Indazole compound and pharmaceutical

Abstract

The present invention provides a compound indicated by general formula (1) and having mPGES-1 inhibitory activity, a pharmaceutically acceptable salt thereof, or a solvate thereof (in the formula, R1 and R2 each independently indicate hydrogen, halogen, or a substitutable alkyl, R3 indicates –SO2R5 or –COR5, R4 indicates a substitutable alkyl, cycloalkyl, aryl, heteroaryl, saturated heterocyclic group, or arylalkyl, and R5 indicates a substitutable alkyl, cycloalkyl, aryl, heteroaryl, saturated heterocyclic group, alkenyl, or arylalkyl.

Description

Indazole compounds and pharmaceuticals

[0001] The present invention relates to a pharmaceutical composition containing, as an active ingredient, a novel indazole compound, or a pharmaceutically acceptable salt or solvate thereof.

[0002] Prostaglandins (PGs) are produced in large quantities at the site of inflammation and are involved in the progression of inflammation. Prostaglandin production begins with the release of arachidonic acid from membrane glycerophospholipids by phospholipase A2, and the released arachidonic acid is then converted to prostaglandin H2 (PGH2) by cyclooxygenase (COX). PGH2 is converted to prostaglandins, including prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), prostaglandin D2 (PGD2), prostaglandin I2 (PGI2), and thromboxane A2 (TXA2). These prostaglandins are known to have various physiological or pathophysiological activities, including proinflammatory effects. PGE2, in particular, is known to act as an inflammation-inducing substance in acute and chronic inflammation, and to induce fever and hyperalgesia. PGE2 is also known to be involved in urinary volume regulation and sodium reabsorption in the kidney (see, for example, Non-Patent Document 1). Non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors exhibit anti-inflammatory and antidiuretic effects by suppressing PGE2 production through COX-1 and / or COX-2 inhibitory activity. PGE2 synthase (PGES) is responsible for the final step in the synthesis pathway of PGE2, an inflammatory mediator. Three subtypes of PGES are currently known to exist: membrane-bound prostaglandin E synthase-1 (mPGES-1) (see, for example, Non-Patent Document 2), mPGES-2 (see, for example, Non-Patent Document 3), and cytosolic PGES (cPGES) (see, for example, Non-Patent Document 4). Of these, mPGES-1, like COX-2, is induced primarily during inflammation and is deeply involved in PGE2 production in inflammatory lesions, and is known to be constitutively expressed in the kidneys in particular. On the other hand, cPGES is a constitutive PGES that coexists primarily with COX-1 and is involved in constitutive PGE2 production (see, for example, Non-Patent Document 5). mPGES-2 is believed to be associated with both COXs.Studies of mPGES-1-deficient mice have suggested the involvement of mPGES-1 in the progression of pathology in various inflammation models, such as the acetic acid-induced writhing model (see, e.g., Non-Patent Document 6), arthritis model (see, e.g., Non-Patent Document 6 and Non-Patent Document 7), multiple sclerosis model (see, e.g., Non-Patent Document 8), and fever model (see, e.g., Non-Patent Document 9). It has also been reported that mPGES-1 deficiency reduces urine output in polyuria models, suggesting the involvement of mPGES-1 in the pathology of polyuria (see, e.g., Non-Patent Document 10). Because mPGES-1 inhibitors inhibit only COX-2-dependent PGE2 production, they are expected to have fewer side effects than NSAIDs or COX-2 inhibitors. The increased risk of cardiovascular events associated with COX-2 inhibitors is thought to be due to enhanced coagulation and vasoconstriction caused by the inhibition of COX-2-dependent PGI2 production (see, e.g., Non-Patent Document 11). In contrast, mPGES-1 inhibitors do not inhibit PGI2 production, and are therefore thought to avoid the increased risk of cardiovascular events that is problematic with COX-2 inhibitors (see Non-Patent Document 12). Furthermore, while mPGES-1 inhibitors inhibit PGE2 production, which is involved in inflammation, they also enhance the production of PGI2, which has anti-inflammatory effects (see Non-Patent Document 13, for example) (see Non-Patent Document 14), and are therefore expected to have a strong anti-inflammatory effect. Furthermore, since PGE2 promotes cell proliferation (see Non-Patent Document 15, for example), while PGI2 inhibits cell proliferation (see Non-Patent Document 16, for example), mPGES-1 inhibitors are also expected to have a strong cell proliferation inhibitory effect. Therefore, drugs that exhibit mPGES-1 inhibitory activity and can selectively suppress PGE2 production are useful for the treatment or prevention of diseases involving mPGES-1, such as inflammatory diseases, proliferative diseases, and dysuria. Although various compounds exhibiting mPGES-1 inhibitory activity are known (see, for example, Patent Documents 1 to 13), no compounds having an indazole skeleton are known.

[0003] International Publication No. WO2011 / 048004 International Publication No. WO2012 / 087771 International Publication No. WO2012 / 022792 International Publication No. WO2012 / 161965 International Publication No. WO2013 / 186692 International Publication No. WO2013 / 072825 International Publication No. WO201 International Publication No. WO2016 / 199104 International Publication No. WO2016 / 069374 International Publication No. WO2016 / 069376 International Publication No. WO2016 / 097013

[0004] Thanksら、. 4. The The heartbeat ,188,DAY257,D424000 snowら、sweet aesthetic SUBS,1999,96,7220722 Thanksgivingら、Appreciation. FASHION,2002,291,484 LIKE THIS ら、THE LIFE. ,2000,275,3277527752 THISら、THE THINGS,20002 75,32783 7527202050ら、2 2004,204,3684 365 THINGSら、THE THINGS, 2008,108,386010866008ら、BlackNightsAsSayS, 2000,106,2180020126 203,2000ら,117113800000ら、S No snowflake snowflake. 2000,296,0112005000ら、M 2009,41,202 7000000ら、2000000,20 06,116,13910169816, 2007,178,7020000000000000 0,2005,280,16570165840 8. The scientists, 203, 4,44414444444444444444444444448 90002,26,2002,1 42000000000,20 4,279,126444126586 20. 20. 20. 20. 20. 20. 20. 20. 20 11,65,77840000 FASHION,2008,62,373 3800000000000000000000 SU,2009,106,2104 21820000000,2 49,36843369505 No,2008,180,861 68,2011,59,2082 40000000000,000000000 11,32,1000000000000000000000000000000000000000000000 DA,2003,278,1939 4500000,2012,32943-2952. Cancer Res. , 2008, 68, 3251-3259. Proc. Natl. Acad. Sci. USA, 2006, 103, 14507-14512. Proc. Natl. Acad. Sci. USA, 2006, 103, 11790-11795. J. Rheumatol. , 2005, 32, 887-895. J. Pharmacol. Exp. Ther. , 2008, 326, 754-763. Kidney Int. , 2011, 79, 77-88. J. Immunol. , 2012, 188, 4093-4102. Am. J. Physiol. Lung Cell Mol. Physiol. , 2004, 287, L981-L991. Am. J. Physiol. Lung Cell Mol. Physiol. , 2005, 288, L1010-L1016. J. Immunol. , 2012, 188, 4093-4102. Oncogene, 2012, 31, 2943-2952. Arthritis Res. Ther. , 2011, 13, R6. ,

[0005] A primary object of the present invention is to provide a novel indazole derivative or a pharmaceutically acceptable salt thereof. Another object of the present invention is to provide a pharmaceutical composition containing such an indazole derivative or a pharmaceutically acceptable salt thereof as an active ingredient.

[0006] The present inventors have found that the novel indazole derivatives or pharmaceutically acceptable salts thereof described below have excellent mPGES-1 inhibitory activity, and have completed the present invention.

[0007] That is, the following (I) to (XXXXIV) can be mentioned as embodiments of the present invention. (I) A compound represented by the following general formula [1]: [In the formula, R １ , R ２ each independently represents hydrogen, halogen, or optionally substituted alkyl; R ３ is -SO ２ R ５ , or -COR ５ represents; R ４represents an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted saturated heterocyclic group, or an optionally substituted arylalkyl; R ５ represents optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted saturated heterocyclic group, optionally substituted alkynyl, or optionally substituted arylalkyl; and the heteroaryl and saturated heterocyclic group are bonded via a carbon atom on the ring, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0008] (II) R １ , R ２ The alkyl in R may be substituted with 1 to 3 halogen atoms; ４ The heteroaryl in R is optionally substituted with 1 to 3 groups independently selected from the group consisting of: (1) alkoxy optionally substituted with 1 to 3 halogens, (2) cyano, (3) halogen, (4) alkyl optionally substituted with (i) 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy, and (5) cycloalkyl; ４ The saturated heterocyclic group in R may be substituted with 1 to 3 groups independently selected from the group consisting of alkyl, alkoxycarbonyl, and alkylcarbonyl; ４ The alkyl in may be substituted with a saturated heterocyclic group or a cycloalkyl; ４ The aryl in R is optionally substituted with 1 to 3 groups independently selected from the group consisting of: (1) alkoxy optionally substituted with 1 to 3 halogens, (2) cyano, (3) halogen, (4) alkyl optionally substituted with (i) 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy, and (5) cycloalkyl; ４The arylalkyl in R may be substituted with alkyl or alkoxy which may be substituted with 1 to 3 halogen atoms; ５ The saturated heterocyclic group in R may be substituted with 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl; ５ The alkyl in R may be substituted with 1 to 3 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, monoalkylamino, dialkylamino, and halogen; ５ wherein cycloalkyl is optionally substituted with 1 to 3 groups independently selected from the group consisting of: (1) hydroxy, (2) cyano, and (3) alkyl optionally substituted with 1 to 3 halogens.

[0009] (III) R ４ the aryl in the formula (I) is phenyl optionally substituted with 1 to 3 groups independently selected from the group consisting of: (1) alkoxy optionally substituted with 1 to 3 halogens, (2) cyano, (3) halogen, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy, and (5) cycloalkyl; ４ the heteroaryl in the formula (I) is imidazolyl, thiazolyl, pyridyl, pyridazinyl, or pyrimidinyl, optionally substituted with 1 to 3 groups independently selected from the group consisting of: (1) alkoxy optionally substituted with 1 to 3 halogens, (2) cyano, (3) halogen, (4) alkyl optionally substituted with (i) 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy, and (5) cycloalkyl; ４ The compound according to the above (I) or (II), or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein the saturated heterocyclic group is piperidinyl or tetrahydropyranyl, which may be substituted with alkyl, alkoxycarbonyl, or alkylcarbonyl.

[0010] (IV) R ５ The aryl in R is phenyl; ５ heteroaryl in is furyl; ５ The compound according to any one of the above (I) to (III), or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein the saturated heterocyclic group in the formula (I) is piperidinyl, tetrahydrofuryl, or tetrahydropyranyl, each of which may be substituted with 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl.

[0011] (V) R ４ is alkyl having 1 to 6 carbon atoms optionally substituted with a saturated heterocyclic group or cycloalkyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to any one of the above (I) to (IV).

[0012] (VI) R ４ is cycloalkyl having 3 to 10 carbon atoms, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to any one of the above (I) to (IV).

[0013] (VII) R ４ The compound according to any one of the above (I) to (IV), or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein is phenyl optionally substituted with 1 to 3 groups independently selected from the group consisting of: (1) alkoxy optionally substituted with 1 to 3 halogens, (2) cyano, (3) halogen, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy, and (5) cycloalkyl.

[0014] (VIII) R ４is imidazolyl, thiazolyl, pyridyl, pyridazinyl or pyrimidinyl optionally substituted by 1 to 3 groups independently selected from the group consisting of: (1) alkoxy optionally substituted by 1 to 3 halogens, (2) cyano, (3) halogen, (4) (i) alkyl optionally substituted by 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy, and (5) cycloalkyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0015] (IX) R ４ is piperidinyl or tetrahydropyranyl, optionally substituted by 1 to 3 groups independently selected from the group consisting of alkyl, alkoxycarbonyl, and alkylcarbonyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0016] (X) R ４ is phenylalkyl optionally substituted with alkyl or alkoxy having 1 to 6 carbon atoms optionally substituted with 1 to 3 halogens, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0017] (XI) R ５ is alkyl having 1 to 6 carbon atoms optionally substituted with 1 to 3 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, monoalkylamino, dialkylamino, and halogen, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to any one of the above (I) to (X).

[0018] (XII) R ５ is a cycloalkyl having 3 to 10 carbon atoms optionally substituted with 1 to 3 groups independently selected from the group consisting of (1) hydroxy, (2) cyano, and (3) alkyl optionally substituted with 1 to 3 halogens, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to any one of the above (I) to (X).

[0019] (XIII) R５ The compound according to any one of the above (I) to (X), or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein: is optionally substituted phenyl.

[0020] (XIV) R ５ is optionally substituted furyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to any one of the above (I) to (X).

[0021] (XV) R ５ is piperidinyl, tetrahydrofuryl, or tetrahydropyranyl, each of which may be substituted by 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0022] (XVI) R ５ is an optionally substituted alkynyl having 2 to 6 carbon atoms, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to any one of the above (I) to (X).

[0023] (XVII) R ５ The compound according to any one of the above (I) to (X), or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein: is optionally substituted phenylalkyl.

[0024] (XVIII) R １ is halogen or alkyl having 1 to 6 carbon atoms optionally substituted with 1 to 3 halogens, or a pharmaceutically acceptable salt thereof, or a solvate thereof according to any one of the above (I) to (XVII).

[0025] (XIX) R ２ The compound according to any one of the above (I) to (XVIII), or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein is hydrogen or halogen.

[0026] (XX) The compounds of Examples 1 to 285 below, or pharmaceutically acceptable salts thereof, or solvates thereof.

[0027] (XXI) A pharmaceutical composition containing the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0028] (XXII) An mPGES-1 inhibitor comprising the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0029] (XXIII) A method for inhibiting mPGES-1 activity, comprising administering the compound according to any one of (I) to (XX) above, or a pharmaceutically acceptable salt thereof, or a solvate thereof, to a subject in need thereof.

[0030] (XXIV) A compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof for use in inhibiting mPGES-1.

[0031] (XXV) Use of the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof in the manufacture of an mPGES-1 inhibitor.

[0032] (XXVI) A PGE2 production inhibitor comprising the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0033] (XXVII) A method for inhibiting PGE2 production, comprising administering the compound according to any one of (I) to (XX) above or a pharmaceutically acceptable salt thereof, or a solvate thereof to a subject in need thereof.

[0034] (XXVIII) A compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof for use in inhibiting PGE2 production.

[0035] (XXIX) Use of the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof in the manufacture of a PGE2 production inhibitor.

[0036] (XXX) A preventive or therapeutic agent for a disease involving mPGES-1, comprising the compound according to any one of (I) to (XX) above, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0037] (XXXI) A method for preventing or treating a disease involving mPGES-1, comprising administering the compound according to any one of (I) to (XX) above or a pharmaceutically acceptable salt thereof, or a solvate thereof to a subject in need thereof.

[0038] (XXXII) The compound of the present invention or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of a disease involving mPGES-1.

[0039] (XXXIII) Use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of an agent for preventing or treating a disease involving mPGES-1.

[0040] (XXXIV) A preventive or therapeutic agent for a disease involving PGE2, comprising the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0041] (XXXV) A method for preventing or treating a disease involving PGE2, which comprises administering to a subject in need thereof the compound according to any one of (I) to (XX) above or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0042] (XXXVI) A compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of a disease involving PGE2.

[0043] (XXXVII) Use of the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof in the manufacture of an agent for preventing or treating a disease involving PGE2.

[0044] (XXXVIII) A preventive or therapeutic agent for a disease which is expected to be effective due to an analgesic effect, anti-inflammatory effect or cell proliferation inhibitory effect, comprising the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof.

[0045] (XXXIX) A method for preventing or treating a disease for which an analgesic effect, anti-inflammatory effect or cell proliferation inhibitory effect can be expected to be effective, comprising administering the compound according to any one of (I) to (XX) above or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0046] (XXXX) A compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of a disease for which an analgesic action, anti-inflammatory action or cell proliferation inhibitory action can be expected to be effective.

[0047] (XXXXI) Use of the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof in the manufacture of a preventive or therapeutic agent for a disease which is expected to be effective due to its analgesic, anti-inflammatory or cell proliferation inhibitory effect.

[0048] (XXXXII) A compound according to any one of (I) to (XX) above or a pharmaceutically acceptable salt thereof, or a solvate thereof, for the treatment of inflammatory bowel disease, irritable bowel syndrome, migraine, headache, lower back pain, lumbar spinal canal stenosis, herniated disc, temporomandibular joint disorder, cervicobrachial syndrome, cervical spondylosis, endometriosis, adenomyosis, premature birth, threatened premature birth, dysmenorrhea, overactive bladder, nocturia, interstitial cystitis, neurodegenerative disease, psoriasis, rheumatoid arthritis, rheumatic fever, fibromyalgia, neuralgia, complex regional pain syndrome, fascial disorder, viral infection, bacterial infection, fungal infection, burns, inflammation after surgery, after trauma, and after tooth extraction. - An agent for preventing or treating pain in malignant tumors, atherosclerosis, stroke, gout, arthritis, osteoarthritis, juvenile arthritis, tenosynovitis, ossification of ligaments, systemic lupus erythematosus, vasculitis, pancreatitis, nephritis, conjunctivitis, iritis, scleritis, uveitis, wound treatment, dermatitis, eczema, osteoporosis, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, allergic diseases, familial adenomatous polyposis, scleroderma, bursitis, uterine fibroids, prostatitis, depression, neurogenic bladder, nocturia, diurnal polyuria, enuresis, central diabetes insipidus, nephrogenic diabetes insipidus, urinary incontinence, benign prostatic hyperplasia, chronic prostatitis, or cancer.

