAB) m / z: 515 (Μ + Η) + HR-MS (FAB) m / z: C24H2406N2Br (M + H) + Calculate · Calculate: 5 1 5 · 0 8 1 8; Measured 値 ·· 5 1 5. 0 8 0 6. (Example 7 3) 3- [2- (5-Bromofuran-2-ylmethoxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy -Phenyl] -propionate (Exemplified Compound Nos. 1-3 5 6) (7 3 a) 3-[2-(5-Bromofuran-2 -ylmethoxy) -4-(6 -Methoxy-1-methyl-1H -benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester_ 3- [2-hydroxy-4 produced in Example (22e) -(6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (500 mg, 1.3 mmol), potassium carbonate ( 539 mg, 3. 902 mmol), 5-bromo-2-chloromethylfuran (1.025 g, 5. 249 mmol) and Ν, Ν-dimethylformamide (13 ml) according to the method of Example (2 2 f) and post-treatment to obtain the target compound (351 mg, yield 50%) ). -210- 200408628 MS (FAB) m / z: 5 4 4 (M + H) +. (73b) 3-[2- (5- Molybran-2-ylmethoxy) -4- (6-methoxy · 1-methyl-1H-benzimidazol-2-ylmethoxy) ) -Phenyl] -propionate salt 3-[2-(5-Bromofuran-2 · ylmethoxy) -4-(6 -methoxy- 1-methyl-1H · benzimidazol-2-ylmethoxy) -phenyl] -propionic acid ethyl ester (351 mg, 0.1 646 mmol), 1N sodium hydroxide (1.3 ml, 1.3 mmol), ethanol (2 ml) and tetrahydrofuran (2 ml). After treatment, the target compound (301 mg, 84%) can be obtained. MS (FAB) m / z: 515 (Μ + Η) + HR-MS (FAB) m / z: C24H2406N2Br (M + H) + Calculated 値: 515. 0818; Found 値: 5 1 5 · 0 7 9 9. (Example 7 4) 3- [4- (6-Methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2-pentafluorobenzyloxy-phenyl]- Propionate (Exemplified Compound No. 1-350) (74a) 3-(2-hydroxy_4-methoxymethoxyphenyl) tert-butyl acrylate The 2-hydroxy group produced in Example (1a) -4 -methoxymethoxybenzaldehyde (4. 4 grams, 24. 153 mmol) was dissolved in tetrahydrofuran (100 ml), and tert-butyl diethyl phosphate (7. 62 grams, 30. 191 millimoles), carbon shavings (11. 8 grams, 36.23 moles), and heat and stir at 70 ° C for 1 day. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained 200408628 residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3 / ;!) to obtain the target compound (2-6 g, 38%). MS (E I) m / z: 2 8 0 (M) +. (7 4 b) 3-(2-Methoxy-4-methoxymethoxyphenyl) -tert-butyl propionate The 3-(2-hydroxy-4-methoxymethyl) produced in Example (74a) Oxyphenyl) tert-butyl acrylate (2. 6 grams, 9.28 millimoles) were dissolved in ethyl acetate (30 ml), the catalyst amount of palladium hydroxide was added, and the mixture was stirred at room temperature for 10 minutes under hydrogen and oxygen. After removing the catalyst through diatomite, the filtrate and liquid were concentrated under reduced pressure to obtain the desired compound (2.  62 g, 100%). MS (EI) m / z: 2 8 2 (M) +. (74c) 3-(4-methoxymethoxy-2-pentafluorobenzyloxy-phenyl) -tertiary butyl propionate The 3- (2-hydroxy-4) produced in Example (74b) -Methoxymethoxyphenyl) -tert-butyl propionate (500 mg, 1. 771 mmol) dissolved in N, N-dimethylformamide (10 ml), and potassium carbonate (734 mg, 5. 312 mmol), 1-bromomethyl-2,3,4,5,6-pentafluorobenzene (0. 4 ml, 2 · 6 5 6 mmol), and stirred at 50 ° C overnight. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in this order, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 5/1) to obtain the target compound (918 mg, yield 100%). MS (EI) m / z: 4 6 2 (M) + 〇 (74d) 3-(4-hydroxy-2-pentafluorobenzooxyphenyl) -propionic acid tert-butyl ester Example (74c) Manufactured 3-(4-methoxymethoxy-2-pentafluorobenzene-212- 200408628 methoxy-phenyl) -tributyl propionate (918 mg, 1. 985 mmol) was dissolved in ethanol (20 ml), p-toluenesulfonic acid (92 mg) was added, and the mixture was heated and stirred at 50 C for 3 hours. Triethylamine was added to the reaction solution, and it was concentrated 'added to water' and extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the target compound (830 mg, yield 100%). MS (El) m / z: 418 (M) + 〇 (74e) 3-[4 · (ό_methoxy · 1-methyl · fluorene · benzimidazole_2 · ylmethoxy) -2- Pentafluorobenzyloxy-phenyl] -tertiary butyl propionate The 3- (4-hydroxy-2-pentafluorobenzyloxyphenyl) -tertiary butyl propionate produced in Example (74d) (830 mg, 1. 771 mmol) and 2-hydroxymethyl-6 · methoxy-1-methyl-1H-benzimidazole (340 mg, 1. 7 7! Mmol) produced in Reference Example (lb) Ear) was dissolved in toluene (20 ml), and tributylphosphine (0. 55 ml, 2. 214 mmol) and 1,1,-(azidodicarbonyl) dipiperidine (558 g, 2. 214 mmol), and stirred at room temperature for 3 days. The reaction solution was purified by silica gel column chromatography (eluent: Jiyuan / ethyl acetate = 1/1) to obtain the target compound (484 mg, yield 4 6%). MS (FAB) m / z: 5 6 5 (M + H) +. (74f) 3- [4- (6-methoxy-1-methyl-iH-benzimidazol-2-ylmethoxy) -2-pentafluorobenzyloxy-phenyl] -propionate The 3-[4-(6 -methoxy-1 · methyl-1H -benzimidazol-2-ylmethoxy) -2-pentafluorobenzyl produced in Example (7 4 e) Oxy-phenyl] -tributyl propionate (484 mg, 0.1 (817 mmol) was added to a 4N salt -213- 200408628 acid-1,4-dioxane solution (10 ml), and stirred at room temperature for 1 day. The crystals were collected by filtration, washed with diisopropyl ether, and dried under reduced pressure to obtain the target compound (316 mg, yield 68%). MS (FAB) m / z: 5 3 7 (Μ + Η) + HR-MS (FAB) m / z: C26H2205N2F5 (M + H) + Calculated 値: 5 3 7 · 1 4 4 9; Measured 値: 5 3 7. 1 4 4 2. (Example 7 5) 3- [2- (4-chlorobenzyloxy) -4- {1-methyl-6- (3-morpholin-4-ylphenoxy) -benzimidazole- 2-ylmethoxy} -phenyl-propionate hydrochloride (exemplified compound number 1-3 6 7) (75a) methyl · {5-(3 · morpholin-4-ylphenoxy) nitrate Phenyl} · tert-butyl carbamate 3-morpholin-4-ylphenol (1. 501 g, 8377 mmoles) dissolved in N, N-dimethylformamide (20 ml), sodium hydride (3.5 mg, 8.37 mmoles) was added under ice cooling, and room temperature After stirring for 1 hour, (5-chloro-2-nitrophenyl) tert-butyl methylcarbamate (2 g, 6.98 1 mol) was added, and the mixture was heated and stirred at 1000 ° C for 1 hour. · 5 hours. After cooling to room temperature, water was added and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order 'and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent ·· hexane / ethyl acetate = 3/1) to obtain the target compound (2. 18 g, yield 73%). MS (EI) m / z: 4 2 9 (M) + 〇 (75b) {2-amino-5- (3-morpholin-4-ylphenoxyphenyl) -methylcarbamic acid third butyl ester -214- 200408628 The methyl- {5-(3-morpholin-4 -ylphenoxy) -2 -nitrophenyl} -carbamic acid third butyl ester produced in Example (7 5 a) (2 . 18 grams, 5. 076 mmol) was dissolved in ethyl acetate (20 ml), 10% palladium hydroxide was added, and the mixture was stirred under hydrogen at room temperature overnight. The catalyst was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2/1) to obtain the target compound (1. (986 g, 98% yield). MS (E I) m / z: 3 9 9 (M) +. (7 5 c) 3-[4-[{2-(Third butoxycarbonylmethylamino) -4-(3 -morpholin-4-ylphenoxy) -anilinemethyl}}-methoxy ] -2- (4-chlorobenzyloxy) -phenyl] -propionic acid ethyl ester The {2 -amino-5-(3 -morpholine-4 -ylbenzene) produced in Example (7 5 b) (Oxy) -phenyl} -methylcarbamate tert-butyl ester (500 mg, 1. 501 mmol) was dissolved in tetrahydrofuran (11 ml), and ethyl 3-carboxycarboxy-2- (4-chlorobenzyloxy) -phenyl} -propionate ethyl acetate (590 mg, 1. 501 mmol), triethylamine (0. 26 ml, 1. 877 millimolar), diethyl cyanophosphate (0. 28 ml, 1.877 mmol), and stirred at room temperature overnight. After the reaction solution was concentrated, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed successively with saturated sodium bicarbonate and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2/1) to obtain the target compound (805 mg, yield 83%). MS (FAB) m / z: 7 7 4 (Μ + Η) + 〇 (75d) 3- [2- (4-chlorobenzyloxy) -4- {1-methyl-6- (3-morpholine -4 -ylphenoxy) -1H-benzimidazol-2-ylmethoxy} -benzene200408628yl] -propionic acid ethyl ester 3-[4- [{2- (Third butoxycarbonylmethylamino) -4-(3-morpholin-4-ylphenoxy) -anilinomethyl} -methoxy] -2- (4-chlorobenzyloxy) -benzene Ethyl] -ethyl propionate (805 mg, 1.04 mmol) was dissolved in 4N hydrochloric acid-1,4-dioxane solution (10 ml) 'and stirred at room temperature overnight. After the reaction solution was concentrated, saturated sodium bicarbonate water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1) to obtain the target compound (343 mg, yield 50%). MS (FAB) m / z: 6 5 6 (M + H) +. (7 5 e) 3-[2- (4-chlorobenzyloxy) -4- {l -methyl-6- (3-morpholin-4 · ylphenoxy) -1H -benzimidazole-2 -Ylmethoxy} -phenyl] -propionate salt 3-[2-(4-chlorobenzyloxy) -4 · {1-methyl-6- ( 3-morpholin-4-ylphenoxy) -1H · benzimidazol-2-ylmethoxy} -phenyl] -propionic acid ethyl ester (343 mg, 0.1 515 mmol), 1 N sodium hydroxide (1.1 ml, 1.1 mmol), ethanol (i ml), and tetrahydrofuran (1 ml). The reaction was carried out according to the method of Example (2 2 g). After treatment, the target compound (267 mg, 74%) can be obtained. MS (FAB) m / z: 6 2 8 (Μ + Η) + (Μ + Η) + HR-MS (FAB) m / ζ: C35H3506N3C1 (Μ + Η) + calculated 値: 628. 2214; Found 値: 628. 2225. -216- 200408628 (Example 7 6) 3-[2- (4-chlorobenzyloxy) _4-[1-methyl-6- {4-(4-methylpiperazin-1-yl) -benzene Oxy} -1Η · benzimidazol-2-ylmethoxy] -phenyl] -propionate (Exemplified compound number 1-368) (76a) 4- [4-{3-(Third-butyl Oxymethylamino) -4 -nitrophenoxy} _phenyl] -piperin-1-carboxylic acid third butyl ester using 4- (4-hydroxyphenyl) -piperine- 丨 -carboxylic acid third Butyl ester (1. 丨 3 6 g, 4. 