[0049] (XXXXIII) A preventive or therapeutic agent for nocturnal polyuria, nocturia, overactive bladder, neurogenic bladder, enuresis, benign prostatic hyperplasia, central diabetes insipidus, nephrogenic diabetes insipidus, chronic prostatitis, interstitial cystitis, or urinary incontinence, comprising the compound according to any one of (I) to (XX) above or a pharmaceutically acceptable salt thereof, or a solvate thereof.

[0050] (XXXXIV) A method for preventing or treating nocturnal polyuria, nocturia, overactive bladder, neurogenic bladder, enuresis, benign prostatic hyperplasia, central diabetes insipidus, nephrogenic diabetes insipidus, chronic prostatitis, interstitial cystitis, or urinary incontinence, which comprises administering the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof, or a solvate thereof to a subject in need thereof.

[0051] (XXXXV) The compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of nocturnal polyuria, nocturia, overactive bladder, neurogenic bladder, bedwetting, benign prostatic hyperplasia, central diabetes insipidus, nephrogenic diabetes insipidus, chronic prostatitis, interstitial cystitis, or urinary incontinence.

[0052] (XXXXVI) Use of the compound according to any one of the above (I) to (XX) or a pharmaceutically acceptable salt thereof in the manufacture of an agent for the prophylaxis or treatment of nocturnal polyuria, nocturia, overactive bladder, neurogenic bladder, bedwetting, benign prostatic hyperplasia, central diabetes insipidus, nephrogenic diabetes insipidus, chronic prostatitis, interstitial cystitis, or urinary incontinence.

[0053] The definitions of the terms used in this specification are explained in detail below.

[0054] "Halogen" refers to a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom. In particular, a fluorine atom or a chlorine atom is preferred.

[0055] Examples of "alkyl" include straight-chain or branched-chain alkyls having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms. Specific examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, isoamyl, -CH(CH ２ CH ３ ) ２ , hexyl, isohexyl, -CH ２ CH ２ C(CH ３ ) ３ , -CH ２ CH (CH ２ CH ３ ) ２, heptyl, isoheptyl, octyl, isooctyl, and the like.

[0056] The alkyl portions of "alkylcarbonyl," "alkoxy," "alkoxycarbonyl," "aralkyl," "monoalkylamino," "dialkylamino," and "arylalkyl" can be the same as those of the above-mentioned "alkyl."

[0057] Examples of "alkoxy" include straight-chain or branched-chain alkoxy having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms. Specific examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy, n-heptyloxy, and n-octyloxy.

[0058] Examples of "cycloalkyl" include saturated hydrocarbon groups having 3 to 10 carbon atoms and having one to three rings. Specific examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.1.0]pentyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, and bicyclo[3.2.1]octyl, adamantyl (tricyclo[3.3.1.1]octyl), and the like. ３，７ ] decanyl) and the like.

[0059] Examples of "alkynyl" include straight-chain or branched-chain alkynyl having 2 to 8 carbon atoms and one or two triple bonds. Specific examples include ethynyl, 1-propynyl, 2-propynyl, 1-methyl-2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, and 1-methyl-4-pentynyl. Alkynyl having 2 to 6 carbon atoms is preferred, and alkynyl having 2 to 4 carbon atoms is more preferred.

[0060] Examples of "aryl" include aromatic hydrocarbon groups having 1 to 3 rings and 6 to 14 carbon atoms. Specific examples include phenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl, and 10-phenanthryl. Phenyl is particularly preferred.

[0061] The aryl moiety of "arylalkyl" can be the same as the above-mentioned "aryl." Specific examples of "arylalkyl" include phenylmethyl (benzyl), phenylethyl (phenethyl), phenylpropyl, phenylbutyl, phenylpentyl, etc.

[0062] Examples of "heteroaryl" include mono- or bicyclic aromatic heterocyclic groups having 1 to 4 heteroatoms selected from nitrogen, sulfur, and oxygen atoms in the ring and 5 to 10 ring-constituting atoms. Specific examples include furyl (e.g., 2-furyl, 3-furyl), thienyl (e.g., 2-thienyl, 3-thienyl), pyrrolyl (e.g., 2-pyrrolyl, 3-pyrrolyl), imidazolyl (e.g., 2-imidazolyl, 4-imidazolyl), pyrazolyl (e.g., 3-pyrazolyl, 4-pyrazolyl), triazolyl (e.g., 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, 1,2,3-triazol-6-yl), 1,2,4-triazol-7-yl, 1,2,4-triazol-8-yl, 1,2,4-triazol-9-yl, 1,2,4-triazol-10-yl), 1,2,4-triazol-11-yl, 1,2,4-triazol-12-yl, 1,2,4-triazol-13-yl, 1,2,4-triazol-14-yl, 1,2,4-triazol-15-yl, 1,2,4-triazol-16-yl), 1,2,4-triazol-17-yl, 1,2,4-triazol-18-yl, 1,2,4-triazol-19-yl, 1,2,4-triazol-20-yl, 1,2,4-triazol-21-yl, 1,2,4-triazol-22-yl, 1,2,4-triazol-23-yl, oxazolyl (e.g., 2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (e.g., 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), oxadiazolyl (e.g., 1,3,4-oxadiazol-2-yl), thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), thiadiazolyl, isoxazolyl, isothiazolyl (e.g., 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridazinyl (e.g., 3-pyridazinyl, 4-pyridazinyl), pyrimidinyl (e.g., 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), pyrazinyl (e.g., 2-pyrazinyl), benzimidazolyl (e.g., 2-benzimidazolyl, 4- benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl), indazolyl (for example, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-indazolyl), isoquinolyl (for example, 1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl).More preferred are furyl (e.g., 2-furyl, 3-furyl), imidazolyl (e.g., 2-imidazolyl, 4-imidazolyl), thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridazinyl (e.g., 3-pyridazinyl, 4-pyridazinyl), and pyrimidinyl (e.g., 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl). ４ As the heteroaryl in R, imidazolyl, thiazolyl, pyridyl, pyridazinyl, and pyrimidinyl are preferred. ５ As the heteroaryl in the formula (I), furyl is preferred.

[0063] Examples of the "saturated heterocyclic group" include saturated heterocyclic groups composed of 3 to 8 atoms and having 1 to 3 heteroatoms, which may be the same or different, arbitrarily selected from the group consisting of nitrogen atoms, sulfur atoms, and oxygen atoms. Specific examples of saturated heterocyclic groups include oxiranyl, azetidinyl (e.g., 2-azetidinyl, 3-azetidinyl), pyrrolidinyl (e.g., 2-pyrrolidinyl, 3-pyrrolidinyl), piperidinyl (e.g., 2-piperidinyl, 3-piperidinyl, 4-piperidinyl), piperazinyl (e.g., 2-piperazinyl, 3-piperazinyl), morpholinyl (e.g., 2-morpholinyl, 3-morpholinyl), thiomorpholinyl (e.g., 2-thiomorpholinyl, 3-thiomorpholinyl), tetrahydrofuryl (2-tetrahydrofuryl, 3-tetrahydrofuryl), and tetrahydropyranyl (2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl). More preferred are piperidinyl (eg, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl), tetrahydrofuryl (2-tetrahydrofuryl, 3-tetrahydrofuryl), and tetrahydropyranyl (2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl).

[0064] R ４is an alkyl having 1 to 6 carbon atoms which may be substituted by a saturated heterocyclic group or a cycloalkyl, examples of the saturated heterocyclic group include those defined above for the "saturated heterocyclic group", and examples of the cycloalkyl include those defined above for the "cycloalkyl".

[0065] R ４ is piperidinyl or tetrahydropyranyl optionally substituted by 1 to 3 groups independently selected from the group consisting of alkyl, alkoxycarbonyl, and alkylcarbonyl, the alkyl can be the same as defined for the above "alkyl", the alkoxycarbonyl can be the same as defined for the above "alkoxycarbonyl", and the alkylcarbonyl can be the same as defined for the above "alkylcarbonyl".

[0066] R ５ is an alkyl having 1 to 6 carbon atoms optionally substituted with 1 to 3 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, monoalkylamino, dialkylamino, and halogen; examples of the alkoxy include the same as those defined for the above "alkoxy", examples of the cycloalkyl include the same as those defined for the above "cycloalkyl", examples of the monoalkylamino include the same as those defined for the above "monoalkylamino", and examples of the dialkylamino include the same as those defined for the above "dialkylamino".

[0067] R ５is piperidinyl, tetrahydrofuryl, or tetrahydropyranyl, each of which may be substituted by 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl, the alkyl can be the same as defined above for "alkyl", and the alkoxycarbonyl can be the same as defined above for "alkoxycarbonyl".

[0068] It is understood that the present invention encompasses all combinations of the substituents described herein. That is, the present invention encompasses all combinations of the substituents R １ , R ２ , R ３ and R ４ The term "substituted" encompasses any combination of substituents independently selected from the groups described for each of the groups, and is not limited to the particular combinations specifically described herein.

[0069] The compounds of the present invention exhibit mPGES-1 inhibitory activity and can selectively suppress the production of PGE2. Furthermore, by suppressing the production of PGE2 in renal collecting duct cells, the compounds of the present invention can promote the reabsorption of sodium and water from urine into blood. Therefore, the compounds of the present invention can exhibit antidiuretic effects without directly affecting plasma sodium concentration, and are therefore expected to have fewer side effects such as hyponatremia.

[0070] The compound of the present invention can be produced using known compounds or intermediates that can be easily synthesized from known compounds, for example, by the methods described below, the Examples described below, or known methods. In producing the compound of the present invention, if the raw material has a substituent that affects the reaction, it is common to first protect the raw material with an appropriate protecting group by a known method before carrying out the reaction. The protecting group can be deprotected by a known method after the reaction.

[0071] The abbreviations used in this specification have the following meanings: DMF: N,N-dimethylformamide, DMA: N,N-dimethylacetamide, DME: 1,2-dimethoxyethane, DMSO: dimethyl sulfoxide, NMP: N-methylpyrrolidone, THF: tetrahydrofuran, MeOH: methanol, EtOH: ethanol, CHCl ３ : Chloroform CH ２ Cl ２ : Methylene chloride HPLC: High performance liquid chromatography MS: Mass spectrometry LCMS: Liquid chromatography mass spectrometry WSCD: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride HBTU: O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate HATU: 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate PyBOP: 1H-benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate １ H-NMR: Proton nuclear magnetic resonance CDCl ３ : deuterated chloroform J: coupling constant s: singlet d: doublet t: triplet q: quartet quin.: quintet m: multiplet v / v: volume / volume

[0072] Method 1 (In the formula, R １ , R ２ , R ３ , R ４are as defined above.) This reaction is a condensation reaction between compound A and compound B, and can be carried out in accordance with a method known per se for condensation reactions. Compound [1] of the present invention can be synthesized by reacting compound A with a carboxylic acid of compound B or a reactive derivative thereof. Examples of reactive derivatives of compound B include those commonly used in amide condensation-forming reactions, such as acid halides (e.g., acid chlorides and acid bromides), mixed acid anhydrides, imidazolides, and activated amides. When compound B, which is a carboxylic acid, is used, the reaction can be carried out in the presence or absence of a base using a condensing agent at a temperature within the range of -20°C to 100°C. Examples of condensing agents that can be used in this reaction include 1,1'-oxalyldiimidazole, 1,1'-carbonyldiimidazole, WSCD, diethyl cyanophosphonate, HBTU, HATU, and PyBOP. Examples of bases that can be used in this reaction include organic bases such as triethylamine, N,N-diisopropylethylamine, N,N-dimethylaniline, pyridine, and 1,8-diazabicyclo[5.4.0]-7-undecene. Solvents that can be used are not particularly limited as long as they are not involved in the reaction, and include, for example, ethers such as THF, 1,4-dioxane, diethyl ether, and DME, amides such as DMF and DMA, nitriles such as acetonitrile and propionitrile, hydrocarbons such as benzene and toluene, and CHCl. ３ , C.H. ２ Cl ２ Examples of suitable solvents include halogenated hydrocarbons such as 1-hydroxybenzotriazole and 1-hydroxy-7-azabenzotriazole, or mixed solvents thereof. If necessary, additives can be used. Usable additives include, for example, 1-hydroxybenzotriazole and 1-hydroxy-7-azabenzotriazole. The reaction time varies depending on the types of raw materials used, the reaction temperature, and other factors, but is typically within the range of 10 minutes to 24 hours. The amounts of compound A and condensing agent used are, for example, within the range of 1 to 3 moles per mole of compound B. The amount of base used is, for example, within the range of 1 to 10 equivalents, preferably 1 to 4 equivalents, per mole of compound B.

[0073] Compound A can be produced, for example, according to the following production method. (In the formula, R ４ has the same meaning as above. １ represents a leaving group such as a chlorine atom, a bromine atom, an iodine atom, or trifluoromethanesulfonate.

[0074] R ４ When R is an aryl or heteroaryl, compound A can be synthesized by reacting a known compound C (which can be synthesized, for example, according to the method described in WO 2006 / 046031) with an aryl halide or heteroaryl halide using a copper catalyst such as copper iodide and a ligand such as trans-1,2-cyclohexanediamine (J. Org. Chem. 2004, 69, 5578-5587; J. Am. Chem. Soc., 2001, 123, 7727-7729). This coupling reaction is carried out in the presence of, in addition to the above reagents, an alkali metal carbonate (e.g., sodium carbonate, potassium carbonate, cesium carbonate, etc.), an alkali metal phosphate (potassium phosphate, etc.), an organic base (triethylamine, diisopropylethylamine, etc.), an alkali metal halide (lithium chloride, cesium fluoride, etc.), or an alkali metal hydroxide (sodium hydroxide, etc.). Specific examples of solvents should be selected according to the types of raw materials and reagents used, and include, for example, toluene, THF, 1,4-dioxane, DME, ethyl acetate, acetone, acetonitrile, DMF, DMA, NMP, alcohols such as MeOH, EtOH, isopropanol, and tert-butanol, and water, which can be used alone or as a mixed solvent. The reaction temperature varies depending on the types of raw materials and reagents used, but is usually 0 to 200°C, preferably 60 to 150°C. The reaction time varies depending on the types of raw materials used and the reaction temperature, but is usually 30 minutes to 24 hours.

[0075] R ４When is an alkyl, arylalkyl, cycloalkyl, or saturated heterocyclic group, Compound A can be synthesized by an N-alkylation reaction. This reaction can be carried out according to conventional methods. For example, it can be carried out in a suitable solvent or without a solvent, in the presence or absence of a base. Examples of the base used include pyridine, triethylamine, N,N-diisopropylethylamine, potassium carbonate, sodium bicarbonate, etc. The solvent used is not particularly limited as long as it does not participate in the reaction, and examples include ethers such as THF and diethyl ether, amides such as DMF and DMA, nitriles such as acetonitrile and propionitrile, hydrocarbons such as benzene and toluene, alcohols such as MeOH and EtOH, water, or a mixture thereof. The reaction temperature varies depending on the types of compounds and reagents used, but is usually 0 to 200°C, preferably 30 to 150°C. The amount of base used is, for example, 1 to 10 equivalents, preferably 1 to 4 equivalents, relative to Compound C. The reaction time varies depending on the types of raw materials used and the reaction temperature, but is usually 30 minutes to 24 hours.

[0076] Compound A can also be produced, for example, by the following production method. (In the formula, R ４represents an alkyl, arylalkyl, or saturated heterocyclic group.) Step 1: This reaction employs a typical Mitsunobu method using a known compound D (which can be synthesized, for example, according to the method described in J. Med. Chem., 2006, 49, 2339-2352) as the starting material, and can be carried out according to methods known per se for the Mitsunobu reaction. Typical reaction conditions include reacting compound D with an alcohol in the presence of triphenylphosphine and diethyl azodicarboxylate in a suitable solvent such as THF, 1,4-dioxane, or DMF at 0°C to room temperature to synthesize compound E. Examples of azodicarboxylate diesters include diethyl azodicarboxylate, di-tert-butyl azodicarboxylate, and diisopropyl azodicarboxylate. The reaction temperature varies depending on the types of starting compounds and reagents used, but is usually 0 to 200°C, preferably 0°C to room temperature. The reaction time varies depending on the types of raw materials used and the reaction temperature, but is typically 30 minutes to 24 hours. Step 2: This reaction is a reduction reaction of compound E to an aromatic amine and can be carried out by a conventional method. For example, this reaction can be carried out in a suitable solvent under a hydrogen gas atmosphere by catalytic hydrogen reduction using compound E and a catalyst containing Raney nickel, palladium, rhodium, platinum, or the like; hydride reduction using lithium aluminum hydride, or the like; iron reduction using a reduced iron reagent and ammonium chloride, or the like; or zinc dust and acetic acid, or the like. Other methods include a method using a sulfide such as sodium hydrosulfite, or a reduction method using ammonium formate, hydrazine, or the like under a metal catalyst such as palladium-carbon. Examples of solvents are selected depending on the types of compounds and reagents used, but include, for example, toluene, THF, 1,4-dioxane, DME, ethyl acetate, acetone, acetonitrile, DMF, alcohols such as MeOH, EtOH, and tert-butanol, and water, and can be used alone or in mixtures. The reaction temperature varies depending on the types of compounds and reagents used, but is usually 0 to 300°C, preferably 20 to 150°C.

[0077] Compound B can be produced, for example, according to the method described in WO2011 / 048004.

[0078] Method 2 (In the formula, R １ , R ２ , R ３ , R ４ has the same meaning as above. PG represents a protecting group.) Step 1 This reaction is a condensation reaction between Compound A and Compound F, and Compound G can be produced in accordance with Production Method 1. Step 2 This reaction is a deprotection reaction of the amino group in Compound G, and Compound H can be synthesized in accordance with a method known per se for deprotecting an amino group. The protecting group for the amino group is not particularly limited as long as it does not affect the reaction, and examples include carbamates such as a tert-butoxycarbonyl group and a benzyloxycarbonyl group. In addition, protecting groups commonly used as protecting groups for amino groups as described in the literature (e.g., Green's Protective Groups in Organic Synthesis, 4th Edition, A John Wiley & Sons, Inc., Publication) can be used. The deprotection reaction can be carried out under acidic conditions using hydrochloric acid, Lewis acid, trifluoroacetic acid, or the like in a suitable solvent. Deprotection can also be carried out by hydrogenolysis in the presence of a catalyst such as palladium. Step 3: This reaction is an amidation or sulfonamidation reaction of Compound H, and Compound [1] of the present invention can be produced in accordance with the above-mentioned Production Method 2, Step 1.

[0079] Compound F can be produced, for example, according to a method described in the literature (for example, WO2011 / 048004; Tetrahedron Letters, 1993, 34, 6263-6264).

[0080] Method 3 (In the formula, R １ , R ２ , R ３ , R ４ , X １are as defined above.) This reaction is a coupling reaction of Compound I with Compound J using a palladium or copper catalyst, and is carried out by a method known per se. The solvent that can be used is not particularly limited as long as it is inert to the reaction, but examples include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane and THF, amides such as DMF, DMA, and NMP, water, and mixtures thereof. This reaction is carried out in the presence of a base at a temperature ranging from 20 to 200°C, preferably from 60 to 150°C, and if necessary, using microwaves. Examples of palladium catalysts that can be used include tris(dibenzylideneacetone)(chloroform)dipalladium(0), tris(dibenzylideneacetone)dipalladium(0), and palladium(II) acetate. The amount of such a palladium catalyst is suitably within a range of 0.001 to 0.3 moles per mole of Compound I. Examples of ligands for palladium catalysts that can be used include 1,1'-bis(diphenylphosphino)ferrocene, 4,5-bis(diphenylphosphino)-9,9'-dimethylxanthene, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, (±)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, 2-(di-t-butylphosphino)biphenyl, and bis[2-(diphenylphosphino)phenyl]ether. Examples of copper catalysts that can be used include copper iodide. Examples of bases that can be used include alkali metal carbonates such as sodium carbonate, sodium bicarbonate, potassium carbonate, and cesium carbonate; alkali metal hydroxides such as sodium hydroxide; alkali metal phosphates such as potassium phosphate; organic bases such as triethylamine and N,N-diisopropylethylamine; and alkali metal halides such as lithium chloride and cesium fluoride. The amount of base used is, for example, 1 to 10 equivalents, preferably 1 to 4 equivalents, relative to Compound I. The reaction time varies depending on the types of raw materials used, the reaction temperature, etc., but is usually within the range of 10 minutes to 24 hours.

[0081] Compound J can be produced, for example, by the condensation reaction of Compound B with ammonia in Production Method 1.

[0082] Compound I can be produced, for example, according to methods described in the literature (e.g., J. Org. Chem., 2009, 74, 9539; WO2009 / 117626), using a benzaldehyde derivative K and a hydrazine derivative L that is commercially available or can be prepared by a known method, as shown below. The solvent that can be used is not particularly limited as long as it is inert to the reaction, and examples include hydrocarbons such as toluene and xylene, ethers such as 1,4-dioxane and THF, amides such as DMF, DMA, and NMP, and alcohols such as MeOH, EtOH, and tert-butanol, which can be used alone or in combination. The reaction temperature varies depending on the types of compounds and reagents used, but is usually 0 to 300°C, preferably 20 to 150°C. (In the formula, R ４ , X １ has the same meaning as above. ２ represents a leaving group such as a fluorine atom, chlorine atom, or bromine atom)

[0083] Method 4 (In the formula, R １ , R ２ , R ３ , R ４ , X １ has the same meaning as above. PG represents a protecting group. Step 1 This reaction is a condensation reaction between Compound M and Compound B, and Compound N can be produced in accordance with Production Method 1. Step 2 This reaction is a deprotection reaction of Compound N, and Compound N can be produced in accordance with Production Method 2, Step 2. Step 3 This reaction is a deprotection reaction of Compound N, and Compound O can be produced in accordance with Production Method 2, Step 3. ４ The compound [1] of the present invention can be produced in accordance with the above-mentioned method for producing compound A.

[0084] Compound M can be produced, for example, according to methods described in the literature (e.g., US2010 / 0063066; WO2004 / 046133).

[0085] The compound of the present invention can be used as a medicine as it is, or can be used in the form of a pharmaceutically acceptable salt prepared by a known method. Examples of such salts include salts with mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, and salts with organic acids such as acetic acid, citric acid, tartaric acid, maleic acid, succinic acid, fumaric acid, p-toluenesulfonic acid, benzenesulfonic acid, and methanesulfonic acid.

[0086] For example, the hydrochloride salt of the compound of the present invention can be obtained by dissolving the compound of the present invention in an alcoholic solution, an ethyl acetate solution, or a diethyl ether solution of hydrogen chloride.

[0087] The compound of the present invention or a pharmaceutically acceptable salt thereof may take up solvent molecules to form a solvate when left in the air or recrystallized, and such solvates are also included in the salt of the present invention. Examples of such solvates include solvates with solvent molecules such as methanol, ethanol, isopropyl alcohol, butanol, dimethyl sulfoxide, and acetonitrile, and hydrates.

[0088] Some of the compounds of the present invention have asymmetric carbon atoms, and both optical isomers and mixtures thereof are included in the present invention. Optical isomers can be produced, for example, by optical resolution of a racemate obtained as in the Examples described below using an optically active acid (tartaric acid, dibenzoyltartaric acid, mandelic acid, 10-camphorsulfonic acid, etc.) by a known method, taking advantage of its basicity, or by using a pre-prepared optically active compound as a starting material. Alternatively, optical isomers can also be produced by optical resolution using a chiral column or asymmetric synthesis.

[0089] The compound of the present invention or a pharmaceutically acceptable salt thereof has mPGES-1 inhibitory activity, as shown in the test examples below.

[0090] Thus, one embodiment of the present invention provides an mPGES-1 inhibitor comprising a compound of the present invention or a pharmaceutically acceptable salt thereof.

[0091] Furthermore, in one embodiment of the present invention, there is provided a method for inhibiting mPGES-1 activity, comprising administering to a subject in need thereof a compound of the present invention or a pharmaceutically acceptable salt thereof.

[0092] Furthermore, in one embodiment of the present invention, there is provided a compound of the present invention or a pharmaceutically acceptable salt thereof for use in inhibiting mPGES-1.

[0093] Furthermore, one embodiment of the present invention provides use of a compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of an mPGES-1 inhibitor.

[0094] Furthermore, the compound of the present invention or a pharmaceutically acceptable salt thereof has mPGES-1 inhibitory activity and therefore inhibits PGE2 production. Therefore, one embodiment of the present invention provides a PGE2 production inhibitor comprising the compound of the present invention or a pharmaceutically acceptable salt thereof.

[0095] Furthermore, in one embodiment of the present invention, there is provided a method for inhibiting PGE2 production, comprising administering to a subject in need thereof a compound of the present invention or a pharmaceutically acceptable salt thereof.

[0096] Furthermore, one embodiment of the present invention provides the compound of the present invention or a pharmaceutically acceptable salt thereof for use in inhibiting PGE2 production.

[0097] Furthermore, one embodiment of the present invention provides use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a PGE2 production inhibitor.

[0098] The compound of the present invention or a pharmaceutically acceptable salt thereof has mPGES-1 inhibitory activity and inhibits PGE2 production, and therefore can be used for the prevention or treatment of, for example, diseases associated with mPGES-1, diseases associated with PGE2, and diseases for which analgesic action, anti-inflammatory action, or cell proliferation inhibitory action can be expected to be effective.

[0099] Therefore, one embodiment of the present invention provides an agent for preventing or treating a disease involving mPGES-1, which comprises the compound of the present invention or a pharmaceutically acceptable salt thereof.

[0100] Furthermore, one embodiment of the present invention provides a method for preventing or treating a disease associated with mPGES-1, which comprises administering the compound of the present invention or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0101] Furthermore, one embodiment of the present invention provides the compound of the present invention or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of a disease involving mPGES-1.

[0102] Furthermore, one embodiment of the present invention provides use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of an agent for the prophylaxis or treatment of a disease associated with mPGES-1.

[0103] Furthermore, one embodiment of the present invention provides a preventive or therapeutic agent for a disease involving PGE2, which comprises the compound of the present invention or a pharmaceutically acceptable salt thereof.

[0104] Furthermore, one embodiment of the present invention provides a method for preventing or treating a disease involving PGE2, which comprises administering the compound of the present invention or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0105] Furthermore, one embodiment of the present invention provides the compound of the present invention or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of a disease involving PGE2.

[0106] Furthermore, one embodiment of the present invention provides use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of an agent for the prophylaxis or treatment of a disease involving PGE2.

[0107] Furthermore, one embodiment of the present invention provides a preventive or therapeutic agent for a disease that is expected to be effective due to its analgesic, anti-inflammatory or cell proliferation inhibitory effect, which contains the compound of the present invention or a pharmaceutically acceptable salt thereof.

[0108] Furthermore, one embodiment of the present invention provides a method for preventing or treating a disease for which analgesic, anti-inflammatory or cell proliferation inhibitory effect can be expected to be effective, which method comprises administering the compound of the present invention or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0109] Furthermore, one embodiment of the present invention provides the compound of the present invention or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of diseases for which analgesic, anti-inflammatory or cell proliferation inhibitory effects are expected to be effective.

[0110] Furthermore, one embodiment of the present invention provides use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a preventive or therapeutic agent for a disease whose effectiveness can be expected due to its analgesic, anti-inflammatory or cell proliferation inhibitory effect.

[0111] Diseases to which the compound of the present invention or a pharmaceutically acceptable salt thereof can be applied include diseases involving mPGES-1, such as inflammatory bowel disease (see, for example, Non-Patent Document 17), irritable bowel syndrome, migraine, headache, lower back pain, lumbar spinal canal stenosis, herniated disc, temporomandibular joint disorder, cervicobrachial syndrome, cervical spondylosis, endometriosis (see, for example, Non-Patent Document 18), adenomyosis, premature labor, threatened premature labor, dysmenorrhea, overactive bladder, nocturia (see, for example, Non-Patent Document 19), interstitial cystitis, and neurodegeneration. Diseases (e.g., Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease) (see, for example, Non-Patent Document 19), psoriasis, rheumatoid arthritis (see, for example, Non-Patent Documents 21 and 22), rheumatic fever, fibromyalgia, neuralgia (see, for example, Non-Patent Document 23), complex regional pain syndrome, myofascial disorders, viral infections (e.g., influenza, colds, shingles, AIDS), bacterial infections, fungal infections, burns (see, for example, Non-Patent Document 24), and hand Inflammation and pain after surgery, trauma, and tooth extraction, malignant tumors (e.g., colon cancer, breast cancer, lung cancer, prostate cancer, etc.) (see, for example, Non-Patent Documents 25, 26, and 27), atherosclerosis (see, for example, Non-Patent Document 28), stroke (see, for example, Non-Patent Document 29), gout, osteoarthritis (see, for example, Non-Patent Documents 30 and 31), juvenile arthritis, tenosynovitis, ossification of ligaments, systemic lupus erythematosus, vasculitis, pancreatitis, and nephritis (see, for example, Non-Patent Document 3 2), conjunctivitis, iritis, scleritis, uveitis, wound healing, dermatitis, eczema, osteoporosis, asthma (see, for example, non-patent document 33), chronic obstructive pulmonary disease (see, for example, non-patent document 34), pulmonary fibrosis (see, for example, non-patent document 35), allergic diseases (see, for example, non-patent document 36), familial adenomatous polyposis (see, for example, non-patent document 36), scleroderma (see, for example, non-patent document 38), bursitis, uterine fibroids, prostatitis, depression, or pain in cancer.

[0112] As shown in the test examples described later, the compound of the present invention or a pharmaceutically acceptable salt thereof has an effect of suppressing the amount of urination in nocturnal polyuria, and therefore can be used for the prevention or treatment of nocturnal polyuria, overactive bladder, neurogenic bladder, enuresis, benign prostatic hyperplasia, central diabetes insipidus, nephrogenic diabetes insipidus, chronic prostatitis, interstitial cystitis, or urinary incontinence.

[0113] Therefore, one embodiment of the present invention provides an agent for preventing or treating nocturnal polyuria, which comprises the compound of the present invention or a pharmaceutically acceptable salt thereof.

[0114] Furthermore, one embodiment of the present invention provides a method for preventing or treating nocturnal polyuria, which comprises administering the compound of the present invention or a pharmaceutically acceptable salt thereof to a subject in need thereof.

[0115] Furthermore, in one embodiment of the present invention, there is provided a compound of the present invention or a pharmaceutically acceptable salt thereof for use in the prevention or treatment of nocturnal polyuria.

[0116] Furthermore, one embodiment of the present invention provides use of a compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of an agent for the prevention or treatment of nocturnal polyuria.

[0117] "Subject" refers to a human or non-human animal having or suspected of having a disease associated with mPGES-1 or a disease associated with PGE2. In one embodiment of the invention, the subject is a mammal. In one embodiment of the invention, the subject is a human.

[0118] When the compound of the present invention or a pharmaceutically acceptable salt thereof is administered as a medicine, it is administered to mammals including humans as it is or as a pharmaceutical composition containing, for example, 0.001% to 99.5%, preferably 0.1% to 90%, of the compound of the present invention or a pharmaceutically acceptable salt thereof in a pharmaceutically acceptable, non-toxic and inert carrier.

[0119] The carrier may be one or more conventional pharmaceutically acceptable solid, semi-solid, or liquid diluents, fillers, and other formulation auxiliaries. The pharmaceutical composition of the present invention is preferably administered in a dosage unit form. The pharmaceutical composition may be administered intramuscularly, orally, intravenously, topically (transdermally, by eye drop, intraperitoneally, intrapleurally, etc.), or rectally. The pharmaceutical composition of the present invention is administered in a dosage form suitable for these administration methods.

[0120] The pharmaceutical dose is desirably adjusted taking into consideration the patient's condition, such as age, body weight, type and severity of disease, the route of administration, the type of compound of the present invention, whether or not it is a salt, and the type of salt, but typically, in the case of oral administration to an adult, the amount of the active ingredient of the compound of the present invention or a pharmaceutically acceptable salt thereof is within the range of 0.01 mg to 5 g per adult, preferably 1 mg to 500 mg per adult, per day. In some cases, a lower dose may be sufficient, or conversely, a higher dose may be required. Typically, the compound is administered once a day or in divided doses, or in the case of intravenous administration, it can be administered as a bolus or continuously for up to 24 hours.

[0121] One or more hydrogen, carbon and / or other atoms of the compounds of the present invention may be replaced with isotopes of the hydrogen, carbon and / or other atoms, respectively. Examples of such isotopes include, for example, ２ H. ３ H. １１ C. １３ C. １４ C. １５ N. １８ O. １７ O. ３１ P. ３２ P. ３５ S. １８ F. １２３ I and ３６ The isotopes of the compounds represented by the general formula [1] include hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine, and chlorine, such as Cl. The compounds represented by the general formula [1] also include compounds substituted with such isotopes. Such isotope-substituted compounds are also useful as pharmaceuticals, and include all radiolabeled compounds of the compounds represented by the general formula [1].

[0122] The present invention will be explained in more detail below with reference to Reference Examples, Examples, Test Examples and Formulation Examples, but the present invention is not limited to these examples.

[0123] MS was measured by LCMS. ESI was used as the ionization method. The observed mass spectrometry values ​​are expressed as m / z.

[0124] The LCMS measurement conditions were as follows: Analytical instrument: ACUITY UPLC MS / PDA system (Waters Corporation) Mass spectrometer: Waters 3100 MS detector Photodiode array detector: ACUITY PDA detector (UV detection wavelength: 210 to 400 nm) Column: Acuity BEH C １８ , 1.7 μm, 2.1 × 50 mm Flow rate: 0.5 mL / min Column temperature: 40 ° C Solvent; Solution A: 0.1% formic acid / H ２ 0 (v / v; the same applies hereinafter) Solution B: 0.1% formic acid / acetonitrile The observed mass spectrometry values ​​are expressed in m / z.

[0125] 1H NMR spectra were measured using a JNM-ECS400 nuclear magnetic resonance spectrometer (manufactured by JEOL RESONANCE Co., Ltd.). The observed peaks are expressed as chemical shift values ​​δ (ppm) (s = singlet, d = doublet, t = triplet, q = quartet, brs = broad singlet, m = multiplet, dd = double doublet, dt = double triplet).

[0126] The compound names in this specification were determined using naming software conforming to IUPAC rules, ACD / NAME (registered trademark, Advanced Chemistry Development Inc.), or ChemBioDraw (version 14.0, manufactured by Cambridge Soft), or were determined according to the IUPAC nomenclature.