081 mmol), N, N -dimethylformamide (20 ml), sodium hydride (180 mg, 4. 489 millimolar), and (5-chloro-2-nitrophenyl) -methylcarbamic acid third butyl ester (1. 28 grams, 4. 489 millimoles), according to the method of Example (75a) and post-treatment, the target compound (1. 894 g, 88%) 〇MS (EI) m / z: 528 (M) + 〇 (76b) 4-[4-{4-amino-3- (third butoxycarbonylmethylamino) -phenoxy Group} -phenyl] -piperidin-1-carboxylic acid tert-butyl ester 4-[4-丨 3_ (third butoxycarbonylmethylamino) -4 -nitrophenoxy produced in Example (76a) } -Phenyl] -pigen-1 -tributyl tert-butyl ester (1. 894 g, 3. 583 mmol), ethyl acetate (20 ml), and 10% palladium hydroxide were reacted and treated in accordance with the method of Example (75b) to obtain the target compound (1.1.  7 51 g, 98%). MS (EI) m / z: 4 9 8 (M) + 〇 (76c) 4- [4-{3-(third butoxycarbonylmethylamino) _4- [2--(4-chlorobenzyloxy ) -4- (2_ethoxycarbonylethyl) _phenoxy 丨 -ethylfluorenyl] -benzyloxy-1-phenyl] -piperazine-1-residue tert-butyl ester-217- 200408628 Use 4- [4-{4-amino-3- (third butoxycarbonylmethylamino) -phenoxyphenyl] -piperin-1-carboxylic acid tert-butyl ester produced in Example (76b) (500 mg, 1. 002 mmol), tetrahydrofuran (10 ml) solution, 3-{4-carboxymethoxy-2- (4-chlorobenzyloxyphenyl propionate ethyl acetate (472 mg, [. 202 mmol), triethylamine (0. 21 ml, 1. 503 millimolar), and diethyl cyanophosphate (0. 23 ml, 1.  503 millimolars), followed by reaction and post-treatment according to the method of Example (75c), to obtain the target compound (790 mg, 90%). MS (FAB) m / z: 8 7 3 (M + H) +. (76d) 3-[2.  (4-chlorobenzyloxy). 4- {1-methyl. 6- (4-pipen-1-ylphenoxy) -benzimidazol-2-ylmethoxy} -phenyl] -propionic acid ethyl ester 4-[4-{ 3-(Third-butoxychimethylamino) -4- [2-{3-(4-chlorobenzyloxy) -4-(2-ethoxycarbonylethyl) -phenoxy} -acetamidamine Phenyl] -phenoxy} -phenyl] -piperidin-1-tricarboxylic acid third butyl ester (790 mg, 904 mmol) and 4N hydrochloric acid 1-4, Eryangyuan solution (10 ml), the reaction and post-treatment were carried out according to the method of Example (75d), and the target compound (2 6 6 mg, 44%) MS (FAB) m / z: 6 5 5 (M + H) +. (76e) 3 [[2- (4 · chlorobenzyloxy) · 4 · [1-methyl-6_ {4 · (4 · methyl pulsewell-1-yl) phenoxy} -1Η-benzimidyl DZ-2-ylmethoxy] -phenyl] -propionic acid ethyl ester 3-[2- (4 · chlorobenzyloxy) -4- {-218- 200408628 1 produced in Example (76d) -Methyl-6- (4-piperidylphenoxy) _1H-benzimidazole-2-ylmethoxy} -phenyl] · propionic acid ethyl ester (266 mg, 0.4 mmol To tetrahydro 1 sulfan (4 ml), add sodium hydride (17. 6 mg, 0.44 mmol) under ice cooling, and stir at room temperature for 1 hour, then add methyl iodide (27 1,0 · 4 4 mmol), and stirred at room temperature for 3 hours. Methanol was added to the reaction solution, and after concentrating, water was added, followed by extraction with ethyl acetate. The organic layer was washed successively with a saturated aqueous sodium hydrogen carbonate solution and a saturated saline solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 2 0/1) to obtain the target compound (186 mg, yield 69%). MS (FAB) m / z: 6 6 9 (M + H) +. (76f) 3-[2- (4-chlorobenzyloxy). 4 · [j • methyl_6 · (4__methylpiperazin-1-yl) phenoxy} -1H -benzimidazol-2-ylmethoxy] -phenyl] -propionate 3- [2- (4-chlorobenzyloxy) _4- [1-methyl-5- {6- (4-methylpiperin-1-yl) phenoxy} produced in Example (76e)} -111-benzimid-2-ylmethoxy] -phenyl] -propionic acid ethyl ester (186 mg, 0.1 278 mmol), sodium hydroxide (0. 56 ml, 0. 56 millimoles), ethanol (1 ml) and tetrahydrofuran (1 ml) were reacted and worked up according to the method of Example (22 g) to obtain the target compound (186 mg, 94%). MS (FAB) m / z: 641 (Μ + Η) + HR-MS (FAB) m / z: C36H3805N4C1 (M + H) + Calculation: 6 4 1. 2 5 3 1; Measured 値: 6 4 1. 2 5 6 5. -219- 200408628 (Example 7 7) (7 7a) 3-{2. Ethyl_4_ [2-(6_methoxy-1-methyl- ιη · benzimidazol-2-yl) -ethoxy] -phenyl 丨 -propionic acid ethyl ester (Exemplified compound numbers 1-3 8 7) 3 · {2- (4-chloro-benzyloxy) -4 — [2- (6-methoxy-1-methyl-1H-benzimidazole- 2-yl) -ethoxy] -phenyl} -ethyl propionate (6. 26 grams, 11. 969 mmol) was dissolved in a mixed solution of ethanol (20 ml) and ethyl acetate (20 ml), and the catalyst was added to the hydrogen hydroxide pin, and the mixture was stirred overnight at 50 ° C under hydrogen. After filtering the catalyst through diatomite, the filtrate was concentrated and recrystallized from methanol to obtain the target compound (3.  373 g, 71%). MS (FAB) m / z: 3 9 9 (M + H) + 〇 (77b) 3- {2- (5-chlorothien-2-ylmethoxy) -4- [2- (6-methoxy 1-methyl-1H-benzimidazol-2-yl) -ethoxy} -phenyl} -propionic acid ethyl ester 3-{2 -hydroxyl · 4 produced in Example (7 7 a) -[2-(6 -methoxy-1-methyl-1H-benzimidazol-2-yl) -ethoxy] -phenyl} -propionic acid ethyl ester (250 mg, 0. 627 mmol) dissolved in acetone (8 ml), added carbonic acid planer (307 mg, 0. 941 mmol), 2-chloro-5-chloromethylthiophene (0.  (12 ml, 0.94 1 mmol), and heat for 6 hours. After the reaction solution was concentrated, saturated sodium bicarbonate water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/3) to obtain the target compound (308 mg-220-200408628, yield 93%). . MS (FAB) m / z: 5 2 9 (M + H) +0 (77c) 3-{2- (5 -chlorothien-2-ylmethoxy) -4- [2-a (6-methoxy -L-methyl-1H-benzimidazol-2-yl) -ethoxy} _phenyl} -propionate salt Example 3 ({3-methyl-2-chlorothiophene manufactured by 77M) Methoxy) -4- [2- (6-methoxy-1 · methyl-1H-benzimidazole · 2 · its) -ethoxy] -phenyl} -propionic acid ethyl ester (308 Mg, 0.582 millimoles), 1N sodium hydroxide (1.5 2 ml, 1. 2 millimoles), ethanol (1 ml) and tetrahydrofuran (1 ml), according to the example (22g) ^; ^, reaction and post-treatment, to obtain the target compound (215 mg, 69%) ° MS (FAB) m / z: 501 (M + H) + HR-MS (FAB) m / z: C25H2605N2C1S (M + H) + Calculation 値: 5 0 1. 1 2 5 1; Measured radon: 5 0 1 · 1 2 5 4. (Example 7 8) 3-{2- (4-chloro-benzyloxy) · 4- [2- (1-methyl-6-phenoxy-1H-benzimidazol-2-yl) -ethyl Oxy] -phenyl} -propionate (exemplified compound number 1-3 7 6) (7 8 a) 3-{2- (4-chloro-benzyloxy) -4- [2- (1 -Methyl-6-phenoxy-1H -benzimidazol-2-yl) -ethoxy] -phenyl} -propionic acid ethyl ester 3-[3-(4 -Chloro-benzyloxy) · 4- (2-ethoxymineethyl) -phenoxy] -propionic acid (0.47 g, 1.2-2.2-200408628 mole) methylene chloride (10 Ml), Grasshopper Chlorine (0.17 ml '1. 9 mmol), Ν, Ν-dimethylformamide (catalyst amount), (2-amino-5-phenoxy-phenyl) -methylcarbamic acid third butyl ester (0.25 g ,1. 2 mmol), dichloromethane (15 ml), and 4N hydrochloric acid-1,4-dioxane (20 ml). The reaction and post-treatment can be carried out according to the method of Example (53b). The target compound (0.30 g, 44%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1). (7 8 b) 3-{2-(4-chloro-benzyloxy) -4- [2- (1-methyl-6-benzyloxy-1H-benzimidazol-2-yl) -ethoxy] -Phenyl} -propionate using 3-{2-(4-chloro-benzyloxy) -4- [2- (1 · methyl-6-benzene) produced in Example (7 8 a) Oxy-1H-benzimidazol-2-yl) -ethoxy] -phenyl} -propionic acid ethyl ester (0.30 g, 0.1 50 mmol), ethanol (5.0 ml), 1,4-dioxane (2. 5 ml) and 1N aqueous sodium hydroxide solution (1.  〇mL), the reaction and post-treatment according to the method of Example (53c), to obtain the target compound (0.21 g, 70%). 1 Η-N M R (4 0 0 MHz, D M S Ο-d 6): (5 p p m 2. 43 (2H, t, J = 7.  7 H z), 2. 74 (2H, t, J = 7.  7 H z), 3. 73 (3 H, s), 4. 42 (2 H, t, J = 6.  6 H z), 5. 11 (2H, s), 6. 50 (1 H, dd, J = 8 · 8, 2. 2 H z), 6. 60 (1H, d, J = 2. 2 H z), 6. 88 (1 H, d d, J = 8.  8, 2.  2 H z), 6. 94 (2 H, d, J = 8. 8Hz), 7. 05 (2H, d, J = 8.  1 H z), 7. 28 (1 H, d, J = 2. 2 H z), 7. 31-7. 36 (2 H, m), 7. 4 3-7. 4 7 (4 H, m), 7. 57 (1 H, d, -222- 200408628 J = 8.  1 Η z), 12. 0 (1 Η, brs), MS (FAB) m / z: 5 5 7 (M + H) + HR-MS (ESI) m / z: C32H30O5N2C1 (M + H) + Calculate 値: 5 5 7 · 1 8 4 4; Real wine I 値: 5 5 7. 1 8 2 4 〇 (Example 7 9) 3-(2- (4-chloro-benzyloxy) -4- {6-[3-(2-hydroxyethylamino) phenoxy] -1-methyl 1H-benzimidazol-2-ylmethoxy} -phenyl) -propionic acid 2 hydrochloride (exemplified compound number 1-3 5 8) (79a) [5- (3-· {三 丁丁Oxycarbonyl- [2- (third butyl-dimethyl-silyloxy) -ethyl] -amino} -phenoxy) -2-nitrophenyl] -methylcarbamic acid 5-(3 -Third-butoxycarbonylamino-phenoxy) -2 _nitrophenyl] -methylcarbamic acid third butyl ester (3. 4 grams, 7. 4 mmol) dissolved in N, N-dimethylformamide (40 ml), sodium hydride (55%, 0.64 g) was added under ice cooling, and the mixture was stirred at room temperature for 30 minutes, and then added ( 2-bromoethoxy) -tert-butyldimethylsilane (1. 6 ml, 7. 4 mmol), and stirred at 60 ° C for 4 hours. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 9/1) to obtain the target compound (2.3 g, yield 50%). 〇1 H-NMR (400 MHz, CDC13): δ ppm 〇〇〇 (6H, s), 0.84 (9H, s), 1.31 (9H, s), 1 · 4 4 (9 Η, s), 3 · 2 6 (3 Η, s), 3 · 7 4 (2 Η, d,-223-200408628 J = 5. 1Hz), 3. 78 (2 Η, d, J = 5.  1 Η z), 6. 83 (1H, dd, J = 2. 9, 9.  5 H z), 6. 8 8-6. 90 (2 H, m), 7. 14 (1H, s), 7. 22 (1H, d, J = 7.  3 H z), 7. 35 (1 H, t, J = 8.  0 H z), 7. 92 (1 H, d, J = 9. 5Hz). (79b) [2-amino-5- (3-(third butoxycarbonyl- [2- (third butyl-dimethyl-silyloxy) -ethyl] -aminophenoxy)) Phenyl] -methylcarbamate tert-butyl ester [5- (3-{Third-butoxyquinyl_] [2- (Di-dibutyl-monomethyl-saraxyl) Group) -ethyl] -amino group phenoxy) -2-nitrophenyl] -methylcarbamic acid third butyl ester (2. 3 grams, 3. 7 milliliters), ethanol (30 mL), and 10% fine-carbon (i. 