[0127] Reference Example 1 2-chloro-5-(cyclopropanecarbonylamino)methyl]benzoic acid Step 1 Methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride Methyl 5-(bromomethyl)-2-chlorobenzoate (10.2 g) (synthesized according to the method described in WO2010 / 132999) was dissolved in MeOH (15 mL), and 20% ammonia / MeOH (v / v, 40 mL) was added. The mixture was stirred at 80°C in a sealed tube for 30 minutes. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. 2N hydrochloric acid was added to the residue to make it acidic. This mixture was washed once with ethyl acetate, and the aqueous layer was adjusted to pH 7-8 with saturated aqueous sodium bicarbonate and then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The remaining yellow oil (2.0 g) was dissolved in MeOH (10 mL), and 2N hydrochloric acid (6 mL) was added at room temperature. The mixture was stirred for 5 minutes. The MeOH was evaporated under reduced pressure, and the residue was solidified using hexane-ethyl acetate, filtered, and dried to give the title compound (1.7 g) as a pale yellow powder. Step 2: Methyl 2-chloro-5-[(cyclopropanecarbonylamino)methyl]benzoate. Methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride (1.2 g) was suspended in THF (25 mL), and N,N-diisopropylethylamine (2.6 mL) was added and the mixture was stirred under ice-cooling. To this was added cyclopropanecarbonyl chloride (0.55 mL) slowly dropwise. After stirring at the same temperature for 1 hour, saturated aqueous sodium bicarbonate was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the title compound (813 mg) as a white powder. Step 3: 2-Chloro-5-[(cyclopropanecarbonylamino)methyl]benzoic acid MeOH (15 mL) and 1N aqueous sodium hydroxide solution (15 mL) were added to methyl 2-chloro-5-[(cyclopropanecarbonylamino)methyl]benzoate (813 mg), and the mixture was stirred at 60°C. After 1 hour, the reaction mixture was allowed to cool to room temperature, and MeOH was evaporated under reduced pressure. Water was added to the residue, and the mixture was stirred under ice-cooling, and the pH was adjusted to 2-3 with 2N hydrochloric acid. The precipitated solid was collected by filtration and dried under reduced pressure at 80°C to obtain the title compound (690 mg) as a white powder.

[0128] Reference Example 2 2-Chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzoic acid The title compound was obtained as a white powder in the same manner as in Reference Example 1, except that pivaloyl chloride was used instead of cyclopropanecarbonyl chloride in Step 2.

[0129] Reference Example 3 3-[(cyclopropanecarbonylamino)methyl]-2,6-difluorobenzoic acid Concentrated sulfuric acid (15 mL) was added to a mixture of N-(hydroxymethyl)cyclopropanecarboxamide (2.76 g) (synthesized according to the method described in Synthesis, 2009, 3,495) and 2,6-difluorobenzoic acid (1.72 g), and the mixture was stirred at 60°C for 20 hours. The reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to obtain the title compound (0.80 g) as a white powder.

[0130] Reference Example 4 2-chloro-5-{[(2,2,2-trifluoroacetyl)amino]methyl}benzoic acid 2,2,2-trifluoro-N-(hydroxymethyl)acetamide (3.2 g) (synthesized according to the method described in Synthesis, 2009, 495-501.) was dissolved in concentrated sulfuric acid (20 mL) and stirred under ice-cooling. 2-Chlorobenzoic acid (3.1 g) was added to this, and the mixture was stirred at room temperature for 3 days. The reaction solution was poured into ice water (100 mL), vigorously stirred, and the precipitated solid was collected by filtration and then thoroughly washed with water. The obtained solid was washed with toluene-methyl ethyl ketone (7:1) to obtain the title compound (2.2 g) as a white powder.

[0131] Reference Example 5 4-Amino-1H-indazole 2-Methyl-3-nitro-aniline (30 g) was dissolved in acetic acid (450 mL) and stirred under ice cooling. To this was added dropwise an aqueous solution (100 mL) of sodium nitrite (20.4 g), followed by stirring at room temperature for 1 day. After acetic acid was distilled off under reduced pressure, water (100 mL) was added to the resulting solid, and the mixture was stirred for a while. The precipitated solid was collected by filtration. This was dried under reduced pressure, washed with chloroform, and then dried to obtain 4-nitro-1H-indazole (22.1 g). 5% palladium-carbon (1.5 g) was added to a solution of 4-nitro-1H-indazole (10 g) in MeOH (100 mL)-THF (50 mL), and the mixture was vigorously stirred overnight under a hydrogen atmosphere at 0.3 MPa. The reaction solution was filtered through Celite, and the mother liquor was concentrated under reduced pressure. The resulting solid was washed with hexane-ethyl acetate (1:1) and collected by filtration. This was dried under reduced pressure to give the title compound (6.8 g).

[0132] Reference Example 6 5-Bromo-2-(methoxymethyl)pyridine To a solution of (5-bromo-2-pyridyl)methanol (200 mg) in THF (5 mL), sodium hydride (content 60%, 51 mg) was slowly added under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes. Thereafter, iodomethane (80 μL) was added, and the mixture was stirred overnight at 60°C. After the reaction mixture was allowed to cool to room temperature, ice water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to obtain the title compound (155 mg) as a yellow oil.

[0133] Reference Example 7 5-bromo-2-(2-fluoropropan-2-yl)pyridine CH ２ Cl ２ The (3 mL) solution was cooled to -78°C, and bis(2-methoxyethyl)aminosulfur trifluoride (264 μL) was added, followed by stirring overnight at room temperature. Saturated aqueous sodium bicarbonate was slowly added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography to obtain the title compound (88 mg) as a colorless oil.

[0134] Example 1 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide [Step 1] 4-amino-1-(4-trifluoromethylphenyl)-1H-indazole Under an argon atmosphere, 4-iodobenzotrifluoride (112 mg) and trans-N,N'-dimethylcyclohexane-1,2-diamine (26 mg) were added to a suspension of 4-amino-1H-indazole (50 mg), copper(I) iodide (7 mg), and tripotassium phosphate (159 mg) in 1,4-dioxane (1 mL), and the mixture was stirred at 100°C. After 18 hours, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain the title compound (74 mg). MS (ESI+) m / z 278 (M+H) ＋ [Step 2] 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide 4-Amino-1-(4-trifluoromethylphenyl)-1H-indazole (36 mg) was added to a solution of 2-chloro-5-[(cyclopropanecarbonylamino)methyl]benzoic acid (30 mg), HATU (64 mg), and N,N-diisopropylethylamine (61 μL) in DMF (1 mL) at room temperature, and the mixture was stirred overnight at the same temperature. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (60 mg) as a white powder. MS (ESI+) m / z 513 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.70 (4H, m), 1.61 (1H, m), 4.35 (2H, d), 7.40 (1H, dd), 7.53-7.57 (3H, m), 7.75 (1H, d), 7.89 (1H, d), 7.95 (2H, d), 8.05 (2H, d), 8.66-8.69 (2H, m), 10.89 (1H, s).

[0135] Example 2 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-(1-phenyl-1H-indazol-4-yl)benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that iodobenzene was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 445 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.67-0.70 (4H, m), 1.61 (1H, m), 4.35 (2H, d), 7.38-7.61 (8H, m), 7.76 (2H, d), 7.83 (1H, d), 8.57 (1H, s), 8.68 (1H, t), 10.84 (1H, s).

[0136] Example 3 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 3-iodobenzotrifluoride was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 513 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.70 (4H, m), 1.61 (1H, m), 4.35 (2H, d), 7.40 (1H, dd), 7.53-7.57 (3H, m), 7.6 7 (1H, d), 7.78 (1H, d), 7.83-7.90 (2H, m), 8.06 (1H, s), 8.14 (1H, d), 8.65-8.69 (2H, m), 10.88 (1H, s).

[0137] Example 4 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-3-yl)-1H-indazol-4-yl]benzamide hydrochloride

[0049] The same procedure as in Example 1 was repeated, except that 3-iodopyridine was used instead of 4-iodobenzotrifluoride, to give 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-3-yl)-1H-indazol-4-yl]benzamide as a white powder. The resulting compound was suspended in MeOH (0.5 mL), and 2N hydrochloric acid (1 equivalent) was added. The mixture was stirred and then concentrated under reduced pressure. The residue was solidified using diethyl ether-MeOH, collected by filtration, and dried to give the title compound (17 mg) as a white powder. MS (ESI+) m / z 446 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.70 (4H, m), 1.61 (1H, m), 4.35 (2H, d), 7.40 (1H, dd), 7.51-7.57 (3H, m), 7.67-7.69 (2H, m), 7.88 (1H, d), 8.28 (1H, m), 8.64 (1H, dd), 8.66 (1H, s), 8.69 (1H, t), 9.06 (1H, d), 10.89 (1H, s).

[0138] Example 5 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-4-yl)-1H-indazol-4-yl]benzamide hydrochloride

[0079] The same procedure as in Example 1 was repeated, except that 4-iodopyridine was used instead of 4-iodobenzotrifluoride, to give 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-4-yl)-1H-indazol-4-yl]benzamide as a white powder. The resulting compound was suspended in MeOH (1.5 mL), and 2N hydrogen chloride in MeOH (1 equivalent) was added, followed by stirring and concentration under reduced pressure. The residue was solidified using diethyl ether-MeOH, collected by filtration, and dried to give the title compound as a pale yellow powder. MS (ESI+) m / z 446 (M+H) ＋

[0139] Example 6 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(4-methylphenyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 4-iodotoluene was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 459 (M+H) ＋

[0140] Example 7 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(3-methylphenyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 3-iodotoluene was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 459 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.70 (4H, m), 1.61 (1H, m), 2.43 (3H, s), 4.33 (2H, d), 7.22 (1H, d), 7.40 (1 H, dd), 7.45-7.49 (2H, m), 7.53-7.61 (5H, m), 7.84 (1H, d), 8.56 (1H, s), 8.69 (1H, t), 10.84 (1H, s).

[0141] Example 8 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 2-iodopyridine was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 446 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.70 (4H, m), 1.61 (1H, m), 4.35 (2H, d), 7.31-7.35 (1H, m), 7.40 (1H, dd), 7.54- 7.58 (3H, m), 7.88 (1H, d), 8.00-8.02 (2H, m), 8.54-8.59 (2H, m), 8.64 (1H, s), 8.69 (1H, t), 10.87 (1H, s).

[0142] Example 9 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(2-methylphenyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 2-iodotoluene was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 459 (M+H) ＋

[0143] Example 10 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide hydrochloride

[0073] The same procedure as in Example 1 was repeated, except that 5-bromo-2-methylpyridine was used instead of 4-iodobenzotrifluoride, to give 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide as a white powder. The resulting compound was suspended in MeOH (0.5 mL), 2N hydrochloric acid (1 equivalent) was added, and the mixture was stirred and concentrated under reduced pressure. The residue was solidified using diethyl ether-MeOH, collected by filtration, and dried to give the title compound as a pale yellow powder. MS (ESI+) m / z 460 (M+H) ＋

[0144] Example 11 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 3-bromo-5-(trifluoromethyl)pyridine was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 514 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.70 (4H, m), 1.61 (1H, m), 4.35 (2H, d), 7.40 (1H, dd), 7.55-7.59 (3H, m), 7.7 6 (1H, d), 7.90 (1H, d), 8.55 (1H, t), 8.68 (1H, m), 8.71 (1H, s), 9.02 (1H, d), 9.39 (1H, d), 10.91 (1H, s).

[0145] Example 12 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 5-bromo-2-(trifluoromethyl)pyridine was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 514 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.70 (4H, m), 1.61 (1H, m), 4.35 (2H, d), 7.40 (1H, dd), 7.55-7.59 (3H, m), 7.83 (1H, d), 7.91 (1H, d), 8.11 (1H, d), 8.52 (1H, dd), 8.68 (1H, t), 8.72 (1H, s), 9.28 (1H, d), 10.92 (1H, s).

[0146] Example 13 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(2-methoxyphenyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a pale yellow powder by the same method as in Example 1, except that 2-bromoanisole was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 475 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 0.66-0.71 (4H, m), 1.61 (1H, m), 3.77 (3H, s), 4.36 (2H, d), 6.97 (1H, d), 7.15 (1H, t), 7.32 (1H, d), 7.33-7.43 (3H, m), 7.51-7.58 (3H, m), 7.75 (1H, d), 8.49 (1H, s), 8.68 (1H, s), 10.79 (1H, s).

[0147] Example 14 N-[1-(4-tert-butylphenyl)-1H-indazol-4-yl]-2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide The title compound was obtained as a white powder by the same method as in Example 1, except that 1-bromo-4-tert-butylbenzene was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 501 (M+H) ＋

[0148] Example 15 2-chloro-N-[1-(3-chloro-2-methylphenyl)-1H-indazol-4-yl]-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide The title compound was obtained as a pale yellow powder by the same method as in Example 1, except that 2-chloro-6-iodotoluene was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 493 (M+H) ＋

[0149] Example 16 3-{[(cyclopropylcarbonyl)amino]methyl}-2,6-difluoro-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 1, except that 3-iodobenzotrifluoride was used instead of 4-iodobenzotrifluoride in Step 1 and 3-[(cyclopropanecarbonylamino)methyl]-2,6-difluorobenzoic acid was used instead of 2-chloro-5-[(cyclopropanecarbonylamino)methyl]benzoic acid in Step 2. MS (ESI+) m / z 515 (M+H) ＋

[0150] Example 17 2-chloro-5-{[(trifluoroacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide CH ２ Cl ２A catalytic amount of DMF was added to a suspension (15 mL) of 1H-THF (2:1), and then oxalyl chloride (907 μL) was slowly added dropwise while stirring under ice cooling, followed by stirring at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and the residue was dried under reduced pressure. This was dissolved in THF (5 mL) and added dropwise to a THF solution (20 mL) of 4-amino-1-(4-trifluoromethylphenyl)-1H-indazole (777 mg) and N,N-diisopropylethylamine (1.46 mL) under ice cooling, followed by stirring for 1 hour. Saturated aqueous sodium bicarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain the title compound (1.2 g) as a white powder. MS (ESI+) m / z 541 (M+H) ＋

[0151] Example 18 5-[(acetylamino)methyl]-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide Step 1 5-(aminomethyl)-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide To a solution of 2-chloro-5-{[(trifluoroacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]indazol-4-yl}benzamide (200 mg) in MeOH (4 mL)-water (1 mL) was added potassium carbonate (256 mg) and the mixture was stirred at 60°C for 4 hours. The solvent was evaporated under reduced pressure, and water was added to the residue, followed by stirring for a while. The insoluble solid was collected by filtration and dried under reduced pressure to obtain the title compound (156 mg) as a white powder. MS (ESI+) m / z 445 (M+H) ＋Step 2: 5-[(acetylamino)methyl]-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide. To a THF solution (2 mL) of 5-(aminomethyl)-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]indazol-4-yl}benzamide (20 mg) and N,N-diisopropylethylamine (19 μL), acetyl chloride (32 μL) was added dropwise under ice cooling, and the mixture was stirred for 10 minutes. Saturated aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was solidified with hexane-ethyl acetate, collected by filtration, and dried to obtain the title compound (19 mg) as a white powder. MS (ESI+) m / z 487 (M+H) ＋

[0152] Example 19 2-chloro-5-[(propanoylamino)methyl]-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that propionyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 501 (M+H) ＋

[0153] Example 20 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that 3,3-dimethylbutyryl chloride was used instead of acetyl chloride. MS (ESI+) m / z 543 (M+H) ＋

[0154] Example 21 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that methoxyacetyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 517 (M+H) ＋

[0155] Example 22 2-chloro-5-{[(phenylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that benzoyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 549 (M+H) ＋

[0156] Example 23 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that cyclopropanesulfonyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 549 (M+H) ＋

[0157] Example 24 2-chloro-5-{[(N,N-dimethylglycyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide hydrochloride 5-(aminomethyl)-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide (25 mg) was added to a solution of N,N-dimethylglycine (64 mg), HBTU (26 mg), and N,N-diisopropylethylamine (29 μL) in DMF (0.5 mL), and the mixture was stirred overnight. Saturated aqueous sodium bicarbonate was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with water and then saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give 2-chloro-5-{[(N,N-dimethylglycyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide (15 mg) as a white powder. To a solution of the obtained compound in MeOH (1 mL) was added 2N aqueous hydrochloric acid (1 equivalent), and the solvent was then evaporated under reduced pressure. The residue was solidified with diethyl ether-MeOH to give the title compound (16 mg) as a white powder. MS (ESI+) m / z 530 (M+H) ＋

[0158] Example 25 2-chloro-5-({[(1-cyanocyclopropyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that 1-cyanocyclopropanecarboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 538 (M+H) ＋

[0159] Example 26 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that 1-trifluoromethylcyclopropane-1-carboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 581 (M+H) ＋

[0160] Example 27 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that 1-hydroxycyclopropanecarboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 529 (M+H) ＋

[0161] Example 28 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 24, except that 2,2-dimethyl-3-hydroxypropionic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 545 (M+H) ＋

[0162] Example 29 2-chloro-5-{[(cyclobutylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that cyclobutanecarbonyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 527 (M+H) ＋

[0163] Example 30 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that cyclopentanecarbonyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 541 (M+H) ＋

[0164] Example 31 2-chloro-5-{[(cyclohexylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that cyclohexanecarbonyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 555 (M+H) ＋

[0165] Example 32 N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]tricyclo[3.3.1.1 ３，７ ]decane-1-carboxamide The title compound was obtained as a white powder in the same manner as in Step 1 of Example 24, except that 1-adamantanecarboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 607 (M+H) ＋

[0166] Example 33 N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]tetrahydrofuran-2-carboxamide The title compound was obtained as a white powder in the same manner as in Step 1 of Example 24, except that tetrahydrofuran-2-carboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 543 (M+H) ＋

[0167] Example 34 N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]tetrahydrofuran-3-carboxamide The title compound was obtained as a white powder in the same manner as in Step 1 of Example 24, except that tetrahydrofuran-3-carboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 543 (M+H) ＋

[0168] Example 35 2-chloro-5-{[(N,N-dimethyl-β-alanyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide hydrochloride The title compound was obtained as a white powder by the same method as in Example 24, except that 3-dimethylaminopropionic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 544 (M+H) ＋

[0169] Example 36 tert-Butyl 4-{[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]carbamoyl}piperidine-1-carboxylate The title compound was obtained as a white powder in the same manner as in Example 24, except that N-(tert-butoxycarbonyl)isonipecotic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 656 (M+H) ＋

[0170] Example 37 2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-5-{[(3,3,3-trifluoropropanoyl)amino]methyl}benzamide The title compound was obtained as a white powder by the same method as in Example 24, except that 3,3,3-trifluoropropanoic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 555 (M+H) ＋

[0171] Example 38 2-chloro-5-{[(cyclopropylacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 24, except that cyclopropylacetic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 527 (M+H) ＋

[0172] Example 39 2-chloro-5-({[trans-(4-hydroxycyclohexyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that trans-4-hydroxycyclohexanecarboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 571 (M+H) ＋

[0173] Example 40 2-chloro-5-({[cis-(4-hydroxycyclohexyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that cis-4-hydroxycyclohexanecarboxylic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 571 (M+H) ＋

[0174] Example 41 2-chloro-5-{[(2-ethyl-2-hydroxybutanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that 2-ethyl-2-hydroxybutyric acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 559 (M+H) ＋

[0175] Example 42 5-[(2-butynoylamino)methyl]-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that 2-butynoic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 511 (M+H) ＋

[0176] Example 43 5-[(butanoylamino)methyl]-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that butyryl chloride was used instead of acetyl chloride. MS (ESI+) m / z 515 (M+H) ＋

[0177] Example 44 2-chloro-5-{[(phenylacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that phenylacetyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 563 (M+H) ＋

[0178] Example 45 N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]furan-2-carboxamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 18, except that 2-furoyl chloride was used instead of acetyl chloride. MS (ESI+) m / z 539 (M+H)＋

[0179] Example 46 2-chloro-5-{[(cyclopentylacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that cyclopentylacetic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 555 (M+H) ＋

[0180] Example 47 2-chloro-5-{[(3-methoxypropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Example 24, except that 3-methoxypropionic acid was used instead of N,N-dimethylglycine. MS (ESI+) m / z 531 (M+H) ＋

[0181] Example 48 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-methoxyphenyl)-1H-indazol-4-yl]benzamide Step 1 4-Amino-1-(4-methoxyphenyl)-1H-indazole By the same method as in Step 1 of Example 1, except that 4-bromoanisole was used instead of 4-iodobenzotrifluoride, the title compound was obtained as a colorless powder. Step 2 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-methoxyphenyl)-1H-indazol-4-yl]benzamide CH ２ Cl ２A catalytic amount of DMF was added to the suspension (2 mL), and then oxalyl chloride (33 μL) was added dropwise under ice cooling, followed by stirring at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and the residue was dried under reduced pressure. This was dissolved in THF (1 mL) and added dropwise to a THF solution (2 mL) of 4-amino-1-(4-methoxyphenyl)-1H-indazole (32 mg) and N,N-diisopropylethylamine (144 μL) under ice cooling, followed by stirring for 18 hours. Saturated aqueous sodium bicarbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain the title compound (47 mg) as a white powder. MS (ESI+) m / z 491 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 1.13 (9H, s), 3.83 (3H, s), 4.31 (2H, d), 7.12-7.16 (2H, m), 7.37 (1H, dd), 7.42- 7.50 (3H, m), 7.53 (1H, d), 7.61-7.65 (2H, m), 7.81 (1H, d), 8.18 (1H, t), 8.51 (1H, s), 10.81 (1H, s).

[0182] Example 49 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-methoxyphenyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 3-bromoanisole was used instead of 4-bromoanisole. MS (ESI+) m / z 491 (M+H) ＋

[0183] Example 50 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 48, except that 4-amino-1-(4-trifluoromethylphenyl)-1H-indazole was used instead of 4-amino-1-(4-methoxyphenyl)-1H-indazole. MS (ESI+) m / z 529 (M+H) ＋

[0184] Example 51 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 1-bromo-4-(trifluoromethoxy)benzene was used instead of 4-bromoanisole. MS (ESI+) m / z 545 (M+H) ＋

[0185] Example 52 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyrimidin-5-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a pale yellow powder by the same method as in Example 48, except that 5-bromo-2-methylpyrimidine was used instead of 4-bromoanisole. MS (ESI+) m / z 477 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 1.13 (9H, s), 2.74 (3H, s), 4.31 (2H, d), 7.37 (1H, d), 7.54 (3H, m ), 7.70 (1H, d), 7.88 (1H, d), 8.18 (1H, t), 8.68 (1H, s), 9.17 (1H, s), 10.89 (1H, s).

[0186] Example 53 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a pale yellow powder by the same method as in Example 48, except that 2-chloro-4-iodotoluene was used instead of 4-bromoanisole. MS (ESI+) m / z 509 (M+H) ＋

[0187] Example 54 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide hydrochloride

[0111] In the same manner as in Example 48, using 5-bromo-2-methylpyridine instead of 4-bromoanisole, 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide (17 mg) was obtained as a pale yellow powder. This was dissolved in ethyl acetate (0.5 mL), and 4N hydrogen chloride / ethyl acetate (1 equivalent) was added and stirred for 5 minutes. The precipitated solid was collected by filtration and dried to obtain the title compound (17 mg) as a pale yellow powder. MS (ESI+) m / z 476 (M+H) ＋

[0188] Example 55 2-chloro-N-[1-(4-cyanophenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a pale yellow powder by the same method as in Example 48, except that 4-bromobenzonitrile was used instead of 4-bromoanisole. MS (ESI+) m / z 486 (M+H) ＋

[0189] Example 56 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide hydrochloride The title compound was obtained as a pale yellow powder by a method similar to that in Example 54, except that 3-bromo-2-methylpyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 476 (M+H) ＋

[0190] Example 57 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 3-bromo-5-(trifluoromethyl)pyridine was used instead of 4-bromoanisole. MS (ESI+) m / z 530 (M+H)＋

[0191] Example 58 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide hydrochloride The title compound was obtained as a pale yellow powder by a method similar to that in Example 54, except that 4-bromo-2-methylpyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 476 (M+H) ＋

[0192] Example 59 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder in the same manner as in Example 48, except that 3-iodo-6-methylpyridazine (synthesized according to the method described in EP 2080761) was used instead of 4-bromoanisole. MS (ESI+) m / z 477 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 1.13 (9H, s), 2.65 (3H, s), 4.31 (2H, d), 7.37 (1H, d), 7.53 (2H, m), 7.62 (1 H, t), 7.79 (1H, d), 7.91 (1H, d), 8.16-8.22 (2H, m), 8.52 (1H, d), 8.71 (1H, s), 10.91 (1H, s).

[0193] Example 60 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide hydrochloride The title compound was obtained as a white powder by a method similar to that in Example 54, except that 3-bromo-5-methylpyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 476 (M+H) ＋

[0194] Example 61 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide hydrochloride The title compound was obtained as a white powder by a method similar to that in Example 54, except that 3-bromo-5-methoxypyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 492 (M+H) ＋

[0195] Example 62 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 4-methoxy-3-(trifluoromethyl)bromobenzene was used instead of 4-bromoanisole. MS (ESI+) m / z 559 (M+H) ＋

[0196] Example 63 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a pale yellow powder by the same method as in Example 48, except that 5-bromo-2-methoxypyridine was used instead of 4-bromoanisole. MS (ESI+) m / z 492 (M+H) ＋

[0197] Example 64 2-chloro-N-[1-(5-cyclopropylpyridin-3-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide hydrochloride The title compound was obtained as a white powder by the same method as in Example 54, except that 3-bromo-5-cyclopropylpyridine (synthesized according to the method described in WO2008 / 091681) was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 502 (M+H) ＋

[0198] Example 65 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-ethoxyphenyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 4-bromophenetole was used instead of 4-bromoanisole. MS (ESI+) m / z 505 (M+H) ＋

[0199] Example 66 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-ethoxyphenyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 3-bromophenetole was used instead of 4-bromoanisole. MS (ESI+) m / z 505 (M+H) ＋

[0200] Example 67 2-chloro-N-[1-(3,4-dimethoxyphenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 4-bromoveratrol was used instead of 4-bromoanisole. MS (ESI+) m / z 521 (M+H) ＋

[0201] Example 68 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(propan-2-yloxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a pale pink powder by the same method as in Example 48, except that 1-bromo-3-isopropoxybenzene was used instead of 4-bromoanisole. MS (ESI+) m / z 519 (M+H) ＋

[0202] Example 69 2-chloro-N-[1-(6-cyclopropylpyridin-3-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide hydrochloride The title compound was obtained as a white powder by a method similar to that described in Example 54, except that 5-bromo-2-cyclopropylpyridine (synthesized according to the method described in WO 2006 / 065215) was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 502 (M+H) ＋

[0203] Example 70 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide hydrochloride The title compound was obtained as a pale yellow powder by a method similar to that described in Example 54, except that 4-bromo-2-cyclopropylpyridine (synthesized according to the method described in WO2010 / 125082) was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 502 (M+H) ＋

[0204] Example 71 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a pale pink powder by the same method as in Example 48, except that 1-bromo-3-(trifluoromethoxy)benzene was used instead of 4-bromoanisole. MS (ESI+) m / z 545 (M+H) ＋

[0205] Example 72 2-chloro-N-[1-(6-cyanopyridin-3-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a pale pink powder by the same method as in Example 48, except that 5-bromo-2-cyanopyridine was used instead of 4-bromoanisole. MS (ESI+) m / z 487 (M+H) ＋

[0206] Example 73 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide hydrochloride The title compound was obtained as a pale orange powder by a method similar to that in Example 54, except that 4-bromo-2-methoxypyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 492 (M+H) ＋

[0207] Example 74 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(methoxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide hydrochloride The title compound was obtained as a pale orange powder by a method similar to that in Example 54, except that 5-bromo-2-(methoxymethyl)pyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 506 (M+H) ＋

[0208] Example 75 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(hydroxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide hydrochloride The title compound was obtained as a pale orange powder by a method similar to that in Example 54, except that 5-bromo-2-hydroxymethylpyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 492 (M+H) ＋

[0209] Example 76 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide hydrochloride The title compound was obtained as a pale yellow powder by a method similar to that in Example 54, except that 4-bromo-2,6-dimethylpyridine was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 490 (M+H) ＋

[0210] Example 77 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained as a pale pink powder by the same method as in Example 48, except that 5-bromo-2-(trifluoromethyl)pyridine was used instead of 4-bromoanisole. MS (ESI+) m / z 530 (M+H) ＋

[0211] Example 78 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(methoxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide hydrochloride The title compound was obtained as a pale yellow powder in the same manner as in Example 54, except that 3-bromo-5-(methoxymethyl)pyridine (synthesized according to the method described in US Pat. No. 5,861,423) was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 506 (M+H) ＋

[0212] Example 79 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 1-bromo-2-methyl-4-(trifluoromethoxy)benzene was used instead of 4-bromoanisole. MS (ESI+) m / z 559 (M+H) ＋

[0213] Example 80 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 2-bromothiazole was used instead of 4-bromoanisole. MS (ESI+) m / z 468 (M+H) ＋ １H-NMR (DMSO-d6) δ: 1.13 (9H, s), 4.30 (2H, d), 7.37 (1H, d), 7.53 (2H, m), 7.64 (1H, t ), 7.73 (1H, d), 7.93 (1H, d), 8.16 (1H, t), 8.30 (1H, d), 8.66 (1H, s), 10.94 (1H, s).

[0214] Example 81 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 3-(difluoromethoxy)bromobenzene was used instead of 4-bromoanisole. MS (ESI+) m / z 527 (M+H) ＋

[0215] Example 82 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 5-bromo-2-(trifluoromethoxy)toluene was used instead of 4-bromoanisole. MS (ESI+) m / z 559 (M+H) ＋

[0216] Example 83 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 4-bromothiazole was used instead of 4-bromoanisole. MS (ESI+) m / z 468 (M+H). ＋ １ H-NMR (DMSO-d6) δ: 1.10 (9H, s), 4.27 (2H, d), 7.33 (1H, d), 7.49 (3H, m), 7.7 3 (1H, d), 7.82 (1H, d), 8.12 (2H, m), 8.56 (1H, s), 9.26 (1H, d), 10.80 (1H, s).

[0217] Example 84 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(2-methoxypropan-2-yl)pyridin-3-yl]-1H-indazol-4-yl}benzamide hydrochloride The title compound was obtained as a white powder by a method similar to that described in Example 54, except that 5-bromo-2-(2-methoxypropan-2-yl)pyridine (synthesized according to the method described in WO 2006 / 048727 ) was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 534 (M+H) ＋

[0218] Example 85 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(2-fluoropropan-2-yl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained as a white powder by the same method as in Example 48, except that 5-bromo-2-(2-fluoropropan-2-yl)pyridine was used instead of 4-bromoanisole. MS (ESI+) m / z 522 (M+H) ＋

[0219] Example 86 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(ethoxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide hydrochloride The title compound was obtained as a white powder by a method similar to that in Example 54, except that 5-bromo-2-(ethoxymethyl)pyridine (synthesized according to the method described in WO2011 / 051342) was used instead of 5-bromo-2-methylpyridine. MS (ESI+) m / z 520 (M+H) ＋

[0220] Example 87 2-chloro-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]-5-{[(trifluoroacetyl)amino]methyl}benzamide hydrochloride

[0123] In the same manner as in Example 48, except that 5-bromo-2-methylpyridine was used instead of 4-bromoanisole and 2-chloro-5-{[(2,2,2-trifluoroacetyl)amino]methyl}benzoic acid was used instead of 2-chloro-5-{[(2,2-dimethylpropanoyl)amino)methyl]}benzoic acid, 2-chloro-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]-5-{[(trifluoroacetyl)amino]methyl}benzamide (15 mg) was obtained. The obtained compound was dissolved in ethyl acetate (0.5 mL), and 4N hydrogen chloride in ethyl acetate (1 equivalent) was added, followed by stirring for 5 minutes. The precipitated solid was collected by filtration and dried to obtain the title compound (11 mg) as a white powder. MS (ESI+) m / z 488 (M+H) ＋

[0221] Example 88 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide hydrochloride In the same manner as in Example 48, 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide was obtained using 5-bromo-2-methylpyridine in place of 4-bromoanisole and 5-{[(2,2-dimethylpropanoyl)amino)methyl]}-2-(trifluoromethyl)benzoic acid (synthesized in accordance with the method described in WO 2011 / 048004 ). The obtained compound was dissolved in ethyl acetate (0.5 mL), and 4N hydrogen chloride / ethyl acetate (1 equivalent) was added and stirred for 5 minutes. The precipitated solid was collected by filtration and dried to obtain the title compound as a white powder. MS (ESI+) m / z 510 (M+H) ＋ Elemental analysis value C ２７ H ２６ F ３ N ５ O２ Calculated values ​​(%) as HCl: C: 59.40, H: 4.98, N: 12.83 Measured values ​​(%): C: 59.28, H: 4.68, N: 12.57

[0222] Example 89 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-methoxybenzyl)-1H-indazol-4-yl]benzamide Step 1 1-[(3-methoxyphenyl)methyl]-4-nitro-1H-indazole The title compound was synthesized according to the method described in WO2011 / 079076. A DMF suspension of 4-nitro-1H-indazole (48 mg), 3-methoxybenzyl chloride (69 mg), and potassium carbonate (61 mg) was stirred at 70°C for 16 hours. After the reaction mixture was cooled to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15% ethyl acetate / hexane → 20% ethyl acetate / hexane), to give 1-[(3-methoxyphenyl)methyl]-4-nitro-1H-indazole (35 mg) from the first eluted fraction, and 2-[(3-methoxyphenyl)methyl]-4-nitro-2H-indazole (28 mg) from the second eluted fraction. 1-[(3-methoxyphenyl)methyl]-4-nitro-1H-indazole: １ H-NMR (CDCl ３ ): δ 3.74 (3H, s), 5.66 (2H, s), 6.72 (1H, s), 6.79 (2H, m), 7.26 (1H, m), 7.45 (1H, t, J = 7.8 Hz), 7.79 (1H, d, J = 8.3 Hz), 8.14 (1H, d, J = 7.3 Hz), 8.68 (1H, s) 2-[(3-methoxyphenyl)methyl]-4-nitro-2H-indazole: １ H-NMR (CDCl ３)), 6.87 (1H, s), 6.90 (2H, m), 7.30 (1H, t, J = 7.8 Hz), 7.41 (1H, t, J = 8.3 Hz), 8.10 (1H, d, J = 7.8 Hz), 8.18 (1H, d, J = 7.3 Hz), 8.57 (1H, s) Step 2 4-Amino-1-[(3-methoxyphenyl)methyl]-1H-indazole A suspension of 1-[(3-methoxyphenyl)methyl]-4-nitro-1H-indazole (35 mg), zinc dust (65 mg), MeOH (1 mL), THF (1 mL), and saturated aqueous ammonium chloride solution (0.5 mL) was stirred at 50°C for 1.5 hours. After the reaction mixture was cooled to room temperature, insoluble materials were filtered off, and the mother liquor was concentrated. The residue was purified by silica gel column chromatography to obtain the title compound (22 mg) as a yellow solid. MS (ESI+) m / z 254 (M+H) ＋ Step 3: 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-methoxybenzyl)-1H-indazol-4-yl]benzamide

[0123] The title compound was obtained as a pale pink powder in the same manner as in Step 2 of Example 48, except that 4-amino-1-[(3-methoxyphenyl)methyl]-1H-indazole was used instead of 4-amino-1-(4-methoxyphenyl)-1H-indazole. MS (ESI+) m / z 505 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 1.12 (9H, s), 3.69 (3H, s), 4.29 (2H, d), 5.61 (2H, s), 6.73 (1H, d), 6.80 (1H, s), 6.8 1 (1H, d), 7.20 (1H, t), 7.35 (1H, m), 7.50 (3H, m), 7.73 (1H, d), 8.18 (1H, t), 8.32 (1H, s), 10.72 (1H, s).