〇g), the reaction and post-treatment according to the method of Example (56 b) to obtain the target compound (2.0 g, 91%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4/1). H-NMR (400 MHz, C D C 1 3): 5 p p m 0. 02 (6 Η, s), 0.  8 6 (9 H, s), 1. 42 (1 8 H, s), 3. 14 (3 Η, s), 3.  7 0 (2 H, d, J = 5.  1 H z), 3. 7 4 (2 Η, d, J: = 5.  1 H z), 6. 7 1-6.  7 5 (2 H, m), 6 · 7 8- 6. 80 (2 H, m), 6 • 89 (1 H, s), 6. 94 (1 H, d, J = 8.  8Hz), 7. 18 (1 H, t, J = 8. 0 H z) 0 (79c) 3-[4-Third-butoxycarbonylmethoxy_2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester Experimental Example (4 5 b) The produced 3- [2- (4-chlorobenzyloxy) -4-hydroxy-phenyl] -propionic acid ethyl ester (1.0 g, 30 mmol) was dissolved in acetone (• 224- 200408628 30 Ml), carbonic acid planer (1.5§) was added, and tert-butyl bromoacetate (0.05) was added.  7 7 ml), and stirred at room temperature for 4 hours. Water was added to the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4/1) to obtain the target compound (1.5 g, 100%). ! H-NMR (400MHz, CDC13): δ ppm 1. 21 (3Η, J = 7. 3Hz), 1. 48 (9H, s), 2. 57 (2 H, t, J = 7.  7 H z), 2. 91 (2 H, t, J = 7.  7 H z), 4. 09 (2 H, q, J = 7.  3 H z), 4. 45 (2H, s), 5. 01 (2H, s), 6. 34 (1H, d d, J = 8.  1, 2. 2 H z), 6. 53 (1H, d, J = 2.  2 H z), 7. 05 (1H, d, J = 8. 1Hz), 7. 35 (4 H, s) ° (7 9 d) 3-[4-Carboxymethoxy-2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester Experimental Example (7 9 c )-(4--Third-butoxycarbonylmethoxy-2_ (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (1. 3 grams, 2. 9 mmol) was dissolved in a solution of 1,4-dioxane (10 ml), 4N hydrochloric acid-1,4-dioxane (30 ml) was added, and the mixture was stirred at room temperature overnight. It was concentrated under reduced pressure, toluene was added, and the precipitated Shen Dian was collected by filtration and dried to obtain the target compound (1.  1 g, yield 100%). MS (FAB) m / z: 3 9 3 (M + H) +. (79e) 3-[4- {2-[4-(3-{Third-butoxycarbonyl- [2- (Third-butyl-dimethyl-salyloxy) -ethyl] -amino group} -Phenoxy-225-200408628) -2- (third butoxycarbonyl-methylamino) -anilinomethyl] -methoxy} -2-(4-chloro-benzyloxy) -phenyl] -Ethyl propionate using [2-amino-5-(3-{third butoxycarbonyl- [2- (third butyl-dimethyl-silyloxy) produced in Experimental Example (7 9 b) ) -Ethyl] · amino} -phenoxy) -phenyl] -methylcarbamic acid third butyl ester (1. 0 grams, 1. 7 mmol), 3- [4-carboxymethoxy-2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (0. 80 g, 2. 0 millimolar), diethyl cyanophosphate (0.30 ml), tetrahydrofuran (30 ml) and triethylamine (0.27 ml), the reaction and post-treatment were performed according to the method of experimental example (56 c) , The target compound can be obtained (1.4 g, yield 84%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 5/1). (79f) 3-(2- (4-chloro-benzyloxy) -4- {6-[3-(2-hydroxyethylamino) phenoxy] -1-methyl-1H -benzimidazole- 2-ylmethoxy} -phenyl) -propionic acid ethyl ester 3-[4-{2-[4-(3-{三 Butoxycarbonyl · · 2) produced in Experimental Example (7 9 e) -(Third butyl-dimethyl-silyloxy) -ethyl] -amino} -phenoxy) -2- (third butoxycarbonyl-methylamino) -anilinomethyl] -methyl Oxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester (1. 4 grams, 1. 4 millimoles) and 4N hydrochloric acid 1,4-di-Dfane (40 ml) according to the method of Example (56 d) and post-treatment, the target compound (0.51 g, yield 60%). 1 Η-N M R (4 0 0 MHz, CD3OD): δ pp m 1. 18 (3 H, t, J = 7.  3 H z), 2. 58 (2 H, t, J = 7. 3Hz), 2.92 (2H, t, J = 7.  3 H z), 3. 47 (2 H, t, J = 5.  1 H z), -226- 200408628 3.  7 7 (2 Η, t, J = 5 · 1 Η ζ), 4.  0 3-4. 0 8 (5 Η, m), 5.  16 (2 Η, s), 5. 6 8 (2 Η, s), 6. 71 (1 Η d d, J = 8.  〇, 2.  2 Η ζ), 6. 8 3 (1 Η, d, J = 2.  2 Η ζ) 5 7.  0 5-7.  2 1 (: 3 Η, m), 7 • 37 -7. 46 (m, 5 Η), 7. 54 (1 Η, t, J = 8. 8 Η ζ) 9 7.  6 6 (1 Η, d, J = 2.  2 Η ζ), 7. 8 5 (1 Η, d,, J = 8 · 8 Η ζ) ο Example (7 9 g) 3 _ (2-(4 -chloro-benzyl: oxy) -4-{6-〔3-( 2-hydroxyethylamine;

Phenoxy] -1-methyl-1H-benzimidazol-2-ylmethoxy} -phenyl) -propionic acid 2 hydrochloride 3-(2- (4 -Chloro-benzyloxy) -4- {6- [3-(2-hydroxyethylamino) phenoxy] -1-methyl-1H -benzimidazol-2-ylmethoxy} -phenyl ) -Ethyl propionate (0.50 g, 0.80 mmol), ethanol (8.5 ml), a solution of 1,4-dioxane (4.0 ml), and a 1 N aqueous sodium hydroxide solution (1.7 ml), The reaction and post-treatment are performed according to the method of Example (56e) to obtain the target compound (

0 · 30 grams, 62%). 1 Η-NMR (400 MHZ, DMS 0-d6): (5 ρ ρ m 2.46 (2 Η, t, J = 7. 7 Η ζ)), 2.77 (2Η, t, J = 7. 7 Η ζ), 3.10 (2 Η, t, J = 5.9 Η ζ), 3.5 (2 Η, t, J = 5.9 Η ζ), 3.94 (3 Η, s), 5.16 (2 Η, s), 5.62 (2 Η, s), 6.29 (1 Η, brs), 6.43 (1 Η, brs), 6.55 (1Η, d, J = 8. 1 Η ζ), 6.72 (1 Η, dd , J = 8. 1, 2. 2 Η ζ), 6.86 (1 Η, d, J = 2.2 Η ζ), 7.12-7.21 (3 Η, m), 7.44 ·-227-200408628 7.50 (4 Η , m), 7.60 (1 Η, d, J = 2.2 Η ζ), 7.79 (1 Η, d, J = 8. 8 Η ζ), MS (FAB) m / z: 6 0 2 (Μ + Η) + HR-MS (ESI) m / ζ: C33H3306N3C1 (Μ + Η) + Calculated 値: 602.2058; Measured 値: 602.2026 ° (Example 8 0) 3-[4- {2- [6- (4- Amino-3, 5-dimethyl-phenoxy) -1 · methyl-1H-benzimidazol-2-yl] -ethoxy}-2- (4-chloro-benzyloxy) -benzene Group] -propionic acid 2 hydrochloride (Exemplified compound number 1-342) (80a) 3-[4- {2- [6- (4-amino-3, 5-dimethyl-phenoxy)- 1-methyl-1H-benzimid-2-yl] -ethoxy} -2- (4-Chloro-benzyloxy) -phenyl] -propionic acid ethyl ester containing 3- [3- (4-chloro-benzyloxy) -4- (2-ethoxy) produced in Example (53a) was used. Carbonylethyl) -phenoxy] -propionic acid (0.80 g, 2.0 mmol) in dichloromethane (20 ml), chloramphenicol (0.19 ml, 2.2 mmol), N, N-dimethyl Formamidine (catalyst amount), {4- [amino-3-(third butoxycarbonyl-methylamino) -phenoxy] -2, 6-dimethyl-phenyl} -carbamic acid Tributyl ester (0.91 g, 2.0 mmol), dichloromethane (30 ml), and 4N hydrochloric acid-1,4-dioxane (20 ml) were reacted according to the method of Example (53b). After work-up, the target compound (0.33 g, 26%) can be obtained. (80b) 3-[4. {2-[6-(4-amino · 3,5_dimethyl_phenoxy) _ 1-methyl-1fluorene-benzimidazol-2-yl] -ethoxy Group} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid 2 hydrochloride-228-200408628 3-[4-{2-[6 -(4-amino-3,5-dimethyl-phenoxy) -1-methyl-111-benzimidazol-2-yl] -ethoxy} -2-(4-chloro-benzyloxy Phenyl) -phenyl] -ethyl propionate (0.33 g, 0.50 mmol), ethanol (5.0 ml), 1,4-dioxane (2.5 ml) and 1 N aqueous sodium hydroxide solution (1 · 0 ml), followed by reaction and post-treatment in accordance with the method of Example (5 3 c), to obtain the target compound ((κ 2 7 g, 77%). 1 Η-NMR (4 〇 Μ Μ H z, DMS 0-d 6): 5 ρ ρ m

2.25 (6 Η, s), 2.42 (2 Η, t, J = 7. 3 Η ζ), 2.73 (2 Η, t, J = 7. 3 Η ζ), 3.63 (2 Η, t, J = 5 9 Η ζ), 3.94 (3 Η, s), 4.44 (2 Η, t, J = 6.2 Η ζ), 5.10 (2Η, s), 6.50 (1 Η, dd, J = 8.1, 2.2 Η ζ), 6.62 (1 Η, d, J = 2.2 Η ζ), 6.74 (2 Η, s), 7.06 (1 Η, d, J = 8. 1 Η ζ), 7.20 (1 Η, dd, J = 8.8, 2.2 Η ζ), 7.43-7.48 (4 Η, m), 7.58 (1Η, s), 7.78 (1 Η, d, J = 9. 5 Η ζ)

MS (FAB) m / z: 6 0 0 (Μ + Η) + HR-MS (ESI) m / z: C34H3505N3C1 (Μ + Η) + Calculated 値: 6 Ο Ο · 2 2 6 5; Measured 値 ·· 6 0 0.2 2 6 4 ° (Example 8 1) 3-[4- {2-[6-(3-Amino-fluorenyloxy) -1-methyl-1H -benzobenzozol-2-yl ] -Ethoxy} -2- (4-chloro-benzyloxyphenyl] -propionic acid 2 hydrochloride (exemplified compound number 1-3 7 9) (8 1 a) [5-(3-amino -Benzyloxy) -2 -nitrophenyl] -methylcarbamic acid No. -229- 200408628 Tributyl ester using 3-aminobenzyl alcohol (5.0 g, 40 mmol), n, N-dimethylformamide Amidine (60 ml), sodium hydride (1.8 g, 40 mmol), (5-chloro-2-nitrophenyl) -methylcarbamic acid third butyl ester (12 g, 40 mmol) 'The reaction and post-treatment were carried out according to the method of Example (5 8 a) to obtain the target compound (11 g, 73%). It was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4 / 1) MS (FAB) m / z: 3 7 3 (M) + o (81b) [5-(3 -Third-butoxycarbonylamino-benzyloxy) _2-nitrophenyl] · methylamine The third butyl formate will be the [5--(3-amino-benzyl) produced in Example (81a) ) -2 -Nitrophenyl] -methylcarbamate tert-butyl ester (4.0 g, 10 mmol), and di-tert-butyl dicarbonate (3.5 g, 15 mmol) are dissolved in ethanol ( 45 ml) and tetrahydrofuran (45 ml) mixed solution, triethylamine (2.2 ml, 15 mmol) was added, and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated, water was added to the residue, and ethyl acetate was added. Ester extraction. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 8/1). The target compound (3.6 g, 72%) can be obtained. MS (FAB) m / z: 4 7 4 (M + H) + 〇 (81c) [2-amino-5 · (3-third Butoxycarbonylamino-benzyloxy) -phenyl] -methylcarbamic acid tert-butyl ester. Iron powder (0.56 g), ammonium chloride (70 mg) were dissolved in ethanol (15 ml), and water (5 · 0 ml) of the mixed solution, stirred at 15 ° C for 15 minutes-230-200408628, and then added the [5-(3-third butoxycarbonylamino-benzyloxy) produced in Example (8 1 b) ) -2-Nitrophenyl] -methylcarbamic acid third butyl ester (l.〇 g), and stirred at 1000 ° C for 3 hours. To the reaction mixture was added a 5% sodium bicarbonate aqueous solution (10 ml), and the precipitate was filtered off, and the filtrate was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2/1) to obtain the target compound (0.83 g, 89%). (8 1 d) 3-[4- {2- [4- (3 -Third-butoxycarbonylamino-benzyloxy) -2-(Third-butoxycarbonyl-methylaminoanilinemethyl)] · Ethoxy}-2- (4-chloro-phenoxy) -phenyl] -propionic acid ethyl ester 3-[3-(4-chloro-benzyloxy) produced in Experimental Example (5 3 a) -4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (0.82 g, 2.0 mmol), [2-amino group produced in Experimental Example (8 1 c), 5-(3 -Third-butoxycarbonylamino-benzyloxy) -phenyl] -methylcarbamic acid, tert-butyl ester (0.74 g, 1.7 mmol), diethyl cyanophosphate (0.30 ml), tetrahydrofuran (20 ml ) And triethylamine (0.28 ml), the reaction and post-treatment in accordance with the method of Experimental Example (56 c), to obtain the target compound (1.2 g, yield 86%). Using a silica gel column Chromatographic purification (eluent: hexane / ethyl acetate = 2/1) 〇 (81e) 3-[4- {2-[6-(3-Amine.benzyloxy) -1-methyl_1H_ Benzimidazol-2-yl] -ethoxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid ethyl ester 3-[4-manufactured by Experimental Example (8 1 d) {2-〔4-(3 -Third butoxycarbonyl amine -Benzyloxy) -2-(third butoxycarbonyl-methylamino) -aniline-231- 200408628 methylamidino] -ethoxy} (4-chloro-phenoxy) -phenyl] -propionic acid Ethyl ester (1.2 g, 1.4 mmol) and 4N hydrochloride-1,4-dioxane (40 ml) were reacted and worked up according to the method of Example (56 d) to obtain the target compound (0.44 (G, yield 50%). (8 1 f) 3-[4-{2-[6-(3-amino-benzyloxy) -1-methyl-1H-benzimidazol-2-yl] -Ethoxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid 2 hydrochloride 3-[4-{2-[6- (3-Amino-benzyloxy) -1-methyl-1H-benzimidazol-2-yl] -ethoxy} -2- (4-chloro-benzyloxy) -phenyl] -propionic acid Ethyl ester (0.43 g, 0.70 mmol), ethanol (7.0 ml), 1,4-dioxane (3.5 ml) and 1 N aqueous sodium hydroxide solution (1.5 ml), according to Example (5 3 c) The reaction and post-treatment can be carried out to obtain the target compound (0.12 g, 2 6%). 1 H-NMR (400 MHz, DMS 0-d6): < 5 ppm 2.42 (2 H, t, J = 7. 3 H z), 2.73 (2H, t, J = 7. 3 H z), 3.64 (2H, t, J = 5. 8 H z), 3.99 (3 H, s), 4.44 (2 H, t, J = 5.8 H z), 5.10 (2 H, s), 5.22 (2 H, s), 6.49 (1 H, dd, J = 8. 0, 2.2 Hz), 6.62 (1 H, d, J = 2 2 H z), 7.06 (1 H, d, J = 8. 0 H z), 7.13 (1H, brs), 7.2 3-7.3 9 (3 H, m), 7.41-7.48 (5H, m), 7.64 (1H, d, J = 2. 1 H z), 7.72 (1 H, d, J = 8. 8 H z) MS (FAB) m / z: 5 8 6 (M + H) + HR-MS (ESI) m / z: C33H3305N3C1 (M + H) + calculation-232- 200408628 値: 5 8 6.2 1 0 9; measured 値: 5 8 6 · 2 1 1 8 (Example 8 2) 3- [2- (4-chloro-benzyloxy) -4- (2-{6- [3- (2-hydroxyethylamino) phenoxy] -1-methyl- 1H · benzimidazol-2-yl} -ethoxy) -phenyl] -propionate (exemplified compound number 1-3 8 5) (82a) 3-[4- {2-[4-( 3-{third butoxycarbonyl- [2- (third butyl-dimethyl-silyloxy) -ethyl] -amino} -phenoxy) -2- (third butoxycarbonyl-methyl Aminoanilinemethyl] -ethoxy 丨 -2-(4-chloro · benzyloxy) -phenyl] -propionic acid ethyl ester 3-[3-(4- Chloro-benzyloxy) -4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (1.1 g, 2.7 mmol), [2-amine produced in Experimental Example (7 9 b) -5-(3 · {Third-butoxy group- [2- (Second-butyl-dimethyl-salyloxy) -ethyl] -amino} -phenoxy) -phenyl] -Third-butyl methylcarbamate (1.3 g, 2.2 mmol), diethyl cyanophosphate (0.41 ml), tetrahydrofuran (20 ml) and triethylamine (0.37 ml), according to the experimental example (5 6 c) The reaction and post-treatment can be performed to obtain the target compound (1.6 g Yield: 7 6%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4/1). (82b) 3-[2- (4-chloro-benzyloxy) -4- ( 2-{6- [3-(2 · Ethylamino) phenoxy] -1-methyl-1H-benzimidazol-2-yl} -ethoxy) -phenyl] -propionic acid ethyl ester 3-[4-{2-[4-(3-{三 Butoxycarbonyl- [2- (third butyl-dimethyl-silyloxy)- Ethyl-233-200408628] -Amino group-phenoxy) -2- (Third-butoxycarbonyl-methylamino) -anilinomethyl] -ethoxy} -2- (4-chloro-benzyl (Oxy) -phenyl] -ethyl propionate (1.6 g, 1.6 mmol) and 4N hydrochloride-1,4-dioxane (45 ml) were reacted in accordance with the method of Example (56d) After treatment, the target compound (0.66 g, yield 67%) can be obtained. (8 2 c) 3-[2_ (4_ chloro-benzyloxy) -4- (2-{6-(3-(2- Hydroxyethylamino) phenoxy] -1-methyl-1H-benzimidazol-2-yl} -ethoxyphenyl] -propionate salt 3-[produced in Example (82b) 2-(4-chloro-benzyloxy)-φ 4- (2- {6- [3-(2-hydroxyethylamino) phenoxy Methyl-1H-benzimidazol-2-yl} -ethoxy) -phenyl] -propionic acid ethyl ester (0.66 g, 1.0 mmol), ethanol (10 ml), 1,4-bis Phenane (5.0 ml) and 1 N aqueous sodium hydroxide solution (2.0 ml) were reacted and worked up according to the method of Example (53c) to obtain the target compound (0.41 g, 2 0%). H-NMR (400 MHz, DMSO-d6): (5 ppm 2.43 (2 H, t, J = 7.3 Hz)), 2.74 (2 H, t, J = 7.3 Hz), 3.02 (2 H, m), 3.50 (2 H, t, J = = 6.6 Hz), 3.72 (3 Η, s), 4.4 .1 (2 H, t, J = 6.6Hz), 4.62 (1 H , Brs), 5.11 (2H, s), 5.62 (1 H, t, J = 5.5 Hz), 6.08 (1 H, dd, J = 8. 1, 1.5 H z), 6.16 (1 H, t, J = 2.2 Hz), 6.28 (1 H, dd, J = 8.1, 2.2Hz), 6.50 (1 H, dd, J = 8 · 1, 2 • 2 Hz), 6 • 60 (1 H, d, J = 2.2 Hz), 6.85 (1 H, dd, J = 8. 1, 2.2 Hz), 6.99 -234- 200408628 (1H, t, J = 8. 1 H z), 7.05 (1H, d, J = 8.1Hz), 7.22 (1H, d, J = 2.2Hz), 7.4 3-7.4 8 (4H, m), 7.53 (1H, d, J = 8.8 H z), 12.0 (1 H, brs), MS (FAB) m / z: 616 (M + H) + HR-MS (ESI) m / z: C34H3506N3C1 (M + H) + Calculation 値: 6 1 6 · 2 2 1 5; Found 値: 6 1 6 · 2 2 1 7. (Example 8 3) 3-(2- (4-chloro-fluorenyloxy) -4- {2- [1-methyl- 6- (tetrachloropyrene-4-yloxy) -1H -benzimidazole- 2-yl] -ethoxy} -phenyl) -propionate (exemplified compound number 1-3 8 0) (83a) methyl- [2-nitro-5- (tetrahydropyran-4 -Yloxy) -phenyl] -carbamic acid third butyl ester using tetrahydro-4 fluorene-pyran-4 · alcohol (1.1 g), N, N-dimethylformamide (15 ml) , Sodium hydride (0.52 g), (5. chloro-2-nitrophenyl) -methyl carbamic acid third butyl ester (3.1 g), the reaction and post-treatment were carried out according to the method of Example (5 8 a) , The target compound can be obtained (2.8 g, 74%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1). (83b) [2-Amino-5- (tetrahydropyran-4-yloxyphenyl) -methylcarbamic acid third butyl ester Using the methyl- [2-produced in Example (8 3a) Nitro-5-(tetrahydropyran-4-yloxy) -phenyl] -carbamic acid tert-butyl ester (2.8 g, 7.9 mmol), ethanol (30 ml), and 10% palladium -Carbon, which was reacted and worked up according to the method of Example (5 6 b) to obtain the target compound (2.4 g, 96%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate Ester 200408628 = 3/1) ° (8 3 c) 3-(2- (4-chloro-benzyloxy) -4- {2- [1-methyl-6- (tetrahydropyran-4-yl (Oxy) -1Η-benzimidazol-2-yl] -ethoxy} -phenyl) -propionic acid ethyl ester 3-[3-(4-chloro-benzyl) produced in Example (5 3 a) (Oxy))-4-(2-ethoxycarbonylethyl) -phenoxy] -propionic acid (0.60 g, 1.5 mmol) in dichloromethane (15 ml), chloramphenicol (0.14 ml, 1.6 mmol), N, N-dimethylformamide (catalyst amount), [2-amino-5- (tetrahydropyran-4-yloxy) produced in Example (83b) -Phenyl] -methylcarbamic acid third butyl ester (0.48 G, 1.5 millimoles), dichloromethane (20 ml), and 4N hydrochloric acid-1,4-dioxane (20 ml), the reaction and post-treatment were carried out according to the method of Example (5 3 b), The target compound (0.37 g, 42%) can be prepared. Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/6). (83d) 3- (2-(4- Chloro-benzyloxy) -4- {2- [1-methyl-6- (tetrahydropyran-4-yloxy) -1H -benzimidazol-2-yl] -ethoxy} -benzene ) -Propionate using 3-(2-(4-chloro-benzyloxy) -4- {2- [1-methyl-6- (tetrahydro Pyran-4-yloxy) -1H-benzimidazol-2-yl] -ethoxy} -phenyl) -propionic acid ethyl ester (0.37 g, 0.62 mmol), ethanol (6 · 0 ml), 1,4-dioxane (3.0 ml) and 1 N aqueous sodium hydroxide solution (1.5 ml), the reaction and post-treatment can be carried out according to the method of Example (5 3 c), the purpose can be obtained Compound (0 · 18 g, 46%) 〇 236-1 H-N M R (400 MHz, 0Ϊ AS 0-d 6): δ PP m 1.6 .0 (2H, m) , 2.00 (2 H, m) 2., 42 (2 H , T, J = 7 .3 Η ζ), 2. 7 3 (2H, t, J =: 7. 3 H z), 3 • 41 (2 H, brs), 3. 4 9 (2: H, m), 3.83 (3 H, s), 3 • 87 (2H, m), 4. 4 0 (2H, t, J = 6 • 2 H z), 4. 6 3 (1 H, m), 5.09 ( 2 Η, s) 6.49 (1 H, dd, J: = 8 • 1 2 .2 H z), 6.59 (1 Η, d, J = 2.2 Hz), 6.95 (1 H d, J = 8.1 Hz) , 7. 0 5 (1 H, d, J = 8 · 1 H z), 7. 3 (1 H, s), 7 • 4 3-7. 4 8 (4 H, m), 7.52 (1 H , D, > J = 8 • 8 H z), 12.0 (1 Η, brs) o MS (FA B) m / z ·· 5 6 5 (M + H) + HR · • MS (E SI) m / z: c 3 1 H 3 4 0 6 N 2 Cl (M + H) + calculated 値: 5 6 5. 2 10 5; measured: 5 6 5.2 11 8 o (Example 8 4) 200408628 3- {2- (4-chloro · benzyloxy) [2- (6-cyclopentyloxy-l-methyl-1H-benzimidazol-2-ylethoxy] -phenyl} -propionic acid Salt (Exemplified Compound No. 1-381) (84a) (5-Cyclopentyloxy-2-nitrophenyl) -Third-Butyl Methamic Acid Use Cyclopentanol (1.6 ml, 17 mmol), N, N -dimethylformamide (25 ml), sodium hydride (0.82 g, 17 mmol), (5-chloro-2-nitrophenyl) -methylcarbamic acid third butyl ester (5 g, 17 millimoles), and the reaction and post-treatment were carried out according to the method of Example (5 8 a) to obtain the target compound (4 g, 70%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 25/1 ~ 20/1). -237 · 200408628 MS (FAB) m / z: 3 3 7 (M + H) + (84b) (2-amino-5-cyclopentyloxy-phenyl) -methylcarbamic acid third butyl ester Example (8 4 a) of (5-cyclopentyloxy-2-nitrophenyl) -methylcarbamic acid tert-butyl ester (4.0 g, 12 mmol), ethanol (50 ml), and 10 % Palladium-carbon (1.5 g) was reacted and worked up according to the method of Example (56 b) to obtain the target compound (3.2 g, 86%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4/1). (8 4 c) 3-{2- (4-chloro-benzyloxy) -4- [2- (6-cyclopentyloxy-1-methyl-1H-benzimidazol-2-yl) -ethyl Oxy] -phenyl} -ethyl propionate 3-[3-(4-chloro-benzyloxy) -4-(2-ethoxycarbonylethyl) -phenoxy produced in Example (53a) was used Group] -propionic acid (600 mg, 1.5 mmol) in dichloromethane (15 ml), chloramphenicol (0.14 ml, 1.6 mmol), N, N-dimethylformamide (catalyst amount ), (2-amino-5-cyclopentyloxy-phenyl) -methylcarbamic acid third butyl ester (0.46 g, 1.5 mmol) produced in Example (84b), dichloromethane ( 20 ml), and 4N hydrochloric acid-1,4-dioxane (20 ml). The reaction and post-treatment were performed according to the method of Example (5 3 b) to obtain the target compound (0.41 g, 4 7 %). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/2). (84d) 3-{2- (4-chloro · fluorenyloxy) -4- [2- (6-cyclopentyloxy-1-methyl-1H-benzimidazol-2-yl) · ethoxy ] · Phenyl} · Propionate using 3-{2- (4-chloro-benzyloxy)--238-200408628 4- [2- (6-cyclopentyloxy) produced in Example (84c) Ethyl-1-methyl-1H-benzimidazol-2-yl) -ethoxy] -phenyl} -propionic acid ethyl ester (0.40 g, 0.69 mmol), ethanol (8.0 ml), 1, 4 -Dioxane (4.0 ml) and 1N aqueous sodium hydroxide solution (2.0 ml) were reacted and worked up according to the method of Example (53c) to obtain the target compound (0.23 G, 54%). H-NMR (4 0 0 MHz, DMSO-d6): ά ppm 1. 5 9 -1.65 (2 H, m), 1.68-1.77 (4H, m), 1.96- 2.. 0 2 (2 Η, m) , 2.42 (2H, t, J = 7 · 3 H z), 2.73 (2 Η, t, J = 7. 3 H z), 3. 6 0 (2 H, t, J = 5. 8 H z) , 3.96 (3 Η, s), 4.4 2 (2 H, t, J = 5.8 H z) 9 4.96 (1H, m), 5 · 0 9 (2 H, s), 6.49 (1 H , Dd, J = 8.1, 2. 2 H z), 6. 6 0 (1 H, d, J = 2.2 Hz), Ί · 0 6 (1 H, d, J = 8. 1 H z), 7.10 (1 H, dd, J = 9. 5 9 2. 2 H z), 7.43- 7.. 4 7 (5 H, m), 7.65 (1 H, d, J = 8. 8 H z), 12.0 ( 1 H, brs).

MS (FAB) m / z: 5 4 9 (M + H) + HR-MS (ESI) m / z: C31H3405N2C1 (M + H) + calculation 値: 5 4 9.2 1 5 6; Measured 値: 549.2147. (Example 8 5) 3-{2-(4-chloro-benzyloxy) -4- [2-(6-cycloheptyloxy-l-methyl-1H-benzimidazol-2-yl)- Ethoxy] -phenyl} -propionic acid (Exemplified compound number 1-3 8 3) (85a) (5-cycloheptyloxy-2-nitrophenyl)-tert-butyl methylcarbamate (2.1 ml, 17 mmol), N, N-dimethylmethyl-239-200408628 amidine (25 ml), sodium hydride (0.82 g, 17 mmol), (5-chloro-2- Nitrophenyl) -methyl carbamic acid tert-butyl ester (5.0 g, 17 mmol) was reacted and worked up according to the method of Example (5 8 a) to obtain the target compound (3.7 g, 6 0%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2 5/1). (85b) (2-Amino-5-cycloheptyloxy-phenyl) -methylcarbamic acid third butyl ester (5-cycloheptyloxy-2-nitrophenyl) produced in Example (85a) -Tert-butyl methylcarbamate (3.7 g, 10 mmol), ethanol (50 ml), tetrahydrofuran (40 ml), and 10% palladium-carbon (1. (^), according to Example (5 6 b ) Method for reaction and post-treatment to obtain the target compound (3.3 g, 100%). Purification by silica gel column chromatography (eluent: hexane / ethyl acetate = 5/1). MS ( FAB) m / z: 3 3 5 (Μ + Η) + 〇 (8 5 c) 3-{2- (4-chloro-benzyloxy) -4- [2- (6-cycloheptyloxy · 1 -Methyl-1H-benzimidazol-2-yl) -ethoxy] -phenyl} -propionic acid ethyl ester 3-[3-(4-chloro-benzyl) produced in Example (5 3 a) (Oxyl) -4-(2 · ethoxycarbonylethyl) · phenoxy] -propionic acid (0.60 g, 1.5 mmol) in dichloromethane (15 ml), chloramphenicol (0.14 ml, 1.6 mmol) Mol), N, N-dimethylformamide (catalyst amount), (2-amino-5-cycloheptyloxy-phenyl) -methanamic acid produced in Example (85b) Butyl ester (0.50 g, 1.5 mmol ), Dichloromethane (20 ml), and 4N hydrochloric acid 1,4-dioxane (20 ml), the reaction and post-treatment according to the method of Example (53b) can be obtained to the target compound (-240 -200408628 0.38 g, 42%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/1). (8 5 d) 3-{2- (4-chloro- Benzyloxy) -4- [2- (6-cycloheptyloxy-1-methyl-1H-benzimidazol-2-yl) -ethoxy} -phenyl} -propionate will be implemented Example (85c) 3-{2- (4 · chloro-benzyloxy) -4- [2-(6-cycloheptyloxy-1-methyl-1H-benzimidazol-2-yl) -Ethoxy] -phenyl} -ethyl propionate (0.38 g, 0.63 mmol), ethanol (8.0 ml), 1,4-dioxane (4.0 ml) and 1N hydroxide Aqueous sodium solution (2.0 ml) was reacted and worked up according to the method of Example (53c) to obtain the target compound (0.15 g, 40%). 1 Η-NMR (4 0 0 MHZ, DMS 〇-d 6): δ ppm 1.4 2-1.5 5 (2 Η 5 m), 1.5 5-1.5 9 (4 Η, m), 1.64- 1.75 (4 Η, m), 1.9 3- 2.0 0 (2 Η, m), 2.43 (2 Η, t, J = 7. 7 Η ζ), 2.74 (2 Η, t, J = 7. 7 Η ζ), 3.27 (2 Η, t, J = 7.6 Η ζ), 3.71 (3 Η, s), 4.39 (2 Η, t, J = 7.6 Η ζ), 4.53 (1 Η, m), 5.10 (2 Η, s), 6.49 (1 Η, dd, J = 8. 1, 2.2 Η ζ), 6.59 (1 Η, d, J = 2.2 Η ζ), 6.74 (1 Η, dd, J = 8. 1, 2 · 2Ηζ), 7.03- 7.06 (2 Η, m), 7.3 8- 7.4 8 (5 Η, m), 12.0 (1 Η, brs), MS (FAB) m / z: 5 7 7 (M + H) + HR-MS (ESI) m / z: C33H3805N2C1 (M + H) + Calculated 値: 5 7 7.2 4 7 0; Measured 値: 577.2460 〇-241- 200408628 (Example 8 6) 3-{2 · (4-chloro-benzyloxy) -4-[2- (6 -cyclohexane Oxy-1-methyl-1H-benzimidazol-2-yl) -ethoxy] -phenyl} -propionate (exemplified compound number 1-3 8 2) (86a) (5-cyclic Hexyloxy-2-nitrophenyl) -methylcarbamate tert-butyl ester using cyclohexanol (3.5 g, 35 mmol), N, N-dimethylformamide (50 ml), hydrogenated Sodium (1.7g), (5-chloro-2-nitrophenyl) -methanamic acid tert-butyl ester (10 g) were carried out according to the method of Example (5 8 a) And post-treatment should be, can be prepared compound (10 g, 83%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 2 0/1). (86b) (2-Amino-5-cyclohexyloxy-phenyl) -methylcarbamic acid third butyl ester (5-cyclohexyloxy-2-nitrophenyl) produced in Example (86a) -Third-butyl methylcarbamate (10 g, 29 mmol), ethanol (90 ml), tetrahydrofuran (60 ml), and 10% palladium-carbon (3.6§), according to Example (5 6 b) The method was reacted and worked up to obtain the target compound (8.8 g, 95%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 4/1). _ MS (FAB) m / z: 321 (M + H) + 〇 (86〇3- {2- (4-chloro-benzyloxy) -4, [2_ (6-cyclohexyloxy-1-methyl -1H-benzimidazol-2-yl) -ethoxy] -phenyl} · Ethyl propionate was produced using 3- (3- (4-chloro-benzyloxy)) produced in Example (53a). 4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (0.60 g, 1.5 mmol) in dichloromethane (15 ml), chloramphenicol (0.4 ml, -242 ml, -242 -200408628 16 mmol), N, N -dimethylformamide (catalyst amount), (2-aminocyclohexyloxy-phenyl) · methanamic acid produced in Example (86b) Tributyl ester (0.48 g, 1.5 mmol), dichloromethane (20 ml), and 4 N hydrochloric acid-1,4-dioxane (20 ml) were carried out according to the method of Example (5 3 b) Reaction and post-treatment 'can obtain the target compound (0.55 g, 62%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/2). (8 6 d) 3 -{2- (4-Gas-fluorenyloxy) -4- [2- (6-cyclohexyloxy and its 1-methyl-1H-benzimidazol-2-yl) -ethoxy] -phenyl} Propionate salt manufactured using Example (86c) 3 -{2- (4 -Chloro-benzyloxy) 4- [2-(6-cyclohexyloxy-1-methyl-1H -benzobenzoyl-2-oxo) ethoxy] -phenyl } -Ethyl propionate (0.54 g, 0.90 mmol) alcohol (9.0 ml), 1,4-dioxane (4.5 ml) and 1N ^ aqueous sodium hydroxide solution (2.5 ml), according to the examples (5 3 c), + / < 10,000 method for reaction and post-treatment, the target compound (0.24 g, 42%) can be prepared 1 Η-NMR (4 0 0 Μ Η ζ, DMS 〇 -d 6): δ ppm ί 7 (6H, m), 1.72-1.75 (2H, m), i H, m), 2.42 (2H, t, J = 7 · 7 H ”, J = 7. 7 H z), 3, .58 (2 H, brs), 3.9c… · 94 '2 · 7 3 (3Η, s), 4.42 (2Η, t, J = 5. 9 Η ζ), 4.49 (1H, J 9 5. 0 9 (2H, s), 6.49 (1H, dd, J = 8.8, 2.2 H 2 \ J, 6 · 6 〇 (1H, d, J = 2.2 Η z), 7.06 (1H, d, j = 8 • 1 Η z),

7.12 (1H, d, J = 8.8 Η z), 7.4 3-7.4 7 (5 H, pull), -243-200408628 7.64 (1 Η, d, J = 8.8 Η ζ), 12.0 (1 Η, brs), MS (FAB) m / z: 5 6 3 (Μ + Η) + HR-MS (ESI) m / z: C32H3605N2C1 (M + H) + calculated 値: 5 6 3.2 3 1 3; measured値: 5 6 3 · 2 2 9 3. (Example 8 7) 3-[4- [2- (6-Allyloxy) -1-methyl-1H-benzimidazol-2-yl] -ethoxy] -2- (4-chloro -Benzyloxyphenyl] -propionate (Exemplified Compound Nos. 1-3 8 4) (87a) (5-allyloxy-2-nitrophenyl) -methylcarbamic acid third butyl ester (5-Chloro-2-nitrophenyl) · Third-butyl methylcarbamate (3.0 g, 10 mmol) was dissolved in allyl alcohol (25 ml), and potassium hydroxide (1.2 g, 2 0 mmol), and stirred at 100 ° C. for 6 hours. The reaction solution was concentrated, water was added to the residue, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 5/1) to obtain the target compound (3.3 g, yield 100%). MS (FAB) m / z: 3 0 9 (M + H) +. (87b) (5-Allyloxy-2-amino-phenyl) -methylcarbamic acid third butyl ester Example ( 87a) The tert-butyl (5-allyloxy-2-nitrophenyl) -methylcarbamate (1.0 g, 3.2 mmol) was dissolved in ethanol (15 ml) And water (5.0 ml), add iron powder (0.86 g, 16 mmol) and ammonium chloride (0.11 g, 2.1 mmol), and stir at 80 ° C for 1 hour. A saturated aqueous sodium bicarbonate solution (10 ml) was added to the reaction solution. The iron powder was filtered off with celite, and the solvent was distilled off under reduced pressure. Water was added to the residue, and the mixture was extracted with -244-200408628 ethyl acetate. The organic layer was saturated with common salt. After washing with water and drying under anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 3/1) to obtain the target compound (〇 · 87 g, yield 98%). MS (FAB) m / z: 2 7 9 (M + H) +. (87c) 3-[4-[2 · (6-Allyloxy-1-methyl -1H-benzimidazole. 2-yl) -ethoxy] -2- (4-chloro-phenoxy-phenyl) -propionic acid ethyl ester 3-[3-manufactured using Example (53a) (4-chloro-benzyloxy) -φ 4- (2-ethoxycarbonylethyl) -phenoxy] -propionic acid (1.3 g, 3.1 mmol) in dichloromethane (30 ml), grasshopper Chlorine (0.54 ml, 6.2 mmol), N, N -dimethylformamide (catalyst amount), Examples 87b) The produced (5-allyloxy-2-amino-phenylmethylcarbamate tert-butyl ester (0.87 g, 3.1 mmol), dichloromethane (40 ml), and 4 N hydrochloric acid- 1,4-Dioxane (40 ml) was reacted and worked up according to the method of Example (53b) to obtain the target compound (0.70 g, 41%). Purified by silica gel column chromatography (eluent: hexane / ethyl acetate = 1/2). (87d) 3- [4- [2- (6-Allyloxy) -1-methyl-1H-benzimidazol-2-yl] -ethoxy] -2- (4-chloro-benzyloxy -Phenyl] -propionate salt 3-[4-[2- (6-Allyloxy_1-methyl-1H-benzimidazole-2-) produced in Example (87c) ) -Ethoxy] -2- (4-chloro-phenoxy-phenyl) -ethyl propionate (0.69 g, 1.3 mmol), ethanol (-245- 200408628 16 ml), 1, 4 -Dinoxane (8.0 ml) and IN sodium hydroxide aqueous solution (4.0 ml) were reacted and worked up in accordance with the method of Example (53c) to obtain the target compound (0.32 g, 4 2%). Η-NMR (400 MHZ, DMS Ο · d 6): (5 ppm 2.42 (2H, t, J = 7. 3 H z), 2, .73 (2 H, t, J = 7. 3 H z), 3.51 (2H, t, J = 5 · 9 H z), 3.90 (3 H, s), 4.41 (2 Η, t, J = 5. 9 H z), 4.67 (2H, d, J = 5. 1 H z), 5.09 (2 H, s), 5.29 (1 H, dd, J = 10.2, 1.5 Hz), 5.46 (1 H, m), 6.10 (1 H, m) , 6.49 (1 H, dd, J = 8.1, 2.2 Hz), 6.60 (1 H, d, J = 2.2 H z), 7.05- 7.08 (2 H, m), 7.40- 7.48 ( 5 H, m), 7 .6 1 (1 H, d, J = = 8. 8 H z), 1 2.0 (1 H, brs),