[0223] Example 90 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxybenzyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a pale pink powder by the same method as in Example 89, except that 2-methoxybenzyl chloride was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 505 (M+H) ＋

[0224] Example 91 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,4,6-trimethylbenzyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a pale pink powder by the same method as in Example 89, except that 2,4,6-trimethylbenzyl chloride was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 517 (M+H) ＋

[0225] Example 92 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)benzyl]-1H-indazol-4-yl}benzamide

[0123] In the same manner as in Example 89, except that 4-(trifluoromethyl)benzyl bromide was used instead of 3-methoxybenzyl chloride, 1-[4-(trifluoromethyl)benzyl]-4-nitro-1H-indazole (65 mg) and 2-[4-(trifluoromethyl)benzyl]-4-nitro-2H-indazole (63 mg) were obtained. In the same manner as in Steps 2 and 3 of Example 89, using 1-[4-(trifluoromethyl)benzyl]-4-nitro-1H-indazole, the title compound was obtained as a white powder. MS (ESI+) m / z 543 (M+H) ＋

[0226] Example 93 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)benzyl]-2H-indazol-4-yl}benzamide The title compound was obtained by the method of Example 92. MS (ESI+) m / z 543 (M+H) ＋

[0227] Example 94 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)benzyl]-1H-indazol-4-yl}benzamide The title compound was obtained as a pale pink powder by the same method as in Example 89, except that 3-(trifluoromethyl)benzyl bromide was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 543 (M+H) ＋

[0228] Example 95 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-phenylethyl)-1H-indazol-4-yl]benzamide

[0123] In the same manner as in Example 89, except that 2-chloroethylbenzene was used instead of 3-methoxybenzyl chloride, 1-(2-phenylethyl)-4-nitro-1H-indazole (32 mg) and 2-(2-phenylethyl)-4-nitro-2H-indazole (26 mg) were obtained. In the same manner as in Steps 2 and 3 of Example 89, using 1-(2-phenylethyl)-4-nitro-1H-indazole, the title compound was obtained as a white powder. MS (ESI+) m / z 489 (M+H) ＋

[0229] Example 96 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-phenylethyl)-2H-indazol-4-yl]benzamide The title compound was obtained by the method of Example 95. MS (ESI+) m / z 489 (M+H) ＋

[0230] Example 97 2-chloro-N-(1-cyclopentyl-1H-indazol-4-yl)-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a white powder by the same method as in Example 89, except that cyclopentyl bromide was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 453 (M+H) ＋ １H-NMR (DMSO-d6) δ: 1.12 (9H, s), 1.68 (2H, m), 1.85 (2H, m), 1.95 (2H, m), 2.10 (2H, m), 4.28 (2H, d), 5.13 ( 1H, quin. ), 7.33 (2H, m), 7.45 (2H, m), 7.51 (1H, d), 7.70 (1H, d), 8.17 (1H, t), 8.26 (1H, s), 10.68 (1H, s).

[0231] Example 98 2-chloro-N-(1-cyclohexyl-1H-indazol-4-yl)-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a white powder by the same method as in Example 89, except that cyclohexyl bromide was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 467 (M+H) ＋

[0232] Example 99 2-chloro-N-[1-(cyclobutylmethyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a white powder in the same manner as in Example 89, except that bromomethylcyclobutane was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 453 (M+H) ＋

[0233] Example 100 2-chloro-N-[1-(cyclohexylmethyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained as a white powder in the same manner as in Example 89, except that bromomethylcyclohexane was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 481 (M+H) ＋ 1H-NMR (DMSO-d6) δ: 1.01 (1H, m), 1.12 (9H, s), 1.10-1.29 (4H, m), 1.45 (2H, m), 1.53-1.67 (3H, m), 1.8 7 (1H, m), 4.22 (2H, d), 4.20 (2H, d), 7.34 (2H, m), 7.43 (2H, m), 7.51 (1H, d), 7.70 (1H, d), 8.25 (1H, s).

[0234] Example 101 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-phenylpropyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 89, except that (3-bromopropyl)benzene was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 503 (M+H) ＋

[0235] Example 102 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 89, except that 2-bromopropane was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 427 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 1.12 (9H, s), 1.46 (6H, d), 2.29 (2H, d), 4.96 (1H, quin.), 7.34 (2H , m), 7.45 (2H, m), 7.51 (1H, d), 7.70 (1H, d), 8.17 (1H, t), 8.27 (1H, d), 10.67 (1H, s).

[0236] Example 103 tert-Butyl 4-(4-{[(2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}phenyl)carbonyl]amino}-1H-indazol-1-yl)piperidine-1-carboxylate Step 1 tert-Butyl 4-(4-nitro-1H-indazol-1-yl)piperidine-1-carboxylate A solution of 4-nitro-1H-indazole (100 mg), tert-butyl 4-hydroxypiperidine-1-carboxylate (148 mg), and triphenylphosphine (241 mg) in THF (6 mL) was stirred under ice-cooling, and a 40% diethyl azodicarboxylate / toluene solution (w / w, 0.42 mL) was added dropwise, followed by stirring at room temperature overnight. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound (51 mg) as a pale yellow powder. Step 2: tert-Butyl 4-(4-amino-1H-indazol-1-yl)piperidine-1-carboxylate. 5% Palladium on carbon (20 mg) was added to a solution of tert-butyl 4-(4-nitro-1H-indazol-1-yl)piperidine-1-carboxylate (51 mg) in MeOH (5 mL)-THF (5 mL), and the mixture was stirred under a hydrogen atmosphere at 0.3 MPa. After 4 hours, the reaction mixture was filtered through Celite, and the mother liquor was concentrated. The residue was purified by silica gel column chromatography to obtain the title compound (43 mg) as a pale yellow powder. Step 3 tert-Butyl 4-(4-{[(2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}phenyl)carbonyl]amino}-1H-indazol-1-yl)piperidine-1-carboxylate

[0123] The title compound was obtained as a white powder by the same method as in Step 2 of Example 48, except that tert-butyl 4-(4-amino-1H-indazol-1-yl)piperidine-1-carboxylate was used instead of 4-amino-1-(4-methoxyphenyl)-1H-indazole. MS (ESI+) m / z 568 (M+H) ＋ １H-NMR (DMSO-d6) δ: 1.12 (9H, s), 1.42 (9H, s), 1.91 (4H, m), 3.23 (2H, m), 4.10 (2H, m), 4.29 (2H, d), 4.84 (1H, quin.), 7.35 (2H, m), 7.44 (1H, s), 7.51 (2H, m), 8.17 (1H, m), 8.28 (1H, s), 10.68 (1H, s).

[0237] Example 104 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 103, except that tetrahydro-2H-pyran-4-ol was used instead of tert-butyl 4-hydroxypiperidine-1-carboxylate. MS (ESI+) m / z 469 (M+H) ＋ １ H-NMR (DMSO-d6) δ: 1.12 (9H, s), 1.89 (2H, m), 2.10 (2H, m), 3.56 (2H, t), 4.01 (2H, m), 4.30 (2H, d), 4.87 ( 1H, quin. ), 7.36 (2H, m), 7.45 (1H, s), 7.51 (2H, m), 7.71 (1H, d), 8.17 (1H, t), 8.29 (1H, s), 10.69 (1H, s).

[0238] Example 105 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 89, except that 2-(bromomethyl)tetrahydro-2H-pyran was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 483 (M+H) ＋

[0239] Example 106 N-[1-(1-acetylpiperidin-4-yl)-1H-indazol-4-yl]-2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide Step 1 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(piperidin-4-yl)-1H-indazol-4-yl]benzamide hydrochloride A solution of tert-butyl 4-(4-{[(2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}phenyl)carbonyl]amino}-1H-indazol-1-yl)piperidine-1-carboxylate (41 mg) in ethyl acetate (2 mL) was stirred at room temperature, and 4N hydrogen chloride in ethyl acetate (2 mL) was added, followed by stirring for 1 hour. The solvent was evaporated under reduced pressure, and the residue was solidified with diethyl ether-MeOH to give the title compound (32 mg) as a white powder. MS (ESI+) m / z 468 (M+H) ＋ Step 2: N-[1-(1-acetylpiperidin-4-yl)-1H-indazol-4-yl]-2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide Pyridine (7 μL) was added to a solution of 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(piperidin-4-yl)-1H-indazol-4-yl]benzamide hydrochloride (13 mg) in THF (0.5 mL), and the mixture was stirred under ice-cooling. Acetyl chloride (3 μL) was added dropwise to the mixture, and the mixture was stirred at room temperature for 2 hours. Saturated aqueous sodium bicarbonate was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to obtain the title compound (7 mg) as a white powder. MS (ESI+) m / z 510 (M+H) ＋

[0240] Example 107 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-(morpholin-4-yl)ethyl]-1H-indazol-4-yl}benzamide hydrochloride

[0111] In a similar manner to Example 103, using 2-morpholinoethanol instead of tert-butyl 4-hydroxypiperidine-1-carboxylate, 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-(morpholin-4-yl)ethyl]-1H-indazol-4-yl}benzamide (33 mg) was obtained. This was dissolved in THF (1 mL), and 2N hydrogen chloride in MeOH (1 equivalent) was added, and the solvent was evaporated under reduced pressure. The residue was triturated with diethyl ether-THF to obtain the title compound (29 mg) as a white powder. MS (ESI+) m / z 498 (M+H) ＋

[0241] Example 108 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-phenylbutyl)-1H-indazol-4-yl]benzamide The title compound was obtained as a white powder by the same method as in Example 103, except that 4-phenylbutan-1-ol was used instead of tert-butyl 4-hydroxypiperidine-1-carboxylate. MS (ESI+) m / z 517 (M+H) ＋

[0242] Example 109 N-(1-benzyl-1H-indazol-4-yl)-2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide Step 1 1-benzyl-4-nitro-1H-indazole By a method similar to that of Example 89, Step 1, except that benzyl bromide was used in place of 3-methoxybenzyl chloride, 1-benzyl-4-nitro-1H-indazole and 2-benzyl-4-nitro-2H-indazole were obtained. Step 2 4-amino-1-benzyl-1H-indazole By a method similar to that of Example 89, Step 2, except that 1-benzyl-4-nitro-1H-indazole was used in place of 1-[(3-methoxyphenyl)methyl]-4-nitro-1H-indazole, the title compound was obtained. Step 3: N-(1-benzyl-1H-indazol-4-yl)-2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 1, except that 4-amino-1-benzyl-1H-indazole was used instead of 4-amino-1-(4-trifluoromethylphenyl)-1H-indazole. MS (ESI+) m / z 459 (M+H) ＋

[0243] Example 110 N-(1-benzyl-2H-indazol-4-yl)-2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide The title compound was obtained by the method of Example 109. MS (ESI+) m / z 459 (M+H) ＋

[0244] Example 111 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide The title compound was obtained as a white powder by the same method as in Example 89, except that iodomethane was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 399 (M+H) ＋ １H-NMR (DMSO-d6) δ: 1.12 (9H, s), 4.01 (3H, s), 4.29 (2H, d), 7.36 (3H, m), 7.4 6 (1H, s), 7.51 (1H, d), 7.73 (1H, d), 8.16 (1H, t), 8.24 (1H, s), 10.68 (1H, s).

[0245] Example 112 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide The title compound was obtained as a white powder in the same manner as in Step 2 of Example 1, except that 4-amino-1-methyl-1H-indazole (synthesized according to the method described in WO2004 / 046133) was used instead of 4-amino-1-(4-trifluoromethylphenyl)-1H-indazole. MS (ESI+) m / z 383 (M+H) ＋

[0246] Example 113 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide The title compound was obtained as a white powder by the same method as in Example 89, except that iodoethane was used instead of 3-methoxybenzyl chloride. MS (ESI+) m / z 413 (M+H). ＋ １ H-NMR (DMSO-d6) δ: 1.12 (9H, s), 1.38 (3H, t), 4.29 (2H, d), 4.41 (2H, q), 7.36 (2H, m ), 7.45 (2H, m), 7.51 (1H, d), 7.70 (1H, d), 8.16 (1H, t), 8.25 (1H, s), 10.67 (1H, s).

[0247] Example 125 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide [Step 1] 4-amino-1-(3-(trifluoromethoxy)phenyl)-1H-indazole In the same manner as in Step 1 of Example 1, the title compound was obtained using 1-bromo-3-(trifluoromethoxy)benzene instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 294 (M+H)＋ [Step 2] tert-Butyl-N-[4-chloro-3-({1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]carbamate 5-[(tert-butoxycarbonyl)amino]methyl-2-chlorobenzoic acid (300 mg) and 4-amino-1-[3-(trifluoromethoxy)phenyl]-1H-indazole (323 mg) were suspended in acetonitrile (5 ml) and stirred at room temperature. To this was added chloro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate (442 mg) and 1-methylimidazole (431 mg), and the mixture was stirred overnight. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was separated, washed with water and then saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (539 mg) as a pale yellow solid. MS (ESI-) m / z 559 (M-H) ＋ [Step 3] 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide t-Butyl-N-[4-chloro-3-({1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]carbamate (530 mg) was suspended in ethyl acetate (5 ml) and stirred at room temperature. 4N hydrochloric acid / ethyl acetate (5 ml) was added to this and the mixture was stirred for 3 hours. The solvent was evaporated under reduced pressure, and the residue was suspended in ethyl acetate. The solid was collected by filtration and dried to give a white solid (430 mg). This was dissolved in DMF (8 ml), and while stirring at room temperature, 3-hydroxy-2,2-dimethylpropanoic acid (133 mg), HATU (493 mg), and N,N-diisopropylethylamine (0.449 ml) were added, followed by stirring at room temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was separated, washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (451 mg) as a white solid. MS (ESI+) m / z 561 (M+H) ＋

[0248] Example 276 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide [Step 1] 4-amino-[1-(6-methoxypyridin-3-yl)-1H-indazole] The title compound was obtained in the same manner as in Step 1 of Example 1, except that 5-bromo-2-methoxypyridine was used instead of 4-iodobenzotrifluoride. MS (ESI+) m / z 241 (M+H) ＋ [Step 2] 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide In a similar manner to Step 2 of Example 125, the title compound was obtained using 5-[(2,2-dimethylpropanoylamino)methyl]-2-(trifluoromethyl)benzoic acid instead of 5-[(tert-butoxycarbonyl)amino]methyl-2-chlorobenzoic acid and 4-amino-[1-(6-methoxypyridin-3-yl)-1H-indazole instead of 4-amino-1-[3-(trifluoromethoxy)phenyl]-1H-indazole. MS (ESI+) m / z 526 (M+H) ＋

[0249] The following compounds were produced using the corresponding starting compounds by reacting and treating them in the same manner as in Example 18 or Example 89. Example 114 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by reacting and treating it in the same manner as in Example 18. MS (ESI+) m / z 559 (M+H) ＋ Example 115 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 557 (M+H) ＋Example 116 2-chloro-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 597 (M+H) ＋ Example 117 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 545 (M+H) ＋ Example 118 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 533 (M+H) ＋ Example 119 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 561 (M+H) ＋ Example 120 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 565 (M+H) ＋ Example 121 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 559 (M+H) ＋Example 122 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 557 (M+H) ＋ Example 123 2-chloro-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 597 (M+H) ＋ Example 124 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 533 (M+H) ＋ Example 126 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 565 (M+H) ＋ Example 127 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 523 (M+H) ＋ Example 128 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(cyclopentylcarbonyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 521 (M+H) ＋Example 129 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 561 (M+H) ＋ Example 130 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 509 (M+H) ＋ Example 131 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 497 (M+H) ＋ Example 132 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(cyclopropylsulfonyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 529 (M+H) ＋ Example 133 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 573 (M+H) ＋ Example 134 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 571 (M+H) ＋Example 135 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 547 (M+H) ＋ Example 136 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 575 (M+H) ＋ Example 137 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 579 (M+H) ＋ Example 138 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 541 (M+H) ＋ Example 139 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 539 (M+H) ＋ Example 140 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 579 (M+H) ＋Example 141 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 527 (M+H) ＋ Example 142 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(methoxyacetyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 515 (M+H) ＋ Example 143 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 543 (M+H) ＋ Example 144 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 547 (M+H) ＋ Example 145 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 509 (M+H) ＋ Example 146 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(cyclopentylcarbonyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 507 (M+H) ＋Example 147 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 547 (M+H) ＋ Example 148 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 483 (M+H) ＋ Example 149 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 511 (M+H) ＋ Example 150 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-([(cyclopropylsulfonyl)amino]methyl)benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 515 (M+H) ＋ Example 151 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 493 (M+H) ＋ Example 152 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 491 (M+H) ＋Example 153 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 531 (M+H) ＋ Example 154 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 479 (M+H) ＋ Example 155 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-([(methoxyacetyl)amino]methyl)benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 467 (M+H) ＋ Example 156 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 495 (M+H) ＋ Example 157 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 499 (M+H) ＋ Example 158 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 513 (M+H) ＋Example 159 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 506 (M+H) ＋ Example 160 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 504 (M+H) ＋ Example 161 2-chloro-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 544 (M+H) ＋ Example 162 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 492 (M+H) ＋ Example 163 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 480 (M+H) ＋ Example 164 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 508 (M+H) ＋Example 165 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 512 (M+H) ＋ Example 166 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 544 (M+H) ＋ Example 167 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 542 (M+H) ＋ Example 168 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 582 (M+H) ＋ Example 169 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 530 (M+H) ＋ Example 170 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 518 (M+H) ＋Example 171 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 546 (M+H) ＋ Example 172 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 550 (M+H) ＋ Example 173 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 544 (M+H) ＋ Example 174 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 542 (M+H) ＋ Example 175 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 582 (M+H) ＋ Example 176 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 530 (M+H) ＋Example 177 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 518 (M+H) ＋ Example 178 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 546 (M+H) ＋ Example 179 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 550 (M+H) ＋ Example 180 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 439 (M+H) ＋ Example 181 2-chloro-N-[1-(propan-2-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 479 (M+H) ＋ Example 182 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 415 (M+H) ＋Example 183 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 443 (M+H) ＋ Example 184 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 447 (M+H) ＋ Example 185 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 427 (M+H) ＋ Example 186 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 441 (M+H) ＋ Example 187 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 482 (M+H) ＋ Example 188 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 480 (M+H) ＋Example 189 2-chloro-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 520 (M+H) ＋ Example 190 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 468 (M+H) ＋ Example 191 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 456 (M+H) ＋ Example 192 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 484 (M+H) ＋ Example 193 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 488 (M+H) ＋ Example 194 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 579 (M+H) ＋Example 195 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 579 (M+H) ＋ Example 196 5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 564 (M+H) ＋ Example 197 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 526 (M+H) ＋ Example 198 N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 529 (M+H) ＋ Example 199 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 593 (M+H) ＋ Example 200 N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 543 (M+H) ＋Example 201 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 502 (M+H) ＋ Example 202 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 461 (M+H) ＋ Example 203 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 413 (M+H) ＋ Example 204 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 411 (M+H) ＋ Example 205 2-chloro-N-(1-methyl-1H-indazol-4-yl)-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 451 (M+H) ＋ Example 206 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-(1-methyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 399 (M+H) ＋Example 207 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide The title compound was obtained by reacting and treating in a similar manner to Example 89. MS (ESI+) m / z 387 (M+H) ＋ Example 208 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 419 (M+H) ＋ Example 209 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 433 (M+H) ＋ Example 210 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 427 (M+H) ＋ Example 211 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 425 (M+H) ＋ Example 212 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 465 (M+H) ＋ Example 213 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 413 (M+H) ＋Example 214 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-{[(methoxyacetyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 401 (M+H) ＋ Example 215 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 429 (M+H) ＋ Example 216 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 433 (M+H) ＋ Example 217 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 447 (M+H) ＋ Example 218 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 543 (M+H) ＋ Example 219 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 541 (M+H) ＋Example 220 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 581 (M+H) ＋ Example 221 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 529 (M+H) ＋ Example 222 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 517 (M+H) ＋ Example 223 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 545 (M+H) ＋ Example 224 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 549 (M+H) ＋ Example 225 5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 563 (M+H) ＋Example 226 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 482 (M+H) ＋ Example 227 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 480 (M+H) ＋ Example 228 2-chloro-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 520 (M+H) ＋ Example 229 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 468 (M+H) ＋ Example 230 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 456 (M+H) ＋ Example 231 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 484 (M+H) ＋Example 232 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 488 (M+H) ＋ Example 233 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 502 (M+H) ＋ Example 234 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 490 (M+H) ＋ Example 235 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 488 (M+H) ＋ Example 236 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 464 (M+H) ＋ Example 237 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 496 (M+H) ＋Example 238 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 510 (M+H) ＋ Example 239 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 490 (M+H) ＋ Example 240 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 488 (M+H) ＋ Example 241 2-chloro-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 528 (M+H) ＋ Example 242 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 476 (M+H) ＋ Example 243 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 464 (M+H) ＋Example 244 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 492 (M+H) ＋ Example 245 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 496 (M+H) ＋ Example 246 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 510 (M+H) ＋ Example 247 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 491 (M+H) ＋ Example 248 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 489 (M+H) ＋ Example 249 2-chloro-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 489 (M+H) ＋Example 250 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 477 (M+H) ＋ Example 251 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 465 (M+H) ＋ Example 252 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 493 (M+H) ＋ Example 253 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 497 (M+H) ＋ Example 254 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 557 (M+H) ＋ Example 255 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 555 (M+H) ＋Example 256 2-chloro-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 495 (M+H) ＋ Example 257 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 543 (M+H) ＋ Example 258 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 513 (M+H) ＋ Example 259 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 559 (M+H) ＋ Example 260 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 563 (M+H) ＋ Example 261 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 573 (M+H) ＋Example 262 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 571 (M+H) ＋ Example 263 2-chloro-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 611 (M+H) ＋ Example 264 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 559 (M+H) ＋ Example 265 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 547 (M+H) ＋ Example 266 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 575 (M+H) ＋ Example 267 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 579 (M+H) ＋Example 268 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 593 (M+H) ＋ Example 269 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 506 (M+H) ＋ Example 270 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 504 (M+H) ＋ Example 271 2-chloro-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 544 (M+H) ＋ Example 272 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by reacting and treating in a similar manner to Example 18. MS (ESI+) m / z 492 (M+H) ＋ Example 273 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 480 (M+H) ＋Example 274 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 508 (M+H) ＋ Example 275 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 512 (M+H) ＋ Example 277 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 504 (M+H) ＋ Example 278 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 502 (M+H) ＋ Example 279 2-chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 542 (M+H) ＋ Example 280 2-chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 478 (M+H) ＋Example 281 2-chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 506 (M+H) ＋ Example 282 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 510 (M+H) ＋ Example 283 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 18. MS (ESI+) m / z 524 (M+H) ＋ Example 284 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-cyclopropyl-1H-indazol-4-yl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 425 (M+H) ＋ Example 285 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-cyclopropyl-1H-indazol-4-yl)-2-(trifluoromethyl)benzamide The title compound was obtained by the same reaction and treatment as in Example 89. MS (ESI+) m / z 459 (M+H) ＋

[0250] The compounds described below in 1 to 55 can be prepared according to any of the methods described in Examples 1, 48, 88 and 89 above. 1. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 2. 2-Chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 3. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 4. 2-Chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide 5. 2,6-Dichloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-3-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide 6. 2-Chloro-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide 7. 2-Chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 8. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 9. 2,6-Dichloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-3-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide 10. 2-Chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide 11.2,12. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide 13. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide 14. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide 15. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide 16. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide 17. 5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide 18. 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide 19. N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide 20. 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide 21. 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide 22. 2,6-dichloro-3-{[(2,2-Dimethylpropanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide 23. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide 24. 2-Chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 25. 2-Chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 26. 2-Chloro-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide 27. 2-Chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 28. 2-Chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 29. 2-Chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 30. 2-Chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 31. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide 32. 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide 33. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide 34. 2-Chloro-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide 35. 2-Chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide 36. 2-Chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide 37. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide 38. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide 39. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide 40. 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide 41. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide 42. 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide 43.2,44. 2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide 45. 2-Chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide 46. ​​2,6-Dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide 47. 2-Chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide 48. 2-Chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]benzamide 49. 2-Chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide 50. 2-Chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide 51. 2-Chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide 52. 2-Chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide 53. 2-Chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(cyclopropylsulfonyl)amino]methyl}benzamide 54.26-dichloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-3-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide 55. N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide,

[0251] The structural formulas of Examples 1 to 285 are shown in Tables 1 to 24.

[0252] Test Example 1: mPGES-1 Inhibitory Activity Test CHO-K1 cells (DS Pharma Biomedical) were transiently transfected with a plasmid encoding human mPGES-1 cDNA using FuGENE 6 Transfection Reagent (Promega) to prepare mPGES-1 microsome preparations. The prepared mPGES-1 microsome preparations were diluted with potassium phosphate buffer (pH 7.4) containing 2.5 mM reduced glutathione (Sigma-Aldrich), and a DMSO solution of the test compound or DMSO was added so that the final DMSO concentration was 1% in both cases. The mixture was then incubated at 4°C for 20 minutes. Next, the enzyme reaction was initiated by adding a solution of PGH2 (Cayman Chemical) substrate adjusted to a final concentration of 1 μM, and the mixture was incubated at 4°C for 60 seconds. The reaction was terminated by adding ferric chloride (STREM CHEMICALS) and citric acid (Wako Pure Chemical Industries) salt solutions to final concentrations of 5 mg / mL and 250 mM, respectively. The amount of PGE2 formed was quantified using an HTRF kit (Cisbio International). A solution without test compound was used as a positive control, and a solution without test compound and microsome preparation was used as a negative control. 100% activity was defined as the PGE2 production in the positive control minus the PGE2 production in the negative control. The PGE2 production inhibition rate at final concentrations of 10 nM and 100 nM of the test compound was then calculated, or the IC50 value was measured using standard methods.

[0253] Test Example 2: Inhibition of PGE2 and PGF2α production using human A549 cells. 2 x 10 human A549 cells (Japan Human Science Foundation) were placed in each well of a 96-well plate. ４Human A549 cells were seeded in 100 μL of RPMI medium (Sigma) containing 10% FBS and incubated overnight. The medium was then removed and washed with phosphate-buffered saline. A DMSO solution of the test compound or RPMI medium containing 3% FBS plus DMSO was added to the wells to a final DMSO concentration of 0.1%. After 60 minutes of incubation, IL-1β (5 ng / well, BioLegend) was added. After 24 hours of incubation at 37°C, PGE2 in the medium was quantified using an HTRF kit (Cisbio International) and PGF2α was quantified using an EIA kit (Cayman Chemical). A solution without the test compound was used as a positive control, and a solution without the test compound or IL-1β was used as a negative control. 100% activity was defined as the PGE2 and PGF2α production in the positive control minus the PGE2 and PGF2α production in the negative control. IC50 values ​​were then determined using standard methods.

[0254] The results of Test Examples 1 and 2 are shown in Tables 25 to 31 (in the tables, "-" indicates that the test was not carried out).

[0255] Test Example 3: PGE2 Production Inhibition Test Using Human Whole Blood A human whole blood assay was performed based on the report by Brideau et al. (Inflamm. Res., vol. 45, p. 68, 1996). Freshly collected venous blood from volunteers was collected into heparin-containing tubes. The subjects were required to have no visible inflammatory symptoms and to have not taken NSAIDs for at least 7 days prior to blood collection. A DMSO solution of the test compound or DMSO (final DMSO concentration of 0.25% in both cases) was added to the blood and incubated at 37°C for 20 minutes. Subsequently, bacterial LPS (Escherichia coli serotype 0111:B4 diluted in phosphate-buffered saline) was added to a final concentration of 100 μg / mL and incubated at 37°C for 24 hours. After 24 hours of incubation, the blood was centrifuged at 2000 rpm for 5 minutes at 4°C, and PGE2 in the supernatant was quantified using an HTRF kit (Cisbio International, product catalog #62P2APEC). A solution without the test compound was used as a positive control, and a solution without the test compound and LPS was used as a negative control. 100% activity was defined as the PGE2 production in the positive control minus the PGE2 production in the negative control. IC50 values ​​were then measured using standard methods. The compounds of the present invention also inhibited PGE2 production in human whole blood. ２ It showed a production inhibitory effect.

[0256] Test Example 4: Pharmacokinetics Test in Rat The test compound was suspended in 0.5% methylcellulose solution to prepare a 10 mg / 5 mL administration solution. 10 mg / kg of the compound was orally administered to female SD rats under fasting conditions, and blood was collected from the jugular vein 1, 2, 4, and 6 hours after administration. The blood was centrifuged to separate plasma, which was then deproteinized and the plasma concentration of the test compound was measured by HPLC.

[0257] Test Example 5: Evaluation of the inhibitory effect on urination volume in a guinea pig water-load polyuria model The inhibitory effect of a test compound on urination volume was evaluated using a water-load polyuria model, a commonly used polyuria model, as follows. Female Hartley guinea pigs (manufactured by Japan SLC Co., Ltd.) were fasted from the evening of the day before the test and placed in metabolic cages (manufactured by Natsume Seisakusho Co., Ltd.) for acclimation. The following day, 20 mL / kg of distilled water was orally administered as a water load, and the animals were then placed back into the metabolic cages. The total urination volume up to 3 hours after the water load was then imported into a personal computer via an electronic balance (GX-200, manufactured by A&D Co., Ltd.) and a data collection and analysis system (PowerLab®, manufactured by AD Instruments), and analyzed using analysis software (LabChart®, manufactured by AD Instruments). The test compound dissolved in 0.5% aqueous methylcellulose solution (vehicle) or the vehicle alone was orally administered immediately before the water load, depending on the kinetics of the compound. Based on the total urination volume of the test compound group and the vehicle group after 3 hours, the urination volume inhibition rate (%) of the test compound group relative to the urination volume of the vehicle group was calculated.

[0258] Test Example 6: Evaluation of the Urine Volume Inhibitory Effect in a Monkey Water Load Polyuria Model The urination volume inhibitory effect of a test compound was evaluated in a water load polyuria model using monkeys, whose urination function is believed to be closer to that of humans. Female cynomolgus monkeys were fasted from the evening of the day before the test. The following day, for acclimatization, 50 mL / kg of distilled water was orally administered as a water load. After that, the monkeys were placed in metabolic cages, and the total urination volume up to 6 hours after the water load was recorded via an electronic balance (GX-6100R, manufactured by A&D Co., Ltd.) into a data acquisition and analysis computer system (hardware: manufactured by Data Sciences International, Inc.; analysis software: manufactured by NOTOCORD SYSTEMS, Inc.) and analyzed. Acclimation was performed a total of three times. The evaluation of the test compound was performed in the same manner as for acclimatization, and the test compound dissolved in 0.5% methylcellulose aqueous solution (vehicle) or the vehicle alone was orally administered either 2 hours before or immediately before the water load, depending on the kinetics of the compound.

[0259] Test Example 7: Evaluation of Plasma Sodium Concentration in a Rat Water Load Polyuria Model The plasma sodium concentration-lowering effect of a test compound was evaluated using a rat water load polyuria model. Female SD rats (Japan SLC Co., Ltd.) were fasted from the evening before the test. After oral administration of 25 mL / kg of distilled water as a water load, blood was collected using a heparinized syringe 2 or 3 hours later. The collected blood was centrifuged at 10,000 rpm for 10 minutes at 4°C to obtain plasma. Plasma sodium concentration was measured using a fully automated electrolyte analyzer (PVA-EXII, A&T Corporation). The test compound dissolved in 0.5% methylcellulose aqueous solution (vehicle) or the vehicle alone was orally administered either 2 hours before or immediately before water load, depending on the kinetics of the compound.

[0260] Desmopressin, an existing drug for treating nocturnal polyuria, is known to cause hyponatremia as a side effect. In this study, the effect of the compound of the present invention on plasma sodium concentration was examined, and it was found that the compound of the present invention did not affect plasma sodium concentration even when exposed to four times the effective dose.

[0261] Formulation Example 1 Tablets (oral tablets) Formulation per 80 mg tablet: Compound of the present invention of Example 1 5.0 mg Corn starch 46.6 mg Microcrystalline cellulose 24.0 mg Methylcellulose 4.0 mg Magnesium stearate 0.4 mg The mixed powder in this ratio is tableted by a conventional method to give oral tablets.

[0262] The compound of the present invention or a pharmaceutically acceptable salt thereof exhibits mPGES-1 inhibitory activity and can therefore be used in the production of a medicament for treating or preventing diseases associated with mPGES-1.

Claims

1. The following general formula [1]: 【Chemistry 1】 [In the formula, R １ , R ２ each independently represents hydrogen, halogen, or optionally substituted alkyl; R ３ is -SO ２ R ５ , or -COR ５ represents; R ４ represents optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted saturated heterocyclic group, or optionally substituted arylalkyl; R ５ represents optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted saturated heterocyclic group, optionally substituted alkynyl, or optionally substituted arylalkyl: The heteroaryl and saturated heterocyclic groups are attached at a carbon atom on the ring. or a pharmaceutically acceptable salt thereof, or a solvate thereof.

2. R １ , R ２ wherein the alkyl may be substituted with 1 to 3 halogen atoms; R ４ The heteroaryl in (1) alkoxy optionally substituted with 1 to 3 halogen atoms; (2) cyano, (3) halogens, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy; and (5) cycloalkyl and optionally substituted with 1 to 3 groups independently selected from the group consisting of: R ４ wherein the saturated heterocyclic group is optionally substituted with 1 to 3 groups independently selected from the group consisting of alkyl, alkoxycarbonyl, and alkylcarbonyl; R ４ The alkyl in may be substituted with a saturated heterocyclic group or a cycloalkyl; R ４ The aryl in (1) alkoxy optionally substituted with 1 to 3 halogen atoms; (2) cyano, (3) halogens, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy; and (5) cycloalkyl and optionally substituted with 1 to 3 groups independently selected from the group consisting of: R ４ The arylalkyl in the formula (I) may be substituted with alkyl or alkoxy optionally substituted with 1 to 3 halogen atoms; R ５ wherein the saturated heterocyclic group is optionally substituted with 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl; R ５ wherein the alkyl is optionally substituted with 1 to 3 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, monoalkylamino, dialkylamino, and halogen; R ５ The cycloalkyl in (1) hydroxy, (2) cyano, and (3) Alkyl optionally substituted with 1 to 3 halogen atoms and optionally substituted with 1 to 3 groups independently selected from the group consisting of:

2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

3. R ４ The aryl in (1) alkoxy optionally substituted with 1 to 3 halogen atoms; (2) cyano, (3) halogens, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy; and (5) cycloalkyl phenyl optionally substituted with 1 to 3 groups independently selected from the group consisting of: R ４ wherein the heteroaryl is (1) alkoxy optionally substituted with 1 to 3 halogen atoms; (2) cyano, (3) halogens, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy; and (5) cycloalkyl imidazolyl, thiazolyl, pyridyl, pyridazinyl, or pyrimidinyl, optionally substituted with 1 to 3 groups independently selected from the group consisting of: R ４ is piperidinyl or tetrahydropyranyl, optionally substituted with alkyl, alkoxycarbonyl or alkylcarbonyl; 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

4. R ５ wherein aryl is phenyl; R ５ wherein heteroaryl is furyl; R ５ wherein the saturated heterocyclic group is piperidinyl, tetrahydrofuryl, or tetrahydropyranyl, optionally substituted with 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl; 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

5. R ４ is alkyl having 1 to 6 carbon atoms which may be substituted with a saturated heterocyclic group or cycloalkyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof according to claim 1.

6. R ４ is cycloalkyl having 3 to 10 carbon atoms, or a pharmaceutically acceptable salt thereof, or a solvate thereof according to claim 1.

7. R ４ but, (1) alkoxy optionally substituted with 1 to 3 halogen atoms; (2) cyano, (3) halogens, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy; and (5) cycloalkyl The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein R is 1 to 3; and ...

8. R ４ but, (1) alkoxy optionally substituted with 1 to 3 halogen atoms; (2) cyano, (3) halogens, (4) (i) alkyl optionally substituted with 1 to 3 halogens, (ii) hydroxy, or (iii) alkoxy; and (5) cycloalkyl The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof, which is imidazolyl, thiazolyl, pyridyl, pyridazinyl, or pyrimidinyl, optionally substituted by 1 to 3 groups independently selected from the group consisting of:

9. R ４ is piperidinyl or tetrahydropyranyl, optionally substituted with 1 to 3 groups independently selected from the group consisting of alkyl, alkoxycarbonyl, and alkylcarbonyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to claim 1 .

10. R ４ is phenylalkyl optionally substituted with alkyl or alkoxy having 1 to 6 carbon atoms optionally substituted with 1 to 3 halogen atoms, or a pharmaceutically acceptable salt thereof, or a solvate thereof according to claim 1.

11. R ５ is alkyl having 1 to 6 carbon atoms optionally substituted with 1 to 3 groups independently selected from the group consisting of hydroxy, alkoxy, cycloalkyl, monoalkylamino, dialkylamino, and halogen, or a pharmaceutically acceptable salt thereof, or a solvate thereof according to claim 1.

12. R ５ is a cycloalkyl having 3 to 10 carbon atoms optionally substituted with 1 to 3 groups independently selected from the group consisting of (1) hydroxy, (2) cyano, and (3) alkyl optionally substituted with 1 to 3 halogens, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to claim 1.

13. R ５ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein is optionally substituted phenyl.

14. R ５ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein is optionally substituted furyl.

15. R ５ is piperidinyl, tetrahydrofuryl, or tetrahydropyranyl, each optionally substituted with 1 to 3 groups independently selected from the group consisting of alkyl and alkoxycarbonyl, or a pharmaceutically acceptable salt thereof, or a solvate thereof, according to claim 1 .

16. R ５ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein is an optionally substituted alkynyl having 2 to 6 carbon atoms.

17. R ５ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein is optionally substituted phenylalkyl.

18. R １ The compound according to claim 1, wherein is halogen or alkyl having 1 to 6 carbon atoms optionally substituted with 1 to 3 halogens, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

19. R ２ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein is hydrogen or halogen.

20. The compound according to claim 1, selected from the group consisting of the following compounds, or a pharmaceutically acceptable salt thereof, or a solvate thereof: (1) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (2) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-(1-phenyl-1H-indazol-4-yl)benzamide, (3) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (4) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-3-yl)-1H-indazol-4-yl]benzamide, (5) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-4-yl)-1H-indazol-4-yl]benzamide, (6) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(4-methylphenyl)-1H-indazol-4-yl]benzamide, (7) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(3-methylphenyl)-1H-indazol-4-yl]benzamide, (8) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(pyridin-2-yl)-1H-indazol-4-yl]benzamide, (9) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(2-methylphenyl)-1H-indazol-4-yl]benzamide, (10) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (11) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (12) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (13) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-[1-(2-methoxyphenyl)-1H-indazol-4-yl]benzamide, (14) N-[1-(4-tert-butylphenyl)-1H-indazol-4-yl]-2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide, (15) 2-chloro-N-[1-(3-chloro-2-methylphenyl)-1H-indazol-4-yl]-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide, (16) 3-{[(cyclopropylcarbonyl)amino]methyl}-2,6-difluoro-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (17) 2-chloro-5-{[(trifluoroacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (18) 5-[(acetylamino)methyl]-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (19) 2-chloro-5-[(propanoylamino)methyl]-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (20) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (21) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (22) 2-chloro-5-{[(phenylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (23) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (24) 2-chloro-5-{[(N,N-dimethylglycyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (25) 2-chloro-5-({[(1-cyanocyclopropyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (26) 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (27) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (28) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (29) 2-chloro-5-{[(cyclobutylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (30) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (31) 2-chloro-5-{[(cyclohexylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (32) N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]tricyclo[3.3.

1. １３，７ ]decane-1-carboxamide, (33) N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]tetrahydrofuran-2-carboxamide, (34) N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]tetrahydrofuran-3-carboxamide, (35) 2-chloro-5-{[(N,N-dimethyl-β-alanyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (36) tert-butyl 4-{[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]carbamoyl}piperidine-1-carboxylate, (37) 2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-5-{[(3,3,3-trifluoropropanoyl)amino]methyl}benzamide, (38) 2-chloro-5-{[(cyclopropylacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (39) 2-chloro-5-({[trans-(4-hydroxycyclohexyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (40) 2-chloro-5-({[cis-(4-hydroxycyclohexyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (41) 2-chloro-5-{[(2-ethyl-2-hydroxybutanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (42) 5-[(2-butynoylamino)methyl]-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (43) 5-[(butanoylamino)methyl]-2-chloro-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (44) 2-chloro-5-{[(phenylacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (45) N-[4-chloro-3-({1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}carbamoyl)benzyl]furan-2-carboxamide, (46) 2-chloro-5-{[(cyclopentylacetyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (47) 2-chloro-5-{[(3-methoxypropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (48) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-methoxyphenyl)-1H-indazol-4-yl]benzamide, (49) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-methoxyphenyl)-1H-indazol-4-yl]benzamide, (50) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (51) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (52) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyrimidin-5-yl)-1H-indazol-4-yl]benzamide, (53) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (54) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (55) 2-chloro-N-[1-(4-cyanophenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (56) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (57) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (58) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (59) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (60) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (61) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (62) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (63) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (64) 2-chloro-N-[1-(5-cyclopropylpyridin-3-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (65) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-ethoxyphenyl)-1H-indazol-4-yl]benzamide, (66) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-ethoxyphenyl)-1H-indazol-4-yl]benzamide, (67) 2-chloro-N-[1-(3,4-dimethoxyphenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (68) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(propan-2-yloxy)phenyl]-1H-indazol-4-yl}benzamide, (69) 2-chloro-N-[1-(6-cyclopropylpyridin-3-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (70) 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (71) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (72) 2-chloro-N-[1-(6-cyanopyridin-3-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (73) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (74) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(methoxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (75) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(hydroxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (76) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (77) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (78) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(methoxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (79) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (80) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (81) 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (82) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (83) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (84) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(2-methoxypropan-2-yl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (85) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(2-fluoropropan-2-yl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (86) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(ethoxymethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (87) 2-chloro-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]-5-{[(trifluoroacetyl)amino]methyl}benzamide, (88) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (89) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-methoxybenzyl)-1H-indazol-4-yl]benzamide, (90) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxybenzyl)-1H-indazol-4-yl]benzamide, (91) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,4,6-trimethylbenzyl)-1H-indazol-4-yl]benzamide, (92) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethyl)benzyl]-1H-indazol-4-yl}benzamide, (94) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)benzyl]-1H-indazol-4-yl}benzamide, (95) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-phenylethyl)-1H-indazol-4-yl]benzamide, (97) 2-chloro-N-(1-cyclopentyl-1H-indazol-4-yl)-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (98) 2-chloro-N-(1-cyclohexyl-1H-indazol-4-yl)-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (99) 2-chloro-N-[1-(cyclobutylmethyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (100) 2-chloro-N-[1-(cyclohexylmethyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (101) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(3-phenylpropyl)-1H-indazol-4-yl]benzamide, (102) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (103) tert-butyl 4-(4-{[(2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}phenyl)carbonyl]amino}-1H-indazol-1-yl)piperidine-1-carboxylate, (104) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(tetrahydro-2H-pyran-4-yl)-1H-indazol-4-yl]benzamide, (105) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-indazol-4-yl]benzamide, (106) N-[1-(1-acetylpiperidin-4-yl)-1H-indazol-4-yl]-2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (107) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-(morpholin-4-yl)ethyl]-1H-indazol-4-yl}benzamide, (108) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-phenylbutyl)-1H-indazol-4-yl]benzamide, (109) N-(1-benzyl-1H-indazol-4-yl)-2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}benzamide, (111) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide (112) 2-chloro-5-{[(cyclopropylcarbonyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide (113) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide (114) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (115) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (116) 2-chloro-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (117) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (118) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (119) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (120) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (121) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (122) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (123) 2-chloro-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (124) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (125) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (126) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (127) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide, (128) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(cyclopentylcarbonyl)amino]methyl}benzamide, (129) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (130) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide, (131) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide, (132) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(cyclopropylsulfonyl)amino]methyl}benzamide, (133) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (134) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (135) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (136) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (137) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (138) 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide, (139) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (140) 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (141) 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide, (142) 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(methoxyacetyl)amino]methyl}benzamide, (143) 2-chloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide, (144) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (145) 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide (146) 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(cyclopentylcarbonyl)amino]methyl}benzamide, (147) 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (148) 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide (149) 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide, (150) 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-([(cyclopropylsulfonyl)amino]methyl)benzamide, (151) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide, (152) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide, (153) 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (154) 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide, (155) 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-([(methoxyacetyl)amino]methyl)benzamide, (156) 2-chloro-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide, (157) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide (158) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]benzamide, (159) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (160) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (161) 2-chloro-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (162) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (163) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (164) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (165) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (166) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (167) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (168) 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (169) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (170) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (171) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (172) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (173) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (174) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (175) 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (176) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (177) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (178) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (179) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (180) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (181) 2-chloro-N-[1-(propan-2-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (182) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (183) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (184) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (185) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (186) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (187) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (188) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (189) 2-chloro-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (190) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (191) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (192) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (193) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (194) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide, (195) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide, (196) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (197) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (198) N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide, (199) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide, (200) N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide, (201) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (202) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (203) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide, (204) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide, (205) 2-chloro-N-(1-methyl-1H-indazol-4-yl)-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (206) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-(1-methyl-1H-indazol-4-yl)benzamide (207) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide, (208) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide, (209) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)-2-(trifluoromethyl)benzamide, (210) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide, (211) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide, (212) 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (213) 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide, (214) 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-{[(methoxyacetyl)amino]methyl}benzamide, (215) 2-chloro-N-(1-ethyl-1H-indazol-4-yl)-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide, (216) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide, (217) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)-2-(trifluoromethyl)benzamide, (218) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (219) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (220) 2-chloro-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (221) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (222) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (223) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (224) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (225) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (226) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (227) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (228) 2-chloro-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (229) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (230) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (231) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (232) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (233) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (234) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (235) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (236) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (237) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (238) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (239) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (240) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (241) 2-chloro-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (242) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (243) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (244) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (245) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (246) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (247) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (248) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (249) 2-chloro-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (250) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (251) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (252) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (253) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (254) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (255) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (256) 2-chloro-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (257) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (258) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (259) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (260) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (261) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (262) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (263) 2-chloro-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (264) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (265) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (266) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (267) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (268) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide, (269) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (270) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (271) 2-chloro-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (272) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (273) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (274) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (275) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (276) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (277) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (278) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (279) 2-chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (280) 2-chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide (281) 2-chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide (282) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (283) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (284) 2-chloro-5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-cyclopropyl-1H-indazol-4-yl)benzamide, (285) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-cyclopropyl-1H-indazol-4-yl)-2-(trifluoromethyl)benzamide, (286) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (287) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (288) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (289) 2-chloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide (290) 2,6-dichloro-N-[1-(3-chloro-4-methylphenyl)-1H-indazol-4-yl]-3-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (291) 2-chloro-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (292) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (293) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (294) 2,6-dichloro-N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-3-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (295) 2-chloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide, (296) 2,6-dichloro-N-[1-(4-chlorophenyl)-1H-indazol-4-yl]-3-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (297) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methoxypyridin-4-yl)-1H-indazol-4-yl]benzamide, (298) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (299) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (300) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(propan-2-yl)-1H-indazol-4-yl]benzamide, (301) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-4-yl)-1H-indazol-4-yl]benzamide, (302) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)-N-{1-[5-(trifluoromethyl)pyridin-3-yl]-1H-indazol-4-yl}benzamide, (303) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(4-fluorophenyl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (304) N-{1-[3-(difluoromethoxy)phenyl]-1H-indazol-4-yl}-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide, (305) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide, (306) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-methyl-1H-indazol-4-yl)benzamide, (307) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-(1-ethyl-1H-indazol-4-yl)benzamide, (308) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (309) 2-chloro-5-{[(3,3-dimethylbutanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (310) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (311) 2-chloro-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (312) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (313) 2-chloro-5-{[(methoxyacetyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (314) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (315) 2-chloro-5-{[(cyclopropylsulfonyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (316) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}benzamide, (317) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[2-methyl-4-(trifluoromethoxy)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide, (318) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(1,3-thiazol-2-yl)-1H-indazol-4-yl]benzamide, (319) 2-chloro-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (320) 2-chloro-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (321) 2-chloro-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (322) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2-methylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (323) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(5-methylpyridin-3-yl)-1H-indazol-4-yl]benzamide, (324) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]benzamide, (325) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methylpyridazin-3-yl)-1H-indazol-4-yl]-2-(trifluoromethyl)benzamide, (326) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (327) 5-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methyl-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}-2-(trifluoromethyl)benzamide, (328) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-{1-[4-methoxy-3-(trifluoromethyl)phenyl]-1H-indazol-4-yl}benzamide, (329) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(6-methoxypyridin-3-yl)-1H-indazol-4-yl]benzamide, (330) 2-chloro-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide, (331) 2,6-dichloro-3-{[(2,2-dimethylpropanoyl)amino]methyl}-N-[1-(2,6-dimethylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (332) 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(3,3-dimethylbutanoyl)amino]methyl}benzamide (333) 2-chloro-5-{[(cyclopentylcarbonyl)amino]methyl}-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]benzamide, (334) 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-[({[1-(trifluoromethyl)cyclopropyl]carbonyl}amino)methyl]benzamide, (335) 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-({[(1-hydroxycyclopropyl)carbonyl]amino}methyl)benzamide, (336) 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(methoxyacetyl)amino]methyl}benzamide, (337) 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(3-hydroxy-2,2-dimethylpropanoyl)amino]methyl}benzamide, (338) 2-chloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(cyclopropylsulfonyl)amino]methyl}benzamide, (339) 2,6-dichloro-N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-3-{[(2,2-dimethylpropanoyl)amino]methyl}benzamide, (340) N-[1-(2-cyclopropylpyridin-4-yl)-1H-indazol-4-yl]-5-{[(2,2-dimethylpropanoyl)amino]methyl}-2-(trifluoromethyl)benzamide.

21. A pharmaceutical composition comprising the compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

22. 21. An mPGES-1 inhibitor comprising the compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

23. A PGE2 production inhibitor comprising the compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

24. 21. A preventive or therapeutic agent for a disease involving mPGES-1, comprising the compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

25. A preventive or therapeutic agent for a disease involving PGE2, comprising the compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

26. 21. A compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, or a solvate thereof, for use in treating inflammatory bowel disease, irritable bowel syndrome, migraine, headache, lower back pain, lumbar spinal stenosis, herniated disc, temporomandibular joint disorder, cervicobrachial syndrome, cervical spondylosis, endometriosis, adenomyosis, premature labor, threatened premature labor, dysmenorrhea, overactive bladder, nocturia, interstitial cystitis, neurodegenerative disease, psoriasis, rheumatoid arthritis, rheumatic fever, fibromyalgia, neuralgia, complex regional pain syndrome, fascial disorder, viral infection, bacterial infection, fungal infection, burns, inflammation after surgery, after trauma, and after tooth extraction. an agent for the prevention or treatment of pain in diseases / pain, malignant tumor, atherosclerosis, stroke, gout, osteoarthritis, juvenile arthritis, tenosynovitis, ossification of ligaments, systemic lupus erythematosus, vasculitis, pancreatitis, nephritis, conjunctivitis, iritis, scleritis, uveitis, wound treatment, dermatitis, eczema, osteoporosis, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, allergic disease, familial adenomatous polyposis, scleroderma, bursitis, uterine fibroids, prostatitis, depression, neurogenic bladder, nocturia, diurnal polyuria, enuresis, central diabetes insipidus, nephrogenic diabetes insipidus, urinary incontinence, benign prostatic hyperplasia, chronic prostatitis, or cancer.

27. A preventive or therapeutic agent for nocturnal polyuria, nocturia, overactive bladder, neurogenic bladder, enuresis, benign prostatic hyperplasia, central diabetes insipidus, nephrogenic diabetes insipidus, chronic prostatitis, interstitial cystitis, or urinary incontinence, comprising the compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, or a solvate thereof.

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