MS (FAB) m / z: 521 (M + H) + HR-MS (ESI) m / z: C29H30O5N2C1 (M + H) + Calculated 値: 5 2 1 · 1 8 4 4; Measured 値: 5 2 1 · 1 8 6 0. (Reference Example 1)

2-Hydroxymethylmethoxy M • methyl-1H-benzimidazole (la) (2-amino group ^ methoxy-phenyl) -methylcarbamic acid third butyl ester 5 8 8 6 〇14 (Japanese Patent Registration No. 3 2 4 9 4 9 0) method ($-methoxy · 2 _ nitrophenyl)-dimethanine-butyl ester (65.l7g) It was dissolved in a solution of ethanol (250 S liter) -tetrahydrofuran (150 strokes), 10% palladium · carbon was added, and the mixture was stirred overnight at room temperature under hydrogen. The catalyst was filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was washed with a small amount of acetic acid, a large amount of hexane, and ultrasonically washed. The target compound -246- 200408628 was collected by filtration (48 · 68 g, 84 · 4%). MS (FAB) m / z: 241 (M + H) +. (lb) 2-hydroxymethyl-6-methoxy- 丨 -methyl_1H-benzimidazole (2-amino-5-methoxy-phenyl) produced in Reference Example (la)- Tertiary butyl methamate (46.68 g) and glycolic acid (44.30 g) were dissolved in 4N hydrochloric acid (300 ml) and heated for 4.5 hours. The solvent was evaporated under reduced pressure. A saturated sodium bicarbonate aqueous solution and ethyl acetate were added to the obtained residue, and the solid was collected by filtration to obtain the target compound (25.92 g, 71%). MS (FAB) m / z: 193 (M + H) + o (Reference Example 2) 3-(6-methoxy-1-methyl-1H-benzimidazol-2-yl) -propan-1 -Alcohol uses (2-amino-5-methoxy-phenyl) -methylcarbamic acid tert-butyl ester (1 5 · 15 g) and-butyrolactone (9 · 7 ml) dissolved in 4N hydrochloric acid (120 ml) and dioxane (60 ml), and heated for 5 hours. Dioxane was distilled off under reduced pressure and neutralized with a saturated aqueous sodium hydrogen carbonate solution. Ethyl acetate was added, and the insoluble matter was collected by filtration to obtain the target compound (1.14 g, 80%). φ MS (FAB) m / z: 221 (M + H) +. (Reference Example 3) [6- (4-amino-3, 5-dimethyl-phenoxy) -i-methyl-1H-benzimidazole-2-yl] -methanol will be in accordance with International Publication No. 9 9/1 8 0 8 1 (Japanese Patent Application Laid-Open No. 1 1-i932 7 6)) method [4- [4 -amino-3- (third butoxycarbonyl-methylamino) -phenoxy Group] -2,6-dimethyl-phenyl} -aminomethyl-247-200408628 tert-butyl acid (12.5g) and glycolic acid (6.23g) were dissolved in 4N hydrochloric acid (120 ml) and heated to flow 3 small poems. The solvent was evaporated under reduced pressure. It was neutralized with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate-methanol. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was washed with tetrahydrofuran and ethyl acetate to obtain the target compound (6.25 g, 77%). MS (FAB) m / z: 2 9 8 (M + H) +. (Reference Example 4) [6- (3-Isopropylamino-phenoxy) -1-methyl-1H-benzimidazol-2-yl] -methanol (4a) N- (5-(3-aminobenzene Oxy) -2 -nitrophenyl) -N-methylcarbamate tert-butyl ester 2.18 g of sodium hydride (55 wt%) was dissolved in 80 ml of anhydrous Ν, Ν-dimethylformamide For amidine, 5.45 g of 3-aminophenol was added, and the mixture was stirred at room temperature for 20 minutes. Added i4.3g of N- (5-Chloro-2-nitrophenyl) -N-methanamic acid produced according to the method of International Publication No. 9 9/1 8 0 8 1 (Japanese Patent Application Laid-Open No. 11-193276) The third butyl ester was stirred at 0 ° C. for 6 hours. The reaction mixture was concentrated, water was added, and neutralized with 3 N hydrochloric acid and sodium bicarbonate powder. The insoluble matter was filtered off, washed with water, and dried under reduced pressure to obtain the title compound (16. 6 g, yield 9 2%). 1 Η-NMR (4 0 0 Μ Η ζ, DMS0-d6) (5 ppm: 1.23 and 1.42 (count 9Η, each s), 3.18 (3Η, s), 5.38 (2H, s; (Disappears), 6.25 (1H, dd, J = 7.6 and 2.4 Hz), 6.31 (1 Η, s), 6.46 (1 Η, dd, J = 8. 1 and • 248-200408628 1. .0 Hz), 6.88 (1 Η, dd, J = 9.0 and 2 · ι Ηζ), 7 〇9 (1 Η, t, J = 8.0 Hz), 7.16 (1, s) > 8.〇〇 (1H? D? J = 9. 0 Hz). (4b) N- (2-amino-5- (3-isopropylamino-phenoxy) _phenyl) · N-methylcarbamic acid third butyl ester 14.4 g of N -(5-(3-Aminophenoxy) -nitrophenyl) -N-methylcarbamate tert-butyl ester, 2.90 g of acetone, 3.00 g of acetic acid, 10.6 g of diacetoxyboron gas The mixture of sodium chloride and 200 ml of anhydrous tetrahydrofuran was stirred at room temperature for 4 days. The reaction mixture was concentrated, added with water, and extracted with ethyl acetate. After the extract was dried under anhydrous sodium sulfate, the solvent was distilled off. Purification by silica gel column chromatography (eluent: ethyl acetate / n-hexane = 2/3), and the intermediate N-(5-(3 -isopropylamino-phenoxy) _ 2 -nitrophenyl) -N- Methylamine Tertiary butyl acid. Dissolve the intermediate in 2000 ml of methanol, add 2.02 g of 10% palladium-carbon, and stir vigorously under hydrogen and room temperature for 2.5 hours. After the reaction is completed, the catalyst is filtered off. The solvent can be distilled off to obtain the labeled compound (12 · 0 g, yield 81%). 1 Η-N [MR (40 0 Μ Η z, D Μ S 0-d 6) 5 ppm: 1.08 (6 Η, d, J = 6 • 4 Hz), 1.29 (9H, s), 2.98 (3 Η, s), 3. 4 0-3.4 7 (1 H, m), 4.7 8 ( 2 H, s; disappears with the addition of heavy water), 5.45 (1 H, d, J = 7.8 H z; disappears with the addition of heavy water), 5.96 (1 Η, d, J = 7.2 Hz), 6.0 7 ( 1 H, t, J = 2.2 Hz), 6.20 (1H, dd, J = 8.1 and 1. 9 H z), 6.60 (1 Η, s), 6 • 7i (2 H, s), 6.93 (l H, t, J = 8.1 Hz). -249- 200408628 (4c) [6- (3- Isopropylamino-phenoxy) -1-methyl-1H -benzimidazole-2 -yl] -methanol N- [2-amino-5- (3-Isopropylamino-phenoxy) -phenyl] -N-methylcarbamic acid tert-butyl ester (; i.5g), glycolic acid (921 mg), 4 N hydrochloric acid (30 ml) and Ershu Alkane (10 ml) was reacted and worked up according to the method of Reference Example 2 to obtain the target compound (716 mg '57%). MS (FAB) m / z: 312 (M + H) +. (Reference Example 5) [6- (4-Amino-phenoxy) -1-methyl-1H-benzimidazol-2-yl] -methanol will be according to International Publication No. 9 9/1 8 0 8 1 [2-Amino-5- (4-Third-butoxycarbonylamino-phenoxy) -phenyl] -methanamic acid produced by a method disclosed in the gazette (Japanese Patent Application Laid-Open No. 1 1 -1 9 3 2 7 6) The third butyl ester (3.0 g) and glycolic acid (1.59 g) were dissolved in 4N hydrochloric acid (30 ml) and dioxane (10 ml) and heated for 2 hours. The solvent was evaporated under reduced pressure. The obtained residue was neutralized with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent: dichloromethane / ethyl acetate = 1 0: 1) to obtain the target compound (857 mg, 46%). MS (FAB) m / z: 2 7 0 (M + H) +. Bovine Test Example (Experiment Example 1) -250- 200408628 Blood glucose decreased for rest Male κ κ mice (purchased from Creea, Japan) were purchased at 6 weeks and raised to 15 weeks to cause hyperglycemia. The mice were individually reared during domestication and during the experiment, and water and feed (F 2, Funabashi Farm) were freely ingested. After body weight measurement at the beginning of the experiment, blood was collected from the tail vein of the mice with a glass tube covered with heparin to measure the blood glucose. Plasma glucose concentration was measured using Glucolotder GXT (A & T), and individuals with blood glucose levels above 350 mg / dl were selected. During the experiment, 3-4 animals were used in each group, and the groups were divided according to the average weight and average blood glucose (approximate). The compound administration group is Xin. Feeds containing 0.01% of each compound are mixed in the feed and administered. The control group was given only feed. The experimental period (drug administration period) was 3 days. In each group, body weight was measured at day 0 and 3, and blood was collected from the tail vein to measure blood glucose. The blood glucose reduction rate can be obtained by the following formula. The blood glucose lowering rate = [(control group blood glucose level-compound administration group blood glucose level) / control group blood glucose level] X 100. The results are shown in Table 3. _ Table 3 Example No. Blood glucose lowering rate (%) 'Example 6 61 ~ " " ——-Example 2 4 Example 2 5 5 5 Example 2 7 Example 2 8 5 9 Example 2 9 4 9 ——-Example 3 6 -251- 200408628 Example 3 7 —5-7 ---— Example 4 2 ~ " 6 ~ 2 --- Implementation Example 4 3 ~ 5 ~ 6 '-~ — Example 4 4 —5-7 I-Example 7 1 ~ Γ3 --- Example 7 2 ~ Γ5 '~~ ---- Example 7 5 ~~ 6 ~ 9' ~-Example 7 9 ~ 61 '--- Example 8 0 ~ 71 1 ---- · ^ Example 8 4 ~ " T1 ~ --- Example 8 7 ~ 51--

In Table 3, the compound of the present invention has an excellent blood glucose lowering effect. Therefore, the compound of the present invention can be used as a therapeutic agent for diabetes. (Experimental Example 2) Antitumor effect on human colorectal cancer cells C 0 L-2-JCK was completed The human colorectal cancer cells C 0 L-2 · JCK (medium differentiated adenocarcinoma) used in the test examples of the present invention were purchased from The solid tumor strain of the Japan Laboratory Animal Center Laboratory was used to culture cells. Furthermore, the secondary cell maintenance and test example experiments were performed using D-M E M / F-1 2 culture medium (G I B C 〇 company) containing 10% bovine fetal blood cells to culture cancer cells.

The test example was performed as follows. That is, in a cell culture dish (Petridish) with an inner diameter of 100 mm, C 0 L-2-JCK cells cultured to a stagnant state were peeled from the dish with EDTA and 0. 05% trypsin solution. Use the culture medium to dilute the cell density to 100 cells / ml. This cell dilution was seeded on a 6-well plate for cell culture, with 3 ml (300 cells / well) in each well. Meanwhile, D M S 0 was used to dissolve the test compounds to a final concentration of -252- 200408628 1ηΜ, 10πΜ, 100ηΜ, 1 // Μ, and 10 # Μ for addition. At the same time, the final concentration of D M S 〇 added to each hole was adjusted to 0 · 1%. 0.1% D M S 〇 was added to the control group. After the test specimens were added, the cells were cultured at 37 ° C for 10 days in the presence of 5% C02. After the end of the culture, the cells in each well were washed with Du 1 be cc 0-phosphate buffered saline (divalent anion), and 1 ml of 10% neutral formalin solution containing 0.22% methyl violet was added and Let stand for 5 minutes to fix and stain the cells. After fixed staining, the cells were washed with water and air-dried, and the image analysis device PCA-11 (System Science) was used to calculate the total area (m m 2) of the fixed stained cancer cell strains. _ From the concentration of the test specimen corresponding to 2 points of the area 1/2 which is 1/2 of the largest area 所得 of the obtained area 算出, calculate the concentration which becomes 1/2 of the area of the primary parameter. The concentration calculated from this was used as the IC50 for each test specimen, and used as an index indicating the antitumor effect of the test specimen. The results obtained are shown in Table 4.

-253-Table 4 Example number IC50 (// M) Example number IC50 (// M) Example 2 0.92 Example 42 0.0016 Example 4 0.92 Example 43 0.0080 Example 6 0.038 Example 44 0.0070 Example 11 0.81 Example 55 0.0032 Example 12 0.37 Example 59 0.049 Example 16 0.45 Example 61 0.070 Example 18 0.81 Example 63 0.0089 Example 22 0.98 Example 65 0.0068 Example 23 0.14 Example 75 0.0057 Example 24 0.88 Example 76 0.030 Example 25 0.93 Example 78 0.0052 Example 27 0.023 Example 79 0.029 Example 28 0.016 Example 80 0.0026 Example 29 0.50 Example 81 0.015 Example 31 0.039 Example 82 0.0081 Example 33 0.12 Example 83 0.011 Example 34 0.041 Example 84 0.0037 Example 36 0.0024 Example 85 0.0042 Example 37 0.0028 Example 86 0.0059 Example 38 0.0072 Example 87 0.0055 200408628 Table 4 shows that the compounds of the present invention have excellent antitumor effects. Therefore, the compound of the present invention can be used as an anticancer agent. Formulation Example -254- (1) Capsule Example 1 Compound 10 mg Lactose 110 mg Corn Starch 58 mg Magnesium Stearate 2 mg Total 1 80 mg The above ingredients powders are uniformly mixed through a sieve (the basis of a sieve) Based on Tyler's standards). The obtained powder was subdivided into 180 mg and filled into a hard capsule (No. 3) to obtain a capsule. (2) Lozenge Example 1 Compound 10 mg lactose 85 mg corn starch 34 mg crystalline cellulose 20 mg magnesium stearate 1 mg 200 408 628 Total 150 mg The above ingredients powders were evenly mixed and compressed into a 150 mg weight tablet . This lozenge can be coated as required. (3) Granules Example 1 Compound 10 mg lactose 839 mg corn starch 150 mg hydroxypropyl cellulose 1 mg total 1000 mg 200408628 The above ingredients powders were uniformly mixed, wet with pure water, Granulate and dry to obtain granules. [Industrial Possibility of Utilization] The novel phenylpropionic acid derivative of the compound of the present invention, its pharmacologically acceptable salt and its pharmacologically acceptable ester have excellent PP ART activation, insulin resistance improvement, blood glucose lowering effect, lipid lowering effect, Inflammatory effect, inhibit the colonization of cancer cells, and can be used as diabetes, hyperlipidemia, hyperglycemia, obesity, hypoglycemic state, insulin resistance non-glycemic state, insulin resistance, cachexia, psoriasis, diabetes Outbreak, arteriosclerosis, hypertension, pancreatitis, polycystic ovary syndrome, fatty liver, gestational diabetes, cancer (eg, gastric cancer, lung cancer, breast cancer, colorectal cancer, prostatic adenocarcinoma, pancreatic cancer, liver cancer ), Leukemia, sarcoma (for example: liposarcoma) and other therapeutic drugs and / or preventive drugs (preferably for diabetes and / or preventive drugs.). [Schematic description] Sister. j \ \\-256-

Claims (1)

200408628, patent application scope 1 · A compound of the following general formula (I) or a pharmacologically acceptable salt or ester thereof: [Wherein X is CH or N; R1 is a C1-6 alkyl group (the alkyl group may be substituted with 1 to 5 substituents selected from the substituent group α), c 3 〇cycloalkyl 'C2-6ene Group (the alkenyl group may be substituted with ^ 5 substituents selected from the substituent group ^), C 6-10 aryl group (the aryl group may be substituted with 1-5 substituents selected from the substituent group α) 'c 7 _ 丨 6 aralkyl (the aralkyl may be substituted with 1 to 5 substituents selected from the substituent group α) or contain 1-3 heteroatoms which are the same or different and selected from nitrogen, oxygen and sulfur 4- to 10-membered heterocyclic group (the heterocyclic group may be substituted with a substituent selected from the substituent group α); R 2 is a C 7-16 aralkyl group (the aralkyl group may have a selected from the substituent group α 1-5 substituents), C9-16 arylalkenyl (the arylalkenyl may be substituted with 1-5 substituents selected from the substituent group α) or contain the same or 5-10 different heteroaromatic cycloalkyl groups with different 1-3 heteroatoms (the heteroaromatic cycloalkyl group may be substituted with 1-5 substituents selected from the group of substituents); r3 is hydrogen, and Cl-6 Or C6-10 aryl (the aryl may be substituted with 1-5 substituents selected from the substituent group α), 11 1 is 1 or 2, 11 is an integer of 1 to 3, (substituent group α)-257-200408628 C 1-6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 Alkylthio, C1-6 alkyloxy, C1-6 halofluorenyl, C2-6 alkyl, C2-6 alkyl, C1-6 alkylsulfonyl, amine, C1-6 amine Group, C 1-6 dialkylamino group, C 1-6 hydroxyalkylamino group, C 3-10 cycloalkylamino group, C 1-6 alkyl C 3-1 0 cycloalkylamino group, C 3-1 〇 Dicyclofluorenylamino, C6-10 arylamino, C1-6 sulfonamido, C6-10 arylsulfonamido, C 1-1 1 aliphatic fluorenamine, C 7-1 1 arylcarbonyl Amine, c 1-6 amine carbonyl, C6-10 arylamine carbonyl, C1-6 alkoxycarbonyl, C7-16 aralkylamine carbonyl, C7-16 aralkyloxy, containing 1-3 selected from nitrogen, 4-10 membered heterocyclic groups of the same or different heteroatoms of oxygen and sulfur, C6-10 aryl, C9-16 aryl, carbamoyl, carbamate, meridian, cyano, nitro, and halogen atoms 〕. 2. The compound or pharmacologically acceptable salt or ester thereof according to item 1 of the scope of patent application, wherein X is C Η. 3. If the compound or the pharmacologically acceptable salt or ester of item 1 or 2 of the scope of patent application, wherein R1 is C1-6 alkyl or C6-10 aryl (the aryl is the same or different, there may be C1-6 Alkyl, amine, ci-6 alkylamino or C 1-6 alkylsulfonamido substituted with i-3 substituents). 4 · If the compound or any of its pharmacologically acceptable salts or esters according to any one of the claims 1 to 3, wherein R2 is a C7-16 aralkyl (the aralkyl is the same or different, there may be a C1-6 alkane Alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkenyl, c 1-6 alkylsulfonyl, C 1-1 1 aliphatic amido, C 7-16 aralkoxy, C 6-10 aryl, C 9-16 arene, carboxyl or halogen atom -258-200408628 1 -3 substituents). 5 · As in any of the items in the scope of the if patent, the compound or a pharmacologically acceptable salt or ester thereof, of which 113 is (: 1-6 alkyl. • The compound in the patent scope, i, or a pharmacologically acceptable salt or ester thereof Where XS CH SN; cl-6 group (the group may be substituted with 5 substituents selected from the substituent group 3), C6_io aryl group (the aryl group may have the group selected from the substituent group 0) 1-5 substituents), C7-16 aralkyl (the aralkyl may be substituted with a substituent selected from the substituent group ^) or containing the same or different 孀 1 selected from nitrogen, oxygen and sulfur -4 to 10 membered heterocyclic groups of 3 heteroatoms (the heterocyclic group may be substituted with 1 to 5 substituents selected from the substituent group α), R2 is a C7-16 aralkyl group (the aralkyl group may be Selected from the group of substituents substituted with 1 to 5 substituents), c 9 _ i 6 arylalkenyl (the arylalkenyl may be substituted with 1 to 5 substituents selected from substituent group α) or 5 to 10 member heteroaromatic cycloalkyl groups of the same or different 1-3 heteroatoms from nitrogen, oxygen and ί / iL (the heteroaromatic cycloalkyl group may have __ 5 substitutions selected from the substituent group α Group substitution); R 3 is hydrogen , C 丨 _ 6 alkyl or c 6 _ 丨 〇 aryl (| The aryl may be substituted with 1 to 5 substituents selected from the substituent group α); m is 1 or 2, n is an integer of 1 to 3 ; Substituent group "is C1_6 alkyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, c 1-6 alkylthio, C 1-6 carboxy, C1-6 halide;): Oxo, C2-6 alkenyl, C2-6 alkyl, C 1-6 alkanesulfonyl, amine, C 1-6 alkylamino, c 1-6 dialkylamino, C 3-1 0 Cycloalkylamino, C 1-6 alkyl C 3 _ 丨 Cycloalkylamine, C 3-10 Bicycloamino, C 6-1 0 Aromatic amino, c 6 alkylsulfonamide -259- 200408628 group, C6-l0 arylsulfonylamino group, C1-11 aliphatic sulfonylamine group, C7-11 arylcarbonylamino group, C 1-6 alkylamine carbonyl group, C 6-1 0 arylamine carbonyl group, C 1- 6 alkoxycarbonyl, C7-16 aralkylamine carbonyl, C7-16 aralkyloxy, 4-10 membered heterocyclyl containing the same or different 1-3 heteroatoms selected from nitrogen, oxygen and sulfur, C6 -10 aryl, C9-16 arylalkenyl, carboxyl, carbamate, hydroxyl, cyano, nitro, and halogen atoms. 7. A compound of the following general formula (II) or a pharmacologically acceptable salt or ester thereof: (II) [wherein R is a C1-6 group (the group may be substituted with b5 substituents selected from the substituent group α), a C3-10 cycloalkyl group, a C2-6 alkenyl group ' It may be substituted with 1 to 5 substituents selected from the substituent group α) CHO aryl (the aryl may be substituted with one selected from the substituent group ^, substituted with a substituent), C 7-16 aralkyl ( The aralkyl group may be substituted with 1-5 substituents selected from the substituent group α) or a 4-10 membered heterocyclic group containing the same or different i-3 heteroatoms selected from nitrogen, oxygen, and sulfur (the The heterocyclic group may be substituted with 1 to 5 substituents selected from the substituent group α); R 2 is an aromatic group (the aralkyl group may be substituted with 5 substituents selected from the substituent group ^), C9_16 Arylalkenyl (the arylalkenyl may be substituted with 1 to 5 substituents selected from the substituent group α) or 5.10 members containing the same or different 丨 3 heteroatoms selected from nitrogen, oxygen, and sulfur Heteroaromatic cycloalkyl-260- (the heteroaromatic cycloalkyl may be substituted with 1-5 substituents selected from the substituent group α); η is an integer of 1 to 3, and (substituent group α) C h 6 alkane Group, C 丨 -6 hydroxyalkyl, C 1 · 6 haloalkyl, C 1 -6 sulfanyl, C1-6 alkoxy , C1-6 haloalkoxy, C2-6 alkyl, d 6 alkyl, C 1-6 alkylsulfonyl, amine, C 1-6 alkylamino, C 1-6 dialkylamino, C 1-6 hydroxyalkylamino, C 3-1 0 cycloalkylamino, C 1-6 alkyl C 3-1 0 cycloalkylamino, C 3-10 dicycloalkylamino, C 6 ^ 1 Arylamino, c 1-6 alkylsulfonamido, C 6-1 0 arylsulfonamido_, c 1-1 1 aliphatic sulfonamido, C 7-1 1 arylcarbonylamino, c 1-6 Oxycarbonyl, C1-6 alkylamine carbonyl, C6-10 arylamine carbonyl, Cl-6 oxycarbonyl, C7-16 aralkylamine carbonyl, C7-16 aralkyloxy containing n selected from nitrogen, oxygen and sulfur 4-10 membered heterocycles of the same or different heteroatoms, C6-l0 aryl, C9-16 arylalkenyl, carboxyl, carbamoyl, chemo, cyano, nitro, halogen atoms]. • If the compound or the pharmacologically acceptable salt or vinegar of item 7 in the scope of patent application, wherein R1 is a C1-6 alkyl group or a C6-10 aryl group (the aryl group is the same or different, there may be a C1-6 alkyl group, 1 to 3 substituents of amine, C1-6 alkylamino or Cl, 6 alkylsulfonamido). • If the compound in the 7th or 8th in the scope of patent application or its pharmacological allowance_ ^ 酉 said 'where R is methyl or phenyl (the phenyl is the same or different, there may be C 1-6 amino, amine , (: I -6 alkylamino or c 丨 · 6 alkanesulfonic acid amine substituted with 1 to 3 substituents). 0 · As a compound or pharmacology of any one of items 7 to 9 of the scope of patent application- 261- 200408628 salt or ester is allowed, in which R2 舄 c7_16 aralkyl (the aralkyl is related or not, may have C; U6 is based on 1-3, C1-6 alkoxy, or halogen atom Substituted by a substituent). The compound of any one of the above items or a drug thereof. For example, the scope of application for a patent is 7 ~ j. Allowable salts or esters, in which R 2 is a benzyl group (the benzyl group is the same or different. It may have a halogen atom. 1-3 milk / upper # 1U substituents). 2) The compound or any of its pharmacologically acceptable salts or esters according to any one of the scope of application patents Nos. 7 to 1 A, where n is 1 or 2. * 3.3 · [4_ [6_ (4 · amino group, 3,5_dimethyl · phenoxy) -p-methyl-1H_benzimid-2-ylmethoxy] -I (Imethoxy-benzyl (Oxy) -phenyl] -propionic acid, 3- 2_ (4_methoxybenzyloxy) + (6 -methoxy-1-methyl-1H -benzimidazolylmethoxy) _phenyl] -propionic acid, 3-[4- [6_ (4 -Amine_3,5_dimethyl, phenoxy) -1-methyl-1H · benzimidazole_2_ylmethoxy] -2- (4-chloro_benzyloxy) -phenyl ] -Propionic acid, 3- [2- (4-iodobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazole_2-ylmethoxy) -phenyl] _Propionic acid, 3- [2- (4-bromobenzyloxy) -4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -phenyl]- Propionic acid, 3- [4- [6--(3-Isopropylamino-phenoxy) -1-methyl-1H-benzimid-2-ylmethoxy] -2- (4-methoxy -Benzyloxy) -phenyl] -propionic acid, 3- [4- (6-methoxy-1-methyl-1H-benzimidazol-2-ylmethoxy) -2- (4- Methylbenzyloxy) -phenyl] -propanoic acid, 3- [4- [6- [3- (isopropylamino-phenoxy) -1-methyl-1H-benzimidazole_2-ylmethoxy Group] -2-(4-chloro-hexyloxy) -phenyl] -propionic acid, or -262- 200408628 its music allowable salts or esters. 14 · 3-[2 -chlorobenzyloxy) -4 · { 1-methyl-6- (3 -morpholine-4 -essentialoxy) -1H -benzimidazole_2- Methoxy 丨 -phenyl-propionic acid, (2 · [6_ (4 · amino_3,5_dimethyl_phenoxy) · 1 · methyl-1Η-benzimidazole · 2-yl]- Ethoxy} (4-chloro-benzyloxy) _phenyl] _propionic acid, 3- {2 · (4-chloro-benzyloxy) [2- (6_cyclopentyloxy-1-methyl- 1Η-benzimidazole · 2-yl) -ethoxy] -phenyl} -propionic acid, 3- [4- [2- (6-allyloxy) -n-based-1H-benzimidazole-2 -Yl] -ethoxy] -2- (4-chloro-benzyloxy |) -benzyl] -propionic acid, or a pharmacologically acceptable salt or ester thereof. 1 5 · A medicine containing the compound according to any one of claims 1 to 1 * in the scope of patent application, or a pharmacologically acceptable salt or ester thereof. 16 · —A pharmaceutical composition for improving insulin resistance, hypoglycemia, or inhibition of colonization of cancer cells, containing the compound according to any one of claims 1 to 14 or a pharmacologically acceptable salt or ester thereof as an active ingredient . 17 ·· A pharmaceutical composition for improving insulin resistance, which contains the compound according to any one of claims 1 to 14 or a pharmacologically acceptable salt or ester thereof as an active ingredient. 1 ··· A pharmaceutical composition for preventing or treating diabetes, insufficient glucose tolerance, obesity, antilipidemia, diabetic outbreak, or cancer, containing a compound according to any one of claims 1 to 14 of the scope of patent application Or its pharmacologically acceptable salt or ester is an effective ingredient. 19. A pharmaceutical composition for preventing or treating diabetes, which contains the compound according to any one of claims 1 to 14 in the scope of patent application or a pharmacologically acceptable salt thereof or • 263-200408628 ester as an active ingredient. 20 · A method for manufacturing a medicine for preventing or treating diabetes, which uses a compound or a pharmacologically acceptable salt or ester thereof according to any one of claims 1 to 14 of the scope of patent application. 2 1 · A method for manufacturing a medicine for improving insulin resistance, which uses a compound according to any one of claims 1 to 14 or a pharmacologically acceptable salt or ester thereof. 2 2-A method for preventing or treating diabetes, which involves administering a pharmacologically effective amount of a compound according to any one of claims 1 to 14 of the patent scope or a pharmacologically acceptable salt or ester thereof to a warm-blooded animal. -264- 200408628 柒. Designated Representative Map (1) The designated representative map in this case is: None. (2) Brief description of the component representative symbols of this representative map: None.捌. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention