TW201206906A - Dihydropyrimidinone derivative and pharmaceutical use thereof - Google Patents

Abstract

This invention provides a compound represented by a general formula (I) wherein R0 is -C(=\O)NRa-, -S(=O)2NRa-, -C(=O)O- or single bond etc., R1 is hydrogen atom, alkyl, alkene, optionally hetero atom-containing 3 to 6 member saturated- or 4 to 6 member unsaturated- aliphatic ring or optionally hetero atom-containing 5 to 6 member aromatic ring etc., R2 is hydrogen atom or alkyl etc., R3 and R4 are each independently hydrogen atom or alkyl etc., L is 5 to 6 aromatic ring or -S(=O)q-, Ar1 and Ar2 are each independently optionally hetero atom-containing 5 to 6 member aromatic ring substituted at one or more position(s), or a pharmaceutically acceptable salt there of, and an agent for prophylaxis and/or treatment of various kinds of inflammatory disease involving elastase comprising the same as an active ingredient.

Description

201206906 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a novel dihydropyrimidinone derivative which is useful as a medicine having an inhibitory activity against elastase. More specifically, it relates to a novel dihydropyrimidine-derivative having a preventive agent and/or a therapeutic agent for use as a disease associated with elastase such as an inflammatory disease. [Prior Art] A class neutrophilic protease (hereinafter, also referred to as elastase) is a kind of a serine protease having a molecular weight of about 30 kDa, and is stored in a succulent azure particles. In the physiological state, elastase acts as a neutrophil to rapidly digest and decompose bacteria and foreign bodies that are devastated. In the sacral extrasphere, it will constitute a living body such as lung, cartilage, blood vessel wall, and skin. The interstitial elastin, collagen (πι type 1ιν type), proteoglycan, fibr〇nectin, etc. of the connective tissue are decomposed to maintain the stability of the tissue. • In vivo, there is an endogenous protein that inhibits elastase. Among them, α1-anti-protease (α1—Ατ) is known, and patients with genetic d-AT deficiency are known to present symptoms such as chronic obstructive pulmonary disease (c_) (Non-patent literature.) When it is considered that the endogenous inhibition of the elastase protein and the elastase causes an imbalance, or when an excessive amount of elastase is released due to a pathological state such as inflammation, the elastase 穑 extremely destroys the normal tissue, and induces various pathologies. Elastase-related pathological diseases such as chronic obstructive pulmonary disease (GGPD), cystic fibrosis, emphysema, adult 323256 4 201206906 respiratory distress syndrome (ARDS), acute lung injury (A LI), idiopathic lung Fibrosis (11P), chronic interstitial pneumonia, chronic bronchitis, chronic respiratory infection, diffuse panbronchiolitis, bronchiectasis, asthma, visceral inflammation, nephritis, liver failure, chronic rheumatoid arthritis, joint stiffness , osteoarthritis, psoriasis, periodontal disease, atherosclerosis, rejection of organ transplants, early water breaks, blisters, rest Gram, sepsis, systemic erythematous sore (SLE), Crohn's disease, disseminated intravascular coagulation (DIC), tissue damage during ischemia-reperfusion, formation of corneal scar tissue, myelitis, scale Lung cancer, lung cancer, lung adenocarcinoma, non-small cell lung cancer, etc., lung cancer, breast cancer, liver cancer, bladder cancer, colorectal cancer, skin cancer, pancreatic cancer, glioma, etc. Thus, an agent that inhibits elastase activity It is useful for the treatment of diseases associated with these elastases or for the expectation of T. Various elastic egg self-enzyme inhibitors have been reported. For example, in Patent Documents 2 and 3, neutrophil elasticity has been revealed. egg

Preparation of the 2-one bite _ derivative. For example, in the correction of the patent I range, the following general formula (A-1) (the same as the common pole = the application of the shoulder compound. Formula I) is shown. 323256 5 201206906 R2

(A-1) It is defined as [wherein A represents an aryl ring or a heteroaryl ring...].

However, since the 4-position of the 2-dihydropyrimidinone derivative has an aryl ring or a heteroaryl ring, it is significantly different in structure from the compound of the present invention to be described later. Similarly, the 2-dihydropyrimidinone derivatives described in the first aspect of Patent Application Nos. 2 and 3 are also structurally distinct from the compounds of the present invention to be described later. Further, as a compound having a function of inhibiting P38 MAP kinase, the compound represented by the following general formula (A-2) (formula I of the same publication) is described in the first item of Patent Document 4 and Patent Document 5.

(A-2) [wherein, ring A represents a 5-membered monocyclic hetero ring having a substituent which may have 1 to 3 atoms selected from an oxygen atom, a nitrogen atom or a sulfur atom as a hetero atom. Ring B a heterocyclic ring containing at least one nitrogen atom which may have a substituent, 6 323256 201206906 Ring D represents a cyclic group which may have a substituent, a cyclic quinone dicyclic group, and R' represents a group containing a nitrogen atom having a tester Wherein ring A represents a 5-membered monocyclic heterocyclic ring having 1 to 3 atoms selected from the group consisting of an oxygen atom and a sulfur atom, which has a substituent, and has a substituent, except for the indicated nitrogen atom; 1 J may contain a heterocyclic ring of from 1 to 3 atoms selected from the group consisting of a ruthenium atom, a nitrogen atom and a sulfur atom, a ring D, a ring group which may have a substituent, and a ring E which may represent a cyclic group which may have a substituent, R It is a neutral group or an acidic group containing an oxygen atom and/or a sulfur atom. (Patent Document 5) However, the compound specifically described in Patent Documents 4 and 5 is substituted with the substituent R1 of the ring a of the 5-membered ring. Position, 4 positions in the order of the binding positions of the ring b and the ring D, the compound of the present invention is different from the structure thereof in the ring A (Formula (1) in the specification of the present application, wherein ^ is unsubstituted, and the position φ of the substituent of Ring A (L of the formula (丨) in the present specification) is 5 bits. 1] International Publication No. 2004/024700 (Patent Document 2) International Publication No. 2005/082863 booklet [Patent Document 3] International Publication No. 2005/082864 booklet [Patent Document 4] International Publication No. 2006/051826 Booklet [Patent Document 5] International Publication No. 2007/040208 Booklet [Non-Patent Document 1] Eur. Respir. J. 2009, 33, 1345-1353 [Summary of the Invention] 323256 201206906 (Problem to be solved by the invention) Inflammation In the case of the "Essence of the problem", the results of the "Essence of the problem" are as follows: [Item 1] shown in the following formula (1) The compound shown in the following f(1) or its physiologically permissible salt:

R1 (I

[wherein, R〇 represents -C(=〇)NRa---c/ Πχ M〇a or a single bond, (,〇) is a group of wind atoms, C11n, Fi*Gan and S The group may have a U4 hetero atom selected from the group consisting of N, 0 to a non-saturated aliphatic ring, and the group of 3 to 6 members is saturated or 40%. a 5- to 6-membered aromatic ring group, wherein the thiol group and the sulfhydryl group are substituted at a position which may be substituted, and may be substituted with one or a plurality of substituents selected from the group consisting of μ + 1, 323256 8 201206906 Substituent List 1: (1) Hydroxy, (2) halogen, (3) cyano, (4) G-6 alkoxy (the alkoxy group, at its substitutable position, can be passed The substituents are: a radical, a halogen atom, a cyano group, -C(=0)0Rb, -C(=0)NRcRd, which may contain 1 to 4 impurities selected from the group consisting of N, 0, and S. A 5- to 6-membered aromatic ring group of an atom (the aromatic ring group, at a substitutable position thereof, may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be a hydroxyl group or a halogen group Atom-substituted Cm alkoxy group, hydroxyl group, halogen atom, cyano group, φ-NRaC(=0)Rb, -NRaC(=0)NRcRd, -NRaS(=0)mRb -C(=0)0Rb, -C(=0)NRcRd, -S(=0)JRcRd, -S(=0)mRb or -NRcRd), or may contain a group selected from N, 0 and S a 3 to 6 membered saturated or 4 to 6 membered unsaturated aliphatic ring group of 1 to 2 heteroatoms of the group (the aliphatic ring group, where it may be substituted, may be substituted by: hydroxy or a C!-3 alkyl group substituted by a halogen atom, a Ch alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, an S atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd, -NRaS (=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NRcRd or pendant oxy)), 323256 201206906 (5) Ch alkylthio (in this alkylthio group, in its Substitutable positions may be substituted by: a radical, a halogen atom, a cyano group, -C(=0)0Rb, -C(=0)NRcRd ' may contain a group selected from N, 0 and S 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms (wherein the aromatic ring group may be substituted at the position where it may be substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom Ci-3 alkoxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaC(=0)NReRd, -NRaS(=0)mRb, -C which may be substituted by a hydroxyl group or a halogen atom ( =0) 0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or -NRcRd), or may contain a group selected from the group consisting of N, 0, and S 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of 2 heteroatoms (the aliphatic ring group, φ at its substitutable position, may be substituted by: a hydroxyl group or a halogen atom Substituted Cu alkyl group, Cm alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd, -NRaS(=0)mRb , -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy))' (6) may contain 1 to 4 heteroatoms selected from the group consisting of N, 0 and S a 5 to 6 membered aromatic ring group (the aromatic ring group, at its substitutable position, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or an iS atom, 10 323256 201206906 may be hydroxyl group Or a halogen atom-substituted Ci-3 alkoxy group, a trans group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd > -NRaS (=0%Rb, -C(= 0) 0Rb, • -C(=0)NRcRd, -S(=0%NRcRd, -S〇0)raRb or -NRcRd) ' (7) may contain a group selected from N, 0, and S. 3 to 6 of 1 to 2 heteroatoms a saturated or 4 to 6 membered unsaturated aliphatic ring group (the aliphatic ring group, at its substitutable position, may be substituted by: φ Ch alkyl (the alkyl group may be via a hydroxyl group, a halogen atom, or a cyano group) , -NRaC(=0)Rb, -NRaC(=0)NRcRd, -陬$(=0)#, -C(=0)0Rb, -C(=0)NRcRd or -NReRd substituted), 1

Cl-3 alkoxy (the alkoxy group may be substituted by a via or a halogen atom), a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb '-NRaC(=0)NReRd, 11 323256 201206906 -NRaS (=0)mRb, -C(=0)0Rb, 'C(=0)NRcRd, -C(=0)Rb, -S(=0), NRcRd, -S(=0)mRb, -NReRd or Side oxy), (8) -NRaRe, (9) -0C (=0)NRcRd, (10) -C(=0)Rf, (11) -S(=0)mRg, (12) mercaptan, (13) Nitro and (14) -0Re, the 3 to 6 membered saturated or 4 to 6 membered unsaturated aliphatic ring group of R1, which may be substituted at a position selected from the list of substituents Group 1 or a plurality of substituents substituted, substituent list 2: (1) hydroxy, (2) halogen atom, (3) cyano group, (4) Ch alkyl group (the alkyl group, in its replaceable position , which may be substituted by the following: 12 323256 201206906 A hydroxyl group, a halogen atom, a cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S ( The aromatic ring group, at the substitutable position thereof, may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or an atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a halogen atom, or a hydroxyl group. , halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, • -S(=0)mNRcRd, -S (=0% Rb or -NRcRd substituted), or a 3- to 6-membered saturated aliphatic ring group (which may contain one to two heteroatoms selected from the group consisting of N, 0, and S) (the aliphatic ring group, Where it may be substituted, it may be substituted by a Ch alkyl group which may be substituted by a hydroxyl group or an il atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy group)), φ(5) Cw alkoxy ( The alkoxy group, at its substitutable position, may be substituted by a hydroxyl group, a halogen atom, a cyano group, and may contain one to four hetero atoms selected from the group consisting of N, 0 and S. a 5- to 6-membered aromatic ring group (wherein the aromatic ring group may be substituted at the position where it may be substituted with a C!-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be via a hydroxyl group or a halogen atom Substituted G-3 alkoxy, hydroxy, || atom, cyano, 13 323256 201206906 -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0 )N RcRd, -SGO^NRf, -S(=0)mRb or -NRcRd), or a 3 to 6 member saturated aliphatic ring which may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S The aliphatic ring group, at the position where it can be substituted, may be substituted by a Cm alkyl group which may be substituted by a hydroxyl group or a functional atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, or a hydroxyl group. , i atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), • ( 6) Cw alkylthio group (the alkylthio group, at its substitutable position, may be substituted by a group: a halogen group, a cyano group, or a group selected from N, 0 and S a group of 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms (the aromatic ring group, at its substitutable position, may be substituted by the following φ: G-3 which may be substituted by a hydroxyl group or a halogen atom Alkyl group, C!-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb , -C(=0)NRcRd, -S(=0)mNRcRd, -S〇0)mRb or -NRcRd), or may contain 1 to 2 selected from the group consisting of N, 0, and S a 3- to 6-membered saturated aliphatic ring group of a hetero atom (the aliphatic ring group, at the position where it may be substituted, may be substituted by a 0-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be a hydroxyl group Or a halogen atom substituted by a Ci-3 alkoxy group, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0) NRcRd, 14 323256 201206906 -NITRd or pendant oxy)), (7) 5 to 6 membered aromatic ring groups which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S A cyclyl group, at a substitutable position thereof, may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a thiol group, Halogen atom, • cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NReRd, -S(=0)mNRcRd, -5( =0)# or --NRcRd), (8) A 3 to 6 member saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group) , where it can be substituted, may be substituted by: G-3 alkyl (the alkyl group may be substituted by a hydroxyl group or a halogen atom),

Ci-3 alkoxy (which may be substituted by a hydroxyl group or a halogen atom), hydroxyl group, _ atom, cyano group, 15 323256 201206906 -NRaC(=0)Rb, -NRaS(=0)mRb, -C( =0) 0Rb, -C(=0)NReRd, -NReRd or side oxy), (9) -NRaRe > (10) -0C(=0)NRcRd ' • (11) -C(=0)Rf , (12) -S(=0)mRg, (13) mercaptan, (14) pendant oxy, (15) nitro, (16) -NRaC (=0) Rb, (17) -NRaC (=0 NRcRd, φ (18) - NRaS (=0) mRb, (19) - C (=0) 0Rb and (20) - C (=0) NRcRd, R1 of which may contain a selected from N, 0 and S The 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group may be substituted by 1 or a plurality of substituents selected from the group consisting of the substituents in Listing 3, and the substituents are listed in Figure 3: ) hydroxy, (2) halogen atom, 16 323256 201206906 (3) cyano, (4) Ch alkyl (the alkyl group, at its substitutable position, may be substituted by: a group, a halogen atom, a cyanogen a 5- to 6-membered aromatic ring group which may contain from 1 to 4 heteroatoms selected from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, may be subjected to Substituted: can be replaced by a hydroxyl group or a halogen atom a G-3 alkyl group, a Cl-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a trans group, a _ atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C( =0) 0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or -NRcRd), or may contain a group selected from the group consisting of N, 0, and S a 3 to 6 membered saturated aliphatic ring group to 2 heteroatoms (wherein the aliphatic ring group may be substituted at the position where it may be substituted with a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, ^ G-3 alkoxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C which may be substituted by a hydroxyl group or a halogen atom 〇0) NRcRd, -NReRd or pendant oxy)), (5) Cm alkoxy group (the alkoxy group, at its substitutable position, may be substituted by: hydroxy group, halogen atom, cyano group, 5 17 323256 201206906 to 6-membered aromatic ring group containing a group of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, may be subjected to the following Substituted: Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)nRb or -NRcRd Or a 3 to 6 membered saturated aliphatic ring group of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group, at a position where it can be substituted, may be Substituted by: G-3 alkyl which may be substituted by a hydroxyl group or a halogen atom, • Ch alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, - NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (6) G-6 alkylthio (the alkylthio group, in The substitutable position may be substituted by: a radical, a halogen atom, a cyano group, and 5 to 6 member atoms which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S. a cyclic group (the aromatic ring group, at the position where it can be substituted, may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a functional atom, a 0-3 alkane which may be substituted by a hydroxyl group or a halogen atom Oxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd , -S(=0)mRb or -NRcRd) Or a 3- to 6-membered saturated aliphatic ring group of one to two heteroatoms selected from the group consisting of N, 0, and S (the aliphatic ring group may be substituted at the position of 18 323256 201206906, It can be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a |S atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a li atom, a cyano group, -NRaC (=0) Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy group)), (7) may contain selected from N, 0 and S 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group (the aromatic ring group, at its substitutable position, may be substituted by: G which may be substituted by a hydroxyl group or an i atom -3 alkyl, • G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a trans group, a halogen atom, a cyano group, -NRaC(=0)Rb, '-NRaS(=0)nRb, -C( =0) 0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -SOO^Rb or -NRcRd) ' (8) may contain a group selected from N, 0, and S A 3 to 6 membered saturated aliphatic ring group of two heteroatoms (the aliphatic ring group, at its substitutable position, may be substituted by:

Cw alkyl (the alkyl group may be substituted by a hydroxyl group or an i atom),

Ci-3 alkoxy group (the alkoxy group may be substituted by a hydroxyl group or an i atom), 19 323256 201206906 via group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C (=0)0Rb, -C(=0)NRcRd, -NReRd or • Side oxy), (9) -NRaRe, (10) -0C(=0)NRcRd, (11) -C(=0)Rf , (12) -S(=0)raRg, (13) mercaptan, (14) nitro, φ (15) -NRaC(=0)Rb, (16) -NRaC(=0)NRcRd, (17) -NRaS (=0) mRb, (18) -C〇0)0Rb, (19) -C〇0)NRcRd and (20) -S(=0)mNRcRd, R2 represents a hydrogen atom, a halogen atom, a cyano group or G-3 alkyl (the alkyl group may be substituted by a hydroxyl group, a halogen atom, -NReRd, -0Ra, -0C(=0)Ra), and R3 and R4 each independently represent a hydrogen atom or a Ch alkyl group (the alkyl group may be Hydroxyl 20 323256 201206906 base or halogen atom substituted), "represents a group of 5 to 6 shell-cyclic groups which may be selected from the group consisting of ^ and "composed groups ^ to ^ heteroatoms (the aryl group, in position and The above-mentioned positions are substituted by the following: a group or a tooth atom substituted with one of a group, a group or a tooth atom substituted with a & oxy group, a trans group, a halogen atom, a cyano group, a nitro group, a phenyl group, Cao c (= Q) Rh, _n - body: (four) NirR d, -C(=0)NReRd, _c(=〇)〇Ra, c(=〇)Ra, ... -S(=0)mNRCRd, _S(=0)nRh or _NRcRd), L means -m contains a 6-membered aromatic ring group of 1 to 4 nitrogen atoms, the following formula PyH, the following formula TrM or the following formula:

Tri-1

Imi-1 (in each group, the bond 1 represents a bond with the dihydrogen money, and the bond 2 and the "bond U" and independently represent the selected from the group (4), the base, and the ? 〇 "The group consisting of 2 or a plurality of substituents substituted by k-alkyl or c2_6 alkenyl, (4), -C(=〇)^ can be selected from the following 6-membered aromatic ring group Substituted position, substituted by 1 or a plurality of substituents selected from the group consisting of: a composition of ruthenium, a hydroxyl group, 'W, -C(=0)NRH-C(=0)0Ra, Nansu, 1 or a plurality of substituents substituted by Ch alkyl or C2-6 alkenes and one, -c(=0)0ir, hydroxyl, _NRCRd, nitro 21 323256 201206906

Ar2 represents a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may be at one position above its replaceable position) Substituted by a Ci-6 alkyl group which may be substituted by a hydroxyl group, a cyano group or a halogen atom, a G-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group, - NRaC (=0) Rh, -NRaS (=0) mRh, -NRaC (=0) NRcRd, -C (=0) NRcRd, -C (=0) 0Ra, -C (=0) Ra, -S ( =0)raNRcRd, -S(=0)nRh or -NRcRd),

Re means • Helium atom,

Cl-6 alkyl group (the alkyl group may be substituted by a base group, a nitrogen group, a halogen atom, a Cl-3 alkoxy group or a -NReRd), -A ' -C(=0)-A,

Ci-6 alkylcarbonyl (the alkyl portion of the alkylcarbonyl group may be substituted by a hydroxyl group, a halogen atom, a cyano group, a G-3 alkoxy group or a -NReRd), φCh alkoxycarbonyl group (the alkoxycarbonyl group) The alkyl moiety may be substituted by a hydroxyl group or a halogen atom), -C(=0)NReRd or -S(=0).Rb,

Rf represents a hydrogen atom, a meridine,

Cl-6 alkyl group (the alkyl group may be substituted by a base group, a nitrogen group, a halogen atom, a Cl-3 alkoxy group or a -NReRd), 22 323256 201206906

Cl-3 alkoxy group (the alkoxy group may be substituted by a phenyl group, a phenyl group, a cyano group, a halogen atom, a CH alkoxy group or a —nw) which may be substituted by a methoxy or a stone succinyl group, A or -NRaRi, indicating the base,

a Ci-e alkyl group (which may be substituted via a thiol group, a cyano group, a _ atom, a hydrazine -3- alkoxy group or a -NReRd), a spring-A or a -NRaRi,

Rh represents a Cl-6 group which may be substituted by a radical or a halogen atom, and f represents a nitrogen atom,

Cl-B alkyl (which may be substituted via a thiol, cyano, _ atom, C1-3 alkoxy, C3_6 cycloalkyl or -NReRd), • A'-C(=0)Rb, - C(=0)A or C!-6 alkylcarbonyl (the alkyl moiety of the group may be substituted by a hydroxyl group, a halogen atom, a nitrogen group, a Cm alkoxy group or a -NReRd), and A and A' respectively represent independently A 5- to 6-membered aromatic ring group of one to four heteroatoms selected from the group consisting of N, 0 and S (the aromatic ring group ' may be substituted at the position where it may be substituted: a Cw alkyl group substituted by a hydroxyl group or a functional atom, a Cw alkoxy group which may be substituted by a radical 323256 23 201206906 or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -C(=〇)〇H or -NReRd), or a 3 to 6 membered saturated or 4 to 6 membered unsaturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group, which may be substituted The position may be replaced by a C!-3 alkyl group which may be substituted with a hydroxyl group or a !I atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a tooth atom, a hydroxyl group, a halogen atom, a cyano group, or -C ( =0) 0H, -NRcRd or pendant oxy),

Ra represents a hydrogen atom or a Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom, and Rb represents a hydrogen atom, a Ch alkyl group which may be substituted by a hydroxyl group or a halogen atom, a benzoquinone group which may be substituted by a methoxy group or a nitro group or may be The (^-63⁄4 alkyl group) and the Rd substituted by a radical or a _ atom respectively represent a hydrogen atom or a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, or may form a bond N together, and may further contain a 4- to 6-membered saturated or unsaturated aliphatic cyclic group of one to two heteroatoms selected from the group consisting of N, hydrazine, and s (the aliphatic ring group, at its position _ where it can be substituted by Ci) -e thiol, hydroxy, halogen or pendant oxy group), m represents an integer 1 or 2, η represents an integer 〇 to 2, and then q represents an integer 〇 to 2]. [Item 2] Item 1 a compound or a physiologically acceptable salt thereof, wherein R represents -C(=〇)NRa-, -S(=0)2NRa-, -C(=〇)〇-, -◦(=〇)_, - S (=C〇2- or a single bond, R represents a hydrogen atom, a Cl-10 alkyl group, a C2-6 alkenyl group, and may contain a group selected from the group consisting of n, 〇323256 24 201206906 and s to 2 5 3 to 6 members of β I solid heteroatoms And or a 4 to b member unsaturated aliphatic cyclic group, which may contain 5 to 6 membered aromatic ring groups of 1 to 4 heterocyclic hetero atoms selected from the group consisting of N, 0 and S, The main elemental soil and the base material may be substituted at a position which can be substituted by a group selected from the group consisting of π early 4 or a plurality of substituents. Substituent List 4: (1) Hydroxyl group , (2) halogen atoms,

(3) Cyano group, (4) Ci-6 alkoxy group (the alkoxy group, at the position where it can be substituted, may be substituted by the following: a group, a _ atom, a chaotic group, or a group 3; 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group consisting of 〇 and S (the aromatic ring group, at the position where the oxime is substituted, may be substituted by: hydroxy or The 〇-3 alkyl group substituted by a functional atom may be substituted with a hydroxyl group or a ί atom to form an alkoxy group, a trans group, a halogen atom, a cyano group, ~NRaC(=〇)Rb. ~NRaS(=0)mRb. -C(=0)〇Rb ' -C(=〇)NRcRd >=〇Rd, 冬〇)mRb or __), or σ each has a group of 1 from N, 〇 and S 3 members of the two heteroatoms are saturated with the aliphatic ring group (the aliphatic ring group, at its substitutable position) can be substituted by the following: C can be substituted by silk or i atom, _ Substituted by a base or a tooth atom, a methoxy group, a thiol group, a _ atom, a cyanide 25 323256 201206906 base, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C( =0) NRcRd, -NReRd or pendant oxy)), (5) Cl-6 alkylthio (the alkylthio group, at its substitutable position, may be substituted by: a group of 5 to 6 membered aromatic ring groups (which may be substituted in the group of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S) The position may be substituted by a 0-3 alkyl group which may be substituted by a hydroxyl group or an atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, an i atom, a cyano group, -NRaC ( =0) Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or -NRcRd), or a 3- to 6-membered saturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0, and S (the aliphatic ring group may be substituted at the position φ, which may be subjected to The substitution: a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or an atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, - NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (6) may contain a group selected from N, 0 and S. 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms (the aromatic ring group, at the position where it can be substituted, may be substituted by: G which may be substituted by a hydroxyl group or a halogen atom -3 alkyl, Ch alkoxy which may be substituted by a hydroxyl group or a halogen atom, 26 323256 201206906, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(= 0) 0Rb, -C(=0)NRcRd ' -S(=0)mNRcRd ' • -S(=0)mRb or -NRcRd), (7) may contain a group selected from N, 0, and S A 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms (the aliphatic ring group, at its substitutable position, may be substituted by:

Cl-3 alkyl (the alkyl group may be substituted by a hydroxyl group or a halogen atom),

Ci-3 alkoxy group (the alkoxy group may be substituted by a hydroxyl group or a _ atom), φ hydroxy group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0 ) 0Rb , -C(=0)Rb , -C(=0)NReRd, -NReRd or 27 323256 201206906 side oxy), (8) -NRaRe > (9) -0C〇0)NRcRd, (10) -C(=0)Rf, (11) -SCRl (12) a mercaptan, the 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring group of R1, which may be selected from a position at which it may be substituted Substituent group 5 consists of group 1 or a plurality of substituents substituted, substituents list 5: (1) hydroxyl group, (2) halogen atom, (3) cyano group, (4) Ch alkyl group (the alkane) a group, at a substitutable position thereof, may be substituted by: φ hydroxy group, halogen atom, cyano group, 5 to 6 which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S Aromatic cyclic group (wherein the aromatic ring group may be substituted at the position where it may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, or a Cl- group which may be substituted by a hydroxyl group or a halogen atom 3 alkoxy, meridin, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(= 0) nNRcRd, -S(=0)mRb or -NRcRd), or 28 323256 201206906 may contain 3 to 6 member saturated aliphatic ring groups of 1 to 2 heteroatoms selected from the group consisting of N, 0 and S ( The aliphatic cyclic group may be substituted at the position where it may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen group. Atom, cyano group, -NRaC(=0)Rb, -NRaS〇0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (5) G- 6 alkoxy group (wherein the alkoxy group may be substituted at the position where it may be substituted: _ hydroxy group, halogen atom, cyano group, may contain a group selected from N, 0 and S 5 to 6 membered aromatic ring groups of 4 heteroatoms (the aromatic ring group, where it may be substituted, may be substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be via a hydroxyl group or Ci-3 alkoxy group substituted with a halogen atom, a hydroxyl group, a halogen atom, a cyano group, ▲-NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0) NRcRd, W . -S(=0)mNReRd, -S(=0)mRb or -NReRd), or may contain a group selected from N, 0, and S a 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms (the aliphatic ring group, at the position where it can be substituted, may be substituted by a G-3 alkane which may be substituted by a hydroxyl group or a halogen atom a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, - C(=0)NRcRd, -NReRd or pendant oxy)), (6) Ch alkylthio group (the alkylthio group, at its substitutable position, may be substituted by 29 323256 201206906: a halogen atom, a cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, in its replaceable position) , may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, • -NRaC (= 0) Rb ' -NRaS(=0)mRb ' -C(=0)0Rb ' -C(=0)NRcRd ' -S(=0)mNReRd, -S(=0)mRb or -NReRd is substituted), or a 3 to 6-membered saturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0, and S (the aliphatic ring group) Where it may be substituted, it may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, I-NReRd or pendant oxy)), (7) may contain a selected from N, 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group consisting of 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: hydroxy or _ Atom-substituted C!-3 alkyl group, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, 30 323256 201206906 -NRaC(=0)Rb, -NRaS(=0) mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or -NRcRd), (8) may contain selected from N, 0 and S One to two heteroatoms of the group consisting of 3 to 6 members of the saturated aliphatic ring group (the aliphatic ring group, at its substitutable position, may be substituted by:

Ch alkyl (the alkyl group may be substituted by a hydroxyl group or a _ atom), 0-3 alkoxy group (the alkoxy group may be substituted by a hydroxyl group or a _ atom), a hydroxyl group, a halogen atom, a cyano group, ^ -NRaC (=0) ) Rb, -NRaS(=0)fflRb ' -C(:0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy), (9) -NRaRe, (10) -0C(=0) NRcRd ' (11) -C(=0)Rf, 31 323256 201206906 (12) -S(=0)fflRg, (13) mercaptan and (14) pendant oxy group, R1 of which may contain a selected from N, 0 And 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group consisting of S, may be substituted with 1 or a plurality of substituents selected from the group consisting of the substituents in Listing 6, substituents : (1) a hydroxyl group, a (2) _ atom, (3) a cyano group, (4) a Cw alkyl group (the alkyl group, at the position where it can be substituted, may be substituted by: a group, a halogen atom, The cyano group, ^ may contain a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms selected from the group consisting of N, 0, and S (the aromatic ring group may be substituted at a position where it may be substituted Substituted: C!-3 alkyl group which may be substituted by a hydroxyl group or a tooth atom, Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom Cyano, -NRaC(=0)Rb ' -NRaS(=0)mRb ' -C(=0)0Rb ' -C(=0)NRcRd > -SkO^NRf, -S(=0)mRb or - NRcRd), or a 3- to 6-membered saturated aliphatic ring group of one to two heteroatoms selected from the group consisting of N, 0, and S (the aliphatic ring group, in its replaceable position, Substituted by: Ch alkyl substituted by hydroxy or _ atom, 32 323256 201206906 Cl-3 alkoxy group substituted via a radical or a halogen atom, a trans group, a halogen atom, a cyano group, -NRaC〇0 Rb, -NRaS (=0) mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (5) Cl-6 alkoxy group (the alkoxy group) , at its substitutable position, may be substituted by: a hydroxyl group, a halogen atom, a cyano group, or a 5 to 6 member which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S An aromatic cyclic group which, at its substitutable position, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or an atom, and a 0-3 which may be substituted by a hydroxyl group or a halogen atom. Alkoxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0) ENReRd, -S(=0)mRb Or -NRcRd), or a 3 φ to 6-membered saturated aliphatic ring group of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group, which may be substituted The position may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cm alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC (=0) Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (6) Cl-6 alkylthio (the alkyl sulphur The group, at its substitutable position, may be substituted by: hydroxy, halogen atom, 33 323256 201206906 cyano group, which may contain 1 to 4 heteroatoms selected from the group consisting of N, 0 and S To a 6-membered aromatic ring group (wherein the aromatic ring group may be substituted at the position where it may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be substituted by a hydroxyl group or a halogen atom Cm alkoxy group, hydroxyl group, atom, cyano group, -NRaC(=0)Rb, -NITSOO^Rb, -C(=0)0Rb, -C〇0)NRcRd, -S(=0)raNRcRd, -S (=0)mRb or -NRcRd), or may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S • Up to 6 members of a saturated aliphatic ring group (the aliphatic ring group, at its substitutable position, may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be via a hydroxyl group or an iS atom Substituted C!-3 alkoxy, hydroxy, _ atom, cyano, -NRaC(=0)Rb, -NRaS(=0)raRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (7) may contain a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, The substitutable position may be substituted by: C!-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyanogen Base, -NRaC(=0)Rb ' -NRaS〇0)mRb, -C(=0)0Rb, 34 323256 201206906 -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0) mRb or -NRcRd), (8) may contain a 3 to 6 member saturated aliphatic ring group of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group may be The location of the replacement can be replaced by:

a Ci-3 alkyl group (the alkyl group may be substituted by a hydroxyl group or a functional atom), a stilbene Cl-3 alkoxy group (the alkoxy group may be substituted by a via group or a halogen atom), a via group, a halogen atom, a cyano group, NRaC(=0)Rb, -NRaS(=0)mRb > -C(=0)0Rb, • -C(=0)NReRd, -NReRd or pendant oxy), (9)-NRaRe ' (10) -0C(=0)NRcRd ' (11) -C(=0)Rf, (12) -S(=0)mRg, (13) mercaptan and (14) nitro, 35 323256 201206906 R2 represents a hydrogen atom, a halogen atom, a cyano group or a Cl-3 alkyl group (the alkyl group may be substituted by a halogen atom, -NRcRd, -0Ra or -〇(:(=〇))3, and R and R each independently represent a nitrogen atom or a Ci- 3 alkyl (the alkyl group may be substituted by a base or a tooth atom),

Ar1 represents a benzene ring or an acridine ring (the benzene ring and the acridine ring are each independently, and at a position where they can be substituted, one position or more may be substituted by a Ci-6 group which may be substituted by a hydroxyl group or a halogen atom, C1-3 alkoxy group, hydroxyl group, halogen atom, cyano group, nitro group, phenyl group, -NRaC(=〇)Rh, -NRaS(=0)mRh '-NRaC(=) which may be substituted by a radical or a halogen atom 〇)NRcRd ^ -C(=0)NRcRd ' -C(=0)0Ra ' -C(=0)Ra, -S(=0)nNRcRd, -S〇〇)nRh or -NRcRd) ' L indicates a 6-membered aromatic ring group having 1 to 4 nitrogen atoms, Pyr-Ι having the following formula, Tri-Ι or the following formula Imi-1:

• (In each group, the bond 1 represents a bond with the dihydropyrimidinone ring, the bond 2 is linked to the Ar2 bond, and Z, Z2 and Z3 are independently represented by a ring atom, C(=0) a group consisting of NReRd and -C(=0)0Ra, t-hydroxyl group, -NReRd, - or a plurality of substituents substituted by Cm alkyl or (^6 alkenyl, halogen, -C(=0)NRcRd, -C(=0)〇Ra, hydroxy, _NRCRd or a hydrogen atom), Ci substituted by one or a plurality of substituents selected from the group consisting of a halogen atom, a hydroxyl group, a -NRCRci, a _C(;=())NRCI Here, when L is a 6-membered aromatic ring group, at the position where it can be substituted, it may be substituted with a group or a plurality of substituents selected from the group consisting of: - C〇0) NReRd and - c(=〇)ORv/t !·Substituting Ci~6 alkyl or (^2_6 dilute 323256 36 201206906 base, halogen, -C(=0)NReRd, -C(=0)0Ra, hydroxyl, -NW, Nitro and -NRaC(=0)Rb,

Ar2 represents a benzene ring or an acridine ring (the benzene ring and the acridine ring are each independently, and at a position where they can be substituted, one position or more may be substituted by a C!-6 alkane which may be substituted by a hydroxyl group or a halogen atom. a Ci-3 alkoxy group which may be substituted by a hydroxyl group or an atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group, -NRaC(=0)Rh, -NRaS(=0)mRh, -NRaC(=0)NRcRd , -C(=0)NRcRd, -C(=0)0Ra, -C(=0)Ra, -S(=0)mNRcRd, -S(=0)nRh or -NRcRd),

Re means 氲 atom,

Ci-6 alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a halogen atom, a Ci-3 alkoxy group or -NReRd), -A, -C(=0)-A',

Cl-6 alkyl group (the alkyl group of the alkyl group may be substituted by a group, a halogen atom, a cyano group, a Cu alkoxy group or a -NReRd), an anthracene-6 alkoxycarbonyl group (the alkoxy group) The alkyl portion of the carbonyl group may be substituted by a hydroxyl group or a halogen atom), -C(=0)NReRd4 -S(=0)mRb,

Rf represents a hydrogen atom, a trans group, a 0-6 alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group, a halogen atom, a Cm alkoxy group or 37 323256 201206906 -NReRd),

Cl-3 alkoxy group (the alkoxy group may be substituted by a phenyl group, a hydroxyl group, a cyano group, a halogen atom, a G-3 alkoxy group or a -NReRd) which may be substituted by a decyloxy group or a nitro group. , -A or -NRaRi,

Rg represents a hydroxyl group,

Cl-6 alkyl (which may be substituted via a base, an aryl group, a halogen atom, a Cl-3 alkoxy group or a spring-NReRd), _A or -咿,

Rh represents a Ci-6 alkyl group which may be substituted by a hydroxyl group or a _ atom, and R1 represents a hydrogen atom,

Cl-6 alkyl (this alkyl group may be substituted via a thiol group, a cyano group, a functional atom, a Cl-3 alkoxy group or a φ-NReRd), -A, -C(=0)A' or a 匕-6 alkyl group a carbonyl group (the alkyl moiety of the group may be substituted by a hydroxyl group, an iS atom, a cyano group, a Cu alkoxy group or a -NReRd), and A and A' each independently represent a group selected from the group consisting of N, 0 and S. a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms (wherein the aromatic ring group may be substituted at the position where it may be substituted with a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, Cm or -MeRd) which may be substituted by hydroxy 38 323256 201206906 or i atom, or

The alkanoyl group, the hydroxyl group, the halogen atom, and the cyano-C(=〇)〇H may each have a group of one to two heteroatoms selected from the group consisting of N 〇 and $, and 3 to 6 members of the saturated I aliphatic group. The base (the aliphatic ring group, at the position where i can be substituted) may be substituted by a C4 group which may be substituted by a radical or an atom, a radical which may be substituted by a radical or a hydrazine, Secret, _ atom, I group, -C(=0)0H, -NRT or pendant oxy), • \ table = atom or Cl_6 alkyl group which can be substituted by a radical or from an atom 'R represents a hydrogen atom, can be a hexyl group substituted by a group or a _ atom, or a phenyl fluorenyl group substituted by a hydrazine or a nitro group, and R and R are represented by an oxygen atom or may be substituted by a via group or a halogen atom (: Alternatively, it may form a bond containing n, and may further contain from 1 to 2 heteroatoms selected from the group consisting of dips and 8 groups, and 4 to 6 members of the aliphatic group. A family of ring groups, at positions where they can be substituted, may be substituted by a C1-6 alkyl group, a hydroxyl group or a _ atom), • m represents an integer of 1 or 2, and then η represents an integer 〇 to 2. [Item 3] Item 1 Or the compound described in item 2 or a physiologically acceptable salt, wherein R represents a Ci-1() alkyl group (the group may be substituted by i or a plurality of substituents as described in the substituent 4), CM alkenyl (the group may be substituted by the list 4) 3 or 6 member-saturated or 4 to 6-membered unsaturated aliphatic ring groups of 1 to 2 hetero atoms selected from the group consisting of N, 0 and s, substituted with 1 or a plurality of substituents described) (The group may be substituted by i 323256 39 201206906 substituents as described in the substituent list 5), or may contain a 5- to 6-membered aromatic ring group selected from the group consisting of N, anthracene and S. The base may be substituted by [1 or a plurality of substituents in Item 6]. The compound described in any one of Items 1 to 3 or the physiologically 5 salt thereof, wherein 'R2' is selectable From the _ atom, -NRcRd, -〇Ra, and -0c (=G) Ra^, the axis 1 or the Wei taken from the Cl_ alkyl group or the hydrogen atom.

[Item 5] The compound according to any one of Items 1 to 4, wherein the Ari represents a benzene ring or a pyridine ring, and the benzene ring or the pyridine ring is independent, and can be substituted therein. The position may be substituted by the same or different 1 to 3 substituents selected from the group consisting of: 可 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom; An anthracene-6 alkyl group, a C3 alkoxy group, a hydroxyl group, a tooth atom, a cyano group, a nitro group, a phenyl group, which may be substituted with one or a plurality of substituents selected from the group consisting of a hydroxyl group and a _ atom. C(=0)NRcRd, -c(=〇)〇Ra, _C(=0)Ra, _s(=〇)nRh and _NRCRd). [Item 6] The compound described in any one of Items 1 to 5, or a physiological salt thereof, wherein

Ar1 represents the following formula Ar1-;!:

323256 40 201206906 (in the base, Κ 1, Κ 2, K3 and K4 when Ar1 is a benzene ring, all represent a carbon atom 'when Ar1 is a pyridine ring', then only one represents a nitrogen atom, the others represent a carbon atom, and X represents a Cw alkyl group substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom, and a Cl_3 alkyl group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a !| atom Oxy group, hydroxyl group, halogen atom, cyano group, nitro group, phenyl group, _C(=〇)NRcRd, -C(=0)0Ra, -C(=0)Ra, -S(=0)nRh or -NRcRd Substituent,

The substitutable position of K to κ4, substituted by the same or different 1 to 2 substituents of the group consisting of: 1 or a plurality of groups selected from the group consisting of a hydroxyl group and a tooth atom a substituent-substituted Ci-6 alkyl group which may be substituted with one or more substituents selected from the group consisting of 26 groups and a ruthenium atom

Cl-3 alkoxy group, hydroxyl group, halogen atom, cyano group, nitro group, -C(=0)NRcRd, C(-0)0Ra, _c(=〇)Ra, _s(=〇)nRh and _NRCRd) . [Item 7] - a compound according to any one of items 1 to 6 or physiologically: a salt thereof, wherein 'Αϊ*2 indicates a benzene ring or a pyridine ring (the benzene ring or the pyridine ring is another) independent Where it may be substituted, it may be substituted with one or three substituents selected from the group consisting of: the same or different: one group selected from the group consisting of a hydroxyl group and a * atom Or a plurality of substituent-substituted Cw alkane may be substituted by a group of 1 or a plurality of substituents selected from the group consisting of a group of a halogen group and a halogen atom, a carboxyl group, a sulfhydryl group, a sulfonyl group, a succinyl group, and a sulfonyl group. , C(~〇)NR Rd, ~C(=0)〇Ra, -C(=〇)Ra, -S(=0)nRh and -NRcRd). [Item 8] Page Q 1 ^ The compound described in any one of the items 7 or its physiological condition 41 323256 201206906 Permissible salt, wherein

Ar2 represents the following formula Ar2-1:

(In the base, when L1, L2, L3 and L4 are in the benzene ring, all represent a carbon atom. When the ratio is pyridine, only one represents a nitrogen atom, and the others represent a carbon atom, and Y represents a hydroxyl group and a group consisting of a halogen atom or a plurality of Ci-6 alkyl groups substituted with a substituent, substituted by one or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom, C!-3 Alkoxy group, hydroxyl group, halogen atom, cyano group, nitro group, -COCONITRd, -C(=0)0Ra, -C(=0)Ra, -S(=0)nRh or -NRf, L1 to L4 The position of substitution, the same or different 1 to 2 substituents of the group consisting of 0-6 which may be substituted by 1 or a plurality of substituents selected from the group consisting of hydroxyl and _ atoms An alkyl group, a G-3 alkoxy group, a hydroxyl group, a halogen atom, a cyano group, a nitro group, a -C〇0) which may be substituted with one or a plurality of substituents selected from the group consisting of a hydroxy φ group and a halogen atom. NReRd, -C(=0)0Ra, -C(=0)Ra, -S(=0)nRh, and -NRcRd). [Item 9] The compound according to any one of Items 1 to 8, or a physiologically acceptable salt thereof, wherein the formula (I) is represented by the following formula (Γ): 42 323256 201206906

Ar1

[In the formula, L represents a benzene ring or a pyridine ring, and the position of the ring and the dihydrogen is bonded to the ortho position of the ring and the A〆 bond, and the benzene ring and the bite ring are independent, respectively. The position of substitution may be substituted by one or more substituents selected from the group consisting of: i atom, hydroxyl group, -NRf, _c(=〇)NRCRd&-C(=〇) One group or a plurality of substituents consisting of 〇RV/f substituted by Ci 6 alkyl, halogen, -C(=0)NR Rd, -C(=〇)〇Ra, _NRCRd, nitro and _ =〇. [Claim 10] The compound according to any one of items 1 to 9 or a physiologically acceptable salt thereof, wherein L is an unsubstituted benzene ring or a pyridine ring. [Item 11] The compound according to any one of Items 1 to 8, or the physiological salt thereof, wherein L represents Pyr-Bu Tri-Ι or Imi-Z, Z2 and Z3 represent a hydrogen atom. [Item 12] The compound according to any one of Items 1 to 8, or a physiologically acceptable salt thereof, wherein L represents Pyr-Bu Tri-Ι or Imi-Bu Z1, Z2 and z respectively represent independently selectable One or a plurality of substituents consisting of _NRCRd and a halogen atom are substituted with a Cl_6 alkyl group, _NReRd or a halogen. 43 323256 201206906 [Item 13] The compound of any one of items 1 to 8, or a physiologically acceptable salt thereof, wherein L represents Pyr-1, Tri-1 or Imi-1 'Z1, Z2 and Z3, respectively Independently denotes Cw alkyl or -C(=0)NReRd which may be substituted by -C(=0)NReRd. [Item 14] The compound according to any one of Items 1 to 8, or a physiologically acceptable salt thereof, wherein L represents Pyr-Ι, Tri-Ι or Imi-1, and Z1, z2 ® and Z3 are independently represented The Cl-6 alkyl group, the hydroxyl group or the -C(=0)0Ra may be substituted with one or a plurality of substituents selected from the group consisting of a hydroxyl group and -C(=0)0Ra. [Claim 15] The compound according to any one of items 1 to 14, wherein R1 represents a substituted one or a plurality of substituents at the position where it can be substituted. a group-substituted alkyl group, or a group which may be substituted at the position where it may be substituted with 1 or a plurality of substituents as described in the following Listing 5 may contain a group selected from the group consisting of N, 0 and S 3 to 6 members of two heteroatoms are saturated aliphatic ring groups. The compound of any one of items 1 to 15 or a physiologically acceptable salt thereof, wherein R represents a Ci-io alkyl group (the alkyl group may be substituted at a position at which it may be substituted) Substituted by a group consisting of 丨 or a plurality of substituents in the group of Listing 7, Substituent Listing 7: 44 323256 201206906 (1) Hydroxyl, (2) Halogen, (3) Cyano, (4) Cm alkoxy ( The alkoxy group, at the substitutable position thereof, may be substituted with one or a plurality of substituents selected from the group consisting of: a base group, a tooth atom, a cyano group and

3 may have from one to two heteroatoms selected from the group consisting of N, G and s to a 6-membered saturated aliphatic ring group (the aliphatic ring group, which may be substituted, may be selected from Group 1 or a plurality of substituents consisting of the following faces, a group consisting of 1 or a plurality of (10) groups of atoms or a plurality of substituted wires ft from the group and (4), a group consisting of: 2: ;r;NR8S(=0)-Rb'-C(=〇)o----- 'At its substitutable position, or a plurality of substituents substituted: 3' in 1 to 2 heteroatoms The substitutable or plural substituents may be taken from (5) ksixian (transalkylthio group is selected from the group consisting of: hydroxyl group, halogen atom, cyano group and to = 〇 and surface group) ' can be selected from tantalum; 323256 45 201206906 generation: a G-3 alkyl group which may be substituted with one or more substituents selected from the group consisting of a trans group and a halogen atom, may be selected from a hydroxyl group and a group consisting of a halogen atom or a plurality of substituents substituted with a Ci-3 alkoxy group, a hydroxyl group, a functional atom, a cyano group, -NR C(-〇)R, -NR S(=〇)mRb, - c(=〇)〇Rb, _c(=〇)NRcRd, -NReRd and pendant oxy)), ( 6) a 5 to 6 membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, at a position where it may be substituted, may be selected from Substituting or plural substituents of the group consisting of: a Cl-3 alkyl group which may be substituted with one or a plurality of substituents selected from the group consisting of «and a halogen atom, may be selected And (4) a group consisting of i or a plurality of substituents substituted with a Cl-3 alkoxy group, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=〇)Rb, -NRaS(=〇)mRb > - C(=〇)〇Rb > -C(=〇)NRcRd. _S(=〇)raNRcRd , - S(=〇)-Rl -NRcRd) ' (7) Two contains two 1 from N:. and: The stomach of the 1 to 2 heteroatoms of the group and the alicyclic group of (10) are (4) ring groups, and at the position of 323256 46 201206906 which can be substituted, may be substituted by 1 or a plurality of groups selected from the group consisting of Base substitution: a Cl-3 alkyl group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom, or 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom Substituted Cl-3 morphoxy, meridine, halogen atom, • cyano group -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRe > -C(=0)Rb, -NReRd and φ side oxy) (8) -NRaRe, (9) -0C (=0)NRcRd > (10) -C(:0)Rf, (11) -S(=0)mRg& (12) Mercaptan. [Item 17] The compound according to any one of Items 1 to 16, or a physiologically acceptable salt thereof, wherein 47 323256 201206906 R1 represents Cl-ι. A thiol group (wherein the alkyl group is substituted at the position where it can be substituted by 1 to 3 substituents selected from the group consisting of the substituents in Listing 8, the substituents are listed in Figure 8: (1) hydroxyl group, (2) halogen atom (3) a cyano group, (6) a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may be The position of the substitution may be replaced by one or a plurality of substituents selected from the group consisting of: Cl- which may be substituted with one or more substituents selected from the group consisting of a hydroxyl group and an iS atom. a calcinyl group, a hydroxyl group, a halogen atom, a cyano group, a -NRaC (=0) Rb, which may be substituted with one or a plurality of substituents selected from the group consisting of a hydroxyl group and a tooth atom. -NRaS(=0)JRb, -C(=0)0Rb > -C(=0)NRcRd, -S(=0)mNrRd, -S(=0)nRb and -NRcRd), (7) may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S 48 323256 201206906 3 to 6 member saturated aliphatic cyclic group (the aliphatic ring group, at its substitutable position, may be selected from Substituting 1 or a plurality of substituents of the group consisting of: And a Cl-3 alkyl group substituted with one or a plurality of substituents of a group consisting of a halogen atom, and a Cl-3 alkoxy group substituted by one or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom Base, hydroxyl group, 1 halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)JRb, -C(=0)0Rb, -C(=0)NRcRd, -C(=0)Rb , φ -NReRd and pendant oxy), (8) -NRaRe and (10) -C(=0)Rf. [Item 18] The compound of any one of items 1 to 15 or physiologically acceptable thereof a salt, wherein R1 represents a substituent which may be substituted by one or a plurality of substituents as shown in the following Table 5, and may contain one to two impurities selected from the group consisting of N, 0 and S. The compound of any one of the items 1 to 15 and the physiologically acceptable salt thereof, wherein 3 is selected from the group consisting of the compound of the present invention. a 3 to 6-membered saturated aliphatic ring group of 1 to 2 solid heteroatoms of the group consisting of N, 0 and S (the saturated aliphatic ring group may be selected from the list of substituents) 1 or a plurality of 9 groups Substituent substitution, substituents Listing 9: (1) via group, (2) halogen atom, (3) cyano group, (4) Cm alkyl group (the alkyl group, at its substitutable position, may be selected from 1 or a plurality of substituents of the group consisting of: a hydroxyl group, a halogen atom, a gas group, a s having a hetero atom selected from the group consisting of N, G, and s a base group (in the place where it can be substituted, may be substituted with a hetero 1 or a complex number consisting of: a group selected from the group consisting of 1 or a complex naphthyl group; One or a plurality of alkoxy groups selected from the group consisting of silk and self-atoms, radicals, halogen atoms, cyano groups, NR S(=0)mRb ' -CC=0)0Rb , ~C(=〇) MRcRd > 323256 50 201206906 -s(|NRns(=〇)mRb and responsibility Rd) and 1 to 2 heteroatoms of the group consisting of N, Q & S 3 = shell saturated fat _ ring base _ fat _ base, in its substitutable position ^ y is replaced by a number of substituents selected from the group of μ face _ group to replace the beauty: t is selected from the group consisting of hydroxy and * atoms, or a plurality of whole soils a C,-3 alkyl group, which may be selected from the group consisting of (4) and a halogen atom. Substituents of Ci road group, group M, _ atoms,

C(=〇)Rb' ~NRas(=〇)^b' -C(=0)0Rb> -C(=〇)NRcRd. -NRR and pendant oxy)), 6 alkoxy groups a group, at a position where it may be substituted, may be substituted with one or a plurality of substituents selected from the group consisting of: a group, a halogen atom, a chaotic group, and a group of 3, N, and 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group consisting of s (the aromatic ring group, at a position where it can be substituted, may be selected from the group consisting of 1 or a plurality of substituent substitutions: a C 3 alkyl group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a base group and a tooth atom, may be selected from the group consisting of a hydroxyl group and an i atom 1 or a plurality of substituents substituted with 3 alkoxy groups, a transradical group, a tooth atom, a cyano group, -NR C(=〇)Rb > -NRaS(=〇)mRb , -C(=0)0Rb ^ -C (=0) NRcRd ' _s("Rd, -S(=〇)nRb and _N〇d) and 3 to 6 which may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and s a saturated aliphatic ring group (the aliphatic ring group, in its replaceable position 51 323256 201206906, may be selected from the group consisting of 1 or a plurality of substituent substitutions: an anthracene-3 alkyl group which may be substituted with one or more substituents selected from the group consisting of a hydroxyl group and a halogen atom, may be selected from the group consisting of a hydroxyl group and a halogen atom. Cm alkoxy substituted with a plurality of substituents, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd , -NReRd and pendant oxy)), (7) may contain a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, Where it may be substituted, one or a plurality of substituents may be substituted by a group selected from the group consisting of: 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a tooth atom; a Cl-3 alkoxy group, a C3 alkoxy group substituted by a group or a plurality of substituents selected from the group consisting of a hydroxyl group and a functional atom, a carboxyl group, a halogen atom, a cyano group, and an -NRaC ( =〇)Rb, -NRaS(=〇)»Rb' -C(=〇)〇Rb, -C(=〇)NRcRd, -S(=〇)^NRcRd' -S〇〇)»Rb and -McRd (8) may contain 1 to 2 heteroatoms selected from the group consisting of N, 0, and S. 323256 52 201206906 3 to 6 full And an aliphatic cyclic group (wherein the substitutable group may be substituted with one or a plurality of substituents selected from the group consisting of: a group selected from a hydroxyl group and a halogen atom; a group of 1 or a plurality of substituent-substituted Cl-3 alkyl groups, which may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom, alkoxy group, hydroxyl group, 1 Halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd and φ side oxy), (9) -NRaRe, (10) -0C (=0) NRcRd > (11) -C(=0)Rf, (12) -S(=0)mRg, and (14) pendant oxy group. [Item 20] The compound according to any one of Item 1 to Item 15, the item 18, or the physiologically acceptable salt thereof, wherein the R1 group may be substituted by the substituent 1 53 323256 201206906 a plurality of substituents substituted with a 3 to 6 membered saturated aliphatic ring group of 1 to 2 hetero atoms selected from the group consisting of N, hydrazine and S, the aliphatic ring group being a C 3-6 saturated carbocyclic ring , aziridines, azetidine, pyrrolidine, pipedine, propylene oxide, tetrahydrofuran, tetrahydrofuran a compound described in any one of items 1 to 20, or a physiologically acceptable salt thereof, wherein the compound is a tetrahydropyran, a morpholine or a piperazine.

Ra represents a hydrogen atom or a Cl_6 alkyl group which may be substituted with one or a plurality of substituents selected from the group consisting of a trans group and a fluorine atom,

Rb represents a Cl_6 alkyl group which may be substituted with hydrazine or a plurality of substituents selected from the group consisting of a hydroxyl group and a fluorine atom, and R and Rd each independently represent a hydrogen atom or may be selected from a group selected from a hydroxyl group and a fluorine atom. a group of 1 or a plurality of substituents substituted with a decyl group, or alternatively: a 4 to 6 membered saturated aliphatic ring group containing a bond N (the aliphatic ring group, at a position where it can be substituted, One or a plurality of substituents selected from the group consisting of (iv) and a fluorine atom,

Re represents a C, -6 alkyl group (the alkyl group may be substituted by a group selected from the group consisting of a hydroxyl group, a cyano group, a fluorine atom, a c--3 alkoxy group, and a thiophene group or a plurality of substituents), - A, -C(=〇)_A,, c] 6 alkyl group (the base portion of the group may be selected from the group consisting of a thiol group, a ft atom, a cyano group, a Cl-channel oxy group, and a _NReRd group) 323256 54 201206906 Group 1 or a plurality of substituents substituted), _c(=0)NReRd4_s(=〇)mRb,

Rf represents a hydroxy group, a C1-3 alkyl group (the alkyl group may be substituted with one or a plurality of substituents selected from the group consisting of a hydroxyl group, a cyano group, a fluorine atom, and -NR°RdK) or -ΜΎ >

Rg represents a hydroxy group, a Cw alkyl group (the alkyl group may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group, a cyano group, a fluorine atom and a -NReRdK) or R represents a group selected from a trans group and a ruthenium atom. One or more than 9 substituents of the group are substituted for the G-3 alkyl group, and R1 represents a G-6 alkyl group (the alkyl group may be selected from the group consisting of a fluorine atom and _NRCRd) or a plurality of substituents substituted), -A, -c(=〇)-A, or a Ci-6 alkylcarbonyl group (the alkyl moiety of the group may be selected from the group consisting of a fluorine atom and _NReRd) A plurality of substituents are substituted), and A and A are independently represented by a phenyl group, a sigma η sitting group (jmidazo 1 y 1), a pyridyl group, an oxaz〇iyi group, an isoxazolyl group. (Isoxazoly 1), an aromatic ring group of a group consisting of pyrazolly 1 , pyrazo 1 y 1 , isothiazolyl and tetrazolyl (the aromatic earth) The group 'in its substitutable position may be substituted by a Ci3 alkyl group substituted by a base or a halogen atom, an anthracene-3 alkoxy group which may be substituted by a super group or a _ atom, a hydroxyl group, a halogen Atom, cyano, -C(= 〇H or -NReRd), or represents a selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyranyl, azetidinyl, pyrrolidinyl, Fat of a group consisting of piperidinyl, piperazinyl and morphol inyl 55 323256 201206906 aliphatic ring group (the aliphatic ring group, in its place of replacement, can be Substituted by: G-3 alkyl group which may be substituted by a hydroxyl group or an i atom, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0)0H, -MeRd or pendant oxy), then in represents 1 or 2. [Claim 22] The compound of any one of items 1 to 21, or a physiologically acceptable salt thereof, wherein R° represents -C〇0)NRa---S(=0)2NRa-, _ _C( =0) _, _S (=0) 2~ or single button. [Item 23] The compound according to any one of Item 1 to Item 8, Item 15, Item 21, or Item 22, or a physiologically acceptable salt thereof, wherein Formula (I) is represented by the following formula (Γ):

Wherein L represents a stupid ring (the position at which the phenyl ring and the dihydropyrimidinone ring are bonded is an ortho position to the position where the benzene ring is bonded to Ar2, and the benzene ring may be selected from a position at which it can be substituted Substituting 1 or a plurality of substituents of the group consisting of: a C alkyl group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a functional atom, -C(=0)NReRd And -C(=0)0H), or the following formula Pyr-Ι or Tri-Ι : 56 323256 201206906

PyM

TrM (in each of the groups 2, the bonding 1 represents a bond with a dihydropyrimidinone ring, and the bonding 2 represents a "bonding" of Z and z2, respectively, which can be independently selected from a halogen atom, a transbasic group, NRR, 'C (=〇) NRCR1-C(=〇)〇H Group of 1 or a plurality of solid substituents substituted thiol, halogen, _c(=Q)NReRd, _c(=〇)〇H,

-NReRd or hydrogen atom), R represents Cim. An alkyl group (wherein the alkyl group' may be substituted at a position selected from the group consisting of: to 3 substituents: (1) a meridine, (2) a tooth atom, () G 6 An alkoxy group (the alkoxy group, at its substitutable position, may be substituted with j or a plurality of substituents selected from the group consisting of: a hydroxyl group, a south atom, a 1 ^ 匕 from &quot; 5 to 5 heteroaroms of the group consisting of 1 to 4 heteroaroms (the aromatic ring group, at the position where it can be substituted, may be 1 or a plurality of substituents selected from the group consisting of rl Substitution: can be selected by the group = _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ , (4), and <(_), 3 may be selected from the group consisting of n, G, and S to 2 heteroatoms 3 323256 57 201206906 to 6-member saturated fat _ county (the lipid (four) ring a group, in the place where it can be substituted, a group of 1 or a plurality of substituents formed by a thief, and 1 or a plurality of substituted soils selected from the group consisting of 26 groups and _ atoms Cm yard base, can be selected from the secret And 1 group or a plurality of substituents consisting of _ atoms substituted by Gi oxy group, secret, halogen atom, _C(=〇X)R, 'C(=Q)NW and pendant oxy)), ( 6) may have 5 to 6 stomach aromatic groups derived from the group consisting of dips and 3 to 4 heteroatoms (the aromatic ring group, at the position where it can be substituted, may be selected from Substituting 1 or a plurality of substituents of the group consisting of: a Cl-3 alkyl group substituted with 1 or a plurality of substituents from the group I and from the group of atoms,

The Cm alkoxy group, the trans group, the halogen atom and the φ-C(=0)0Rb) may be substituted by one or more substituents selected from the group consisting of 11 atoms, and (7) may be selected from diphine And 3 to 6 member saturated aliphatic ring groups of i to 2 hetero atoms of the group consisting of 3, wherein the aliphatic ring group, at a position where it can be substituted, may be selected from the group consisting of Substituting i or a plurality of substituents. The Ci-3 leukoxyl group may be substituted by a group or a plurality of substituents selected from the group consisting of a base group and a tooth atom, and may be selected from a group consisting of a base group and a halogen atom. a group of 1 or a plurality of substituents substituted with a Ci 3 alkoxy group, a trans group, a tooth atom, -C(=0)0Rb, -C(=0)NRCRd, _c(=〇)Ri side oxy), And (8)-NRaRe), 323256 58 201206906 or represents one or two heteroatoms which may contain a group selected from the group consisting of N and 〇3 to 6 members of a saturated aliphatic ring, which may be selected from the following classes. Substitutable substituted (1) hydroxy, group 1 or a plurality of substituents substituted: (2) a halogen atom, (3) a cyano group, (4) a C-e-alkyl group (the alkyl group, Its replaceable position can be selected from hydroxyl and halogen atoms The group of cylinders is η ping, and 1 or a plurality of substituents are substituted), (5) Ci-6 alkoxy groups (the oxygen-burning group, at the position where it can be substituted, may be selected from the group And the s atom consists of a group of 1 or a plurality of substituents substituted, (9) -NRaRe, (10) -〇C(=〇)NReRd, 01) -C(=0)Rf &gt; (12) - S(=〇)mRg and φ(14) side oxy), R0 represents -C(=0)NRa-, ~S(=0)2NRa-, _c(=〇)_, _s(=〇)2_ or a single bond, R2 represents a Ci 3 alkyl group which may be substituted with a group consisting of a tooth atom, an NRCRd, a 0Ra and a 〇c (=〇) Ram, or a plurality of substituents, and R and R4 are independently represented by a single bond. Cl-3 alkyl or hydrogen atom, X represents a Cl_3 alkyl group or a nitro group which may be substituted by 1 or a plurality of fluorine atoms, and γ represents a cyano group, a chlorine atom or a nitro group, 59 323256 201206906 R represents a hydrogen atom or may be selected a group of 1 or a plurality of substituents substituted with a hydroxyl group and a fluorine atom, and a C 3 -alkyl group substituted by 1 to 3 fluorine atoms, and RC and Rd respectively represent a Ci 3 alkyl or a hydrogen atom substituted by a fluorine atom, or a bond N together represents pyrrolidine pyrr〇lidine) or piperidine (piperidine),

Re represents a G-6 alkyl group (the alkyl group may be substituted with 1 or a plurality of substituents selected from the group consisting of a fluorine atom and _NReRd), _A, _c(=〇)-A, G•alkyl a carbonyl group (the alkyl moiety of the group may be substituted with 1 or a plurality of substituents selected from the group consisting of a fluorine atom and _NReRd) or _s(=〇)2Rb,

Rf represents a trans group or -NITRi, indicating a G-3 alkyl group,

Rh represents a 2Ci3 alkyl group which may be substituted by 1 or a plurality of fluorine atoms, and R1 represents a alkyl group (which may be substituted by 1 or a plurality of substituents selected from the group consisting of a fluorine atom and _NReRd) or _8. • A and A' are independently selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl (3261; 1 (111171), 吼11 each 1) pyrrolidinyl, piperidine An aliphatic cyclic group of a group consisting of piperidinyl, piperazinyl, and morph〇linyl (the aliphatic ring group, at its substitutable position, may be substituted by a C3-3 alkyl group which may be substituted by a hydroxyl group or a crypto atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a trans group, a halogen atom, a cyano group, a -NReRd or a pendant oxy group), and then m represents 2 323256 60 201206906 [Item 24] The compound according to any one of Item 1 to Item 8, Item 15, or Item 23 or the physiologically acceptable salt thereof, wherein Z1 and Z2 represent a hydrogen atom. [Item 25] The compound according to Item 1, or a physiologically acceptable salt thereof, wherein the compound is selected from the group consisting of Group: Lu 4-(4-(3-isopropyl-6-methyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2, 3, 4-tetra Hydropyrimidin-5-yl)-4Η-1,2,4-triazol-3-yl)benzonitrile, (R)-4-(4-(3-(1-hydroxypropane-2-yl)) -6-methyl-2-indolyl-(3-(di-(indenyl)))-1,2,3,4-tetrahydromethane-5-yl)-4H- 1,2, 4-tris(y)-3-yl)benzonitrile, 4-(4-(3-isopropyl-6-methyl-2-oxooxyl~-m-phenylene)

- azole~4-yl)-oxime, 4-dimethyldihydropyrimidin-1(6Η)-nonylamine, 4-(5-(3-isopropyl-6-methyl-2-oxooxy) -1,2,3,4-tetrahydropyrimidin-5-yl)-ih- 5-(3-(4-cyanophenyl)-4H-l,2,4-trisole-2-side Oxy-3-(3-(trifluoromethyl)phenyl)carbamide, 5-(3-(4-cyanophenyl)-4H-l,2,4-tri-y-2-oxo Benzyl-3-m-tolyl-2,3_dif 323256 61 201206906 5-(3-(4-cyanophenyl)-4Η-1,2,4-triazol-4-yl)-N- (2-methoxyethyl)-4-mercapto-2-oxo-3-m-tolyl-2,3-dihydropyrimidin-1 (6H)-indole amine, 5-(3- (4-cyanophenyl)-4Η-1,2,4-triazol-4-yl)-4-mercapto-2-yloxy-N-0pyridin-2-ylmethyl)-3 -m-phenylphenyl-2,3-dihydropyrimidin-1(6H)-carbenamide, 5-(3-(4-cyanophenyl)-4H-1,2,4-triazole-4 -yl)-N-ethyl-4-mercapto-2-oxo-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidine '-K6H)-decylamine 4-[4-(6-(Hydroxymethyl)-3-isopropyl-2~-oxytrifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl -4Η-1,2,4-triazol-3-yl]benzonitrile, 5-(1-(4-cyanophenylazole) 5-yl)-N,4-dimercapto-2-oxooxy-3-(3-(trifluoromethyl)phenyl 2,3-dihydropyrimidine-1(6H)-decylamine, 2 -(5-(1-(4-cyanophenylpyrazole-5-yl)_4-methyl-2-oxooxy φ-3-(3-(difluoroindolyl)phenyl)_2, 3 - Dihydro-bite-i(6H)-yl)propionic acid, 2-(5-(3-(4-cyanophenyl)-4Η-1, 2,4-triazol-4-yl)-4 -mercapto-2-oxooxy-3-(3-(trifluoromethyl)phenyl)_2,3-dihydropyrimidin-l(6H)-yl)propionic acid, 4-(5-( 1- (4-cyanophenylpyrazol-5-yl)-4-methyl-2-oxooxy 3 (3-(difluoromethyl)phenyl)_i,2,3,6-tetrahydro" dense Buty-1-cartoamine)butyric acid, N-(4-amino-4-oxobutyl)_5_(1_(4-cyanophenyl)_1Η_π-biazole-5-yl)-4-A Benzyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-2,3-di 62 323256 201206906 Hydropyrimidine-1(6H)-nonylamine, N-(2-amino group -2-Sideoxyethyl)-5-(1-(4-cyanophenyl)-1Η-oxazol-5-yl)-4-methyl-2-oxo-3-(3- (trifluoromethyl)phenyl)_2,3-dihydropyrimidin-1(6H)-decylamine, and 1-(4-cyanophenyl)-5-(3-isopropyl-6-oxime Keto-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4- Tetrahydropyrimidin-5-yl)-1 oxime-oxazole-4-decanoic acid. [Item 26] A pharmaceutical composition comprising the compound according to any one of Items 1 to 25, or a physiologically acceptable salt thereof, and a carrier for the preparation. [Item 27] An elastase inhibitor comprising the compound according to any one of Items 1 to 2, or a physiologically acceptable salt thereof, as an active ingredient. [Item 28] A therapeutic or prophylactic agent for an inflammatory disease, which comprises the compound according to any one of Items 1 to 25 or physiologically acceptable. [Item 29] 1 A disease preventive agent which is required to have an inhibitory activity against elastase, which has a compound of any one of items 1 to 25 or a physiologically acceptable salt thereof. . Moreover, the present application also provides the following aspects. [Item 30] 323256 63 201206906 In the manufacture of a medicine for the treatment or prevention of an inflammatory disease, the compound described in any one of Items 1 to 25 or a physiologically acceptable salt thereof. [Item 31] A compound described in any one of Items 1 to 25, or a physiologically acceptable salt thereof, for use in the treatment or prevention of an inflammatory disease, or a pharmaceutical composition contained as an active ingredient. [Item 32] A method for treating or preventing an inflammatory disease, which is a therapeutically effective amount of a compound described in any one of Items 1 to 25 or a physiologically acceptable salt thereof. Further, as a result of intensive studies, it has been found that the novel compound shown by the following formula (1) exhibits an inhibitory action on elastase, and the present invention has been completed. According to the present invention, a dihydrogen domain organism (hereinafter also referred to as "the compound of the present invention") of the following formula (1) is provided. [Item Γ] A compound represented by the formula (1)' or a physiologically acceptable salt thereof:

[wherein, R represents -C(=〇)NRal-, -S(=0)2NRa2-, -C(=〇)〇—, _c(=〇)_, ~S(=〇)2- or Single bond, 323256 64 201206906 R1 represents a hydrogen atom, a Cho alkyl group, a C2-6 alkenyl group, and may contain one to two heteroatoms selected from the group consisting of N, 0 and S, and 3 to 6 members are saturated or not. a saturated aliphatic cyclic group or a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S, wherein the alkyl group and the alkenyl group are Substitutable positions may be substituted with one or more substituents selected from the group consisting of: (1) hydroxy, (2) halogen atom, • (3) cyano, (4) Cl-6 alkoxy (The alkoxy group, at the position where it can be substituted, may be substituted by: a radical, a halogen atom, a cyano group, -C(=0)0Rbl-, • -C(=0)NRclRdl-, may contain a 5- to 6-membered aromatic ring group of one to four heteroatoms selected from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: a G-3 alkyl group substituted with a hydroxyl group or an iS atom, a Cl-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a trans group, a halogen atom, a cyano group, -NRa3C (=0)Rb2 ' -NRa4C(=0)NRc2Rd2 ' -NRa5S(=0).Rb3 ' -C(=0)0Rb4, -C(=0)NRc3Rd3, -S(=0)mNRc4Rd4, -S( :0%Rb5 or -NRdR·15), or may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S. 3 65 323256 201206906 to 6-membered saturated or unsaturated aliphatic cyclic group ( The aliphatic cyclic group may be substituted at the position where it may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, or a hydroxyl group. , halogen atom, cyano group, -NRa6C(=0)Rb6, -NRa7C(=0)NRc6Rd6, -NRa8S(=0)mRb7, -C(=0)0Rb8, -C(=0)NRc7Rd7, -NRc8Rd8 or Side oxy)), (5) Cl-6 alkylthio (the alkylthio group, at its substitutable position, may be substituted by: a base, a halogen atom, a cyano group, -C ( =0) 0Rb9-, -C(=0)NRe9Rd9-, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring) a group, at a substitutable position thereof, may be substituted by a Cm alkyl group which may be substituted with a hydroxyl group or an iS atom, a G-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, Halogen atom, cyano group, -NRa9C(=0)Rbl° ' -NRal0C(=O)NRcl0Rdl° ' -NRal,S(=0)mRbn ' -C(=0)0Rbl2, -C(=0)NRcllRdU, -S (=0; LNRcl2Rd12, -SOCOoR1313 or -NRel3Rd13), or a 3- to 6-membered saturated or unsaturated aliphatic cyclic group which may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S (The aliphatic cyclic group, where it may be substituted, may be substituted by a 0-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, Hydroxyl group, halogen atom, cyano group, -NRal2C(=0)Rbl4, -NRal3C(=0)NRcl4Rdl4, 66 323256 201206906 -NRal4S(=0)mRbl5, -C(=0)0Rbl6, -C(=0)NRcl5Rdl5 , -NRcl6Rd16 or pendant oxy)), (6) may contain a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, Where it may be substituted, it may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a functional atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a trans group, a halogen atom, Cyano, -NRal5C(=0)Rbl7, -NRal6C〇0)NRel7Rdl7, -NRal7S(=0)ERbl8, -C(=0)0Rbl9 -C (= 0) NRcl8Rdl8, φ -S (= 0) mNRcl9Rdl9 '-S (= 0) raRb2. Or -NRc20Rd20) &gt; (7) A 3 to 6 membered saturated or unsaturated aliphatic cyclic group (which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S) (the aliphatic ring group, Where it can be substituted, it can be substituted by: G-3 alkyl (the alkyl group can be via a hydroxyl group, a halogen atom, a cyano group, -NRal8C(=0)Rb21, -NRal9C(=0)NRc21Rd21 &gt; -NRa20S(=O).Rb22 ' -C(=0)0Rb23 ' -C(=0)NRc22Rd22 or -NRe23Rd23 substituted), 67 323256 201206906

Cm alkoxy group (the alkoxy group may be substituted by a hydroxyl group or a halogen atom), a mesogenic group, a halogen atom, a cyano group, -NRa21C(=0)Rb24'-NRa22C(=0)NRc24Rd24'-NRa23S〇0)raRb25, -C(=0)0Rb26, • -C(=0)NRc25Rd25 ' -S(=0)mNRc26Rd26 &gt; -S(=0)mRb27, -NRe27Rd27 or pendant oxy), (8) -NRa24Re, (9 ) - 0Re', φ (10) -C(=0)Rf, (11) -S(=0)mRg, (12) mercaptan and (13) exact base * here, the saturated or unsaturated aliphatic A cyclic group, at a substitutable position thereof, may be substituted by a radical, a halogen atom, a cyano group, an exact group, a Cl-6 alkyl group (the alkyl group, at a position where it may be substituted, may be via a hydroxyl group, _Atom or cyano substituted), Ci-6 alkoxy (the alkoxy group, at its substitutable position, may be taken via a hydroxyl group, a halogen atom or a cyano group, 68 323256 201206906 generation), -NRa25C(=0)Rb28 -NRa26C(=0)NRc28Rd28, -NRa27S(=0)mRb29, -C(=0)0Rb3°, -C(=0)Rb31, -C(=0)NRc29Rd29 or -NRc3°Rd30, here, The aromatic ring group, at its substitutable position, may be substituted by a group: a halogen group, a halogen atom, a cyano group, a nitro group, a Cl-6 group (the alkyl group, in which Substituted position, may be substituted by a hydroxyl group, a halogen atom or a cyano group) Cm alkoxy group (the alkoxy group, at a position where it may be substituted, may be substituted by a via group, a halogen atom or a cyano group), -NRa28C (=0 Rb32, -NRa29C(=0)Nr31Rd31, -NRa3°S(=0)raRb33, ® -C(=0)0Rb34, -C(=0)Rb35, -C(=0)NRc32Rd32, -S(= 0) «〇NRc33Rd33, -S〇0)»Rb36 or -NRc34Rd34, R2 represents a G-3 alkyl group (the alkyl group may be substituted by a hydroxyl group or a ii atom), and R3 and R4 each independently represent a hydrogen atom or a G-3 alkane. a group (the alkyl group may be substituted by a hydroxyl group or a halogen atom),

Ar1 represents a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may have a position at the position where it can be substituted The above is substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom, an anthracene-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group or a -NRe35Rd35), L. a 5- to 6-membered unsubstituted aromatic ring group or -S(=〇X-, which may contain from 1 to 4 heteroatoms selected from the group consisting of N, 0 and S,

Ar2 represents a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may be at one position above its replaceable position) Substituted by a Cw alkyl group which may be substituted by a hydroxyl group, a cyano group or a halogen atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom. 69 323256 201206906 group, a hydroxyl group, a halogen atom, a cyano group, a nitro group, -S(=〇)nRh or _NRc36Rd36), Re represents a hydrogen atom,

Cl-6 alkyl group (the alkyl group may be substituted by a thiol group, a cyano group, a halogen atom, an alkoxy group or -NRc37Rd37), -A ' -C〇0)A,

Ci-e sulphide-based (the alkyl group of the base of the compound can be taken via a base or a halogen atom),

Cl-6 alkoxy oxime group (the alkyl group of 5 oxime oxime group may be substituted by a base or a tooth atom), -C(=0)NRc38Rd38 or -S(=0)mRb37,

Re' represents -AM or -C〇0)NRc39Rd39,

Rf represents φ hydrogen atom, hydroxyl group,

Cm alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group or a halogen atom),

Cl_3 alkoxy group (the alkoxy group may be substituted by a phenyl group, a hydroxyl group, a cyano group or a halogen atom which may be substituted by a decyloxy group or a succinyl group), -B or -NR,1,

Rg represents hydroxyl, 70 323256 201206906

Cl-6 alkyl (which may be substituted by a base, a nitrogen or a halogen atom), -D or -NRa31Rr,

Rh represents an anthracene-6 alkyl group which may be substituted by a hydroxyl group or a functional atom, and f represents a hydrogen atom,

Ci-6 alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a halogen atom, a G-3 alkoxy group, a C3-6 cycloalkyl group or a -NRe4°Rd4°), • -B' or -C(= 0) Rb38, R1 represents a hydrogen atom,

Ci-6 alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a halogen atom, a G-3 alkoxy group, a C3-6 cycloalkyl group or -ΝΓ41!^41) or -D', φ A, A' , A&quot;, B, B', D, and D, respectively, independently represent a 5- to 6-membered aromatic ring group of 1 to 4 heteroatoms selected from the group consisting of N, 0, and S (the aromatic A cyclic group, at a substitutable position thereof, may be substituted by a 0-3 alkyl group which may be substituted with a hydroxyl group or an !i atom, a Cw alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom. , cyano, -C(=0)0H or -NRe42Rd42) or a 3- to 6-membered saturated or unsaturated aliphatic cyclic group which may contain from 1 to 2 heteroatoms selected from the group consisting of N, 0 and S (The aliphatic cyclic group, at its substitutable position, may be substituted by a Cw 71 323256 201206906 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a C 3 alkoxy group which may be substituted by a hydroxyl group or a tooth atom, a hydroxyl group , a south atom, a cyano group, -C(=0)0H, -NRe43Rd43 or a pendant oxy group), and R to R31 each independently represent a hydrogen atom or a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom.

Rbl, Rb4, Rb8, Rb9, Rbl2, Rbl6, Rbl9, Rb23, Rb26, Rb3. and

Rb34 independently represents a hydrogen atom, a 〇6 alkyl group which may be substituted by a hydroxyl group or a tooth atom, or a stupid methyl group which may be substituted by a methoxy group or a nitro group.

Rb2, Rb3, Rb5, broad, Rb7, Rbl. , Rbll, Rbl3, Rbi4, Rbi5, Rbi7,

Rbl8, Rb2D, Rb21, Rb22, Rb24, Rb25, 俨7, 俨9, PM, 俨, Rb35, Rb36, and Rb38 each independently represent a G-6 alkyl group which may be substituted by a base or a tooth atom or may be &amp; 6 cycloalkyl substituted by hydroxy or halogen atom, m, RC4, rc6, rc7, rc8, rc9, rc 丨. , rc&quot;, "12, RCl4, RCl5, RC17, RC18, RC19, RC21, r gas rc24, r gas", &quot;, ^, R-, R-, r, RC38, RC39, Rd丨, Rd2, Rd3 , Rd4, Rd6, Rd7,

Rd8, Rd9, R&lt;U. , R«m, Rdl2, Rdl4, Rdl5, Rdl7, Rdl8, Rdi9, Rd2i,

Rd22, Rd24, Rd25, Rd26, Rd28, Rd29, Rd31, Rd32, Rd33, Rd38 and Rd39 each independently represent a hydrogen atom or a C13 alkyl group which may be substituted by a hydroxyl group or a halogen atom, or a substituent bonded to the same nitrogen atom. A 4- to 6-membered saturated or unsaturated aliphatic cyclic group which may contain a group selected from the group consisting of N and 0 to 2 hetero atoms (the saturated or unsaturated aliphatic ring group may be substituted therein) The position can be replaced by a hydroxyl group or a tooth atom), c5 :13 &gt;cl6 &gt;°2〇^ pc23

Rc27, Rc3. , IT4, Rc37, Rm〇 &gt; c34 c41, RC, RC, Rd5, Rdl3, Rdl6, Rd20, Rd23, Rd27, Rd3. And Rd34, W, Μα, Μ41, R&lt;142, and F43 each independently represent a hydrogen atom or a G-3 alkyl group which may be substituted by a base or a halogen atom at 72 323256 201206906 or a substituent bonded to the same nitrogen atom. A 4- to 6-membered saturated or unsaturated aliphatic cyclic group (which may be contained in a group selected from the group consisting of 2 to 2 hetero atoms) (which may be substituted, It may be substituted by a hydroxyl group, a halogen atom or a pendant oxy group), and RC35, Re36, Rd35 and Rd36 each independently represent a hydrogen atom or a Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom, or a substituent bonded to the same nitrogen atom may be used. Forming together a 4- to 6-membered saturated aliphatic ring group containing hydrazine to 2 N (the saturated aliphatic ring group may be substituted by a hydroxyl group or a halogen atom at a position where it may be substituted), and πι represents an integer of 1 or 2, η represents the integer 2 to 2, and Q represents the integer 0 to 2]. [Item 2,] The compound described in Item 1, or a physiologically acceptable salt thereof, wherein: R° represents ~C(=〇)NRal-, ~S(=〇)2NRa2-, -C(=〇)〇 -, -C(=〇)_ or -S(=0)2-. [Item 3,] the compound described in the item Γ or the item 2' or a physiologically acceptable salt thereof, wherein Λι·1 represents the following formula Ari-丨, or ArL2\

(In each group, E\E2, E3, and E4 independently represent carbon atoms or nitrogen atoms (except for 323256 73 201206906 E1, E2, E3, and E4 all indicating nitrogen atoms at the same time), and g, G2, and G3 are independent. a hetero atom representing a carbon atom or a group selected from the group consisting of n, q &amp; s, X represents a Ci 6 alkyl group which may be substituted by a hydroxyl group or a tooth atom, a Cl_3 alkoxy group which may be substituted by a radical or a functional atom, Substituents having a group consisting of: a group selected from the group consisting of a base, a tooth atom, a nitrogen group, a stone base or a gas E1, E2, E3, E4, G1, G2 or a substitutable position: a Cl-6 alkyl group substituted by a radical or an i atom, a Cl-3 alkoxy group which may be substituted by a radical or a (tetra) group, a hydroxyl group, a halogen atom, a cyano group, a nitro group and a NR (:35Rd35, RC35 and Rd35) (1) The compound described in any one of Item 3, or the physiologically acceptable salt thereof, wherein Ar1 represents the following formula, or Ar〗 _2,:

(In each group, 'KU and K4 each independently represent a carbon atom or a nitrogen atom (except that K, K, K3, and K4 all represent a nitrogen atom at the same time), and y, L2, and L3 independently represent a carbon atom or are selected from N, a miscellaneous group in the group consisting of 〇 and s? 'γ denotes a Ci 6 alkyl group which may be substituted by a cyano group or a _ atom, a C 3 alkoxy group which may be substituted by a hydroxyl group or an i atom, a hydroxyl group, a halogen atom, The substitutable position of the murine group, the stone succinyl group, the -S(=0)nRh or _NRe36Rd36, κ1, K2, K3, K, L, L or L may further have a selected from the group consisting of: a substituent which may be substituted with a hydroxy group, a cyano group or a halogen atom, a 烷6 alkyl group, a Ch alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom 323256 74 201206906 == base, a stone succinyl group, a _s (four), and a The definitions listed in item 1' are the same). n RR Μ [Item 5,] Item Γ to item 4, as indicated by the above-mentioned compound or its physiological N'0ASW&quot; (I,), as shown below: To 6 unsubstituted Family ring

Ar1 R·2丫CQr^r3^ R0** R1 ·).

[Item 6,] The salt allowed in the project I' to the project, where [item 7'] is the salt allowed in the project, and the Cm alkyl group. [Item 8,] The project shall be allowed to the salt on the project, where [item 9,] the project shall be allowed to the salt permitted on the project, of the compound described in any one of 4' or its physiology, L system-S (= 〇)q_·, q is 1 or 2. The compound according to any one of 6 or the physiological 'R3 and R4 thereof' are each independently a hydrogen atom or a compound described in any one of the unsubstituted 7's or a physiological group thereof - C(=〇)nh- or - S (= 〇) 2NH-. A compound according to any one of 8' or a physiological 'R-based hydrogen atom or Cl-l. a burnt group (which may be substituted at the position substituted by 323256 75 201206906, may be substituted with the same substituent as defined in item r) or may contain a group selected from the group consisting of ruthenium, osmium and S to 2 A 3 to 6 membered saturated or unsaturated aliphatic ring group of a hetero atom (the aliphatic ring group, at a substitutable position, may be substituted with the same substituent as defined in the item 记载). [Item 10] The compound according to any one of the items 9 to 10, or a physiologically acceptable salt thereof, wherein φ R is a hydrogen atom or a Ci group, and the alkyl group is at a position replaceable. Substituted by the same substituents as defined in the item )), A and A" are each independently selected from the group consisting of phenyl, sulphonyl, and pyridinyl, pyrazinyl, stil, Heterogeneous base, ^ seat base, plug base, and 11 plugs. Sitting on the base. An aromatic ring group of a group consisting of pyrimidinyl, oxadiazolyl, thiadiaz〇lyl, toazolyl, and tetrazolyl Substituted from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, hexanyl, azetidinyl, pyrrolidinyl, piperidinyl, pyrrolinyl (Human (6) (tetra)), dihydroanthracene (dihydr〇pyHdinyi) and a saturated aliphatic ring group of a group consisting of tetrachloroacridinyl groups, A, which may be substituted, selected from the group consisting of a stupid base, a salivary group, a benzyl group, a (tetra) group, an isoindole, and a ton a Tujia ring group of a group consisting of a stagnation base and a sessile sinyl group or a substitutable group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, yl, azetidinyl &quot; A saturated aliphatic cyclic group consisting of piroxicam, π Chen, 哄 及, and 琳 基 基 323 256 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 Pyridyl, η ratio arsenic, carbazolyl, isoindole, etc., pyrazolyl, pyrazolyl, thiazolyl, isothiazolyl, pyrimidinyl, fluorenoxadiyl, thiadiazolyl, tri The aromatic ring group of the group consisting of a tetrazole group and a tetrazolyl group or a substituent which may be substituted is selected from the group consisting of a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a quaternary nitrogen alkene butyl group, and a π ratio 唆, imidaz〇lidinyl, • piperidinyl, piperazinyl, morpholinyl, oxazolidinyl, thiaz〇iidinyl, heterosexual A saturated aliphatic cyclic group of the group consisting of isoxazolidinyl and isoxazinlidinyl, and B and D' are independently substituted from phenyl, imidazolyl and pyridine. An aromatic cyclic group of a group consisting of a carbazolyl group, an oxazolyl group, an isoxazolyl group, a pyrazolyl group, a thiazolyl group, an isothiazolyl group, a oxazolyl group, and a tetrazolyl group, or a substituted propyl group a saturated aliphatic ring group of a group consisting of cyclobutyl, cyclopentyl, cyclohexyl, piperidyl, azetidinyl, pyrrolidinyl and piperidinyl, in this case, substituted The substituent of the group ring group is a Ch alkyl group which may be substituted by a hydroxyl group or an atom, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a tooth atom, a trans group, a halogen Substituent, cyano, _c(=〇)〇H or —NRC42 Μ 42 and Rd42 are the same as defined in item 1,), and the substituent of the substituted saturated aliphatic ring group may be hydroxy or halogen. An atom-substituted Cw alkyl group, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a s atom, a hydroxyl group, a self atom, a cyano group, -C(=〇)〇H, -NRc43Rd43 (this &quot; and Rd43 table 323256 77 201206906 =,;, the same as defined in the description) or a pendant oxy group. The compound described in the item 1' to the item in'rb/,., the middle item, or the physiological salt thereof, wherein

Rl is a gas atom or C1 -1. An alkyl group (which may be substituted at a substitutable position by one or more substituents selected from the group consisting of: (1) a hydroxyl group, (2) a tooth atom, (3) a cyano group, (6) a 5-membered aromatic ring group which may be selected from the group consisting of n, fluorene and S, to 4 hetero atoms (the aromatic ring group, at the position where it can be substituted, may be as follows) Substitution: 1 G-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, Ci-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a _ atom, a chaotic group, -NRa, 5C (=0) Rbl7 &gt; ~NRaI6C(=0)NRcl7Rdl7 ' -NRal7S(=0)mRbl8, -C(=0)0Rbl9, -C(=0)NRcl8Rdl8 ' -S(=0)raNRcl9Rdl9 &gt; -S(=0)fflRb2 ° or 323256 78 201206906 -NRc20Rd20) &gt; (7) A 3 to 6 member saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group) And at a substitutable position thereof, may be substituted by: G-3 alkyl (the alkyl group may be via a hydroxyl group, a fluorine atom, a cyano group, -NRal8C(=0)Rb21, -NRal9C(=0)NRc21Rd21, -NRa2°S(=0)mRb22, -C(=0)0Rb23, -C(=0)NRe22Rd22 or -NRe23Rd23 instead),

Cw alkoxy (the alkoxy group may be substituted by a hydroxyl group or a fluorine atom), • a trans group, a fluorine atom, a cyano group, _NRa21C(=0)Rb24, -NRa22C(=0)NRc24Rd24'-NRa23S(=0)mRb25 , -C(=0)0Rb26, φ -C(=0)NRe25Rd25, -NRe27Rd27 or pendant oxy), (8) -NRa24Re, (9) -0Re', (10) -C(=0)Rl ( 11) -S(=0)mRg),

Ral to Ral7, 1^25 to Ra29 independently represent a hydrogen atom or a sulfhydryl group,

Ral8 to Ra24, Ra3° to Ra31 independently represent a hydrogen atom or a Cl-3 sapon group which may be substituted with a hydroxyl group 79 323256 201206906 or a fluorine atom.

Rbl, Rb4, Rb8, Rbg, Rbl2, Rbl6, RbI9, Rb23, Rb26, Rb3. and

Rb34 independently represents a hydrogen atom or an unsubstituted G-6 alkyl group.

&gt;b5

Rb6, Rb7

.blO

R b!3

Rbl4, R bl5

Rbl8, Rb20, Rb21, Rb22, Rb24, Rb25, Rb27, Rb28, Rb29, R*&gt;31, Rb32,

Rb33, Rb35, Rb36, Rb37 and Rb38 each independently represent a Ci.6 alkyl group which may be substituted by a hydroxyl group or a fluorine atom or a C3-6 cycloalkyl group which may be substituted by a hydroxyl group or a fluorine atom.

RC17, RC18, RC19, rC21, RC22, RC24, RC25, RC38, Rdl7, Rdl8,

Rdl9, Rd21, Rd22, Rd24, Rd25 and Rd38 each independently represent a hydrogen atom or a Cl-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, or may be formed together to form a group which may be selected from the group consisting of N and 0. 4 to 6 member saturated aliphatic ring groups of 2 heteroatoms (the saturated aliphatic ring group, at its substitutable position, may be substituted by a hydroxyl group or a fluorine atom), RC20, rc23, rc27, rC37, Rc40, rc41 , RC42, "43, Rd20, Rd23

Rd27, Rd37, Rd4Q, Rd41, ^42 and Rd43 each independently represent a hydrogen atom or a CM alkyl group which may be substituted by a hydroxyl group or a fluorine atom, or may together form a group which may contain a group selected from N and 0 to 4 to 6 member saturated aliphatic ring groups of 2 heteroatoms (the saturated aliphatic ring group 'substituted at a position where it can be substituted by a hydroxyl group, a fluorine atom or a pendant oxy group)' RC35, Re36, Rd35 and independently a hydrogen atom or a Cl-3 group which may be substituted by a base or a fluorine atom,

Re indicates

Cm alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a fluorine atom, a Cm alkoxy group or a ~*NRe37Rd37), 80 323256 201206906 -A ' -C(=0)A,

Ci-6 alkylcarbonyl (the alkyl portion of the alkylcarbonyl group may be substituted by a hydroxyl group or a fluorine atom), -C〇0)NRe38Rd38 or -S(=0)mRb37,

Re_ means -A&quot;,

Rf means • hydroxyl, _B or -NR,

Rg represents a trans group, a G-6 alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group or a fluorine atom), ~D or φ-NRa31Rr &gt;

Rh represents a methyl group, and R1 represents a hydrogen atom,

Ci-6 alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a fluorine atom, a G-3 alkoxy group, a C3-cycloalkyl group or a -NRe4°Rd4°) or -B, and R1' represents a hydrogen atom, 81 323256 201206906

Ch alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a fluorine atom, an alkoxy group, a c36 cycloalkyl group or a -NRe41Rd41) or -D,, A and A&quot; respectively, independently selected from the group consisting of imidazolyl and anthracene An aromatic ring group of a group consisting of azolyl, isoxazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl (the aromatic group) a cyclic group which may be substituted by an alkyl group which may be substituted by a hydroxyl group or a φ fluorine atom, a Cl-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyano group, —c(=〇 〇H or, 1, or a group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl &quot;endanyl, heterocyclobutyl, pyrrolidinyl and piperidinyl a saturated aliphatic cyclic group (the saturated aliphatic cyclic group may be substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Ci3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, Cyano, -C(=〇)〇H, -NRc43Rd43 or pendant oxy), A' is selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, thiorulyl and iso. base The aryl ring group of the group consisting of (the aromatic ring group, which may be substituted by a Ci 3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Cl-channel oxygen which may be substituted by a base group or a fluorine atom) Or a radical, a fluorine atom, an aryl group, -C(=0)0H or -NRe42Rd42) or alternatively selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, hexanyl, azetidinyl a saturated aliphatic cyclic group of a group consisting of a bite group, a bite group, a transyl group, and a morphine group (the saturated aliphatic ring group may be substituted by the following: may be substituted by a light or fluorine atom) a Ch alkyl group, a Ch alkoxy group which may be substituted by a radical or a gas atom, a hydroxyl group, a fluorine atom, a cyano group "c(=〇)〇H, _NRe43Rd43 323256 82 201206906 or a pendant oxy group), B represents an imidazole selected from the group consisting of a group consisting of a group consisting of a carbazole group, a carbazolyl group, an isoxazolyl group, a pyrazolyl group, a thiol group, a snail group, a ruthenium group, a ruthenium group, a trisyl group and a tetradecyl group. a cyclic group (the aromatic ring group which may be substituted by a CW alkyl group which may be substituted by a group or a fluorine atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyanogen group , -C(=〇)〇H or -NRc42Rd42) or a saturated aliphatic ring group selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperidinyl and morpholinyl (The saturated aliphatic cyclic group may be substituted by a Cl-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, an anthracene-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyanogen group Base, -C(=0)0H, -NRc43Rd43 or pendant oxy), D is selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, 嗟σ, 嗟, 嗟, 曙An aromatic cyclic group of a group consisting of a succinyl group, a succinyl group, a trisalyl group, and a tetradecyl group (the aromatic ring group may be substituted by: ci which may be substituted by a hydroxyl group or a fluorine atom) a -3 alkyl group, a Ci_3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a certain group, a gas atom, a cyano group, -c(=〇)〇h or -NRe42Rd42) or alternatively selected from a cyclopropyl group and a cyclobutyl group a saturated aliphatic ring group of a group consisting of a group consisting of a cyclopentyl group, a cyclohexyl group, a cyclopentyl group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, a piperidine group, and a morpholinyl group (the saturated fat) Family ring base Substituted by: anthracene-3 alkyl which may be substituted by a hydroxyl group or a fluorine atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyano group, -c(=〇)〇 H, -NRe43Rd43 or pendant oxy), 323256 83 201206906 B' represents an aromatic cyclic group selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, thiazolyl and isothiazolyl (The aromatic cyclic group may be substituted by a Ci_3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Cw alkoxy group which may be substituted by a trans group or a deficient atom, a trans group, a fluorine atom, a cyano group, - C(=0)0H or -NRc42Rd42) or alternatively selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl&quot; decyl, azetidinyl, pyrrolidinyl and piperidinyl a group of saturated aliphatic cyclic bases (the saturated aliphatic ring group, which may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, or a Ci_3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom. , a hydroxyl group, a fluorine atom, a cyano group, -C(=〇)〇H, -NRc43Rd43 or a pendant oxy group), D' represents an imidazolyl group, a carbazolyl group, an isoxazolyl group, a pyrazolyl group An aromatic cyclic group consisting of a thiazolyl group and an isothiazolyl group (the aromatic ring group may be substituted by a Ch alkyl group which may be substituted by a hydroxyl group or a fluorine atom, may be substituted by a trans group or a fluorine atom) a Cw alkoxy group, a hydroxyl group, a fluorine atom, a cyano group, -C(=0)0H or -NRe42Rd42) or a component selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and piperidyl a group of saturated 爿a aliphatic % groups (the saturated aliphatic ring group, which may be substituted by a Ci-3 group which may be substituted by a group or a fluorine atom, may be substituted by a base or a gas atom G-3 alkoxy group, hydroxyl group, fluorine atom, cyano group, _c(=〇)〇H, -NRe43Rd43 or pendant oxy group). [Claim 12] The compound of any one of the above-mentioned items, or a physiologically acceptable salt thereof, wherein R1 represents a Cl-Π)alkyl group (the alkyl group, at a substitutable position, may be One or a plurality of substituent substitutions selected from the group consisting of: 323256 84 201206906: (1) a hydroxyl group, (2) a fluorine atom, (3) a cyano group, and (6) may be selected from N, 0, and S. A 5-membered aromatic ring group of 1 to 4 heteroatoms of the group formed (the aromatic ring group, at its substitutable position, may be substituted by: Ci- which may be substituted by a hydroxyl group or a fluorine atom 3 alkyl, ® Ch alkoxy, hydroxy, _ atom, cyano, -C(=0)0H, -C(=0)NRel8Rdl8 or -NRc20Rd20) φ (7) which may be substituted by a hydroxyl group or a fluorine atom. a 3 to 6 membered saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of ruthenium, 0 and S (the saturated aliphatic ring group, at the position where it can be substituted, may be as follows Substituted: G-3 alkyl (the alkyl group may be substituted by hydroxyl group, fluorine atom, cyano group, -C〇0)0H or -C(=0)NRe22Rd22), G-3 alkoxy group (the alkoxy group) Can be substituted by hydroxyl or fluorine atom), hydroxyl, fluorine Sub, cyano, 85 323256 201206906 -NRa2, C(=0)Rb24 &gt; -NRa22C(=0)NRe24Rd24, -NRa23S(=0)mRb25, -C(=0)0H, -C(=0)NRe25Rd25 , -NRe27Rd27 or pendant oxy), (8) -NRa24Re,

(10) -C(=0)RfA (11) -S(=0)mRg),

Ra to Ra 3, ^3. To Ra31 each independently represents a hydrogen atom or a methyl group, and Ra24 represents a hydrogen atom or a Ch alkyl group which may be substituted by a hydroxyl group or a fluorine atom.

Rb24 to Rb25 and Rb37 each independently represent a c3-6 cycloalkyl group which may be substituted with a hydroxyl group or a fluorine atom, or may be substituted with a hydroxyl group or a fluorine atom.

RCl8, RC22, RC24, RC25, Rc38, Rdl8, Rd22, and R3, respectively, independently represent a hydrogen atom or a pyridyl group or a fluorine atom-substituted alkyl group, or alternatively form a base selected from azetidin, a bite , brigade bite, ^ 哄 and ^, and the group of saturated heteroalicyclic ring groups (the saturated heteroaliphatic ring group, in which it can replace you P., W (four) can be replaced by the base ) R, RC4. , Rc41, RC43, Rd2. 7 7 . The group may be taken from a fluoro group or a fluorine atom, and both of them form a group selected from the group consisting of azetidine, pyrrolidine, 疋, _, material, imi, and screaming 323256 86 201206906 a heteroalicyclic ring group (the saturated heteroalicyclic ring group, at a position where it may be substituted, may be substituted by a hydroxyl group, a fluorine atom or a pendant oxy group),

Re35, Re36, Rd35&amp; Rd36 independently represent a hydrogen atom, a thiol group or an ethyl group.

Re indicates

Cw alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a fluorine atom, a hydrazone-3 alkoxy group or -NRe37Rd37), -A, y-C(=0)A,

Cm alkylcarbonyl (the alkyl portion of the alkylcarbonyl group may be substituted by a hydroxyl group or a fluorine atom), -C(=0)NRe38Rd38 or -S(=0)mRb37,

Rf represents a hydroxyl group, a _B or a -NR,

Rg means

Ci-6 alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group or a fluorine atom), -D or -NRa31Rr, R1 represents a hydrogen atom, an anthracene-6 alkyl group (the alkyl group may be via a hydroxyl group, a cyano group, a fluorine atom) , Ci-3 alkoxy, c3-87 323256 201206906 cycloalkyl or -NRe4°Rd4° substituted) or -B', R1 represents a hydrogen atom, CW alkyl group (the alkyl group may be via a hydroxyl group, a cyano group, a fluorine atom) , &amp; 3 alkoxy, ^ 6 cycloalkyl or -NRc41Rd41 substituted) or soil 3'6 -D,

.A represents a saturated aliphatic ring group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, perylene, azetidinyl, pyrrolidinyl and piperidinyl (this a saturated aliphatic cyclic group which may be substituted by a C 3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, an alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a trans group, a fluorine atom, a cyano group, —C (= 〇)〇jj or _NRC43Rd43), A" means selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, hexanyl, nitrogen heterocyclic T group, scale, Qianji, (tetra) and The saturated moon of the group consisting of linji is a fatty ring group (the saturated fatty sap can be replaced by a ruthenium 3 group which can be substituted by a base or a fluorine atom, and can be passed through a base.

Or a fluorine atom substituted Gi-channel oxy group, recorded, IU subm^)H or -NRe43Rd43), B is not selected from azetidinyl, pyrrolidinyl, acridinyl, piperidyl = Marinky The saturated fat (tetra) ring group of the group consisting of (the saturated aliphatic group) can be substituted by a Cm which can be substituted by a hydroxyl group or a fluorine atom: a (iv) group or a fluorine atom can be substituted for one alkoxy group, secret , I atom, fluorenyl, -C(=〇)〇H or _NRC43Rd43), D represents a group selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenanthrene 88 323256 201206906, azetidin a saturated aliphatic cyclic group of a group consisting of pyridyl, pyrrolidinyl, piperidinyl, piperidinyl and morpholinyl groups (the saturated aliphatic ring group may be substituted by a hydroxyl group or a fluorine atom) a substituted G-3 alkyl group, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a trans group, an I atom, a cyano group, _c(=〇)〇jj or -NRe43Rd43), and B' represents a ring selected from the group consisting of Saturation of groups consisting of propyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidyl, aza-butyl, beta-beta, and beta-based groups

An aliphatic cyclic group (the saturated aliphatic ring group may be substituted by an anthracene-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine group Atom, cyano group, _C(=0)0H or _expansion 43), D' represents a saturated aliphatic group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and piperidyl. a cyclic group (the saturated aliphatic ring group, which may be substituted by a sulfhydryl group which may be substituted by a secret or a fluorine atom, may be taken through a red or fluorine atom, a Cl_3 silk group, a fluorine atom, an aryl group , -C(=〇)〇H or _NRc43Rd43), R0 represents -C(=〇)NH- or -S(=〇)2nh-, R2 represents a methyl group, and R and R each independently represent a hydrogen atom or a methyl group. , ^ denotes a stupid ring group &quot;cepene ring group, bite-ring ring group, scaly ring group, fluorene group: pyridine ring group, ring group, isoxazole ring isothiazole ring group, pyrimidine Storm: tender: well ring base, seat ring base, oxime ring group, fluorenyl group, tetrazole ring group or -S (=〇)~, q system 1 or 2,

Ar1 represents the following formula αη—ρ,: 323256 89 201206906 and Ε each independently represents a carbon atom or a nitrogen atom, and the quinone (the k-chain which can be substituted by a hydroxyl group or a fluorine atom in each group may be substituted by a secret or a gas atom) The Cw alkoxy group, the halogen atom, the cyano group or the nitro group, the substitutable position of &amp;, E2 or π may have a substituent selected from the group consisting of a hydroxyl group or

a Cr atom-substituted Ch alkyl group, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a halogen atom, a cyano group, and _NRc35Rd35),

Ar2 represents the following formula Ar2-l&quot;:

(each of the bases 7, κ2, κ3, and K4 independently represent a carbon atom or a nitrogen atom (except that Κ, Κ, Κ, and Κ4 all represent a nitrogen atom at the same time), γ represents a halogen atom, a cyano group, or a nitro group, Κ1 a substitutable position of Κ, Κ2, Κ3 and κ4, • may have a substituent selected from the group consisting of a Ci-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a C1_3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, Hydroxyl, tooth atom, cyano group and -NRe36Rd36). [Item 13] The compound of any one of the items γ to 5, and the item R to the item 12, or a physiologically acceptable salt thereof, wherein L represents a benzene ring group, a thiophene ring group, a furan ring group. , cyclyl, imidazocyclyl, acridine ring, anthracenyl, isoxazole ring, carbazole ring, isothiazole ring, pyrimidine ring, anthracenyl, indazole ring , thiazole ring group, triazole ring group or tetrazole ring group 323256 90 201206906. The compound represented by the following formula (r)':

The compound of the present invention, or the physiologically acceptable salt thereof, wherein the q' system or the following formula (Γ')' is represented by the item 2' to the item 12'. Compound: -W / T II,,,,, August 1 "A .. .

[Item 15,] Item Γ to the compound of Item 5', Item 7' to Item 12', or a physiologically acceptable salt thereof, wherein L' represents a benzene ring group, an imidazole ring group, or a hydrazine The following formula (I&quot;&quot;) of a pyridine ring group, a hydrazine ring group, an isoxazole ring group, an η-biazole ring group, a pyrimidine ring group, an indazole ring group, a triazole ring group or a tetrazole ring group Compounds shown:

91 323256 201206906 [Item 16,] A pharmaceutical composition, which comprises the compound of any one of Item 1 to Item 15', or a physiologically acceptable salt thereof, and a carrier for preparation, which contain the active ingredient. [Item 17,] - an elastase inhibitor comprising, as an effective age, a compound described in any one of items 1 to 5 or a physiologically permissible dry sputum 〇® [item 18'] A therapeutic or prophylactic agent for a disease, which comprises the compound described in the item to the item 15' or the physiologically acceptable salt thereof. [Item 19,] A therapeutic or preventive agent for a disease in which an inhibitory activity against an enzyme of an elastic egg is required, which comprises the compound according to any one of Items 1 to 4 or a physiologically acceptable salt thereof. φ (Effect of the Invention) According to the present invention, a compound having an inhibitory activity against elastase can be provided, and a therapeutic or prophylactic agent for a disease associated with elastase such as an inflammatory disease can be provided. As diseases showing elastase-related pathologies, for example, chronic obstructive pulmonary disease (c〇pD), pulmonary cystic fibrosis, emphysema, adult respiratory distress syndrome (ARDS), acute lung injury (WLI), and special diseases are known. Pulmonary fibrosis (ΠΡ), chronic interstitial pneumonia, chronic bronchitis, chronic respiratory infection, diffuse panbronchiolitis, bronchiectasis, qi%, pancreatitis, nephritis, liver failure, chronic rheumatic joints Inflammation, joint 323256 92 201206906 Stiff, deformed joint disease, psoriasis, periodontal disease, atherosclerosis, rejection of organ transplantation, early water break, blisters, shock, sepsis, systemic lupus erythematosus (SLE), Crohn's Crohn's disease, disseminated jk intraductal coagulation '(DIC), tissue damage during devascularization-reperfusion, formation of corneal scar tissue, myelitis, squamous cell lung cancer, lung adenocarcinoma, non-small cell lung cancer, etc. Lung cancer, breast cancer, liver cancer, bladder cancer, colorectal cancer, skin cancer, pancreatic cancer, glioma, and the like. [Embodiment] ® Hereinafter, the compounds represented by the formula (I) and the formula (I)' of the present invention will be further described. The physiologically acceptable salt of the compound of the formula (I) and the formula (I)' means physiologically a compound of the formula (I) and the formula (I)' having a group capable of forming an acid addition salt in the structure. A permissible acid addition salt, or a physiologically acceptable salt formed with a base of a compound of the formula (I) and formula (I)' having a structure capable of forming a salt with a base. Specific examples of the acid addition salt include inorganic acid salts such as hydrochloride, Φ hydrobromide, hydroiodide, sulfate, peroxy acid salt and phosphate, and oxalate and malonate. , maleic acid salt, fumarate, lactate, malate, citrate, tartrate, benzoate, trifluoroacetate, acetate, methanesulfonate, p-benzoquinone An organic acid salt such as a sulfonate or a trifluorosulfonium sulfonate, and an amino acid salt such as a glutamic acid salt and an aspartic acid salt. Specific examples of the salt formed with the base include an alkali metal or an alkaline earth metal salt such as a sodium salt, a potassium salt or a calcium salt, an organic alkali salt such as a pyridinium salt or a triethylamine salt, and an aminic acid or a fine acid. a salt of an amino acid such as an amine acid. The compound of the formula (I) and the formula (I)' and the salt thereof are also present in the form of a hydrate and 93 323256 201206906 / or a solvate, and thus the hydrates and/or solvates are also included in A compound of the invention. That is, the "compound of the present invention" includes the compound represented by the above formula (I) and formula (I)' and the physiologically acceptable salts thereof, together with the hydrates and/or solvates thereof. . Further, the compounds of the formula (I) and the formula (I) have a case of having one or more asymmetric carbon materials, and further, geometrical chimerism and axial chirality are generated, and thus It exists as several stereoisomers. In the present invention, the stereoisomers, the mixtures and the racemates are contained in the compounds of the formula (I) and the formula (I) of the present invention. The following is a description of the terms used in this specification. "alkyl" means a linear or branched saturated hydrocarbon group, and "C13 炫", "Cw alkyl" and "Cm. alkyl" mean that the number of carbon atoms is i to 3, 1 to 6, respectively. And the base of 1 to 1〇. As a specific example, a "Ci 3 alkyl group" may, for example, be a methyl group, an ethyl group, a propyl group or an isopropyl group. Examples of the "Ci6 alkyl group" include a butyl group and an isobutyl group. The second butyl group, the third butyl group, the pentyl group, the isopentyl group, the neopentyl group, the hexyl group, etc., and the "Ci iq alkyl group" may be exemplified by the addition of an octyl group, a decyl group, a decyl group or the like. The alkyl group may be linear and may be branched. Preferably, the "CN 3 alkyl group" may, for example, be a methyl group, an ethyl group, a propyl group or an isopropyl group, and the "Ci-e alkyl group" may, for example, be a mercapto group, an ethyl group, a propyl group or an isopropyl group. The butyl group, the tributyl group, the pentyl group and the hexyl group may be exemplified by a mercapto group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a pentyl group or a hexyl group. The alkyl group of the alkyl group is synonymous with the above-mentioned "hospital group". Specific examples of the "alkylthio group" include a methylthio group, an ethylthio group, a propylthio group, and an isopropylthio group. The third butylthio group or the like is preferably a methylthio 323256 94 201206906 group and an ethylthio group. The alkyl moiety of the "alkylcarbonyl group" has the same meaning as the above "alkyl group", and specific examples of the "alkylcarbonyl group" include a methylcarbonyl group, an ethylcarbonyl group, a propylcarbonyl group, an isopropylcarbonyl group, and a butylcarbonyl group. The third butylcarbonyl group (trimethylethenyl group) is preferably a mercaptocarbonyl group, an ethylcarbonyl group, a propylcarbonyl group, an isopropylcarbonyl group or a tert-butylcarbonyl group. The "cycloalkyl group" means a cyclic hydrocarbon group, and preferably means a cyclic saturated hydrocarbon group. For example, "Ca-e cycloalkyl group" may, for example, be cyclopropane, cyclobutane, cyclopentane or cyclohexane. Preferred are cyclopropane, cyclobutane and cyclopentane. The "saturated carbocyclic ring" means a cyclic saturated hydrocarbon group. For example, the "Cm saturated carbon ring" may, for example, be a cyclopropane, a ring, a ring, or a ring. Preferred are cyclopropane, cyclobutane and cyclopentane. The alkenyl group means a linear or branched unsaturated hydrocarbon group. For example, "c26 alkenyl group" means a group having 2 to 6 carbon atoms and having an unsaturated bond. Specific examples thereof include ethylene, 1-propene, 2-propene, 1-butene, 2-butadiene, 3-butene, pentene, 2-pentene, 3-pentene, and 4-pentene. , 1-hexene, 2-hexene, 3-hexene, 4-hexene, 5-hexene, 2-methyl_3_butan, 2-methyl-2-pentene, 3-methyl 2-pentene and the like. Preferred are ethylene, 2-propylene and 2-butadiene. The "halogen atom" may, for example, be a fluorine atom, a gas atom, a bromine atom or an iodine atom. Preferred are a fluorine atom, a gas atom and a bromine atom. The "oxygen group" is a group in which a base is bonded to an oxygen atom, and the "alkyl group" is synonymous with the above "burning group". For example, a specific example of the "Ch alkoxy group" may, for example, be a methoxy group, an ethoxy group, a n-propoxy group or an isopropoxy group, and a specific example of "C! 6 95 323256 201206906 alkoxy group" may be mentioned. The foregoing is exemplified by n-butoxy group, isobutoxy group, second butoxy group, tert-butoxy group, pentyloxy group, hexyloxy group, etc., preferably exemplified by decyloxy group and ethoxy group. , n-propoxy, isopropoxy and n-butoxy. The "alkoxycarbonyl group" is a group in which an alkoxy group is bonded to a carbonyl group, and the "alkoxy group" and the above-mentioned "silk group" (4) are exemplified as a soil type of "green base". The ethoxy group, the propoxy group, the isopropoxy group, the oxy group, the quinoneoxycarbonyl group #, preferably methoxycarbonyl, ethoxy, propoxy, Isopropoxy group and a third butoxycarbonyl group. As the "5 to 6 membered aromatic ring group which may contain a group selected from the group consisting of N, 0 and 3 to 3 hetero atoms", means a phenyl group and is selected from a gas atom, an oxygen atom and a sulfur atom. One to three heteroatoms of the group formed, and a monocyclic 5- to 6-membered aromatic heterocyclic group composed of a broken atom. Specific examples thereof include a phenyl group; a thiophene group, a thiol group, a squaring group, a sulphate group, a hydrazinyl group, a thiol group, a Pf sulph group, an isoindolyl group, and a thiol group.嗔Saliva, Li «base, base, 喽 disali, Naji, triterpene and so on. Preferably, the phenyl group is a butyl group, a fluorenyl group and a triterpene group. The "5 to 6 member aromatic ring group which may contain a hetero atom selected from the group consisting of N, hydrazine and S" may be mentioned. It means a hetero atom and a hetero atom of a group consisting of a nitrogen atom and a sulfur atom selected from a nitrogen atom, and a monocyclic 5- to 6-membered aromatic heterocyclic group composed of a stone. For example, an example of a member group of a hetero atom belonging to a group consisting of N, 0, and S can be exemplified, and a tetrasyl group or the like can be added. Preferred are a base group, a pyridyl group, a pyridinyl group and a triazolyl group. 323256 96 201206906 as "a 5-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S", means consisting of a nitrogen atom, an oxygen atom and a sulfur atom The monocyclic 5-membered aromatic heterocyclic group consisting of 1 to 4 hetero atoms and carbon atoms in the group may, for example, be an oxazolyl group such as a thienyl group, a furyl group, a tonyl group, an imidazolyl group or an anthracene group. Carbazolyl, pyrazolyl, thiazolyl, isothiazolyl, fluorene fazolyl, thiadiazolyl, triazolyl, tetrazolyl, and the like. Preferably, an imidazolyl group, a pyrazolyl group and a triazolyl group are exemplified. Lu as "a 6-membered aromatic ring group which may contain 1 to 4 nitrogen atoms" means a phenyl group and a monocyclic 6-membered aromatic heterocyclic group composed of 1 to 4 nitrogen atoms and carbon atoms. . Specifically, a strepyl group, a pyridyl group, a pyrimidinyl group, a trimorphyl group, a tetramorphyl group or the like can be exemplified. Phenyl and pyridyl are preferred. The "3 to 6 member saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S" may, for example, be a monocyclic saturated hydrocarbon having 3 to 6 carbon atoms. An aliphatic cyclic group, and a 3 to 6 membered monocyclic saturated heteroalicyclic group having 1 to 2 atoms of the same or different species selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom. The nitrogen atom, the oxygen atom and the sulfur atom are all atoms constituting the ring. Specifically, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a tetrahydropyranyl group, an azetidinyl group, a π-pyridyl group, an imidazolidinyl group, a pyrazolidine group, and a piperidyl group are mentioned. Pyridyl, piperidinyl, morpholinyl, thiomorpholinyl (丨〇丨〇111〇印}1〇1丨1^1), oxazolidinyl, tetrahydrothiazolyl, isoxazolidinyl, iso Tetrahydrothiazolyl, tetrahydrofuranyl and the like. Preferred examples thereof are a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, an azetidinyl group, a pyrrolebityl group, a butyl group, a piperidinyl group, a morpholinyl group, a thiomorpholinyl group, and a carbazole. Pyridyl, isoindole. Base and tetrahydrofuranyl. 323256 97 201206906 as "a group of 4 to 6-membered saturated aliphatic rings which may be selected from the group consisting of N and oxime: 2 to 6 hetero-atoms, and the clothing I", specifically &amp; Azetidinyl, phenylidene, brittle base, D- phenanthryl, chlorpyrifos, miso base, sputum base, etc. Preferably, azacyclobutyl, a butyl group, a sulfhydryl group, a thiol group, a fluorene group, and a fluorene-based group are exemplified. As the "4 to 6-membered unsaturated aliphatic cyclic group which may contain i to 2 hetero atoms selected from the group consisting of N, G and 3", a single ring having a carbon number of 4, 6 may be exemplified. An unsaturated hydrocarbon aliphatic cyclic group, and a 4 to 6-membered unsaturated heteroalicyclic ring group having from i to 2 atoms of the same or different species selected from the group consisting of a gas atom, an oxygen atom, and a sulfur atom. The gas atom, the oxygen atom and the sulfur atom are all atoms constituting the ring. Specifically, a cyclobutylcarbyl group, a cyclodecenyl group, a cyclohexyl group, a dihydron-brenyl group, a diazepane group, a π-pylinyl group, an imidazolinyl group, a pyrazoline group can be exemplified. (pyraz〇Hnyl), oxazolinyl, thiazporin*, dihydropyridyl and tetrahydropyridyl. Preferably, a cyclobutenyl group, a cyclopentenyl group, a dihydro φ pentanyl group, and a tetrahydrogen ratio are defined. The "4 to 6-membered unsaturated aliphatic cyclic group containing hydrazine to two hetero atoms selected from the group consisting of N and hydrazine" may, for example, be of the same or different species selected from the group consisting of a nitrogen atom and an oxygen atom. An early % unsaturated heteroalicyclic ring group of 1 to 2 atoms of 4 to β Chang mussel. Both the nitrogen atom and the oxygen atom are atoms constituting the product. Specifically, it may, for example, be a dihydropiperidyl group, a dihydrofuranyl group, a long-saltyl group, an imidazolinyl group, a carbazino group, a hydrazone group or a hydrazine group. Preferably, dihydropiperidyl and tetrahydro-pyridinyl are exemplified as "4 to 6-membered saturated aliphatic 323256 98 201206906 containing 1 or 2 oxime may be exemplified by having 1 or 2 nitrogen atoms to 4 The above-mentioned nitrogen atom is an atom constituting a ring. Specific examples thereof include azacyclobutyl group, pyrrolidinyl group, piperidinyl group, piperidinyl group, imidazolidinyl group and the like. The azacyclobutyl group, the pyrrolidinyl group, the piperidinyl group, the piperylene group, and the imidazolidinyl group may be exemplified as "a bond N together" and may further contain a group selected from N, 0, and S. The 4 to 6-membered saturated or unsaturated aliphatic cyclic group of 1 to 2 hetero atoms may be exemplified to contain a nitrogen atom, and may further contain 1 to 2 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. 4 to 6 members of the saturated and/or unsaturated heteroaliphatic ring group. Specific examples thereof include azetidinyl group, 0-p each α-based group, bridging β-based group, morphinyl group, thio-indenyl group, D-indenyl group, tetra-argon- 0-indenyl group, and dihydrogen ratio. 17 bases and so on. Preferably, azetidinyl group, a pyridine group, a brittle base, a morphine group, an α bottom basing group, and a tetrahydro α ratio α group are exemplified. The "3 to 6-membered saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N and 0" may, for example, be a monocyclic saturated hydrocarbon aliphatic having 3 to 6 carbon atoms. a cyclic group, and a 3 to 6 membered saturated heteroalicyclic group having 1 to 2 hetero atoms selected from a nitrogen atom and a φ oxygen atom. Specifically, it may, for example, be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a tetrahydro-schemantyl group, a tetrahydropyranyl group, an azetidinyl group, an alpha ratio 17 each bite group, or a brigade. Biting base, morpholinyl, piperage, and the like. Preferred examples thereof are a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a tetrahydrofuranyl group, a tetrahydropyranyl group, an azetidinyl group, a pyridyl group, a piperidinyl group, a morpholinyl group and a piperidine. base. The "alkyl group substituted with a halogen atom" is one or more (e.g., 1 to 5, preferably 1 to 3) hydrogen atoms of the above alkyl group are substituted by a halogen atom. Specifically, a fluoromethyl group, a difluorodecyl group, a trifluoromethyl group, 2, 2, 2-99 323256 201206906 dioxetyl group, 1,1_difluoroethyl group, 1_mercaptoyl group 2 may be mentioned. , 2,2-Trifluoroethyl, 3,3,3_trifluoropropyl, 4,4,4-trifluoro 1 butyl, chloromethyl, gas ethyl, chloropropyl, butyl butyl, bromine Sulfhydryl, bromoethyl, bromopropyl, bromobutyl, iodomethyl, iodoethyl, iodopropyl, iodobutyl and the like. Preferred are fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trifluoroiethyl and 1,1-difluoroethyl. The "alkoxy group substituted with an iS atom" is one or more (e.g., 1 to 5, preferably 1 to 3) hydrogen atoms of the above alkoxy group are substituted by a halogen atom. Specific examples thereof include a fluoromethoxy group, a difluoromethoxy group, a trifluoro*decyloxy group, a 2,2,2-trifluoroethoxy group, a 1,1-difluoroethoxy group, and a 1-fluorene group. -2, 2, 2-trifluoroethoxy, 3, 3, 3-trifluoropropoxy, 4, 4, 4-trifluorobutoxy, chloromethoxy, chloroethoxy, chloroprop Oxyl, chlorobutoxy, bromoethoxy, bromopropoxy, bromobutoxy, iodoethoxy, iodopropoxy, iodobutoxy and the like. Preferred are fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trieethoxy and 1,1-diethoxyethoxy. The "alkylthio group substituted by an iS atom" is a hydrogen atom of 2 or more (e.g., 1 to 5, preferably 1 to 3) of 1 or φ of the above alkylthio group, which is substituted with a halogen atom. Specifically, a trifluoromethylthio group, a 2, 2, 2-trifluoroethylthio group, a 2-fluoroethylthio group, a 3-fluoropropylthio group, a 3, 3, 3-three group is exemplified. The fluoropropylthio group is preferably a trifluoromethylthio group and a 2, 2, 2-trifluoroethylthio group. The "alkylcarbonyl group substituted by a halogen atom" is one or more (e.g., 1 to 5, preferably 1 to 3) hydrogen atoms of the above alkylcarbonyl group substituted by a halogen atom. Specifically, a trifluoromethylcarbonyl group, a 2-fluoroethylcarbonyl group, a 2, 2, 2-trifluoroethylcarbonyl group, a 3, 3, 3-trifluoropropylcarbonyl group, etc. may be mentioned, which is better than 100 323256 201206906. A trifluoromethyl group, a 2-fluoroethyl group, and a 2, 2, 2-trifluoroethylcarbonyl group are mentioned. The alkoxy group substituted by a halogen atom is one or more (e.g., 1 to 5, preferably 1 to 3) hydrogen atoms of the above alkoxy group substituted by a halogen atom. Specific examples thereof include a trifluoromethoxycarbonyl group, a 2-fluoroethoxycarbonyl group, a 2,2,2-trifluoroethoxycarbonyl group, a 3,3,3-trifluoropropoxycarbonyl group, and the like. A trifluoromethoxycarbonyl group, a 2-fluoroethoxycarbonyl group, and a 2,2,2-trifluoroethoxycarbonyl group are exemplified. The "aromatic ring group substituted with a halogen atom" means the above aromatic ring group substituted with oxime to three substituents selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. "saturated aliphatic cyclic group substituted by _ atom" means a monocyclic 3 to 6-membered saturated fat substituted with 1 to 3 substituents selected from the group consisting of a fluorine atom, a bromine atom and an iodine atom. Family ring base. Specific and ancient, can be solved I cyclopropyl 'di(tetra)propyl, I cyclobutyl, dicyclobutene i, = soil, -chlorocyclobutyl, fluorocyclopentyl, dicyclopentyl, gas cyclopentane Earth fluorocyclohexyl, difluorocyclohexyl and the like. Preferred are fluorocyclopropyl, difluorocyclopropyl, fluorocyclobutyl and difluorocyclobutyl. "Atomically substituted unsaturated aliphatic cyclic group" means a group consisting of a group consisting of a fluorine atom, a bromine atom and an iodine atom, and is replaced by three mountains and soils. Unsaturated aliphatic cyclic group. Specific and two:! Gas cyclobutenyl, dicyclopentenyl, cyclobutadienyl, difluoro, fluorocyclopentenyl, divirenyl, chlorocyclopentyl, gas, and nicotine A mess of hexene and so on. Preferably, a fluorocyclobutenyl group, 323256 101 201206906 difluorocyclobutenyl group, and difluorocyclopentenyl group are exemplified. The "hydroxyl-substituted alkyl group" is a hydrazine of the above alkyl group or a hydrogen atom of two or more (e.g., 1 to 5, preferably 1 to 2) groups substituted by a hydroxyl group. Specifically, a hydroxymethyl group, a 2-hydroxyethyl group, a 2-hydroxypropyl group, a hydroxypropyl group, a 1,3-dihydroxypropyl group, a 2,3-dihydroxypropyl group, and a 2-diyl group can be exemplified. , 3-hydroxybutyl, 4-hydroxybutyl, 2,3-dihydroxybutyl, &amp; = dihydroxybutyl, 2,4-di-butylbutyl, 2-ylpentyl, 3_ By pentyl group, 4-secuylpentyl, 5-M base filament, base filament, 3,5-di-p-pentyl group, 2-p-hexyl group, 3-p-hexyl group, 4, hexyl group, yl group, 6 - via hexyl group, 2,6-di-diylhexyl, 3,6-diylhexyl, 4,6-di-hexyl, 2, isopropyl, sec-butyl, 3_second Butyl, 2-trans-tert-butyl, 3-methyl-5-ylpentyl, 3-methyl-methyl 3-methylpentyl, 4-methyl+-peylamyl, 4-methyl 4_ylpentyl, sulfonyl-3, pentyl group and the like. Preferred examples thereof include a methyl group, a 2-methyl group, a 2'-propyl group, a hydroxy-2-propyl group, a 3-hydroxypropyl group and a dihydroxy-2-propyl group. "The warp-based silk-based group" is a hydrogen atom hetero group substitution of i or more than two (for example, 1 to 5, preferably ～!), and specifically, 2 , ethoxylated, 2-propenyloxy, 3 _ propyloxy, i,3-di-propylpropoxy, 2,3-di-propoxy, 2-hydroxyloxy, 3- By-butoxy group, 4-monobutyloxy group, 2,3-di-butyryoxy group, 3,4-di-butylbutoxy A, 2,4-di-butylbutoxy group, 2-cysyl group Pentyloxy, 3'-ylpentyloxy, 4,ylpentyloxy, 5-depentyloxy, 2,5-di-dipentylpentyloxy, 3,5-di-transpentyloxy, 2-hydroxyl Oxygen, 323256 102 201206906 ^Hexyloxy, 4, hexyloxy, 5-hydroxyhexyloxy, 6-ylhexyloxy-2,6-fluorenylhexyl, 3,6-dihydroxy Hexyloxy, 4, dihydroxyhexyloxy, hydroxy-2-propoxy, 2-hydroxy-2-butoxy, 3-hydroxy-2-butoxy, 3-methyl-5-hydroxypenta Oxyl, 3-mercapto-3-hydroxypentyloxy, 4-methyl-5-hydroxypentyloxy, 4-methyl-4-hydroxybutoxy, 4-methyl J3 hydroxypentyloxy and the like. Preferably, it is 2-ethoxymethyl, propyloxy, 1-hydroxy-2-propoxy, 3-hydroxypropoxy and anthracene, 3 dihydroxy-2-propoxy. The "alkyl group substituted by a radical" is one or two of the above alkylthio groups, and a hydrogen atom of the above (e.g., 1 to 5 'preferably 1 to 2) groups are substituted with a base. (4) A 2-carbylethylthio group, a 2-carbyl-1-propylthio group, a 3-hydroxypropylthio group, a 1-hydroxy-2-propylthio group or the like can be exemplified. Preferably, 2'-ethylthio group, 3-myl group + sulfenyl group and dipyridyl-2-propylthio group are exemplified. The "alkyl group substituted by a radical" is a hydrogen atom of 1 or 2, (e.g., 1 to 5 'preferably 1 to 2) of the above alkylcarbonyl group, which is substituted with a base. (4) For the sake of exemplification, it may be exemplified by a methyl group, a (tetra)ethyl-Wiki group, a propyl group-based group, a isopropyl group-based group, and a base group. Preferably, it is exemplified by a benzyl group, a benzyl group, a (tetra) propyl group and a butyl group. The oxycarbonyl group in which 〆 ', ' is substituted by a hydroxy group is one or two or more (for example, 1 to 5 'preferably 1 to 2) hydrogen atoms of the above oxycarbonyl group are substituted with a &amp; Specific examples thereof include a heteroethoxymethyl group, a propyloxycarbonylcarbonylisopropoxycarbonyl group, a hydroxybutoxycarbonyl group and the like. Preferably, 103 323256 201206906 =! Lifting wire ethoxy group, listening to propoxy (tetra) and reducing isopropoxy group "hetero-substituted silk ring group" is on the group ring of ι or 2 (for example, 1 to 2) The ruthenium atom is replaced by a base. "_丝丝鲜白_基" is a saturated aliphatic group: one or more hydrogen atoms of the soil (for example, to two) are substituted by a base 2, and specifically, a cyclopropyl group and a hydroxyl group are exemplified. Cyclobutyl, cyclized, nucleus and the like. Preferably, a cyclopropyl group, a transcyclobutyl group and a hydroxycyclopentyl group are exemplified. The "hydroxy-substituted unsaturated aliphatic cyclic group" is one in which one or more (e.g., two to two) hydrogen atoms of the above unsaturated aliphatic ring group are substituted with a base. Specifically, (iv) a cyclobutenyl group, a transcyclopentylene group, an interesting cyclohexene, or the like can be exemplified. Preferably, a cyclopentenyl group and a minus group are exemplified. The "alkyl group substituted by an alkyl group" is one in which one or more (for example, 1 to 2) hydrogen atoms of the above aromatic ring group are substituted with an alkyl group. The aryl group-substituted aromatic ring group is one or more (for example, 1 to 2) hydrogen atoms of the above aromatic ring group substituted by a cyano group. The "cyano-substituted alkyl group" is one or two or more (e.g., one to two) hydrogen atoms of the above alkyl group substituted by a cyano group. Specifically, a cyanoguanidino group, a cyanoethyl group, a cyanopropyl group, a cyanoisopropyl group, a cyanobutyl group, a cyanoisobutyl group, a cyanopentyl group, a cyanohexyl group, a cyano group may be exemplified. Octyl, cyanoguanidino, cyanoguanidyl and the like. Preferred are cyanoguanidino, 2-cyanoethyl, cyanoethyl, 3-cyanopropyl, 1-cyano-2-propyl and 4-cyanobutyl. 323256 104 201206906 The "cyano-substituted alkane group" is one in which two or more (for example, 1 to 2) hydrogen atoms of the above alkoxy group are substituted with a cyano group. Specifically, a cyanomethoxy group, a cyanoethoxy group, a cyanopropoxy group, a cyanoisopropyl group, a cyanobutoxy group, a cyanopentyloxy group, a cyanohexyloxy group, Cyanooctyloxy, cyanomethoxy, cyanomethoxy and the like. Preferred are cyanomethoxy, cyanoethoxy, 3-cyanopropoxy, 1-cyano-2-propoxy and cyanobutylation. &quot; • The "cyano-substituted alkyl group" is one or more (e.g., 1 to 2) hydrogen atoms of the above-described alkyl group substituted by a cyano group. Specific examples thereof include a cyanoguanidinyl group, a cyanoethyl group, a cyanopropyl group, a nitrogen isopropylcarbonyl group, a cyanobutylcarbonyl group, a cyanopentylcarbonyl group, and a cyanohexyl group. A few bases, etc. Preferably, a cyanononylcarbonyl group, a cyanoethylcarbonyl group, an allylmethyl group, a cyanoisopropyl group, and a cyanobutyl group are exemplified. The "cyano-substituted saturated aliphatic ring group" is one or more (e.g., 1 to 2) hydrogen atoms of the above saturated aliphatic ring group substituted by a cyano group. Specifically, a cyanocyclobutyl group, a cyanocyclopentyl group, a cyanocyclohexyl group, a cyanopyrrolidyl group, a cyanopiperidinyl group, a cyanopiperazinyl group, or a cyanomorpholino group can be exemplified. , cyanotetrahydrofuranyl and the like. Preferred are cyanocyclobutyl, cyanocyclopentyl, cyanocyclohexyl, cyanopyrrolidyl and cyanopiperidinyl. The "cyano-substituted unsaturated aliphatic ring group" is one or more (e.g., 1 to 2) hydrogen atoms of the above unsaturated aliphatic ring group substituted by a cyano group. Specifically, the exemplification is cyanocyclobutenyl, cyanocyclopentenyl, cyanocyclohexenyl, cyanodihydropentanyl, cyanodihydrofuranyl, cyanodihydropyridinium. Base, cyanotetrahydropyridyl and the like. Preferred are cyanocyclopentenyl, 323256 105 201206906 cyanocyclohexenyl, cyanodihydroacridinyl and cyanotetrahydroacridinyl. The "alkoxy-substituted alkyl group" is a hydrazine of the above alkyl group or a hydrogen atom of two or more (e.g., 1 to 3) substituted by the above alkoxy group. Specifically, a methoxyethyl group, an ethoxyethyl group, a propoxyethyl group, and an isopropyloxy group can be mentioned. Ethyl ethyl, methoxypropyl, ethoxypropyl, propoxypropyl, isopropoxypropyl, decyloxyisopropyl, ethoxy isopropyl, propoxy isopropyl, Isopropoxy isopropyl, methoxybutyl, ethoxybutyl, propoxy butyl, isopropoxy butyl, methoxyisobutyl, ethoxyisobutyl, propoxy Isoyl, isopropoxyisobutyl, and the like. Preferred examples are methoxyethyl, ethoxyethyl, propoxyethyl, isopropoxyethyl, methoxypropyl and propyl. The "alkoxy-substituted aromatic ring group" is one in which the above aromatic ring group or two or more (e.g., up to three) hydrogen atoms are substituted by the above alkoxy group. The alkyloxy group substituted by an alkoxy group is one or more (for example, 1 to 3) hydrogen atoms of the above-mentioned alkyl group to be substituted by the above alkoxy group. Specific examples thereof include a methoxymethylcarbonyl group, an ethoxylated carbonyl group, a methoxyethyl group, an ethoxyethyl group, a methoxypropyl group, a methoxyisopropylcarbonyl group, and the like. . Preferably, a methoxycarbonylcarbonyl group, an ethoxymethylcarbonyl group, a methoxyethylcarbonyl group, and an ethoxyethylcarbonyl group are exemplified. "Alkoxy-like saturated saturated tree group" is a saturated aliphatic (tetra) group. One or more (for example, i to three) hydrogen atoms are substituted by the above alkoxy group. Specifically, fresh oxime methoxypropyl, ethoxycyclopropyloxycyclobutyl, ethoxycyclobutyl, methoxycyclopentyl, methoxycyclohexyl, decyloxytetraindole Piperidyl, methoxyindolepyridyl, oxime 323256 106 201206906 hydrazinyl, decyloxytetrahydrofuranyl and the like. Preferred are methoxycyclopropyl, ethoxycyclopropyl, methoxycyclobutyl, ethoxycyclobutyl, decyloxycyclopentyl and decyloxycyclohexyl. The "alkoxy-substituted unsaturated aliphatic cyclic group" is one or two or more (e.g., one to three) hydrogen atoms of the above unsaturated aliphatic cyclic group substituted by the above alkoxy group. Specifically, an oxiranylcyclobutenyl group, a decyloxycyclopentenyl group, a decyloxycyclohexenyl group, an ethoxycyclobutenyl group, an ethoxycarbonylcyclopentenyl group, an ethoxy group A cyclohexene group, a decyloxydihydropyranyl group, a methoxydihydrofuranyl group, a decyloxytetrahydropyridyl group or the like. The "house group substituted with a substituted aromatic ring group" is one or more hydrogen atoms of the above-mentioned base group which are substituted by a "substitutable aromatic ring group". Specifically, 'any of the alkyl groups having a carbon number of 1 to 6 may be exemplified by an aromatic ring group such as a phenyl group, a pyridyl group, a sulfonyl group, a succinyl group or a π-bisazolyl group which may be substituted. Specific examples of the substituent in which the hydrogen atom is substituted with the alkyl group as the substituted aromatic ring group include an anthraceneoxy group, a methanesulfonyl group, a dinonylamine C# group, a cyano group and the like. The "alkoxy group substituted with an aromatic ring group which may be substituted" is bonded to the group of the oxygen atom by the above-mentioned "alkyl group substituted with a substituted aromatic ring group". The "alkylthio group substituted with an aromatic ring group which may be substituted" is bonded to the group of the sulfur atom by the above-mentioned "alkyl group substituted with an aromatic ring group substituted". The saturated aliphatic ring group substituted by a pendant oxy group is a hydrogen atom of the above-mentioned saturated aliphatic group 2 ring group substituted by i or two pendant oxy groups, for example, f 2 to pendant oxycyclopentyl group, side Oxycyclopentyl, 2-oxocyclohexyl, Cyclohexyl, 4-sided oxocyclohexyl, 2-tertiary oxy-[o-bite, 323256 107 201206906 3: sideoxy stellate, 2 , 5_di-terminated oxyfilament, 2-side oxothyridinyl, 3-oxopiperidinyl, 4-oxoxypiperidinyl, 2,6-di- oxy oxyl, 2 - sideoxy squara, 3_sideoxy (tetra)yl, 2_sideoxy^-linyl, 2,oxythio-recommended, occupational (four) silk, two-sided oxy miso base, side oxygen Based on the (four) base, the two-side oxygen-based group, and the two-side gas-based sigh base. Preferably, it is a 4-oxocyclohexyl group, a 2-sideoxy^(tetra)yl '3'oxyl group, a 2-sideoxyl group, and a 3-sideoxycarbonyl group. The earth is an unsaturated aliphatic ring group substituted by a pendant oxy group, and the hydrogen atom of the above unsaturated aliphatic ring group is substituted by 1 or 2 pendant oxy groups, for example, a side oxy ring reading group, side Oxycyclocyclohexenyl, pendant oxyfluorenyl, pendant oxyzirthene, pendant oxy group, side oxygen (tetra) sialyl, side, hydroxydi-t-butyl, pendant oxytetrahydrogen Base. It is difficult to exemplify the side = reduction, the (4) base, the pendant oxy group H-based scopolyltetrahydropyridyl.

Other bases are also defined and exemplified in the same manner as the above examples. Further, an aliphatic cyclic group means an alicyclic group. "(Aromatic) heterocyclic group" and "(aromatic)" The heterocyclic group in the specification of the present application is synonymous. The various bases of the invention are described. Hereinafter, the base in the formula (I) will be explained. F represents a hydrogen atom or a Ci 6 alkyl group which may be substituted by a hydroxyl group or a (tetra) group, preferably a hydrogen atom or a fluorinated atom or a fluorine atom. 3 323256 108 201206906 More preferably represents a hydrogen atom, a methyl group, an ethyl group, Trifluoromethyl, difluoromethyl, hydroxyindenyl, hydroxyethyl. R represents an atomic group of a Ci-6 group substituted by a radical or a halogen atom which may be substituted by a decyloxy group or a nitro group or a C3-6 cycloalkyl group which may be substituted by a hydroxyl group or a tooth atom. a hydrogen atom, a C1-6 alkyl group which may be substituted by a hydroxyl group or a functional atom, a phenylhydrazine group which may be substituted by a decyloxy group or a nitro group, more preferably a hydrogen atom, a Cm alkane group which may be substituted by a hydroxyl group or a fluorine atom. .

Rc' Rd independently represents a hydrogen atom or a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, or together represents a bond n, and further contains a group selected from N, 0 and S 4 to 6 members of two heteroatoms, saturated or unsaturated aliphatic cyclic groups (the aliphatic ring group, at its substitutable position, may be substituted by a Cm alkyl group, a hydroxyl group, a halogen atom or a pendant oxy group), Preferably, Rd independently represents a hydrogen atom or a Ci-3 sapon group which may be substituted by a hydroxyl group or a fluorine [sweet atom, or together represent i to 2 hetero atoms which may be selected from the group consisting of n and oxime. a 4- to 6-membered saturated heteroalicyclic group (the aliphatic ring group may be substituted by a Cm alkyl group, a trans group, a fluorine atom or a pendant oxy group at a substitutable position thereof), and a more preferred land of Re, Rd Each of which independently represents a hydrogen atom or a thiol group which may be substituted by a hydroxyl group or a fluorine atom, or together represents a saturated heterolipid group selected from the group consisting of azetidin, pyrrolidine, piperidine, piperazine and morpholine. a cyclic group (the saturated heteroaliphatic ring group, at its substitutable position, may be d-alkyl, hydroxy or fluoro Atomic substitution). 13 323256 109 201206906

Re represents a hydrogen atom, a Cw alkyl group (which may be substituted by a hydroxyl group, a cyano group, a halogen atom, a Ci-3 alkoxy group or a -NRcRd), _c(=〇)A, a Ci 6 alkylcarbonyl group (this The alkyl moiety of the alkylcarbonyl group may be substituted by a hydroxyl group, a halogen atom, a cyano group, a Ci 3 alkoxy group or —NR Rd), a Ci-6 alkoxycarbonyl group (the alkyl moiety of the alkoxycarbonyl group may be via a hydroxyl group or a halogen atom substituted), _C(=〇)NReRd4_s(=〇)iaRb, preferably a Cm alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group, a fluorine atom, a C&quot; alkoxy group or a -NRcRd), - a, -c(=〇)A,, G-6 alkyl carbonyl group (the alkyl portion of the alkylcarbonyl group may be substituted by a hydroxyl group or a halogen atom), ~C(=〇)NRcRd or -S(=〇 „Rb. represents a hydrogen atom, a trans group, a Ci-e alkyl group (the alkyl group may be substituted via a thiol group, a cyano group, a halogen atom, a G-3 alkoxy group or a —NRcRd), a Cu alkoxy group (the The oxy group may be substituted by a strepyl group, a thiol group, a cyano group, a dentate atom, a G-3 alkoxy group or a -NRcRd), -A or _NRaRi, which may be substituted by a decyloxy group or a nitro group. Preferred is a hydrogen atom, a hydroxyl group, a C1-3 alkyl group, a C1-3 alkoxy group, or -NITRi. 8 represents a hydroxyl group, a Ci-6 alkyl group (which may be substituted by a hydroxyl group, a cyano group, a functional atom, a Cm alkoxy group or a -NRcRd), -A or -NRf, preferably a G-6 alkyl group (this is preferably The alkyl group may be substituted by a hydroxyl group, a cyano group or a gas atom), -A or -NO1, more preferably a Cw alkyl group (the alkyl group may be substituted by a cyano group or a fluorine atom), -A or -NRaRi.

Rh represents a Ci-e alkyl group which may be substituted by a radical or a halogen atom, preferably a methyl group, an ethyl group, a trifluoromethyl group, p

Ri represents a hydrogen atom, a Cm alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group, a tooth U3256 110 201206906 atom, a Cl-3 alkoxy group, a Ch cycloalkyl group or a -NRcRd), -A, ~C (=: 〇) Rb, -C(=0)A' or Cw alkylcarbonyl (the alkyl moiety of the group may be substituted by a hydroxyl group, a halogen atom, a cyano group, a Cw alkoxy group or a _NReRd), preferably a hydrogen atom Ci 6 alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a fluorine atom, a Cl-3 alkoxy group, a c3_6 cycloalkyl group or a _NReRd). VIII represents a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position) may be as follows Substitution: a Cl_3 alkyl group which may be substituted by a hydroxyl group or a tooth atom, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or an i atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0)0H or -NReRd), or a 3 to 6 membered saturated or 4 to 6 membered unsaturated aliphatic ring group which may contain a group selected from the group consisting of n, fluorene and S to 2 heteroatoms (the aliphatic ring group, which may be substituted The position may be substituted by a Cw alkyl group which may be substituted by a hydroxyl group or an # atom, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0) 0H, -NReRd or pendant oxy), C. preferably represents a substitutable selected from the group consisting of phenyl, imidazolyl, pyridyl, pyridyl, oxazolyl, isoxazolyl, pyrazolyl, carbazole a group of a tricyclic group consisting of a group consisting of an isoxazolyl group, a pyrimidinyl group, a oxadiazolyl group, a thiadiazolyl group, a triazolyl group, and a tetrazolyl group, or a substitutable group selected from the group consisting of a cyclopropyl group, Cyclobutyl, Pentyl group, a cyclohexyl group, a pyran group, azetidinyl, pyrrolidinyl, floor of the mouth bite ratio η ° each group Lin Ji, ^ N. a saturated aliphatic-like ring group of a group consisting of a bite group and a tetrabite group (here, the substituent of the aromatic ring group is a Ci 3 alkyl group which may be substituted by a via group or a halogen atom, and may be subjected to a trans group. Or Cm methoxy, Schiff, dentate, ortho, -C(=0)0H or -NRcRd substituted by a tooth atom, lipid 111 323256 201206906 The substituent of the aliphatic ring group may be substituted by a hydroxyl group or a tooth atom C|_3 alkyl group, G-3 alkoxy group which may be substituted by a hydroxyl group or a tooth atom, a hydroxyl group, a tooth atom, an aryl group, -C(=0)〇H, -NR°Rd or a pendant oxy group), more preferably It is selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl. ratio. Sitting on the base. An aromatic heterocyclic group of the group consisting of a sulfonyl group, an isothiazolyl group, an oxadiazolyl group, a thiadiazolyl group, a triazolyl group, and a tetradecyl group (the aromatic heterocyclic group may be substituted by the following a Cl-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Ci-3 alkoxy group which may be substituted by a thiol or a fluorinated fluorine atom, a trans group, a fluorine atom, a cyano group, _c(=〇)〇h or - NReRd) 'or a saturated aliphatic ring group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperanyl, azetidinyl, pyrrolidinyl and piperidinyl (The aliphatic ring group may be substituted by a Cl-3 group which may be substituted by a hydroxyl group or a gas atom, a Ci-3 alkoxy group which may be substituted by a group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyanogen group Further, _c(=〇)〇H, md or pendant oxy), more preferably selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, C.-piperidyl, azetidin a saturated aliphatic ring group of a group consisting of a pyrrolidinyl group and a piperidinyl group (the aliphatic ring group may be substituted by a C, -3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom; Taked by hydroxyl or fluorine atom The burning Ci 3 group, a hydroxyl group, a fluorine atom, a cyano group, _C (= square) 〇H, or _NRcRd). A' represents a 5- to 6-membered aromatic ring group which may be selected from the group consisting of N, 0 and S to 4 heteroatoms (the aromatic ring group, at its substitutable position, can be passed down Said substitution: an alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cl 3 alkoxy group which may be substituted by a hydroxyl group or an atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0)0H or -NRf), or a 3- to 6-membered saturated or * to 6-membered unsaturated aliphatic ring group which may contain one to two heteroatoms selected from the group consisting of N, 〇323256 112 201206906 and S (the aliphatic ring group, The substitutable position may be substituted by the following: an alkoxy group substituted by a aryl group or an atom, an alkoxy group which may be substituted by a hydroxyl group or a _ atom, a hydroxyl group, a _ atom, a group, a -C (= 0) 0H, -NReRd or pendant oxy),

Preferably, it is a group 1 aromatic ring group which is selected from the group consisting of a phenyl group, a succinyl group, a butyl group, a fluorenyl group, an iso-yl group, a fluorenyl group, a sulfhydryl group, and a (tetra) ray. Representing a group selected from the group consisting of a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a (tetra)yl group, an azetidinyl group, a butyl group, a butyl group, a squara group, and a morphyl group. a saturated aliphatic fluorenyl group (herein, the substituent of the aromatic ring group is a (tetra) group or a (tetra) sub-substituted heart-burning group: a G-hydroxy group substituted with a brio group or an i atom, a dentate atom, an aryl group —c(=_ or Ca(R), the substituent of the aliphatic ring group is a Cm alkoxy group, a radical, a functional atom, an aryl group which can be substituted by a thiol group or a tetranuclear group. , &lt;(3))md or pendant oxy), more preferably a group selected from the group consisting of a sulphate, a sulphate, a sessile, a sulphonyl, an oxime, and an iso(tetra) group. a sulfhydryl group (the aromatic heterocyclic group can be substituted by a cyclyl or a gas atom substituted by a Cl_3, a methoxy group or a fluorine atom substituted by a G oxo group, a minus fluorine atom, a cyano group , -C(.H or |Rd), or Saturated bribes selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, S hexyl, (tetra), azetidinyl, trans-base, brigade, naji and # a ring group (the lipid-ring group is replaced by a blanking material.) (4) a fluorine atom substitution 323256 113 201206906 Cl_3 alkyl group, a C 3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, an I atom, a cyano group, _C(=0)0H, -NRcRd or pendant fluorenyl), more preferably selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, hexyl, fluorenyl, pyrrolidinyl a saturated aliphatic ring group of a hydrazine group of a piperidinyl group, a piperidinyl group and a morpholinyl group (the aliphatic ring group system may be substituted by a Cl-3 compound which may be substituted by a hydroxyl group or a fluorine atom) a Cl-3 alkoxy group, a hydroxyl group, a fluorine atom, a cyano group, φ ~ C (=0) 〇 H ' or a pendant oxy group which may be substituted by a hydroxyl group or a fluorine atom. R° represents, C (= 〇) NRa-, -S(=〇)2NRa-, -C(=0)〇-, -C(=〇)-, -S〇0)2- or a single bond, preferably R° means -C(= 0) NRa-, -S(=0)2NRa-, -c(=0)0_ or single bond, 〆 better indicates -C(=0)NRa-, -S(=〇)2NRa- or single , Based again more preferably represents -C (= square) NH- or a single bond. C· R represents a hydrogen atom, a C丨- ίο alkyl group, a CM alkenyl group, and may contain from 3 to 6 members of the group consisting of N and s, and 3 to 6 members are saturated or 4 to 6 members. An unsaturated aliphatic cyclic group, or means that it may contain a group selected from (a) and composed of! a 5- to 6-membered aromatic ring group of 4 heteroatoms, wherein the alkyl group and the base group are substituted at the position where they can be substituted from the group consisting of the substituents listed in Table 1. : # &amp; 3叮 Multiple substituent substituents Listing 1: (1) Hydroxy, (2) Halogen, 323256 114 201206906 (3) Cyano, (4) C!-6 alkoxy (the alkoxy The base, at its substitutable position, may be substituted by: a radical, a halogen atom, a cyano group, -C〇0)0Rb, -C(=0)NRcRd, ® may contain a group selected from N, 0, and S. 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group formed (the aromatic ring group, at its substitutable position, may be substituted by: substituted by a hydroxyl group or an i atom Ch alkyl, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd, -NRaS(=0)mRb , -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNReRd, -S(=0)mRb or -NRcRd) or may contain a group selected from N, 0 and S Group of 1 to 2 heteroatoms 3 (sweet to 6-membered or 4 to 6-membered unsaturated aliphatic ring group (the aliphatic ring group, which can be substituted The position may be substituted by a Ch alkyl group which may be substituted by a hydroxyl group or an atom, a Ch alkoxy group which may be substituted by a hydroxyl group or a functional atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd, -NRaS(=0)mRb, -C(=0)0Rb, -C〇0)NRcRd, -NRcRd or pendant oxy)), (5) G-6 alkylthio (The alkylthio group, at its substitutable position, may be substituted by: hydroxy, 115 323256 201206906 halogen atom, cyano group, _C(=0)0Rb, -C(=0)NRcRd, may contain 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: a G-3 alkyl group substituted with a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a zero-NRaC (=0) Rb, -NRaC (=0) NReRd, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)nRb or -NRcRd) may alternatively be selected from 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of 1 to 2 hetero atoms of the group consisting of N, 0 and S (the aliphatic ring group, which can be substituted The position may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or an atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC (= 0) Rb, -NRaC(=0)NRcRd, -NRaS(=0)raRb, -C(=0)0Rb, -C(=0)NRcRd, -NRcRd or pendant oxy)), (6) may contain A 5- to 6-membered aromatic ring group of one to four heteroatoms selected from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: G-3 alkyl group substituted by a hydroxyl group or a halogen atom, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, 116 323256 201206906 cyano group, -NRaC(=0)Rb, -NRaC( =0) NRcRd, -NRaS (=0%Rb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or • -NRcRd), (7) 3 to 6 member-saturated or 4 to 6-membered unsaturated aliphatic ring groups which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group in which The place that can be replaced can be replaced by:

Ch alkyl (the alkyl group may be via a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaC〇0)NRcRd, -NRaS(=0)〇&gt;Rb, -C(=0)0Rb , -C(=0)NRcRd or -NReRd substituted), f·Cl-3 alkoxy (the alkoxy group may be substituted by a hydroxyl group or a halogen atom), a trans group, a halogen atom, a cyano group, -NRaC (=0) Rb, -NRaC(=0)NRcRd ' -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd ' 117 323256 201206906 -C(=0)Rb, -S(: 0: URcRd, -S(=0)mRb, -NReRd or pendant oxy), (8) -NRaRe, (9) -0C(=0)NRcRd, (10) -C(=0)Rf, ® ( 11) -S(=0)mRg, (12) a mercaptan and (13) a nitro group, wherein the saturated or unsaturated aliphatic ring group, at a substitutable position thereof, may be selected from the list of substituents Substituted by a group of 1 or a plurality of substituents, the substituents are listed in Table 2: • (1) hydroxy, (2) halogen, (3) cyano, (4) alkyl (the alkyl group in which The position of substitution may be substituted by: a hydroxyl group, a halogen atom, a cyano group, and 1 to 4 hetero atoms which may be selected from the group consisting of N, 0 and S. 5 118 323256 201206906 to 6 member aromatic a ring group (the aromatic ring group, in which The position of substitution may be substituted by a Cm alkyl group which may be substituted by a hydroxyl group or an !i atom, a C!-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC (=0) Rb, -NRaS〇0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0%NReRd, -S(=0)nRb or -NRcRd), or a 3- to 6-membered saturated aliphatic ring group having 1 to 2 hetero atoms selected from the group consisting of N, 0, and S (the aliphatic ring group, at the position where it can be substituted, may be as follows) Substitution: a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS (=0)mRb, -C〇0)0Rb, -C(=0)NRcRd, -NFTRd or pendant oxy)), (5) Cl-6 alkoxy group (which can be substituted in it) The position may be substituted by a hydroxyl group, a halogen atom, a [φ cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of ruthenium, 0 and S ( The aromatic ring group, at the substitutable position thereof, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, and may be substituted with a hydroxyl group. Or a halogen atom-substituted Cl-3 alkoxy group, a hydroxyl group, a _ atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)raRb, -C(=0)0Rb, -C(=0) NRcRd, -SOO^NRf, -S(=0)mRb or -NRcRd), or a 3 to 6 member saturated aliphatic ring which may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S The aliphatic ring group, in its substitutable position, 119 323256 201206906, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a G- group which may be substituted by a hydroxyl group or a tooth atom. 3 alkoxy, hydroxy, _ atom, cyano, -NRaC(=0)Rb, -NRaS(=0)nRb, -C〇0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy group )), (6) G-6 alkylthio group (the alkylthio group, at its substitutable position, may be substituted by: a hydroxyl group, a halogen atom, a cyano group, may contain a selected from N, 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group consisting of 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: hydroxyl or halogen Atom-substituted G-3 alkyl group, anthracene-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb -NRaS(=0)raRb, -C(=0)0Rb, -C(=0)NRcRd, -SGCOoNRf, -S〇0)mRb or -NRcRd), or (φ may contain a selected from N, 0 and S 3 to 6 membered saturated aliphatic ring groups of 1 to 2 heteroatoms of the group formed (the aliphatic ring group, at its substitutable position, may be substituted by: may be substituted by a hydroxyl group or a halogen atom匕-3 alkyl, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a functional atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(= 0) 0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (7) 5 to 6 members which may contain 1 to 4 heteroatoms selected from the group consisting of N, 0 and S An aromatic cyclic group which, at its substitutable position, may be substituted by: 120 323256 201206906 Ci-3 alkyl group which may be substituted by a hydroxyl group or a _ atom, may be substituted by a hydroxyl group or a halogen atom G-3 alkoxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb ' -C(=0)0Rb, 0 -C(=0)NRcRd, -S (=0) mNRcRd, -S(=0)raRb or -NRcRd), (8) 3 to 6 member saturated aliphatic group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S Cyclic group The aliphatic ring group, at its substitutable position, may be substituted by: ^ Ci-3 alkyl (the alkyl group may be substituted by a hydroxyl group or a halogen atom),

Cm alkoxy (the alkoxy group may be substituted by a hydroxyl group or a halogen atom), a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb &gt ; -C(=0)NRcRd, 121 323256 201206906 -NReRd or side oxy), (9) -NRaRe, (10) -0C(=0)NRcRd, (11) -C(=0)Rf , (12 -S(=0)mRg ' (13) mercaptan, (14) pendant oxy, • (15) nitro, (16) -NRaC (=0) Rb, (17) -NRaC (=0) NRcRd '(18) -NRaS(=0)mRb, (19) -C(=0)0Rb and (20) -C(=0)NRcRd &gt; Here, the aromatic ring group is in its replaceable position , which may be substituted by one or more substituents selected from the group consisting of the list of the substituents, and the substituents are listed in Table 3: (1) hydroxyl group, (2) halogen atom, (3) cyano group, (4) Cm alkyl (the alkyl group, at its substitutable position, may be substituted by: hydroxy, halogen atom, 122 323256 201206906 cyano group, may contain a group selected from N, 0 and S 1 to 5 to 6 membered aromatic ring groups of 4 heteroatoms (the aromatic ring group, at the position where it can be substituted, may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, Hydroxyl or halogen atom substitution C!-3 alkoxy, hydroxy, _ atom, cyano, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, - S(=0)mNReRd, -SOO)# or -NRcRd), or 3 Φ to 6-member saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S ( The aliphatic cyclic group, at the substitutable position thereof, may be substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a functional atom, a hydroxyl group, a halogen Atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (5) Cw An alkoxy group (in the place where it can be substituted, may be substituted by: a hydroxyl group, a halogen atom, a cyano group, or a group 1 to 4 which may be selected from the group consisting of N, 0 and S; a 5- to 6-membered aromatic ring group of a hetero atom (wherein the aromatic ring group may be substituted at the position where it may be substituted with a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may pass through a hydroxyl group Or a halogen atom substituted C!-3 alkoxy group, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0 )NRcRd, -S( =0) mNRcRd, -S(=0)raRb or -NReRd), or 123 323256 201206906 may contain 3 to 6 member saturated aliphatics of 1 to 2 heteroatoms selected from the group consisting of N, 0 and S a cyclic group (wherein the aliphatic ring group may be substituted at the position where it may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, or a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a functional atom. Base, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)) (6) C!-6 alkylthio group (the alkylthio group, at its substitutable position, may be substituted by: a benzyl group, a halogen atom, a cyano group, and may be selected from N, 0 And 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group consisting of S (the aromatic ring group, at the position where it can be substituted, may be substituted by a hydroxyl group or a halogen atom Substituted Ci-3 alkyl, C!-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, _-NRaC(=0)Rb, -NRaS(=0)mRb, - C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNReRd, -S(=0)mRb or -NReRd), or may contain selected from N, 0 and S a 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms of the group consisting of (wherein the aliphatic ring group may be substituted at the position where it may be substituted by a hydroxyl group or a halogen atom) G-3 alkyl, C!-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a tooth atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(= 0) 0Rb, -C(=0)NRcRd, -NRf or pendant oxy)), (7) may contain 1 to 4 heteroatoms selected from the group consisting of N, 0 and S 124 323256 201206906 of 5 To a 6-membered aromatic ring group (wherein the aromatic ring group may be substituted at the position where it may be substituted: a Ci-3 alkyl group which may be substituted by a hydroxyl group or an atom, may be substituted by a hydroxyl group or a halogen atom匕-3 alkoxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, • -NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NRcRd, -S (=0) 〇, NRcRd ' -S(=0)mRb or -NRcRd), (8) may contain 3 to 6 members of the group consisting of N, 0 and S. An aliphatic cyclic group (in the place where it can be substituted, may be substituted by: 匕-3 alkyl (the alkyl group may be taken via a hydroxyl group or a _ atom) ),

Cl-3 alkoxy (the alkoxy group may be substituted via a base or a _ atom), a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb &gt; 125 323256 201206906 - C(=0)0Rb, -C(=0)NRcRd &gt; -NReRd or side oxy), (9) -NRaRe, (10) -0C(=0)NRcRd, (11) -C(=0) Rf, (12) -S(=0)mRg, • (13) mercaptan, (14) schlossyl, (15) -NRaC(=0)Rb, (16) -NRaC(=0)NRcRd &gt; (17 -NRaS(=0)mRb ' (18) -C(=0)0Rb, (19) -C(=0)NRcRd and (φ(20) -S(=0)mNRcRd, R1 is preferably C ^oalkyl, or may contain from 3 to 6 members of the group consisting of 1 to 2 heteroatoms selected from the group consisting of N, 0 and S, or 4 to 6 moles of unsaturated aliphatic soil base 'here, the alkane The group may be substituted at a substitutable position thereof with a plurality of substituents selected from the group consisting of 1 or 3 of the group consisting of (1) to (13) of the substituent list 1, where the saturation or the sum The aliphatic cyclic group, at the position where it can be substituted, may be substituted with a plurality of substituents selected from the group consisting of (1) to (20) of the substituent list 2, 126 323256 201206906 or 3, and R1 is more Good line means 匕-1 (1 alkyl' or a 3 to 6-membered saturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, hydrazine, and s, wherein the alkyl group may be selected from a position at which it may be substituted Substituted by a plurality of substituents of 1 or 3 or less of the group consisting of (1) to (4), (6) to (10) of the early morning, φ is in this 'saturated aliphatic cyclic group, The substitutable position may be substituted with a plurality of substituents selected from the group consisting of 1 to 3 or less of the group consisting of (1) to (4), (7) to (10) of the substituent list 2, and R1 is more preferable. It means that a Chg alkyl group (the alkyl group at a substitutable position thereof) may be substituted with a plurality of substituents of 1 or less of the group consisting of (1) a meridine, (2) a fluorine atom, (3) Cyano, G) Ch alkoxy (the alkoxy group, at its substitutable position, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, may be via a hydroxyl group or a fluorine atom-substituted Ci-3 alkoxy group, a hydroxyl group, a halogen atom, a murine group, ~C(=〇)〇H, 127 323256 201206906 -C(=0)NReRd or -NRcRd), (6) may be selected from 1 to 4 of the group consisting of N, 0, and S A 5-membered aromatic ring group of an atom (wherein the aromatic ring group may be substituted at the position where it may be substituted by a Ch alkyl group which may be substituted by a hydroxyl group or a fluorine atom, or a Ci which may be substituted by a hydroxyl group or a fluorine atom -3 alkoxy, meridine, halogen atom, murine group, -C(=0)0H, -C(=0)NReRd or -NRcRd), (7) may contain a composition selected from the group consisting of N, 0 and S A 3 to 6-membered saturated aliphatic ring group of 1 to 2 heteroatoms of the group (the saturated aliphatic ring group, where it may take a φ substitution, may be substituted by:

Ci-3 alkyl (the alkyl group may be substituted by a hydroxyl group, a fluorine atom, a cyano group, -C(=0)0H or -C〇0)NReRd),

Cl-3 alkoxy (the alkoxy group may be substituted by a base or a hydride atom), a hydroxyl group, a sulphur atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd, 128 323256 201206906 -NRaS (=0).Rb ' -C(=0)0H , -C(=0)NRcRd, -NReRd or pendant oxy), (8) -NRaRe, and (10) -C(=0)Rf) Or a ¥3 to 6 member saturated aliphatic ring group which may contain one to two hetero atoms selected from the group consisting of N, 0 and S (the saturated aliphatic ring group may be substituted at the position Substituted by a plurality of substituents of 1 or less of the group consisting of: (1) a meridine, (2) a fluorine atom, (3) a cyano group, and a φ(4) Cl-6 alkoxy group (this The alkoxy group, at the substitutable position thereof, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a halogen group Atom, cyano group, -C(=0)0H ' -C(=0)NReRd or 129 323256 201206906 -NRcRd), (7) may contain 1 to 2 groups selected from the group consisting of N, 0 and S A 3- to 6-membered saturated aliphatic ring group of a hetero atom (the aliphatic ring group, at its substitutable position, may be substituted by: C !-3 alkyl (the alkyl group may be via a hydroxyl group, a fluorine atom, a cyano group, -C(=0)0H or -C(=0)NReRdSR), a G-3 alkoxy group (the alkoxy group may be via a hydroxyl group) Or a fluorine atom substituted), a meridine, a fluorine atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd ' -NRaS(=0)mRb, -C(=0)0H, -C (=0) NRcRd, φ - NReRd or pendant oxy), (8) -NRa24Re, and (10) -C(=0)Rf R2 represents a hydrogen atom, a halogen atom, a cyano group or a 0-3 alkyl group ( The alkyl group may be substituted by a hydroxyl group, a halogen atom, -NReRd, -0Ra4-0C(=0)Ra), preferably a hydrogen atom or a G-3 alkyl group (the alkyl group may be via a hydroxyl group, a halogen atom, -NReRd) , -01^ or -0 (: (=0) 1 ^ substituted), more preferably represents a hydrogen atom, a methyl group, a hydroxymethyl group. 130 323256 201206906 R, R4 independently represent a hydrogen atom or a G 3 alkyl group (this The alkyl group may be substituted by a hydroxyl group or a _ atom, preferably each independently represents a hydrogen atom or an unsubstituted Ci 3 alkyl group, and more preferably each independently represents a hydrogen atom or a fluorenyl group. m represents an integer of 1 or 2, Preferably, π represents an integer 2 to 2, preferably represents 2. L·表不-S(=0)q-(q represents an integer 2 to 2, preferably 2), a 6-membered aromatic ring group which may contain 1 to 4 nitrogen atoms (the aromatic ring group, at the position where it may be substituted, may be substituted by 1 or a plurality of groups selected from the group consisting of Substituent: Ci 6 alkyl or C2- which may be substituted with i or a plurality of substituents selected from the group consisting of a halogen atom, a hydroxyl group, _NRCRd, _c(=0)NRCRd and -C(=0)0Ra 6 alkenyl, halogen, a c (= 〇) NRCRd, a c (= 〇) 〇 Ra, a hydroxyl group, -NR R, an exact group and -NR C (=0) Rb), the following formula Pyr_i, the following formula Tri_i or the following formula Imi-1:

(In each group, the bonding 1 indicates bonding with the dihydropyrimidinone ring, the bonding 2 indicates bonding with Ar, and Z, Z and Z3 respectively indicate that it can be selected from a halogen atom, a light group, -NRR, -C(=0)NRcRd and -C(=0)0R&gt;/f· group consisting of 1 or a plurality of substituents substituted with 匕-6 alkyl or Cw alkenyl, halogen, -C(=0) NReRd, -C(=0)0Ra, hydroxy, -NRcRd or a hydrogen atom), when L represents a 6-membered aromatic ring group which may have 1 to 4 nitrogen atoms, the preferred bonding position of the aromatic ring is As shown by the following formula (I,), the dihydrogen blasting 323256 131 201206906 is the same as the carbon atom bonded to the skeleton and the Ar system and the square, bear:

L is preferably a benzene ring group, an acridine ring group or a formula pyr-丨, a hydrazine or a formula Imi-1, more preferably an L-based phenyl ring group. A pyridyl ring group, a formula pyr-丨 or a formula Thy. _ Ar represents a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms selected from the group consisting of N, hydrazine and S (the aromatic ring group may have a position at a position where it may be substituted The above is substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group, a phenyl group, or a NRac ( =〇)Rh, _NRas(=〇)jh, -NRaC(=0)NReRd, -C(=〇)NReRd, -c(=0)〇Ra, -C(=〇)Ra, -S(=0 mNRcRd, -S(=〇)nRh or "service#), • Preferably, the benzene ring or pyridine ring represented by the following formula Ar1-;!

(In the base, when K^K^K3 and K4 are stupid rings, all represent carbon atoms. When the ring is bitten, only one represents nitrogen. Others represent carbon atoms, and X means can be selected. One or more substituents of a group consisting of a radical and a halogen atom are substituted for one of the filaments, and one or more substituents of the group consisting of the atom and the atom are substituted for the Ci3 alkoxy group, (iv) 132 323256 201206906 Sub, cyano, nitro, phenyl, -C(=0)NReRd, -C(=0)0Ra, -C〇0)Ra, -S(=0)nRh or -NReRd substituent And the substitutable position of K1 to K4 may further have the same or different 1 to 2 substituents selected from the group consisting of: 1 which may be selected from the group consisting of a hydroxyl group and a halogen atom Or a plurality of substituent-substituted Ch alkyl groups, a G-3 alkoxy group substituted with one or more substituents selected from the group consisting of a hydroxyl group and a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group -C(=0)NRcRd, -C(=0)0Ra, -C(=0)Ra, -S(=0)nRh or -NRcRd), w is more preferably expressed by the following formula Ai^-lO Show: ΓΤΧ

Ar1-10

X (X represents a Cw alkyl group, a chlorine atom, a cyano group or a nitro group which may be substituted by 1 to 3 fluorine atoms).

Ar2 represents a 5- to 6-membered aromatic ring group which may have 1 to 3 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may have a position at the φ position which may be substituted The above is substituted by a Ch alkyl group which may be substituted by a hydroxyl group, a cyano group or a halogen atom, a Ci-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group, a -NRaC. 〇0) Rh, -NITSOO^Rh, -NRaC(=0)NRcRd, -C(=0)NRcRd, -C(=0)0Ra, -C(=0)Ra, -S(=0)&lt; 〇NRcRd, -S(=0)nRh or -NRcRd), preferably a benzene ring or a pyridine ring represented by the following formula Ar2-1:

Y 133 323256 201206906 (In the base, when LL, L· and L are benzene rings, all represent carbon atoms. When 啶" 啶 ring, only one represents a nitrogen atom, others represent a carbon atom, Y means a Cl-6 group substituted with hydrazine or a plurality of substituents selected from the group consisting of a hydroxyl group and a _ atom, may be substituted by one or a plurality of substituents selected from the group consisting of a trans group and a halogen atom. Cl_3 alkoxy group, hydroxyl group, halogen atom, cyano group, nitro group, -C(=〇)NReRd, -C(=0)0Ra, -C(=〇)Ra, -S(=0)nRh or -NRcRd And the substitutable position of L1 to L4 may be further substituted with the same or different 1 to 2 substituents selected from the group consisting of: a group selected from the group consisting of a hydroxyl group and a halogen atom 1 or a plurality of substituent-substituted C1-6 alkyl groups, a C!-3 alkoxy group substituted with 1 or a plurality of substituents selected from the group consisting of a trans group and a halogen atom, a hydroxyl group, a tooth atom, Cyano, nitro, -C(=0)NRcRd, -C(〇)〇Ra, -C(=〇)Ra, -S(=0)nRh or -NRcRd), preferably means that the position of L2 is Unsubstituted or via 匕-6 alkyl, Cl-3 alkoxy, hydroxy, dentate Substitution. The better formula is not shown by the following formula Α γ2_ 10:

Ar2,

Y (Y represents a cyano group, a chlorine atom or a nitro group). Next, the basis in the formula (I') will be explained.

Ral to Ra31 independently represent a hydrogen atom or a Cl-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, preferably Ral to Ral7, and Ra25 to Ra29 each independently represent a hydrogen atom or a ruthenium 134 323256 201206906 base 'it sm π respectively independent It is a hydrogen atom or a Cl-3 group which may be substituted by a base or a defeat atom, and more preferably it to m "independently represent a nitrogen atom or a sulfhydryl group, respectively.

Rbl, Rb4, Rb8, Rb9, Rbl2, Rbl6, Rbi9, Rb23, Rb26n

Rb34 independently represents a hydrogen atom, a c&quot;alkyl group which may be substituted by a (iv) or halogen atom, or a benzoquinone group which may be substituted by a methoxy group or a schochyl group.

Preferably, Rbl, Rb4, Rb8, Rb9, Rb2, Rbl6, Rb9, Rb23, Rb26, R and R each independently represent a hydrogen atom or an unsubstituted 6-alkyl group.

Rb2, Rb3, Rb5, Rb6, Rb7, Rbi. , ",", Rbl4, Rbl5, Rbl7, R, Rb20, Rb21, Rb22, Rb24, Rb25, Rb27, Rb28, Rb29, Rb31, Rb32, RR, R, R and "separately represent a transatom or a tooth atom Substituted Cw alkyl group, C3 6 cycloalkyl group which may be substituted by a hydroxyl group or a halogen atom, preferably Rb2, Rb3, Rb5 Rbl5, Rbl8, ^20, Rb21 Rb31, Rb32, Rb33, broad, broad, Rb6, Rb7 , Rbl. And Rb丨丨, Rbl3, Rb", R»22, Rb24, Rb25, Rb27, Rb28, Rb29, R and R each independently represent an anthracene-6 alkyl group which may be substituted by a radical or a fluorine atom, and may pass through a hydroxyl group. Or a fluorine atom substituted 匸3 6 cycloalkyl. RCl, IT2, Re3, R", Re6, "7, Re8, Re9, RelG, Ren, rc12, RCU, Rcl5, Rcl7, Rci8, RCl9, rc2 丨, Rc22 , Rc24, Re25, rc26, "28,

Rc29, Re31, RC32, r, rc38, rc39, Rdl, Rd2, Rd3, Rd4, Rd6, Rd7, Rd8, Rd9, Rdl. Rdii, Rd12, Rdl4, Rdl5, Rdl7, Rdl8, Rdl9, broad, Rd22, Rd24, Rd25, Rd26, Rd28, Rd29, Rd31, Rd32, Rd33, Rd38 and Rd39 each independently represent a hydrogen atom or may be via a hydroxyl group or a functional atom Substituted Cm alkane 135 323256 201206906, or a substituent bonded to the same nitrogen atom together represents a 4 to 6 member saturated or unsaturated heteroatom containing from a group consisting of N and 0 to 2 heteroatoms. An aliphatic cyclic group (which may be substituted by a hydroxyl group or a _ atom at a position where it may be substituted), preferably R 17 , Rcl 8 , Rcl 9 , RC 21 , r C 22 , RC 24 , RC 25 , rc 38 , Rdl 7 , im n, Rd25 and Rd38 each independently represent a nitrogen atom or a Gi_Domain group which may be substituted by a lignin or a fluorine material, or

4 to 6-membered saturated heterolipids containing from i to 2 heteroatoms selected from the group consisting of oxime and oxime (the county (10), which may be substituted by a thiol or a fluorine atom at the position of substitution),旯 tr tr » η K , Rtn « , Rd22 , Rd2 d C and 1rrm table material μ - silk sewing material replaced = base or - starting from a nitrogen heterocyclic burning , scale bite = and = 3 A group of saturated heteroalicyclic groups (the aliphatic r position ' can be substituted with a _ atom). C, Rc34, Rc37, RC4 d23 ^d27 r.dao R, R, R, RC20, RC23, Rc27 r], R-, r3, Rd5, Rdl3, . ,

In, Rd41, Rd42 R, R ^ . The knives independently indicate that the hydrogen atom is 鲤 = the atom is substituted by C, and the : sub! = BASE-based means that it is selected from N and . : 4 to 6 members of the hetero atom are saturated or unsaturated. The 1 to 2 base, at the position where it can be substituted, can be passed = "refers to the aliphatic preferred system r'R gas ~37; ^^

Rd23 &gt; Rd27^ R-&gt; R-. Rd41. Rd4 'R4^r^R- R independently represent hydrogenogen II 323256 136 201206906 or a Cl_6 alkyl group which may be substituted by a radical or a fluorine atom, or together a 4- to 6-membered saturated heteroalicyclic ring group containing from 1 to 2 heteroatoms selected from the group consisting of N and hydrazine (the aliphatic ring group, at its substitutable position, may be via a hydroxyl group, a fluorine atom or The pendant oxy group is substituted, and more preferably Rc2°, Rc27, Rc37, Rc4D, Rc41, Rc43, γ. And R.sup.7, R.sup.1, R, R and R each independently represent a hydrogen atom or a Cl-6 group which may be substituted by a group or a fluorine atom, or together represent a selected from azetidine, exopurine, a saturated heteroalicyclic group of a group consisting of piperidine, piperazine, morpholine, imidazolium, and U, etc. (the aliphatic ring group, at its substitutable position, may be via a hydroxyl group, a fluorine atom or a side Oxygen substitution). R. 35. Re36, Rd35 and Rd36 each independently represent a hydrogen atom or a Ci_3 alkyl group which may be substituted by a hydroxyl group or an S atom, or a substituent bonded to the same nitrogen atom together represents 4 to 6 members having 1 or 2 nitrogen atoms. The saturated heterocyclic ring is an aliphatic ring group (the aliphatic ring group may be substituted at the position where it may be substituted by a base &lt; a halogen atom), preferably R. 35. Re36, Rd35 and Rd36 each independently represent a hydrogen atom or a Cw alkyl group which may be substituted by a hydroxyl group or a fluorine atom. More preferably, Re35 and R are used. 36. Rd35 and Rd36 each independently represent a hydrogen atom, a methyl group or an ethyl group.

Re represents a hydrogen atom, a Ci-e alkyl group (which may be substituted via a thiol group, a cyano group, a halogen atom, a Cw alkoxy group or a -Nir37Rd37), -A, ~c(=〇)A, s Ci 6 alkane a carbonyl group (the alkyl moiety of the alkylcarbonyl group may be substituted by a hydroxyl group or a _ atom), a C alkoxycarbonyl group (the alkyl moiety of the alkoxycarbonyl group may be substituted by a hydroxyl group or a halogen atom), -C(=〇 NRc38Rd38 or _S(=0)mRb37, soil 3 323256 137 201206906 preferably denotes a Cl-6 alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group, a fluorine atom, a C a 3 alkoxy group or a -NRc37Rd37) , -A, -C(=0)A', Ci-6 alkylcarbonyl (the alkyl portion of the alkylcarbonyl group may be substituted by a hydroxyl group or a fluorine atom), -C(=0)NRc38Rd38 or -S(=〇 )raRb37.

Re' represents or -C(=〇)NRe39Rd39, preferably -Απ.

Rf represents a hydrogen atom, a hydroxyl group, a Ci-6 alkyl group (the alkyl group may be via a hydroxyl group, a cyano group or a tooth atom), a hydrazone-3 alkoxy group (the alkoxy group may be substituted by a methoxy group) The phenyl group substituted with a nitro group, a hydroxy group, a cyano group or a halogen atom), -B or -3ΝΙΓ, preferably represents a hydroxyl group, -Β or -NRa3°Ri.

Rg represents a hydroxyl group, a G-6 alkyl group (which may be substituted by a hydroxyl group, a cyano group or a halogen atom), -D or -ΝΐηΓ, preferably a hydroxyl group, a Ci-e alkyl group (the alkyl group may be via a hydroxyl group, More preferably substituted by cyano or fluorine atom, -D or -NITf, more preferably G-6 alkyl (the alkyl group may be substituted by a hydroxy, cyano or fluoro atom), -D or -NRaMR1.

Preferably, the Rh-based group of the Ci-e alkyl group substituted by a radical or a halogen atom represents a fluorenyl group. f represents a hydrogen atom, a C1-6 alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group, a halogen atom, a Ci-3oxy group, a C3-6 cycloalkyl group or a -NRc4()Rd4()), - '' or -C(=0)Rb38, preferably # represents a hydrogen atom, a Cw alkyl group (the alkyl group may be via a hydroxyl group, a nitrogen group, a fluorine atom, a Ch alkoxy group, a G-6 cycloalkyl group or a -NRe4°). Rd4. Replace) or °

Ri, a hydrogen atom, a Ch alkyl group (the alkyl group may be via a hydroxyl group, a gas group 'function 323256 138 201206906 atom, a G-3 alkoxy group, a Ch cycloalkyl group or a substituent) or a _D, preferably a system The table is not a hydrogen atom, a Cl 6 alkyl group (the alkyl group may be bitten by a base group, a nitrogen group, a fluorine atom (^13 alkoxy group, 〇3-6 ring alkyl group or _ fertilizer 41 ft (141 substitution)). A represents a group of 5, which may contain a group of 5, 6 to 6 aromatic ring groups selected from the group consisting of N, 0 and S (the steroid group may be substituted at the position where it can be substituted: A hard group or an i atom substituted with one alkyl group, a b-oxy group substituted by a base or a tooth atom, a thiol group, a dentate atom, a nitrogen group, a -c(=〇)〇H or,,, or a 3 to 6 membered saturated or unsaturated aliphatic cyclic group which may be selected from the group consisting of n, yttrium and s to 2 heteroatoms (the aliphatic ring group, at its substitutable position, may be Substituted by: a group which may be substituted by a radical or a halogen atom, a Cl_3 alkoxy group which may be substituted by a via group or a tooth atom, a transatom group, a tooth atom, a nitrogen group, C(=0)0H, -NR , d43 or pendant oxy), preferably means Substituted from the stupid base, the taste olfactory "than the bite base, Erki, 曙. Sit-base, the word wow-based" than the salivation, sigh, scorpion, scorpion, #钱基, 嗜二" An aromatic cyclic group of the group consisting of a di-sialyl group, a tri-waxy group and a tetra-salt group or a substitutable group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and pyranyl a saturated heterocyclic group of a group consisting of azetidinyl, alkaloid, squama, dihydroanthracene, and tetrahydrogen (wherein the substituent of the aromatic ring group may be Substituted by a hydroxyl group or a tooth atom, the L group, the ke group or the (4) group is reduced by L alkoxy group, a hydroxyl group, a halogen atom, a cyano group, -C(=〇)〇H or -NRc42Rd42, and the substitution of an aliphatic ring group The base is a Ci 3 alkyl group which may be substituted by a hydroxyl group or a tooth atom, and the hydrazine may be substituted by a trans group or a (tetra) group (V oxo group, (tetra), ^ atom, an aryl group, 323256 139 201206906 -C(=0)0H, -NRe43Rd43 or pendant oxy), more preferably selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, oxime, isoindolyl, hydrazinyl, hydrazide, triple Salivary and four soils a group of aromatic heterocyclic groups (the aromatic heterocyclic group may be substituted by a Cl_3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Ch alkoxy group which may be substituted by a hydroxyl group or a fluorine atom) , a hydroxyl group, a fluorine atom, a cyano group, or a group of -NRe42Rd42), or a ring propyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a piperidyl group, an azetidinyl group, a pyrrole group a saturated aliphatic ring group of a group of a pyridyl group and a piperidinyl group (the aliphatic ring group may be substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a fluorine atom, may be hydroxyl group or fluorine) Atomic substituted C!-3 alkoxy, hydroxy, fluoro, cyano, _c(=〇)〇H, -NRe43Rd43 or pendant oxy), more preferably selected from cyclopropyl, cyclobutyl, a saturated aliphatic cyclic group of a cyclopentyl group, a cyclohexyl group, a pyridyl group, an azetidinyl group, a group consisting of a π-bite group and a brittle group (the aliphatic ring group can be replaced by the following) : a radical which may be substituted by a hydroxy group or a gas atom, a Cl_3 alkoxy group which may be substituted by a radical or a deficient atom, a transradical, a fluorine atom, a cyano group, a _C(=Q)QH or 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: Substituted by a radical or a halogen atom, Cw, s- or (d), sub-substituted &amp;oxy, (tetra), s atom, cyano, -C(=0)0H or NRC42Rd42), or may contain a group selected from the group consisting of n, 〇 and s to 3 to 6 members of a saturated or unsaturated I ring group of 2 heteroatoms (the lipid (tetra) ring group, in its replaceable position, 323256 140 201206906 Substituted by: Cl_3 alkyl group which may be substituted by a hydroxyl group or an i atom, Cl-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a tooth atom, an atmosphere, -C(=0)0H, - NRc43Rd43 or pendant oxy), preferably means a substitutable phenyl, imidazolyl group. An aromatic cyclic group of a group consisting of a pyridyl group, a decyl group, an iso-yl group, a W group, a thiol group, and an iso-eryl group, or a ring propyl group, a cyclobutyl group, or a ring group which may be substituted a saturated aliphatic ring A of a group consisting of pentyl, cyclohexyl, piperidyl, azetidinyl, pyrrolidinyl, piperidinyl, piperidinyl and morpholinyl (here, aromatic ring) The substituent of the substituent is an alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0)0H or an aliphatic ring. The substituent of the substituent is a k-alkyl group which may be substituted by a radical or a halogen atom, a Cw alkoxy group which may be substituted by a radical or a functional atom, a hydroxyl group, a halogen atom, a cyano group, _c(=〇)〇η, _Νρν43 or The pendant oxy group), more preferably, is selected from the group consisting of imidazolyl, anthraquinone, etc., an oxazolyl group, an isoxazolyl group, a pyrazolyl group, an anthracene group, and an aromatic heterocyclic ring of a group consisting of a group (the aromatic heterocyclic group may be substituted by a ^3 alkyl group, a ke group or a fluorine atom substituted by a group or a halogen atom, an oxy group, a (iv) atom, a cyano group. ^(4) Qing or replace Or a group selected from the group consisting of cyclopropylbutylbutyl, pentylpentyl, cyclohexyl, eryl, azetidinyl, thiol, thiol and oxime Saturated fat pure base (the lipid ring base is defined by a substitute: a Ci-3 alkyl group which may be substituted by a hetero group or a fluorine atom, a &amp; 3 alkoxy group which is substituted by a base or a gas atom, a base group, Fluorine atom, gas group, -C(=0)0H, -NRc43Rd43 or side oxygen 141 323256 201206906 base substitution), and more preferably, the ring is not selected from cyclopropyl, cyclobutylhydropyranyl, azetidinyl , pyrrole hexyl hexyl, which is exemplified by hydrazino, hydrazino, piperidinyl and morpholine: a saturated aliphatic ring group of the group of the genus (this aliphatic ring group can be taken by t A substitute for Gi, a methoxy group, a sulfhydryl atom, a nitrogen atom, a -C(=〇)〇H or a -NRc43Rd43

Further, the definition is the same as that of the preferred embodiment, and the preferred embodiment is the same as the preferred definition of A. B represents a 5- to 6-membered aromatic ring group which may contain a hetero atom selected from the group consisting of N, 0 and S (the base of the substituent may be replaced by the following: Or a substituted alkyl group, a C 3 alkyl group which may be substituted by a via group or a halogen atom, a thiol group, a dentate atom, a nitrogen atom, a -C(=0)0H or -NR, or a group of 3 to 6 members of a group consisting of n, hydrazine and s, saturated or unsaturated aliphatic ring group (the aliphatic ring group, at the position where it can be substituted, may be subjected to the following Substituted: Ci_3 alkyl group which may be substituted by a hydroxyl group or a functional atom, C,-3 alkoxy group which may be substituted by a hydroxyl group or S atom, a hydroxyl group, a picture atom, a cyano group, ~C(=0)〇H, -NRe43Rd43 Or a pendant oxy group, preferably a substitutable group selected from the group consisting of stupid, imidazolyl, beta butyl, pyridyl, oxazolyl, isoxazolyl, pyrazolyl, thiazolyl, isothiophene ^, an aromatic ring group of a group consisting of a bite base, an if, a ruthenium, a trifilament, and a tetrafilament, or a substitutable ring propyl, cyclobutyl, cyclopentane Base, cyclohexyl, piperazine , azacyclobutyl, pyrrolidinyl, 323256 142 201206906 sulfhydryl, fluorenyl, (tetra), oxime, fluorene (tetra), fluorenyl, (iv) money, and (iv) money group of saturated aliphatic a ring group (herein, the substituent of the group is a brio group or a G-3 alkyl group derived from an atom, a ring which can be substituted by a radical or a tooth atom, a silk group, a base atom, a cyano group, a -c (=_ or 2Rd42, aliphatic cyclic group: the substituent is a Ci_ group which may be substituted by a carboxyl group or a halogen atom, a Cm alkoxy group which may be substituted by a radical or a self atom, a hydroxyl group, a halogen atom, a cyano group, —c(=〇)卯,, -NRe43Rd43 or pendant oxy), ,

More preferably, it is selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, fluorenyl, isodecyl, 曙二录&quot; cedaryl, trisal, and tetrasal. Group of aromatic heterocyclic groups (the aromatic heterocyclic group may be substituted by a CH group which may be substituted by a base or a fluorine atom, or substituted by a radical or a fluorine atom; Alkoxy, hydroxy, fluoro, cyano, _C(=〇)〇H or -NRe42Rd42), or selected from azetidinyl, pyrrolidinyl, piperidinyl, piperidinyl and morpholinyl a saturated heteroalicyclic group of the group consisting of (the aliphatic ring group may be substituted by a Cw alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Cl_3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyano group, -C(=0)〇H, -NRe43Rd43 or a pendant oxy group), and more preferably a group selected from azetidinyl group, pyrrolidinyl group, piperidinyl group, pyridyl group and a saturated heteroalicyclic group of a group consisting of morpholinyl groups (the aliphatic ring group may be substituted by a Cl-3 group which may be substituted by a group or a fluorine atom, may be via a hydroxyl group or a fluorine atom take The burning Cl-3 alkoxy, hydroxy, fluorine atom, a cyano group, -C (= 0) 0H or substituted -NRe43Rd43). The D system is the same as the definition of B, and is preferably the same as the preferred definition of B. 143 323256 201206906 is more preferably selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl, pyridyl, thiazolyl, isothiazole. a group of aromatic heterocyclic groups consisting of oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl groups (the aromatic heterocyclic group may be substituted by the following groups) a C3-alkyl group substituted with a ruthenium atom, a Ci_3 alkoxy group, a light group, a fluorine atom, a cyano group, a _c(=〇)〇h or a -NRe42Rd42) which may be substituted by a radical or a fluorine atom, or a ring selected from a ring Saturated aliphatic ring of a group consisting of propyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidyl, azetidinyl, pyrrolidinyl, piperidinyl, pyridyl and morphinyl The aliphatic ring-based group may be substituted by a Ci 3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyanogen group Further, -C(=0)〇H, -NRe43Rd43 or pendant oxy), more preferably selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidyl, azetidinyl , a saturated aliphatic ring group of a group consisting of a pyridyl group, a piperidinyl group, a piperidinyl group, and a morpholinyl group (the aliphatic ring group system may be substituted by a Ci 3 which may be substituted by a hydroxyl group or a fluorine atom) An alkyl group, a C!-3 alkoxy group which may be substituted with a hydroxy group or a fluorine atom, a hydroxyl group, a fluorine atom, an aryl group, ~C(=0)0H or -NRc43Rd43). B' represents a 5- to 6-membered aromatic ring group which may contain a group selected from the group consisting of N, 0 and S to 4 hetero atoms (the aromatic ring group, at its substitutable position, can be passed down The substitution: a & calcination group substituted by a radical or a 4 atom, a Cl-3 alkoxy group which may be substituted by a trans group or a (tetra), a radical, a functional atom, a cyano group, -C(=0)0H Or -ΝΡγ, or a 3- to 6-membered saturated or unsaturated aliphatic cyclic group which may contain from i to 2 heteroatoms selected from the group consisting of N, hydrazine and S (in this aliphatic ring group) Substitutable position, 323256 144 201206906 Substituted by: Ci_3 which may be substituted by a hydroxyl group or a functional atom, a C 3 alkoxy group substituted by a hydroxyl group or a _ atom, a hydroxyl group, a halogen atom, a cyano group, -C (=0) ) 0H, -NRc43Rd43 or pendant oxy), ^ preferably represents a substitutable selected from the group consisting of phenyl, pmiazolyl, pyridinyl, stilbene, iso-saltyl, alpha-saltyl, beta-sialyl An aromatic cyclic group of a group consisting of isoindole β, a stilbene, and a tetrazolyl group, or a ring which may be substituted with a ring selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and piperidin喃基, a saturated alicyclic ring group of a heterocyclic butyl group, a pyrrolidinyl group and a piperidinyl group (wherein the substituent of the 'aromatic ring group is a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom a Ci 3 alkoxy group, a group, a halogen atom, a cyano group, a -C(=0)0H or a -NRc42Rd42 which may be substituted by a hydroxyl group or a _ atom, and the substituent of the aliphatic &quot;' ring^ may be via a hydroxyl group or a Ch group substituted with a chiral atom, a C1-3 alkoxy group which may be substituted by a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0)〇H, -NRe43Rd43 or a pendant oxy group), more preferably An aromatic heterocyclic group which is selected from the group consisting of imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, •thiazolyl and isothiazolyl (the aromatic heterocyclic group may be as follows) Substitution: a 3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a hydrazone 3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyano group, -C(=〇)〇H or -NRe42Rd42), Or a saturated aliphatic ring group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperanyl, azetidinyl, pyrrolidinyl and piperidinyl (the fat) Family The cyclic group may be substituted by a Cm alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a hydroxyl group, a fluorine atom, a cyano group, -C(=〇) 〇H, -NRe43Rd43 or pendant oxy), 323256 145 201206906 (4): more ί represents a group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, saturated alkyl, thiol and fluorenyl Group:: a cyclic group (this aliphatic ring group can be substituted by a Gl 3 alkyl group substituted by a hydrazine, a Cl_3 substituted with a cleavable atom, a bis 2 group, a fluorine atom , cyano, -c(=〇)〇H or _NRC43Rd43). The same meaning is the same as that of B, and B is preferred.

More preferably, it is selected from the group consisting of a stilbene, a sulfhydryl group, and a heterophilic group. Substituent: a calorificyl group substituted with a hydrazinyl group or a fluorochemical group, a Ci.3 alkoxy group which may be substituted by a trans group or a fluorine atom, a trans group, a fluorine atom cyano group, -C(=〇)〇H or - NRe42Rd42), or a saturated aliphatic ring group selected from the group consisting of a cyclopropyl group, a ring T group, a cyclopentyl group, a cyclohexyl group, and a μ group (the aliphatic ring group may be substituted by the following: It is better to use the C4 oxy group, the trans group, the fluorine atom, the cyano group, the _g(=〇)〇h, the -NRe43Rd43 or the pendant oxy group which can be substituted by a secret or a gas atom. Is a saturated aliphatic ring group selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and piperidyl (the aliphatic ring group may be substituted by a hydroxyl group) Or a Ci 3 alkyl group substituted by a fluorine atom, a Cl-3 alkoxy group which may be substituted by a light or fluorine atom, a trans group, a ruin atom, a cyano group, -C(=0)0H or -. 43^43) R0 represents -C(=0)NRal-, -S(=〇)NRa2-, s(=〇)2NRa2-, -C〇0)0-, -C(=0)~, -s(=0)~~, -§(:=〇)2_ or single bond, 323256 146 201206906 The best R° means -C(=0)NRal -, -S(=0)2NRa2-, -C(=0)0-, _C(=0)-, -S(=0)2- or single bond More preferably, -C(=0)NRal---S〇0)2NRa2-, -C(=0)〇-, _C(=0)- or -S(=0)2-, more preferably It means -C(=0)NH- or -S(=0)2NH-, and more preferably -C(=0)NH-. R1 represents a hydrogen atom, a Ch.alkyl group, a C2-6 alkenyl group, a 3 to 6 member saturated or non-saturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0 and S or may contain a group selected from N, 0 and S a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms, wherein the alkyl group and the alkenyl group are at a position where they can be substituted, and may be one or three selected from the group consisting of Substituted by a plurality of substituents, (1) a meridine, (2) a halogen atom, (3) a cyano group, a φ(4) C!-6 alkoxy group (the alkoxy group, at a position where it can be substituted, Can be substituted by: a group, a halogen atom, a cyano group, -C(=0)0Rbl, -C(=0)NRclRdl, which may contain a group selected from N, 0, and S 4 A 5- to 6-membered aromatic ring group of an atom (the aromatic ring group, at its substitutable position, may be substituted by the following 147 323256 201206906: 〇3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may pass through a hydroxyl group Or a halogen atom-substituted Ci-3 alkoxy group, a hydroxyl group, a halogen atom, a cyano group, -NRa3C(=0)Rb2, -NRa4C(=0)NRc2Rd2, -NRa5S(=0)mRb3, -C(=0) 0Rb4, -C(=0)NRc3Rd3, -S(=0)mNRc4Rd4, -S(=0)mRb5 or -NRe5Rd5) or may contain 1 to 2 impurities selected from the group consisting of N, 0 and S a 3- to 6-membered saturated or unsaturated aliphatic ring group of an atom (the aliphatic ring group, where it may be substituted, may be substituted by a G-3 group which may be substituted by a hydroxyl group or a halogen atom; Ci-3 alkoxy group, hydroxyl group, halogen atom, cyano group, -NRa6C(=0)Rb6, -NRa7C(=0)NRc6Rd6, -NRa8S(=0)mRb7, -C (substitutable with a hydroxyl group or a halogen atom) =0) 0Rb8, -C(=0)NRe7Rd7, -NRe8Rd8 or pendant oxy group)), (5) Cl-6 alkylthio group (the alkylthio group, in its replaceable position, can be passed Said substitution: a hydroxyl group, a halogen atom, a cyano group, -C(=0)0Rb9, -C(=0)NRc9Rd9 &gt; may contain a selected from N a 5 to 6 membered aromatic ring group of 1 to 4 heteroatoms of the group consisting of 0 and S (the aromatic ring group, at its substitutable position, may be substituted by a hydroxyl group or Ci-3 alkyl group substituted by halogen atom, Cl-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, hydroxyl group, functional atom, cyano group, -NRa9C(=0)Rbl° &gt; -NRal0C(=O)NRcl0Rdl ° ' -NRallS(=0)mRbl1 ' -C(=0)0Rbl2, -C(=0)NRcllRdl1, -S(=0)mNRcl2Rdl2, -S(=0)nRbl3 148 323256 201206906 or -NRel3Rd13) a 3- to 6-membered saturated or unsaturated aliphatic cyclic group containing from 1 to 2 heteroatoms selected from the group consisting of N, 0 and S (the aliphatic ring group, at its substitutable position) The substitution is: a Cl_3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cl_3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRal2C(=0)Rbl4, -NRal3C (=0) NRcl4Rdl4, ~NRal4S(=〇)mRb15, -c(=0)0Rbl6, -C(=0)NRcl5Rdl5, -NRcl6Rd16 or pendant oxy)), • (6) may be selected from N, 0 and S 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group (the aromatic ring group, The substitutable position may be substituted by a C!-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, and a cyanide. Base, -NRal5C(=0)Rbl7 &gt; -NRal6C(=0)NRcl7Rdl7 ' -NRal7S(=0)mRbl8, -C(=〇)〇Rb19, ~C(=〇)NRcl8Rd18 &gt; ~S(=〇 )raNRcl9Rd19, ~S(=〇)raRb2. Or ~NRc20Rd20) &gt; 149 323256 201206906 (7) A 3 to 6 member saturated or unsaturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic group) The cyclic group, at its substitutable position, may be substituted with a plurality of substituents selected from one or less of the group consisting of:

Cw alkyl (the alkyl group may be via a hydroxyl group, a halogen atom, a cyano group, -NRal8C(=0)Rb21, -NRal9C(=0)NRc21Rd21, -NRa2t)S(=0)mRb22, -C(=0)0Rb23 , -C(=0)NRc22Rd22 or -NRc23Rd23 instead),

Cw alkoxy (the alkoxy group may be substituted by a hydroxyl group or a halogen atom), • a trans group, a halogen atom, a cyano group, -NRa21C(=0)Rb24, -NRa22C(=0)NRc24Rd24 &gt; -NRa23S(=0 mRb25, -C(=0)0Rb26, φ -C(=0)NRc25Rd25, -S(=0)mNRc26Rd26, -S(=0)mRb27, -NRe27Rd27 or pendant oxy), (8)-NRa24Re, (9) -0Re', (10) -C(=0)Rf, (11) -S(=0)raRg, 150 323256 201206906 (12) Mercaptan and (13) nitro, saturated or unsaturated here An aliphatic cyclic group, at its substitutable position, may be substituted by: a radical atomic group, an exact group, a C1-6 alkyl group (the alkyl group, at its substitutable position) may be interesting. Or cyano substituted) 46 alkoxy (this

Alkoxy group # can be substituted at a position which can be taken by a hydroxyl group, a halogen atom or a cyano group. -NR C(=〇)Rb28 ^ _NRa26C(=〇)NRc28Rd28 ^ _NRa27s(=〇)mRb29 ^ -C(=0 )0R ' ~C(=:〇)Rb31 ^ _C(=〇)NRc29Rd29 ^_NR〇30Rd30 , where the anthracene ring group can replace the i atom, the nitrogen group, or the like at the position where it can be substituted Indeed, c (a) alkyl (the alkyl, in place of the "location" can be substituted by a radical, a halogen atom or a cyano group), G-6, the base (the base, in its replaceable position 'CO-based, secluded atom or cyano substituted), -NRa\(=Q)Rb32, n(=_id3i &gt;

-NRa30S(=O), Rb33 -S(=0), NRc33Rd33 R1 is preferably a group I and a saturated aliphatic ring group composed of S, ^C(=〇)〇Rb34^-C(=〇) Rb35 &gt; -C(=0)NRc32Rd32 &gt; , S〇〇)mRb36 or -NRc34Rd34, phoenix atom, Ci-i. An alkyl group or a group of 3 to 6 members which may be selected from n to 2 hetero atoms selected from n to 2, or 1 or 3, which may be selected from the group consisting of (1) to (13) above. Substituted by a plurality of substituents, wherein the 'saturated or unsaturated aliphatic cyclic group, at its substitutable position', may be substituted by a plurality of substituents selected from the group consisting of 1 or less selected from the group consisting of Substituent hydroxyl group, tooth atom, cyano group, nitro group, Cl_6 alkyl group (the 323256 151 201206906 group, at its substitutable position, may be substituted by a hydroxyl group, a halogen atom or a cyano group), Cl-6 alkoxylate a group (the alkoxy group, which may be substituted at a position where it may be substituted by a hydroxyl group, a halogen atom or a cyano group), -NRa25C(=0)Rb28, -NRa26C(=0)NRc28Rd28, -NRa27S(=0)mRb29, -C(=0)0Rb3°, -C(=0)Rb31, -C(=0)NRc29Rd29 or -NRe3°Rd3D, R1 preferably represents a hydrogen atom or an alkyl group, and the alkyl group may be selected from the above (1) Substituting a plurality of substituents of 1 or 3 or less of the group consisting of (3), (6) to (11), and R1 is more preferably Ch. An alkyl group (wherein the alkyl group, at the position where it may be substituted, may be substituted with a plurality of substituents selected from the group consisting of 1 or 3 selected from the group consisting of: (1) a radical, (2) a fluorine atom, (3) a cyano group, (6) a 5-membered aromatic ring group which may contain one to four hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, in its replaceable position Substituted by the following: a Ci-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a trans group, a halogen atom, a cyano group, -C ( =0) 0H , -COO^RWRd18 or 152 323256 201206906 _NRc20Rd20), (7) 3 to 6 member saturated aliphatic ring groups which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (The aliphatic ring group, where it can be substituted, can be replaced by:

Cl-3 alkyl (the alkyl group may be substituted by a hydroxyl group, a fluorine atom, a cyano group, -C(=0)0H or -C〇0)NRe22Rd22),

Cl-3 alkoxy (the alkoxy group may be substituted by a base or an atom), a hydroxyl group, a fluorine atom, a cyano group, -NRa21C(=0)Rb24, -NRa22C(=0)NRc24Rd24, -NRa23S(= 0) mRb25, -C(=0)0H, -C(=0)NRe25Rd25, $-Nr27Rd27 or pendant oxy), (8) -NRa24Re, (10) -C(=0)Rf&amp; (11) - S (=0) mRg). R2 represents a Cw alkyl group (which may be substituted by a hydroxyl group or a halogen atom), and more preferably represents a methyl group. R3 and R4 each independently represent a hydrogen atom or a G-3 alkyl group (the alkyl group may be substituted by a hydroxyl group or a halogen atom), and 153 323256 201206906 preferably independently represents a hydrogen atom or an unsubstituted G-3 alkyl group, respectively. The preferred systems each independently represent a hydrogen atom or a sulfhydryl group. m represents 1 or 2 of an integer, and preferably represents 2. η represents 0 to 2 of an integer, and preferably represents 2. L represents a 5- to 6-membered unsubstituted aromatic ring group or -S (=〇X- (q represents an integer of 0 to 1 to 4 hetero atoms) selected from the group consisting of ruthenium, 0, and S. 2), L represents a preferred bond of the aromatic ring when it contains 5 to 6 unsubstituted aromatic ring groups of 1 to 4 heteroatoms selected from the group consisting of N, 0 and S The position of the knot is as shown by the following formula (Γ)', the form of the carbon atom adjacent to the dipyrimidinone skeleton and the Ar2 linkage and the aromatic ring:

L preferably represents a benzene ring group, a thiophene ring group, a furan ring group, a pyrrole ring group, an imidazole ring group, an acridine ring group, a β ratio cultivating ring group, an isoxazole ring group, an oxazole ring group, an isothiazole group. a cyclic group, a pyrimidine ring group, an anthracenyl group, an indazole ring group, a thioxyl ring group, a tris(beta) ring group or a tetras(sigma) ring group, and more preferably a benzene ring group, a taste sigma ring group, an acridine group a ring group, a hydrazine ring group, an isoxazole ring group, a azole ring group, a pyrimidine ring group, a carbazole ring group, a triazole ring group or a tetrazole ring group (dihydropyrimidinone skeleton and Ar2 bonding position and In the same manner as described above, when L represents -S(=0)q-, it is preferred that q represents 1 or 2.

Ar1 represents a 5 S 6 member aromatic ring group which may contain 1 to 3 154 323256 201206906 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, in its replaceable position, - a position above which is substituted by a c- or hexa-substituted c, -6 alkyl group, a Ci 3 alkoxy group which may be substituted by a hydroxyl group or a functional atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group or _NRc35Rd35), preferably represents the following formula Ar1-:!' or Ar1·^,:

(In each group, 'Ε, Ε, Ε, and Ε4 each independently represent a carbon atom or a nitrogen atom (except that Ε, Ε, Ε3, and Ε4 all represent a nitrogen atom at the same time), and gi, g2, and G each independently represent a carbon atom or a hetero atom selected from the group consisting of N, hydrazine and s, X represents a Ci 6 alkyl group which may be substituted by a hydroxyl group or an atom, a Cm alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a substitutable position of cyano, nitro or -NRe35Rd35, Ε1, Ε2, Ε3, E4, G1, G2 or G3, which may further have a ci 6 alkane group which may be substituted by a hydroxyl group or a _ atom, More preferably, the substituent of the group consisting of a Cm alkoxy group, a hydroxyl group, a tooth atom, a cyano group, a nitro group and a group consisting of -NRe35Rd35 substituted by a dentate atom, or more preferably a group represented by the following formula: Αι^-Γ': i6rx A, (Ε Ε and Ε each independently represent a carbon atom or a nitrogen atom' χ denotes a Ci-3 alkyl group which may be substituted by a radical or a fluorine atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, an i atom, a cyanogen Or a nitro group at a substitutable position of Ε1, E2 or E3 may have a selected from the group consisting of a C group which may be substituted by a hydroxyl group or a fluorine atom, 155 3 23256 201206906 A Cl_3 alkoxy group, a hydroxyl group, a halogen atom, a cyano group and a substituent of -NRe35Rd35 which may be substituted by a radical or a fluorine atom, and more preferably a formula of the following formula Ar^-l,',:

fVX

Ar1-r&quot; (X represents a C--3 alkyl group, a gas atom, a cyano group or a nitro group which may be substituted by 1 to 3 fluorine atoms).

Ar2 represents a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms selected from the group consisting of n, fluorene and s (the aromatic ring group may be at one position above its replaceable position) Substituted by: a C 6 alkyl group which may be substituted by a hydroxy group, a cyano group or a functional atom, a hydrazine _3 alkoxy group substituted with a hydroxyl group or a functional atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group, a _S group (=〇)nRh or _NRc36Rd36 substituted), preferably represents the following formula Ar2-1, or Ar2-2,:

Ar2-!'

Αγ2·2· (In each group, Π2, κ3, and κ4 each independently represent a carbon atom or a nitrogen atom (except when Κ, κ, Κ3, and Κ4 all represent a nitrogen atom at the same time), and L», L2, and L are independent. a hetero atom representing a carbon atom or a group selected from the group consisting of ν, 〇 and s, Υ represents a Cl-6 group which may be substituted by a hydroxyl group, a cyano group or a tooth atom, and a C1 group which may be substituted by a via group or an _ atom a position of -3 alkoxy, a transyl group, a halogen atom, a cyano group, a nitro group, -S(=0)nRh or -NRc36Rd36, κ丨, K2, K3, KL, L or L, which may have Selected from Cw alkyl which may be substituted by hydroxy, 323256 156 201206906 cyano or a functional atom, Cl_3 alkoxy which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group, _s(=〇)nRh And the substituent of the group consisting of ^6^36), more preferably the following formula Ar2-r,:

(K, K2, K3 and K4 each independently represent a carbon atom or a nitrogen atom (except that κι, K2, Κ and Κ4 all represent a nitrogen atom at the same time), γ represents a halogen atom, a cyano group or an exact group, Κ1, Κ2. The substitutable positions of Κ3 and Κ4 may have a C1-3 alkyl group which may be substituted by a hydroxyl group or a fluorine atom, a Cl-3 alkoxy group which may be substituted by a hydroxyl group or a fluorine atom, a mercapto group, a halogen atom, a cyano group and _ Service. 3% &lt; 136 substituents) Further, the system represents the following formula Ar2-1 &quot;,:

(Y is not a gas atom, a chaotic base or a nitro group). Process for producing a compound of the present invention The compound of the present invention represented by the formula (I) and the formula (I)' can be produced by the production methods A to P shown below. The compound of the formula (I) and the formula (I), or a physiologically acceptable salt thereof, can be produced, for example, according to the production method described below, the examples described later or the methods known in the art. [Production Method A] 157 323256 201206906 In the formula (I), a compound in which R3 and R4 represent a hydrogen atom simultaneously [a compound of the following formula 4] is produced by the following production method.

Step 3 1 (wherein, VIII 1*1, 八 1*2, [, 1^°, 1^, 1^ are the same as defined in item 1, R3a, R4a all represent hydrogen atoms, or together represent foreign Asia曱基_ (exomethylene) carbon atom). [Step 1]: When R3a of Compound 1 represents a hydrogen atom, Compound 3 can be produced by subjecting Compound 1 and Compound 2 to an addition reaction in a usual manner. For example, the reaction is carried out in a suitable solvent or without a solvent by using the compound 1 and the compound 2 in an aldehyde reagent such as furfural or polyfurfural, titanium tetrahydride or boron difluoride/diethyl ether complex, and the like. It is achieved by a reaction in which a copper reagent such as Lewis acid or copper vapor is coexisted. The reaction may be carried out in an acid reagent solvent such as hydrochloric acid or acetic acid or an appropriate amount of an acid reagent such as salicylic acid or acetic acid. When R3a and R of the compound 1 are collectively referred to as a carbon atom of an exomethylene group, the compound 3 can be produced by subjecting the compound i and the compound 2 to an addition reaction in a usual manner. For example, the reaction is in a suitable solvent. Or, in the absence of a solvent, by reacting the compound i and the compound 2 with a copper reagent such as a Lewis acid or a vaporized copper such as a tri-vaporation/diethyl test compound, the reaction is carried out. It can be carried out in an acid reagent solvent such as hydrochloric acid or acetic acid, or can be carried out under the conditions of coexistence of an acid reagent such as hydrochloric acid or acetic acid. 323256 158 201206906 [Step 2]: cyclization of Compound 3 can be carried out according to a general method. The reaction is carried out to produce a compound 4. For example, the reaction is carried out by reacting the compound 3 with an acid reagent such as acetic acid or p-toluenesulfonic acid in a suitable solvent or without a solvent (see Example 22). 3]: When both R3a and R4a of the compound 1 represent a hydrogen atom, the compound 4 can be produced by subjecting the compound 1 and the compound 2 to a cyclization reaction in a usual manner. For example, the reaction is carried out in a suitable solvent or without a solvent. borrow The compound 1 and the compound 2 are reacted in the presence of an aldehyde reagent such as furfural or polyacetal, a Lewis acid such as tetrasulphuric titanium or a tri-phosphoric acid/diethyl ether complex, or a copper reagent such as vaporized copper. The reaction may be carried out in an acid reagent solvent such as hydrochloric acid or acetic acid, or in the presence of the above reagent in combination with an acid reagent such as hydrochloric acid or acetic acid. R3a and R4a of the compound 1 represent a carbon atom which becomes an exoarylene group. Compound 4 can be produced by subjecting Compound 1 and Compound 2 to a cyclization reaction according to a general method. For example, the reaction is carried out in a suitable solvent or without a solvent by using Compound 1 and Compound 2 in boron trifluoride. And a copper reagent such as Lewis acid or copper chloride is reacted in the presence of a copper reagent such as diethyl ether complex. The reaction may be carried out in an acid reagent solvent such as hydrochloric acid or acetic acid, or in the above reagents and hydrochloric acid or acetic acid. (Examples 1, 2, 3, 109 to 120) Specific examples of the solvent for each reaction in the production method A are selected according to the type of the raw material compound, etc., for example, Chlorodecane, trioxane, dichloroethane, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, acetonitrile, toluene, ethyl acetate, acetic acid, or decyl alcohol, ethanol, isopropyl Alcohol, etc. 159 323256 201206906 Alcohol or the like is used singly or as a mixed solvent. The reaction temperature varies depending on the type of the material and the reagent, and is generally from _4 to fine c, preferably from 0C to 15 ( TC, depending on the case, can be carried out under pressure. [Manufacturing method B] &quot; In the formula (1), 'L means that it can contain 5 selected from N, (^s group ^ 1 to 4 heteroatoms 5 To a 6-membered aromatic ring group (La), R3 and R4 each represent a compound of the formula [a compound of the following formula 7] which is gas-made by the following production method, and L represents a group described in the item i (_s) When (=〇)q_except), it is produced by the following manufacturing method.

In the formula ^^, the term "士^^ is the same as the item ^, and the L table cannot contain i to 4 heteroatoms selected from the group consisting of N, 〇 and S, 5 to 6 member aromatic ring groups, R3a , R4a is the same as defined above, ... table

a non-hydrogen atom, an amine group or an i atom, a substituent on the 21-line Ar2, which represents a metal substituent such as an acid, a boric acid vinegar, an organotin, a zinc halide, a functional group, an organic stone, and a lithium, and a Z2 system Ar2 ring. a substituent on a carbon atom, which represents a halogen atom). [Step 1] Compound 6 can be produced by subjecting Compound 5 and Compound 2 to a cyclization reaction in the same manner as in the production of A. (See Example 17) A" [Step 2]: Manufacturing Method B-1: 323256 160 201206906 When W1 of Compound 6 represents an i atom, Compound 6 and Z Ar (Z are as defined above) can be The coupling reaction is carried out according to a general method, and the compound 7 is produced, for example, in a suitable solvent or in the absence of a solvent, by using the compound 6 and Zi-Ar2 as a palladium represented by tetrakis(triphenylphosphine). Catalyst, copper catalyst represented by copper iodide, nickel catalyst, zinc reagent and iron chelating reagent represented by nickel chloride 1,2 -bis(monophenylphosphine)ethane complex In the presence of a phosphorus ligand represented by 2, 2, bis (diphenylphosphino M' 1-binaphthalene, 2-(di-tert-butyl)phosphinobiphenyl, etc., as the case may be, In the coupling reaction, in addition to the above reagents, there are also alkali metal carbonates (for example, sodium carbonate, potassium carbonate, carbonic acid planing, etc.), alkali metal phosphates (potassium phosphate, etc.), organic Alkali (triethylamine, diisopropylethylamine, etc.), _ alkali metal (lithic gasification, fluorinated planing, etc.), alkali metal hydroxide (hydrogen) (Sodium oxide, etc.), metal alkoxide (such as potassium t-butoxide), etc. are carried out in the coexistence. (Examples 8 to 18) Production method B-2: Further, when W1 of the compound 6 represents a hydrogen atom, The compound can be produced, for example, by subjecting the La group of the compound 6 to a coupling reaction with ZLAr2, for example, the halogenation reaction is carried out in a suitable solvent or in the absence of a solvent, by deuterating the compound 6 with N-deactivated amber. The reaction is carried out by reacting a halogenating agent such as sulfimine, bromosuccinimide, or bromine, and the coupling reaction is carried out in the same manner as in the production method. Production method B-3: I and 'W1 of compound 6 indicates a halogen atom The compound can be converted into a boronic compound, a zincated body, a coupling agent such as a (10) body, and the like, and the compound and z2-Ar2 (z2 are the same as described above) can be obtained according to a general method by 323256 161 201206906. Compound 7 is produced by performing a coupling reaction. For example, the reaction is carried out in a suitable solvent in a silk solvent by using compound 6 with boronic acid pinacol

The reagent (=s(Pinac〇iato)diboron) is a boron reagent represented by a reagent represented by tetrakis(triphenylphosphine), and the compound 3 is reacted with zinc powder to prepare 4 a zinc compound, or a coupling reagent such as a magnesium halide body prepared by reacting compound 6 with magnesium powder, and z2_Ar2, a catalyst represented by tetrakis(triphenylphosphine) or a molybdenum copper In the presence of a catalyst, a nickel catalyst, a zinc reagent, and an iron chelate, which are represented by an aural-1,2-bis(diphenylphosphino) ethene complex, a double is added Stupid phosphinyl)-ΐ, ι_binaphthene, second third) bile biphenyl, etc., represented by a conformational position, or organically coordinated-sub-chemicals: . In the coupling reaction, in addition to the above reagents, there are also alkali metal carbonates (for example, 'sodium carbonate, potassium carbonate, carbonic acid monopoly), acid filling metal (filling acid, etc.), organic testing (three Ethylamine, diisopropylethylamine, etc.), halogenated alkali metal (lithium gasification, fluorinated planer, etc.), alkali metal hydroxide (sodium hydroxide, etc.), metal alkoxide (potassium tert-butoxide) Etc.) etc. Production method B-4: When W1 of the compound 6 represents an amine group, the mixture can be converted into a halogen atom such as bromine or iodine by a Sandmeyer reaction according to a general method. Compound 7 was produced by subjecting f-Ar2 to a coupling reaction in the same manner as in Production Method B-1. For example, the reaction is carried out in a suitable solvent or in a solvent without reacting the compound 6 with a nitrite represented by sodium nitrite of 162 323256 201206906 and a copper halide represented by copper bromide or copper. Achieved. Production Method B-5: Further, when La of the compound 6 has an NH group in the ring, that is, when the group constituting La contains an NH group, the compound 6 and z2-Ar2 (the Z2 system is the same as defined above) can be used. Or Z3-Ar2 (a substituent on a carbon atom in the ring of Z3-based Ar2, which means a boric acid or a boric acid ester) is subjected to a substitution reaction or a coupling reaction according to a general method to produce a compound 7. For example, the person should be in a suitable solvent

In the middle or no solvent, 'by the La ring and Z2-Ar2 having an NH group in the ring, the metal (for example, sodium carbonate, potassium carbonate, carbonic acid), the acid test (potassium phosphate, etc.), It is achieved by carrying out a reaction in the presence of an organic base (such as triethylamine or diisopropylethylamine), an alkali metal halide (such as lithium gas hydride or a fluorinated planer), or an alkali metal hydroxide (such as sodium hydroxide). Further, by using a La ring having an NH group in the ring and Z3-Ar.2', a copper catalyst represented by tetrakis(triphenylphosphine) or acetic acid, represented by copper iodide In the presence of a medium or a zinc reagent or an iron sonic reagent, etc., depending on the situation, add 0 to 2,2,_bis(diphenyl scaly)-1, binaphthalene, 2-(di-t-butyl) Phosphine-based biphenyl, etc., represented by scaly catalysts, and 1,2-diaminocyclohexane, etc.

The diamine reagent represented by hydrazine is subjected to a cross-coupling reaction to reach a reaction. Further, 扃&gt;#, A in the coupling reaction, in addition to the above-mentioned reagents, there are also alkali metal carbonates (for example, sodium sulphate, potassium carbonate, carbonic acid, etc.), and miscellaneous metals (five)%. Etc.), organic test (triethylamine, diisopropylethylamine, etc.), reduced metal (mi alkali metal (sodium argon oxide, etc.), metal rolled decane emulsion (third potassium butoxide, etc.) ), etc., in the case of coexistence, for example, can be divided into secrets ^ # can be based on § J. Am. Chem. Soc. 323256 163 201206906 1998, 120, 827-828., J. Am. Chem. Soc. 2001 , 123, 7727-7729., J. 〇rg. Chem. 2002, 67, 1699-1702., etc., or manufactured by the method of the standard. Manufacturing method B-6: According to the general method, Z^Ar2 is produced by substituting Z4-Ar2 (a substituent on a carbon atom in the ring of Z4-based Ar2, which represents a tooth atom or a hydrogen atom) with various metal atoms, for example, in a suitable solvent or without a solvent. The boron reagent such as Z4-Ar2' and pinacol borate can be reacted with a palladium catalyst represented by tetrakis(triphenylphosphine)palladium, or by After reacting Z4-Ar2 with an alkyllithium reagent such as a butyl group, a boron reagent is produced by reacting with a trialkoxyboron reagent such as a trimethyl borate reagent. In a suitable solvent or without a solvent, Z4 can be used. -Ar2 is reacted with an alkyllithium reagent such as butyllithium, and then reacted with an alkyltin reagent such as tributyltin chloride to produce an organotin reagent. In a suitable solvent or without a solvent, by using Z4-Ar2 with a powder The reaction can be carried out to produce a zinc halide reagent. The magnesium halide reagent can be produced by reacting Z4-Ar2 with a magnesium powder in a suitable solvent or without a solvent. In a suitable solvent or without a solvent, by Z4 -Ar2 is reacted with an alkyllithium reagent such as butyllithium, and then reacted with an alkylhydrazine reagent such as trialkylsulfonium chloride to produce an organic hydrazine reagent. In a suitable solvent or without a solvent, Z4- An organic lithium reagent can be produced by reacting Ar2 with an alkyllithium reagent such as butyllithium. Specific examples of the solvent for each reaction in the production method B are selected depending on the type of the raw material compound, and the like, for example, dichloromethane is exemplified. , three gas methane, dichloroethane, four Hydrofuran, 1,4-dioxane, dimethoxyethane, Ν'N-dimercaptomethylamine, acetonitrile, dimercaptosulfoxide, toluene, ethyl acetate, 164 323256 201206906 acetic acid' or Alcohols such as methanol, ethanol, and isopropanol may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent, and is generally -4 (TC to 20 (TC, preferably). :. (: to 15 (rc, depending on the case, the reaction can be carried out under pressurized conditions. [Production Method C] In the formula (1), L represents 1 to 4 impurities which may contain a group selected from N and MS. 5 to 6 membered aromatic ring groups of atoms (1/), R. A compound (a compound of the following formula 11) which represents a single bond is produced by the following production method. Further, when L is described in the basis of the item ( (except for _s(〇)q_), it is produced by the following manufacturing method.

(In the formula, Ar1, Ar2, R1, R2, R3, and V are the same as the definition of the item i, and L, Z1, and Z2 are the same as defined above, and χι means a halogen atom). • [Step 丨]: Compound 9 can be produced by subjecting the cyclization reaction of Compound 8 in accordance with a general method. For example, the reaction is carried out by reacting the compound 8 in the presence of an acid reagent such as acetic acid or p-toluenesulfonic acid in a suitable solvent or without a solvent. (Refer to Reference Example 28) [Step 2]: Compound 10 can be produced by performing the crystallization of Compound 9 in accordance with a general method. For example, the reaction is carried out in a suitable solvent or without a solvent 'by compounding 9 with Ν-iodosuccinimide, Ν-bromosinium succinimide, potassium iodide and ammonium cerium nitrate, iodine, bromine, etc. The agent is reacted to achieve. Although the alkyl group of R2 is halogenated depending on the case, it is reacted with a reducing agent such as hydrogenation roasting 165 323256 201206906, and the halogen atom substituted by R2 can be selectively converted into a hydrogen atom. (Refer to Reference Examples 29, 30, 33, and 34) [Step 3]: A coupling reaction can be carried out according to the method of Production Method B-1 by using the compound 1 〇 and zi_La-Ar 2 (z! is the same as the above). And the compound 11 was produced. (Reference Example 7) Further, the compound X can be converted by a coupling reagent such as a boride, a zincated body or an i-magnesium according to the method of the production method B-3, and the compound can be converted. Compound 11 was produced by performing a coupling reaction with Z2-La-Ar2 (Z2 is the same as defined above). According to a general method, Z4-La-Ar2 (Z4 is the same as defined above) can be produced by substituting various metal atoms in accordance with the method of Production Method B-6 to produce Ζ^Γ-Αγ2. For example, it can be produced by a method described in, for example, w〇2〇〇7/129962, or a method based thereon. Z4-La can be produced by using a known compound or by using Z4_La-Zl*Ar2_Z2 or Z4-La-Z2 and AP-Z1, and performing the coupling reaction of the aromatic ring φ La and Ar2 in the same manner as in the production method B-丨. -Ar2. In Z-La-Ar2, when the bond of the aromatic ring La and Ar2 is an N-C bond, it can be produced by performing a substitution reaction. For example, the reaction is carried out in a suitable solvent or without a granule by using an aromatic ring z4-La having an NH group in the ring and Z-Ar or Z-Ar (Z is the same as defined above). The method of the manufacturing method is carried out by performing a reaction. In Z4-La-Ar2, when the bond of the aromatic ring/red 2 is a C_N bond, it can be produced by performing a substitution reaction. For example, the reaction is carried out by reacting Ar2 having an NH group in the ring with Ζ2_Γ_Ζ4 or 323256 166 201206906 Z3-La-Z4 in a suitable solvent or without a solvent according to the method of Production Method B-5.

Specific examples of the solvent for each reaction in the production method C are selected according to the type of the raw material compound, and examples thereof include, for example, methylene chloride, tri-gas, trichloroethane, tetrahydrofuran, and 1,4-two.萼 萼, 曱 曱 乙, Ν 'N-dimethyl decylamine, acetonitrile, dimethyl sulfoxide, toluene, ethyl acetate, acetic acid' or methanol, ethanol, isopropanol and other alcohols It can be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 〇C to 200. (:, preferably "(: to 15 (rc, depending on the case, the reaction can be carried out under pressurized conditions. [Production Method D] In the formula (I), 'RD indicates a single bond 'L indicates that it may contain a selected from N,化 and 3) The chemical substance of the 5 to 6-membered aromatic ring group (1) of the group of the four hetero atoms (the compound of the following formula 11) is produced by the following production method. It is shown in the following manufacturing method for the case of the item 1 (-s (excluding 〇v)'.

^二一广一系 is identical to the project (10). The X system is the same as the above definition). The method can be carried out by coupling the compound 1 〇 with the Z1 7-w1 (Z1 system and the upper compound 12° β I, the production method B), and the method can be made according to the manufacturing method B_3. Method 323256 167 201206906 X of compound 10 is converted by a coupling reagent such as a side-by-side body, a zinc halide body or a toothed magnesium body, and the compound and the ZLIZ-W^Z2 system are the same as defined above), and a coupling reaction is carried out. Compound 12 was produced. [Step 2]: When W1 of the compound 12 represents _ atom, the compound 11 can be produced by a coupling reaction of the compound 12 and the oxime Α ΧΖ 1 system as defined above according to the method of the production method B-1. Further, when W1 of the compound 12 represents a halogen atom, the W1 of the compound 12 can be converted by a coupling reagent such as a boronized body, a toothed word, or a fused magnesium halide according to the method of the production method Β-3, and then carried out. The compound U is produced by a coupling reaction of the compound and Z2-Ar2 (Z2 is as defined above). Further, when W1 of the compound 12 represents a hydrogen atom, the compound 11 can be produced by subjecting the La group of the compound 12 to halogenation followed by coupling reaction with f-Ar2 according to the method of the production method B-2. Further, when the compound 12 has a non-amino group, the W1 can be converted into a φ atom such as bromine or argon by the Sandermeer reaction according to the method of the production method B-4, and then the Z1-Ar2 is added. Compound 11 was produced by performing a coupling reaction in the same manner as in Production Method B-1. Further, when L of the compound 12 has an NH group in the ring, that is, when the group constituting La contains an NH group, the compound 12 and Z2-Ar2 (Z2 may be the same as defined above) by the method according to the production method B-5. Or a compounding reaction is carried out by performing a substitution reaction or a coupling reaction, or 23_纡2 (23 is the same as defined above). Specific examples of the solvent for each reaction in the production method D are selected according to the type of the raw material compound, etc., for example, 'dioxane, dioxane, dichloroethane, tetrahydrofuran, 1,4-two Decane, dimethoxy ethane, 323256 168 201206906 N,N-dimethyl decylamine, acetonitrile, dimethyl sulfoxide, toluene, ethyl acetate, or alcohol such as decyl alcohol, ethanol, isopropanol Classes, etc., can be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 C to 200 ° C, preferably a system. 〇 to i5 〇 °c, depending on the situation, can be carried out under pressure. [Production Process E] In the formula (I), a compound wherein R° represents a single bond and R1 represents a hydrogen atom [a compound of the following formula 14] is produced by the following production method.

(In the formula, Ar1, Ar, L, R2, R3, and R4 are the same as defined in the item i, and W° represents a protective group such as a benzyl group which may be substituted with a methoxy group or a nitro group). Compound 14 can be produced by performing a reduction reaction of Compound 13 in accordance with a general method. For example, the reaction is carried out by reacting the compound 13 in a hydrogenation state or ammonium acetate in a suitable solvent or in the absence of a solvent, or in the presence of an acid such as trifluoroacetic acid, in the presence of a catalytic reduction reagent such as palladium carbon or palladium hydroxide. The reaction 'or reacts in the presence of 2,3-disorganized-5,6-monooxy-in the presence of an oxidizing agent such as Stuffing 1 to achieve a specific example of the solvent for each reaction of the production method E, and should be based on the type of the raw material compound. And the like, for example, may be exemplified by dichloromethane, chloroform, dichloroethane, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, N,N-didecyl decylamine, Acetonitrile, dimethyl sulfoxide, toluene, ethyl acetate, or an alcohol such as decyl alcohol, ethanol, or alcohol can be used alone or as a mixed solvent 323256 169 201206906. The reaction temperature varies depending on the type of the raw material compound and the reagent to be used, etc., and is generally -40 ° C to 20 (TC, preferably 〇ΐ to 150. (:, depending on the case, the reaction can be carried out under pressurized conditions. Production method F] In the formula (I), R° represents a single bond, R1 represents a Cn alkyl group which may be substituted, a C2-6 thin group, or may contain a group selected from the group consisting of N, hydrazine and S. A compound of 3 to 6 members saturated or 4 to 6 members of an unsaturated aliphatic cyclic group (Rla) of two hetero atoms (a compound of the following formula 15) is produced by the following production method.

(wherein, Ar1, Ar2, L, R2, R3, and R are the same as defined in Item 1, and ^ is as defined above (indicating a substituted ClMO alkyl group, a c2-6 alkenyl group, or may be selected from the group consisting of N, 〇 and S are composed of 1 to 2 heteroatoms which are 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups, and X2 represents a halogen atom or trifluoromethanesulfonic acid ( Triflate) is the base of the deduction. Compound 15 can be produced by carrying out the firing reaction of compound 14 in accordance with a general method. For example, the reaction is carried out in a suitable solvent or without a solvent, and the compound 14 is subjected to a hydrogenation metal reagent such as sodium hydride or an alkali metal carbonate reagent such as potassium carbonate, an alkali metal phosphate reagent such as potassium phosphate, or an organic reagent such as triethylamine. In the presence of a halogenation test metal reagent, a nitrogen oxide test metal (sodium hydroxide or the like), a metal oxide (third butoxy group, etc.), etc., it is achieved by reacting with x2-zla. (Refer to Examples 23 to 28, 142 to 丨48) 170 323256 201206906 Specific examples of the solvent for each reaction in the production method F are selected depending on the type of the raw material compound, etc., for example, dichlorocarbyl, three Chloroform, dichloroethane, tetrahydro 0, 11, 1,4-diπ, etc., dimethoxyethane, N,N-dimethylformamide, acetonitrile, dimethyl hydrazine Toluene, ethyl acetate, etc. may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally -4 Torr. ^ to 2 〇〇 °c, preferably 0C to 150 ° C, depending on the case, the reaction can be carried out under pressure. [Production Method G] In the formula (I), R0 represents a compound of -C〇〇)〇-, -C(=〇)-, -S(=〇)2-based (R) [Formula 16 below] The compound] was produced by the following production method.

(In the formula, eight "1, person 1:2, 1^1^, 1^, 1^, 1^ are the same as the definition of item 1 R system and the above definition (indicating _C(=〇)〇-, _c(=〇)-, _s(=〇)2-base) the same). Compound 16 can be produced by performing the urethanization, acetylation, and chemical reaction of Compound 14 according to a general method. For example, the reaction is carried out in a suitable solvent or without a solvent, in a metal hydride such as sodium hydride, a metal reagent such as carbonic acid, a metal reagent such as potassium silicate, or an organic alkali reagent such as triethylamine. Lithium oxide and other functional alkali metal reagents, metal hydroxide (sodium hydroxide, etc.), metal alkoxide (potassium potassium butoxide, etc.), etc. - by derivatization of compound 14, and Ri derived from carboxylic acid And sulfonic acid derivative 171 323256 201206906 biological active ester, R1 anhydride, Ri acid toothing and the like to achieve. Specific examples of the active ester include p-nitrophenyl ester, 2,4,5-trichlorophenylhydrazine, N-transalkyl ruthenium imide, N-based imidate, and ι. _-Phenylbenzotriazole, N-hydroxypiperidinate, 2-pyridine pyridyl ester (2_pyridylthi〇1 ester), N-methylimidazolium ester, and the like. As the acid anhydride, a symmetrical acid anhydride or a mixed acid anhydride can be used. Specific examples of the mixed acid anhydrides include a mixed acid anhydride such as ethyl chlorocarbonate and isovaleric acid. (Examples 31, 32, and 33) Specific examples of the solvent for each reaction in the production method G are selected depending on the type of the raw material compound, and the like, and examples thereof include dichloromethane, trigas tetrification, and second gas. Burning, tetrahydroanthracene, 1,4-dioxane, dimethoxyethane, N,N-dimethylamine, acetonitrile, dimercaptopurine, toluene, ethyl acetate, etc. Used alone or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally _4〇. (: to 2〇〇. (:, preferably 〇 °C to 15 (TC, depending on the case, the reaction can be carried out under pressure. [Manufacturing method H] In the formula (I), 'R° means -C〇 0) A compound of NH- [a compound of the following formula 17] is produced by the following production method.

Wherein 'Ar1, Ar2, L, R1, R2, R3, R4 are the same as defined in the item 1 'R1 represents a substitutable alkyl group or a substitutable group). The compound 17 can be produced by performing the urealation reaction of the compound 14 according to a general method, and 172 323256 201206906. For example, the reaction is carried out in a suitable solvent or without a solvent, such as a metal reagent for deuteration, a metal reagent for carbonation, a metal phosphate reagent such as potassium phosphate, an alkali metal reagent such as potassium phosphate, or an organic alkali reagent such as triethylamine. In the presence of a halogenation metal reagent, a metal hydroxide (such as sodium hydroxide), a metal oxide oxide (potassium potassium butoxide, etc.), etc., by using compound 14, and an isocyanate compound (RK = 0) or an amine phthalate (RL-〇_c = 〇_Nm) was produced by reaction. (Examples 39, 121 to 127) Specific examples of the solvent for each reaction in the production method are selected depending on the type of the raw material compound, and the like, and examples thereof include dichloromethane, chloroform, and Ethyridae, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, hydrazine, hydrazine-dimercaptoamine, acetonitrile, dimethyl sulfoxide, toluene, ethyl acetate, etc. It can be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally _4〇.匚 to 2〇〇. 〇, preferably 〇 ° C to 15 (TC, depending on the case, the reaction can be carried out under pressure. [Production Method I] • In the formula (1), 'R. represents a compound of -S(=0)2NRa- The compound of the above formula 20 is produced by the following production method.

14 18 « 20 (in the formula, Ar, Ar2, L, R1, R2, R3, R4, Ra are the same as those in the project). 斤 [Step 1]: according to the general method, in a suitable solvent or without solvent, A metal hydride reagent such as sodium hydride or an alkali metal reagent such as potassium carbonate; an alkali metal phosphate reagent such as phosphorus 173 323256 201206906 potassium acid; an organic alkali reagent such as triethylamine; a halogen metallurgical reagent such as lithium vapor, or a metal hydroxide; In the presence of (sodium hydroxide or the like), a metal alkoxide (potassium butoxide, etc.), etc., by using compound 14 with sulfonyldiamine or 2-oxo-oxyl-1,3- The oxazolidine_3_sulfonyl group is reacted to produce compound 18 or 19. (Refer to Embodiment 1〇5)

[Step 2]: According to the general method, a metal hydride such as sodium hydride, a metal reagent such as potassium citrate 43⁄4 acid, a metal reagent such as ruthenium acid, an organic alkali reagent such as triethylamine, lithium hydride, etc. In the presence of a functional alkali metal reagent, a metal hydroxide reagent (sodium hydroxide or the like), a metal alkoxide (potassium third potassium oxide, etc.), etc., it can be produced by reacting compound 18 or 19 with ? Compound 20. Depending on the case, for example, compound 18 can be trifluoroacetic acid vinegar with trifluoroacetic acid in accordance with the method described in j. 〇巧. Chei 68' 115, et al. After the reaction, it is produced by reacting with hydrazine. As the respective (four) material axis of the manufacturing method I, it should be selected according to the type of the compound to be used, etc., for example, a product of dichloromethane can be exemplified: a hospital, a second gas, a tetrahydrogen scream, 1, 4 - II, dioxin, a certain amount of N, N-dimethylformamide, acetonitrile, dimercaptosulfoxide, ψ 4 ^ τ, ethyl acetate or methanol, ethanol, isopropanol and other alcohols Etc., can be used alone or as a mixed source. The reaction temperature varies depending on the starting compound used and the type of test sword, and is usually -40 ° C to 200 ° C, preferably 0 ° C to allow the reaction to be carried out under pressure. L5〇°C, depending on the situation, 323256 174 201206906 is manufactured by these methods. [Production Method J] In the formula U), a compound in which R° represents -C(=〇)NRa- [a compound of the following formula 22] is produced by the following production method.

(In the formula, Ar1, Ar2, L, R1, R2, R3, R4, and γ are the same as defined in the item i, and W° represents a phenyl group, a p-nitrophenyl group, or the like). According to a general method, a metal hydride reagent such as sodium hydride, an alkali metal reagent such as potassium carbonate, an alkali metal phosphate such as potassium phosphate, an organic alkali reagent such as triethylamine, or an alkali metal reagent such as lithium chloride, or sodium hydroxide. Compound 22 can be produced by reacting compound 21 with RffTNH in the presence of a metal alkoxide such as a metal hydroxide or potassium t-butoxide. Specific examples of the solvent for each reaction in the production method J are selected according to the type of the original φ compound, and the like, for example, dichloromethane, tri-methane, monochloroethane, tetrahydrofuran, hydrazine, 4_ Dioxane, dimethoxyethane, :, N-dimethylformamide, acetonitrile, dimethyl hydrazine, toluene or ethyl acetate, etc., may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally _4〇. 〇 to 2〇〇. 〇, preferably from 0 ° C to 150 ° C, depending on the case, the reaction can be carried out under pressure. [Manufacturing Method K] &quot; In the formula (I), R1 represents a Ci 1 alkyl group or a Cw alkenyl group substituted by -C〇0)0H or -s(=〇)2〇H, via -C(=0) The 0H substitution may contain 3 to 6 member saturated or 4 to 6 member unsaturated aliphatic ring groups of 1 to 2 hetero atoms selected from the group consisting of n, 〇 and $ 323256 175 201206906, or via -C (=0) a compound of 5 to 6 membered aromatic ring group (Rle) which may be substituted with 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (compound of the following formula 24) And R1 represents Ci-i substituted by -COOHITR'-SbOhNRaRi or -C(=0)0Rb (Rb is the same as the definition of the item )). An alkyl or C2-6 alkenyl group substituted by -C(=〇)NRcRd or -C(=0)0Rb may contain 3 to 2 heteroatoms selected from the group consisting of N, 0 and S Up to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring group, substituted by -C(=0)NrRd or -C(=0)0Rb may contain a group selected from the group consisting of N, 〇 and S The compound of the 5 to 6-membered aromatic ring group (Rid) of 1 to 4 hetero atoms [the compound of the following formula 25] is produced by the following production method.

(wherein, Ar1, Ar2, L, R°, R2, R3, and R4 are the same as the definition of item i.] Rule 113 indicates that -(](=0)01^ or -8(=0)2〇1 Substituting (1), or a Cw alkenyl group, which may be substituted with -C(=0)0Rb, may contain from 1 to 2 heteroatoms selected from the group consisting of n, fluorene and s. a saturated or 4 to 6 membered unsaturated aliphatic ring group ' or substituted with -C(=〇)〇Rb may contain 5 to 1 hetero atom selected from the group consisting of N, 0 and S to 5 The 6-membered aromatic ring group 'Rle' indicates that the Cho group or the C2-6 alkenyl group substituted by -C(=0)0H or -S(=〇)2〇H may be substituted by -C(=0)0H. 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups containing 1 to 2 hetero atoms selected from the group consisting of n, hydrazine and s, or substituted by -C(=0)0H a 5 to 6-shell aromatic ring group containing 1 to 4 hetero atoms selected from the group consisting of n, 〇323256 176 201206906 and S, Rld represents -C(=〇)NRaR1, _S(=〇)2NRaRl Or C(=〇)〇Rb substituted Ci-ioalkyl or alkenyl group, which may be substituted by -C(=〇)NReRd or ~C(=〇)〇Rb may be selected from N, 〇 and 3 to 6 members of the group of 1 to 2 heteroatoms are saturated 4 to 6 member unsaturated aliphatic ring groups, or substituted by _c (=〇) NirRd or -C(=0)0Rb, may contain 1 to 4 impurities selected from the group consisting of N, 〇 and S 5 to 6 membered aromatic ring groups of atoms, Rb, Ra, Ri, RC &amp; Rd are the same as defined in item 1). [Step 1]: can be produced by performing hydrolysis reaction of compound 23 according to a general method. Compound 24. For example, the reaction is carried out in a suitable solvent or in a solvent-free state under an alkaline condition such as an aqueous sodium hydroxide solution or an acidic condition such as hydrochloric acid by a hydrolysis reaction (see: 8: 98) Further, when Rb of the compound 23 represents a phenylhydrazine group which may be substituted by a decyloxy group or a nitro group, the compound 24 may be produced by performing a reduction reaction of the compound 23 according to a general method, for example, 'the reaction system is appropriate In a solvent or without a solvent, reacting with a contact reducing agent such as oxidizing or oxidizing in the presence of a nitriding state or ammonium acetate, or reacting in the presence of an acid such as trifluoroacetic acid, or in the presence of 2, 3-diox-5. , 6-dicyano group - is achieved by reacting in the presence of an oxidizing agent such as awkward. [Step 2]: by In general, the imidization or esterification of compound 24 is carried out to produce compound 25. For example, the reaction is carried out by converting the compound 24 into a reactive derivative (for example, an active ester, an acid anhydride, or an acid) in a suitable solvent or without a solvent. _, etc.), react with various amines or various alcohols up to 177 323256 201206906. Specific examples of the active ester include p-nitrophenyl ester, 2,4,5-trichlorophenyl ester, N-hydroxysuccinimide, N-hydroxy quinone, and hydroxybenzotriene. Azole ester, N-hydroxypiperidinyl ester, 2-pyridylthiol ester, N-methyl taste. Sitting on the ester and so on. As the acid anhydride, a symmetric acid anhydride or a mixed acid anhydride can be used. Specific examples of the mixed acid anhydride include mixed anhydrides such as ethyl chlorocarbonate and isovaleric acid. Further, the compound 25 can be produced by reacting the compound 24 with various amines and various alcohols in the presence of a condensing agent according to a general method. Specific examples of the condensing agent include N, Ν'-dicyclohexylcarbodiimide, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide·1 hydrochloride. ,Ν,Ν'-carbonyldiimidazole, dinonylaminosulfonic acid, 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, benzotriazol-1-yl - Oxygen tris(oxaridinyl) scale-hexafluorophosphate or the like. These condensing agents may be used singly or in combination with a peptide synthesis reagent such as hydrazine-hydroxysuccinimide or hydrazine-hydroxybenzotriazole. (Example 85) Specific examples of the solvent for each reaction in the production method are selected depending on the type of the raw material compound, and the like, and examples thereof include dioxane, trigas tetroxide, dichloroethane, and tetra.氲σ夫喃, 1,4-二曙院, dimethoxy ethene, hydrazine, hydrazine-dimethyl decylamine, acetonitrile, dimercapto sulfoxide, toluene, ethyl acetate, acetic acid, or methanol Alcohols such as ethanol and isopropyl alcohol may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 ° C to 200 ° C, preferably 0 ° C to 150 ° C, and the reaction can be carried out under pressure, as the case may be. [Manufacturing Method L] 178 323256 201206906 In the formula (I), 'R' represents a Ci-i substituted with a certain acid group (SCbH), a thiol group (s〇2r), and a sub-wind (S0R). An alkyl group, a C2-6 dilute group, may contain from 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of one to two heteroatoms selected from the group consisting of n, oxime and §, or A 5- to 6-membered aromatic ring group containing 1 to 4 hetero atoms selected from the group consisting of N, 〇 &amp; s (the compound of R [the compound of the following formula 27] is produced by the following production method) .

(In the formula, eight 1'1, eight 1'2, 1^, ruler °12, ruler 3, and ^ are the same as the definition of item 1 'R represents Cu substituted by a mercaptan, a mercaptothio group or a subordinate. a base group, a ruthenium 2 - a dilute group, which may contain from 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of one to two hetero atoms selected from the group consisting of N, 0 and S, or A 5- to 6-membered aromatic ring group containing 1 to 4 heteroatoms selected from the group consisting of N, 0, and S, represents a reductive acid group (S〇3jj), an obstacle (ie, r), continued Substituted by Ruthenyl (S〇2R), Ci-i. An alkyl group, a G-6 dilute group, may contain 3 to 6 members of 1 to 2 heteroatoms selected from the group consisting of n, 〇' and S. A saturated or 4 to 6 membered unsaturated aliphatic ring group, or a 5 to 6 membered aromatic ring group of 1 to 4 hetero atoms selected from the group consisting of N, 〇 &amp; s). Compound 27 can be produced by oxidizing compound 26 according to a general method. For example, the reaction is carried out in a suitable solvent by reacting compound 26 with an oxidizing agent such as m-chloroperoxybenzoic acid, hydrogen peroxide, potassium oxone or borohydride. Specific examples of the solvent for each reaction of the production method L should be selected according to the type of the compound of the original 323256 179 201206906, and for example, dioxane, trichlorodecane, dichloroethane, tetrahydrofuran, hydrazine can be exemplified. , 4_ dioxane, dimethoxyethane, toluene, ethyl acetate, acetic acid, etc., may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally -40 ° C to 20 (TC, preferably (Tc to i5 〇 t, depending on the case, the reaction can be carried out under pressure). Method M]

In the formula (I), R1 represents a Cl_1() alkyl group substituted by a pendant oxy group, and a C2_e alkenyl group, which may have from 3 to 6 of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S. The compound of the saturated or 4 to 6-membered unsaturated aliphatic cyclic group (Rih) [the compound of the following formula 29] is produced by the following production method.

(In the formula 1, Ar1, Ar2, L, R., R2, R3, and R4 are the same as the definition of the item i'. Rlg represents a Ci substituted by a hydroxy group, an alkyl group, a C2_6 thin group, and may be selected from N, 0 and The group consisting of S consists of 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of 2 heteroatoms, indicating substitution by a pendant oxy group.

Cl-ίο alkyl, C 2-6 alkenyl, may contain 3 to 6 membered saturated or 4 to 6 membered unsaturated aliphatic ring groups of 1 to 2 heteroatoms selected from the group consisting of N, 0 and S 9 can be produced by oxidizing compound 28 according to a general method. For example, the reaction is carried out in a suitable solvent or without a solvent, and the compound 28 is treated with Dess-Martin reagent, potassium dichromate, 180 323256 201206906 - human chlorine self-text steel, jones reagent, Dichromic acid is achieved by reacting with an oxidizing agent such as a bite. Specific examples of the solvent for each reaction in the production method are selected according to the type of the raw material compound, etc., and examples thereof include dichloromethane, tri-methane, dichloroethane, tetrahydrofuran, and 1,4-dioxane. Alkane, dimethoxyethane, hydrazine, hydrazine-dimethyl decylamine, acetonitrile, dimethyl sulfoxide, toluene, ethyl acetate, acetic acid, etc. may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the raw material compound and the reagent to be used, and is generally _4 〇艽 to 2 〇〇 t) c, preferably 〇 C to 15 (TC, depending on the case, the reaction can be carried out under pressure. [Production Process N] In the formula (I), R1 represents a compound substituted with an aldehyde substituted Cl-10 or a C2 6 alkenyl group (Rlj) [a compound of the following formula 31], and R1 represents a substitution with CH2NRcRd.

A compound of Cl, an alkyl group or a C2-6 alkenyl group (Rlk) [a compound of the following formula 32] is produced by the following production method.

(Former sergeant ^b^^ is the same as the definition of the item ,, to indicate that the acetal group (CH(0Rh), Rh is the same as the definition of the item!) is substituted by Cl-ίο alkyl or C2-6 alkenyl , represents a Q ^ substituted by a disk. Or a C 2-6 alkenyl group, γ represents a CH substituted by a CH 2 NRT (the definition of Re and Rd is the same as the term soil i). Alkyl or C 2-6 alkenyl). [Step 1]: According to a general method, the compound 32 can be produced by deprotecting the acetal group of the compound 3〇. For example, the reaction is carried out by reacting compound 30 with an acid reagent such as p-toluenesulfonic acid, trifluoroacetic acid or hydrochloric acid in a suitable solvent at 323256 181 201206906 or without a solvent. [Step 2]: Compound 32 can be produced by performing a reductive amination reaction of Compound 31 according to a general method. For example, the reaction is carried out in a suitable solvent or without a solvent, and the compound 31 and NRaRe are hydrogenated reagents such as sodium borohydride, sodium triethoxy hydride hydride, sodium cyanoborohydride, and acetic acid, citric acid reagent. Coexistence of the reaction to achieve. Specific examples of the solvent for each reaction of the production method N are selected according to the type of the raw material compound, and the like, and examples thereof include di-methane, trichloromethane, dichloroethane, tetrahydroc-butan, and 1, 4-dithizone, dimethoxyethane, toluene, ethyl acetate, acetic acid, or an alcohol such as methanol, ethanol or isopropanol, or the like, may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally _4 〇〇 c to 2 〇〇〇 c, preferably 〇 C to 150 ° C, and may be subjected to a reaction under pressure, as the case may be. . [Manufacturing Method 0] • In the formula (1), R1 represents C!, substituted by NHRa, an alkyl group or a C2-6 alkenyl group, and may be substituted by NHRa to contain 2 groups selected from the group consisting of dip and 5 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of a hetero atom, or 5 to 6 substituted with NHRa may contain 1 to 4 hetero atoms selected from the group consisting of N, 〇 and s a compound of the aromatic ring group (R1-) [compound of the following formula 34], and Ri represents NRaC(=〇)-A, NRac(=〇)Rh (Rh is the same as defined in item 1), NRac(=〇)〇Rh, NRaC(=〇)NRcRd or NRS(=0)mR substituted alkyl or c2_6 alkenyl, via _NRac(=〇)Rb, -NRC(=0)NRR or -NRaS( =〇) nRb substituted 3 to 6 member saturated or 4 to 6 member unsaturated aliphatic ring groups of 1 to 2 heteroatoms selected from the group consisting of N, 〇 and δ 182 323256 201206906, or -NRaC(=〇)Rb, -NRaC(=0)NRcRd or -NRaS〇0) mRb substituted 5 to 6 members which may contain 1 to 4 heteroatoms selected from the group consisting of n, 〇 and S The compound of the aromatic ring group [the compound of the following formula 35] is produced by the following production method.

(wherein, Ar1, Ar2, L, R°, R2, R3, and R4 are the same as defined in the item 1] R11 represents a Gu) alkyl group or a C2-6 alkenyl group substituted by NRaC(=0)0Rb, via NRaC 〇0) 0Rb substituted may contain 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S, or via NRaC (= 0) The 0Rb substitution may contain a 5- to 6-membered aromatic ring group of 1 to 4 hetero atoms selected from the group consisting of n, 0, and S, and Rlm represents a Ci-id alkyl group or G- substituted by NHRa. a 6 alkenyl group, which may be substituted by NHRa, may contain 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S, or The NHRa substituted may contain 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S, and Rln represents NRaC(=0)-A, NRaC (=0 Rh, NRaC (=0) 〇 Rh, NRaC (=0) NRcRd or NRaS (=0) mRb replaced by Ch. An alkyl or C2-6 alkenyl group which may be substituted with from 1 to 2 heteroatoms selected from the group consisting of N, 0 and S, 3 to 6 membered saturated or 4 to 6 membered unsaturated aliphatic ring groups Or substituted by -NRaC〇〇)Rb, -NRaC(=0)NRcRd or -NRaS(=0)mRb may contain •183 323256 201206906 1 to 4 of groups selected from N, 0 and S 5 to 6 member aromatic sulfhydryl groups of heteroatoms. Here, m represents an integer of 1 or 2' Ra, Rb, A, Rh, 1^, and Rd are the same as the definition of item 1. [Step 1]: According to a general method, compound 34 can be produced by subjecting a hydrolysis reaction or reduction reaction of compound 33 to deprotection of a carbamate group. For example, the reaction is carried out by the same method as the [Step U of the production method K). (Refer to Examples 100 and 101) φ [Step 2] - According to a general method, Compound 35 can be produced by performing a hydrazine amination reaction of Compound 34. For example, the reaction is carried out by reacting the compound 34 with various active agents derived from the acid-derived acid derivative and the horizontal acid derivative, various kinds of g or various (tetra) compounds, etc., in the solvent or in the absence of a solvent. Specific examples of the active ester include p-nitrophenyl ester, 2,4,5-trichlorophenyl ester, N-hydroxysuccinimide ester, hydroxy hydroxy imidate, and hydroxy hydroxy benzoate. g, N-based base brigade, 2-n ratio bite-pyridylthiol ester, N-methylimidazolium ester and the like. As the acid anhydride, # may be a symmetric acid anhydride or a mixed acid anhydride. Specific examples of the mixed acid anhydride include mixed anhydrides such as ethyl chlorocarbonate and isovaleric acid. (Refer to Examples 1 to 2 to 104) Further, Compound 35 can be produced by reacting Compound 34 with various carboxylic acids and sulfonic acids in the presence of a condensing agent according to a general method. Specific examples of the condensing agent include N,N,-dicyclohexylcarbodiimide, ethylethyl-3-(3-monomethylaminopropyl)carbodiimide.1 hydrochloride, N, hydrazine. '_几·基一米 angry dimethylamino-based acid, 1-ethoxylated t-_2-ethoxy-monoquinoline, benzotriazol-1-yl-oxytri(pyrrole) Pyridyl) squamous-hexafluorophosphate 323256 184 201206906 et al. These condensing agents may be used singly or in combination with a peptide synthesis reagent such as N-hydroxysuccinimide or N-hydroxybenzotriazole. Further, according to a general method, compound 35 can be produced by urea-forming compound 34. For example, the reaction is carried out by reacting the compound 34 with various isocyanate-substituted compounds or the like in a suitable solvent or without a solvent. Further, according to a general method, the compound 35 can be produced by converting the compound 34 into a reactive derivative (e.g., a reactive amine phthalate) to react with various amine groups. For example, the reaction is carried out by reacting compound 34 with phenyl chloroantimonate or carbodiimidazole in a suitable solvent or without a solvent, and then reacting with various amines. The urealation reaction may be a hydrogenation metal reagent such as sodium hydride or potassium hydride, an inorganic base such as potassium carbonate or sodium hydrogencarbonate or triethylamine, ethyldiisopropylamine or N-methylmorpholine, as the case may be. The pyridine, 4-dimethylamino group is carried out in the presence of an organic reagent such as α. Specific examples of the solvent for each reaction in the production method 0 are selected depending on the type of the raw material compound, and the like, and examples thereof include di-methane, trichloro-cyclodecane, dichloroethane, tetrahydrofuran, and 1,4-two. Decane, dimethoxy ethane, hydrazine, hydrazine-dimethyl decylamine, acetonitrile, dimercapto sulfoxide, toluene, ethyl acetate, acetic acid, or alcohols such as methanol, ethanol, isopropanol, etc. It can be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 ° C to 200 ° C, preferably 0 ° C to 150 ° C, and the reaction can be carried out under pressure, as the case may be. [Production Method P] The compound of the formula (1) wherein L represents -S(=0)- or -S(=0)2- [the compound of the following formula 37] is produced by the following production method. 185 323256 201206906

(wherein, Ar1, Ar2, L, R°, R1, R2, R3, and R4 are the same as those defined in Item 1, and q1 represents an integer of 1 or 2). Compound 37 can be produced by oxidizing compound 36 according to a general method. For example, the reaction is carried out by reacting a compound 35 with a peroxidizing agent such as m-chloroperoxybenzoic acid, hydrogen peroxide, potassium peroxymonosulfate or sodium perborate in a suitable solvent. (Reference Example 106) Specific examples of the solvent for each reaction in the production method P are selected depending on the type of the raw material compound, etc., and examples thereof include dichloromethane, trioxane, dichloroethane, and tetrahydrofuran. 1,4-dioxane, dimethoxyethane, toluene, ethyl acetate, acetic acid, etc., may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally φ -40 ° C to 200 ° C, preferably 0 ° C to 150 ° C, and depending on the case, the reaction can be carried out under pressure. Next, the synthesis of various raw material compounds of the above production methods A to C is shown. [Production Method Q] L indicates that the raw material compound of pyrazole is produced by the following production method. 186 323256 201206906

(wherein, Ar2 and R2 are the same as defined in item 1, and R6 represents a Cl_6 alkyl group). The compound 38 is a known compound, or can be produced by a method of preparing a known compound. For example, 'by being recorded in journa丨〇f

Fluorine Chemistry, 2007, 128, 1255-1259, etc., or manufactured by these methods. [Step 1]: Compound 39 can be produced by subjecting an addition reaction of a propargyldialkyl carboxylic acid compound of Compound 38 according to a general method. For example, the reaction is carried out by reacting a propargyldialkyl acetalized oxime compound with an alkyl metal reagent such as butyllithium in a suitable solvent or without a solvent, followed by reaction with the compound 38. In the addition reaction, it is also carried out in the presence of triammonium hexamethyl phosphate, iodine or the like. For example, the reaction can be achieved by a method described in J. Am. Chem. Soc. 2003, 125, 14702-14703, or the like, or a method based on the standards. [Step 2]: Compounds 41, 42, 43 can be produced by reacting a compound of the compound 39 with a carbon atom in the ring of Ar2 with a hydrazine-substituted compound (Ar2-NHNH〇) in a suitable solvent according to a general method. The reaction of 187 323256 201206906

Ar2-NHNH2 may be a hydrochloride, and may be carried out in the presence of an acid such as hydrochloric acid, sulfuric acid or acetic acid, as the case may be. (Refer to Reference Examples 2, 3, 4, and 5) [Step 3]: According to a general method, in a suitable solvent or without a solvent, the compound 41 can be used in an acid such as hydrochloric acid or acetic acid or a Lewis acid such as gold trichloride. The compounds 42 and 43 were produced by carrying out a cyclization reaction in the presence of a cyclization reaction. (Refer to Reference Example 6) [Step 4]: Compounds 44 and 45 can be produced by performing the oxidation reaction of Compounds 42, 43 in accordance with a general method. For example, the reaction is carried out by reacting the compounds 42, 43 with an oxidizing agent such as a Dess-Martin reagent, a Jones reagent, or a pyridine dichromate in a suitable solvent or without a solvent, or by performing a Swern oxidation reaction or the like. The oxidation reaction is achieved. (Reference Example 7) Specific examples of the solvent for each reaction in the production method Q are selected depending on the type of the raw material compound, and the like, and examples thereof include dichlorosilane, trichloropyrene, dichloroethane, and tetra Hydrogen ketone, 1,4-dioxan, dimethoxy ethene, φ N,N-didecyl decylamine, acetonitrile, dimethyl sulfoxide, toluene, ethyl acetate, acetic acid, or Alcohols such as decyl alcohol, ethanol, and isopropanol may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 ° C to 200 ° C, preferably 0 ° C to 150 ° C, and the reaction can be carried out under pressure, as the case may be. [Production Method R] L represents a raw material compound of triazole which is produced by the following production method. 188 323256 201206906

(wherein, Ar2 and R2 are the same as the definition of item 1). The compound 46 is a known compound, or can be produced by a method using a known compound. For example, it can be produced by a method described in J. Org. Chem. 2009, 74, 6410-6413, or the like. [Step 1]: According to a general method, the compound 48 can be produced by subjecting a cyclization reaction of the compound 46 and the compound 47. For example, the reaction is carried out by reacting compound 46 and compound 47 in the presence of N,N-dimercaptoguanamine dimethyl acetal and acetic acid in a suitable solvent or without a solvent. For example, it can be produced by the method described in Org. Lett. 2004, 17(6), 2969-2971, or the like, or by the method of these standards. (Reference Reference Examples 8, 43, 44) The compound 47 is a known compound, or can be produced by a method using a known compound. For example, it can be manufactured by the method described in W02008122767 or the like, or by the method of these standards. [Step 2]: According to a general method, Compound 49 can be produced by performing an oxidation reaction of Compound 48. This reaction was carried out in the same manner as in [Step 4] of Production Method Q. (Reference Reference Examples 9, 45, and 46) Specific examples of the solvent for each reaction of the production method R are selected according to the type of the compound of the original 189 323256 201206906, and the like, for example, dichloromethane, trichloropurine Alkane, dichloroethane, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, N,N-dimethyldecylamine, acetonitrile, dimercaptosulfoxide, toluene, acetic acid An ester, acetic acid, or an alcohol such as methanol, ethanol or isopropanol may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 ° C to 200 ° C, preferably 0 ° C to 150 ° C, depending on the case, the reaction can be carried out under pressure. [Production Method S]. ® L indicates that the raw material compound of imidazole is produced by the following production method.

(wherein, Ar2 and R2 are the same as the definition of item 1). The compound 505 is a known compound, or can be produced by using the φ method of a known compound as a standard. For example, it can be produced by performing a reduction reaction of Ar2-C〇2R7 (R7 represents a Ch alkyl group or a hydrogen atom), an oxidation reaction of Ar2-CH2〇H, an Ar2 oximation reaction, or the like. [Step 1]: Compound 51 can be produced by reacting Compound 47 and Compound 50 according to a general method. For example, the reaction is carried out by reacting compound 47 and compound 50 in the presence of an acid catalyst such as p-toluenesulfonic acid in a suitable solvent or without a solvent. The reaction can be carried out by a method described in J. Med. Chem. 2003, 46, 3463-3475, or the like, or by the method of 190 323256 201206906. [Step 2] · The cyclization reaction of Compound 51 and Compound 52 (tosylmethyl isocyanide) can be carried out by a general method 'in a suitable solvent or without a solvent. Compound 53 was produced. For example, the reaction is carried out by a method described in J. Med. Chem. 2003, 46, 3463-3475 or the like, or a method based on the standards. [Step 3]: According to a general method, Compound 54 can be produced by performing an oxidation reaction of Compound 53. For example, the reaction is carried out in the same manner as in [Step 4] of the production method q. Specific examples of the solvent for each reaction in the production method S are selected according to the type of the raw material compound, and the like, and examples thereof include a dichlorocarbyl group, a trimethylmethane, a dichloroethane, a tetrahydrofuran, a hydrazine, and a bismuth. Alkane, dimethoxy ethane, N,N-dimethyl decylamine, acetonitrile, dimethyl hydrazine, toluene, ethyl acetate, acetic acid, or alcohols such as methanol, ethanol, isopropanol, etc. Used alone or as a mixed solvent. The reaction temperature is 0 depending on the type of the starting material compound and the paste, and is generally -4 (TC to 20 (TC, preferably from 15 to rc, depending on the case, the reaction can be carried out under pressure). T] L represents a raw material compound which can contain 5 to 6 member aromatic ring groups aa) of a hetero atom selected from the group consisting of N and 〇AS, and is produced by the following production method. The basis of 1 (except for -s(〇)q-) is also produced by the following manufacturing method. 323256 191 201206906

® (wherein Ar2 and R2 are the same as defined in item 1, and La represents a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S, X1 Indicates a halogen atom). The compound 5 5 is a known compound, or can be produced by a method using a known compound. For example, it can be produced by performing an oxidation reaction of Ar2-CH0HCH3, an Ar2 acetylation reaction, or the like. [Step 1]: According to a general method, compound 56 can be produced by subjecting compound 55 to an addition reaction of compound 38. For example, the reaction is carried out with a compound 38 by reacting a compound 55 with a metal reagent such as lithium bis(triethylsauryl)amide or lithium diisopropylguanamine in a suitable solvent or without a solvent. And reached. For example, the reaction can be achieved by a method described in Tetrahedron Letters, 1991, 32, 7583-7586, or the like. [Step 2]: According to a general method, Compound 58 can be produced by subjecting Compound 57 to the addition reaction of Compound 38. For example, the reaction is carried out by reacting compound 57 with a butyl group such as a butyl group, 192 323256 201206906 metal s-type agent, and reacting with compound 38 in a suitable solvent or without a solvent. The addition reaction is carried out in the presence of hexamethylene sulfonate, tridecylamine, hydrazine or the like. For example, the reaction can be achieved by a method according to the method described in J. Am. Chem. Soc. 2003, 125, 14702-14703, or the like. Compound 57 is a well-known compound or can be described by J Am.

The method of Chem. Soc. 2010, 53, 699-714 and the like is a standard, and Ar2 is produced by reacting with an acetylene reagent. [Step 3]: Compound 56 can be produced by performing an addition reaction of water to compound 38® according to a general method. For example, the reaction is carried out in a suitable solvent or in the absence of a solvent by reacting compound 58 with triammonium sulphate and citric acid. For example, the reaction can be achieved by a method described in Eur. J. Org. Chem. 2008, 546, 5469, or the like, or a method based on the standards. [Step 4]: Compound 59 can be produced by performing a halogenation reaction of Compound 56 in accordance with a general method. For example, the reaction is carried out in a suitable solvent or φ without solvent by functionalizing compound 56 with N-iodosuccinimide, N-bromosinium iodide potassium iodide, ammonium nitrate, iodine, bromine, etc. The agent is reacted to achieve. [Step 5]. According to a general method, Compound 60 can be produced by subjecting a cyclization reaction of Compound 59. For example, the reaction is carried out by reacting compound 59 with thioformamide, guanamine, methanimidamide or the like in a suitable solvent or without solvent. These cyclization reactions include alkali metal carbonate (for example, sodium carbonate, potassium carbonate, carbonic acid planing, etc.), alkali metal phosphate (potassium phosphate, etc.), and organic base (triethylamine, diisopropylethylamine, etc.). ), 193 323256 201206906 Alkali metal halides (lithium chloride, barium fluoride, etc.), alkali metal hydroxide (sodium hydroxide, etc.), metal oxide oxides (potassium tert-butoxide, etc.), acetic acid, etc. The situation. For example, the reaction can be achieved by a method described in WO2006137685, Bioorganic &amp; Medicinal Chemistry Letters, 2007, 17, 5115-5120., or the like. [Step 6]: According to a general method, Compound 61 can be produced by performing an oxidation reaction of Compound 6. For example, the reaction is carried out in the same manner as in [Step 4] of the production method. (Refer to Reference Example 15) The specific example of the solvent for each reaction of the production method T is selected according to the type of the raw material compound, etc., and examples thereof include dichloromethane, = chlorodecane, and second gas. Alkane, tetrahydrofuran, 1,4-dioxane, etc., dimethoxyethane', N,N-didecylguanamine, acetonitrile, dimercaptosulfoxide, toluene, acetic acid B:, acetic acid, or Alcohols such as decyl alcohol, ethanol, and isopropanol may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent used, and is generally -4 (TC to 20 (TC' is preferably rc to 15 Torr, and can be reacted under pressure in the case of φ. [Manufacturing Method U] L represents a raw material compound which can contain 5 to 6-membered aromatic ring-based oxime/) of a hetero atom selected from the group consisting of dip and 8 is produced by the following production method. When it is described in the base of item i (excluding "s(=〇)q_), it is produced by the following manufacturing method.

323256 194 201206906 (In the formula, the definitions of Ar and R are the same as those of item 1, and the definitions of La, W1, and Z1 are the same, and indicate the bell, magnesium, and zinc halide). And di-L-M2 are known compounds, or can be produced by the method 4 of the known compound. For example, according to a general method, it is possible to react with a butyl clock such as a butyl group by the same method as defined in the above 4, and when z is not halogen, according to a general method, Z4 and bromination are carried out. The methyl group can be reacted with a dentate magnesium reagent, and Z4 can be substituted with a halogenated town. Similarly, Z4 can be substituted with zinc hydride by reacting with zinc powder and chiral. However, when w1 represents an amine group, it is protected by a third butoxy group or the like. For example, the reaction can be achieved by a method described in org Lett 2001, 3 835_838., or the like. [Step 1] The compound 62 can be produced by subjecting the addition reaction of W-IZ-M2 to the compound 38 in a suitable solvent or without a solvent according to a general method. In the addition reaction, it is also carried out in the presence of triammonium hexamethyl phosphate, iodine or the like. For example, the reaction can be achieved by a method described in φ Bioorganic &amp; Medicinal Chemistry Letters, 2009, 19 1559-1563, or the like. [Step 2]: When W1 of the compound 62 represents 4 atoms, the compound 60 can be produced by a coupling reaction of the compound 62 and Z^ArYz1 in the same manner as defined above in accordance with the production method B-1. Further, when W1 of the compound 62 represents a halogen atom, the compound of the compound 62 can be converted by a coupling agent such as a boride, a zincated body or a halogenated precursor according to the production method B-3, and then the compound and the compound are carried out. Compound 60 is produced by a coupling reaction of Z2-Ar2 (Z2 is as defined above). Further, when W1 of the compound 62 represents a ruthenium atom, the La group of the compound 62 can be halogenated by a method according to the method of Production Method B-2, and then a coupling reaction with Z^Ar2 can be carried out to produce a compound 60. Further, when W1 of the compound 62 represents an amine group protected by a third butoxycarbonyl group or the like, the amine group is deprotected, and converted to a halogen atom such as bromine or iodine by a Sandermeer reaction according to a general method. This and Z^Ar2 were subjected to a coupling reaction in the same manner as in Production Method B-1 to produce Compound 60. Further, when La of the compound 62 has an NH group in the ring, that is, when the group constituting the La group contains an NH group, the compound 62 and Z2-Ar2 (Z2 and the above can be obtained by the method according to the production method B-5. The definition is the same) or Z3-Ar2 (Z3 is the same as defined above) to carry out a substitution reaction or a coupling reaction to produce compound 60. [Step 3]: According to a general method, Compound 61 can be produced by performing an oxidation reaction of Compound 60. For example, the reaction is carried out in the same manner as in [Step 4] of the production method Q. Specific examples of the solvent for each reaction in the production method U are selected depending on the type of the original φ compound, and the like, and examples thereof include dichloromethane, trichloromethane, di-ethane, tetrahydrofuran, and 1,4-. Dioxane, dimethoxyethane, N,N-didecylguanamine, acetonitrile, dimercaptosulfoxide, toluene, ethyl acetate, acetic acid, or alcohols such as decyl alcohol, ethanol, isopropanol Classes, etc., can be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 ° C to 20 (TC, preferably 0 ° C to 150 ° C, depending on the case, and the reaction can be carried out under pressure. The manufacturing method V] L represents a raw material compound which can contain 5 to 6 member aromatic ring groups (La) of 1 to 4 196 323256 201206906 hetero atoms selected from the group consisting of N, 0 and S, and is manufactured by the following In the case of 'L (except for -S(=〇)q-), it is also produced by the following manufacturing method.

(wherein 'Ar2, R2 are the same as the definition of item 1, and La and M2 are the same as defined above).

Ar2-La-M2 is a known compound, or can be produced by using Ar2-La-Z4 in accordance with the synthesis method of W^IZ-M2 in the production method. [Step 1]: Compound 60 can be produced by subjecting an addition reaction of Ar2-La-M2 to Compound 38 in a suitable solvent or without a solvent according to a general method. In the addition reaction, it is also carried out in the presence of triammonium hexamethyl phosphate, iodine or the like. For example, the reaction can be achieved by a method described in Φ Bioorganic &amp; Medicinal Chemistry Letters, 2009, 19, 1559-1563, etc. or by such methods. [Step 2]: According to a general method, the compound 61 can be produced by performing the oxidation reaction of the compound 6 oxime. For example, the reaction is carried out in the same manner as in [Step 4] of the production method q. Specific examples of the solvent for each reaction in the production method V are selected depending on the type of the raw material compound, and the like, and examples thereof include dioxane, trichlorodecane, dihaloethane, tetrahydrofuran, and 1,4. -dioxane, dimethoxy ethene, N,N-dimethyl decylamine, acetonitrile, dimercapto sulfoxide, toluene, ethyl acetate, 323256 197 201206906 acetic acid, etc., alone or as a mixed solvent use. The reaction temperature varies depending on the type of the raw material compound and the reagent to be used, and is generally _4〇〇chuang 2〇〇C, preferably 0 ° C to 15 (Tc, depending on the case, the reaction can be carried out under pressure [ Production Method W] The following raw material compounds are produced by the following production methods.

63 • (wherein Ar2, L, and R2 are the same as defined in item 1). Compound 64 can be produced by performing a compound 63 other than the general method. For example, the reaction is carried out in the presence of an amine reagent such as acetic acid, citric acid, and piperidine or dimethylamine by using a compound 63 in a suitable solvent or a non-permeabilizing agent. The reaction is far. (Refer to Reference Examples 16, 17, 47, 48, 51) Further, according to a general method, in a suitable solvent or without a solvent, φ is derived from the compound 63 in the presence of acetic anhydride with N, N, N, N- Compound 64 is produced by reacting tetradecyldiamine decane. This reaction can be achieved by a method described in J. Med. Chem. 1987, 30, 1497-1502., or the like. (Refer to Reference Example 13) Further, according to the general method, compound 63 can be reacted with dimethyl sulfonium moth amine (Me2N+=CH2r) in a suitable solvent or without solvent. Compound 64 was produced. Specific examples of the solvent for each reaction in the production method W are selected according to the type of the raw material compound, and the like, for example, dioxane, trichloro 198 323256 201206906 decane, dichloroethane, tetrahydrofuran, 1, 4-dioxane, dimethoxyethane, N,N-didecylguanamine, acetonitrile, dimercaptosulfoxide, toluene, ethyl acetate, acetic acid, or decyl alcohol, ethanol, isopropanol Alcohols and the like may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually -40 ° C to 200 ° C, preferably 0 ° C to 150 ° C, and the reaction can be carried out under pressure, as the case may be. [Production Method X] The following raw material compounds were produced by the following production methods.

(In the formula, Ar2, L, and R2 are the same as defined in the item 1, and Re and Rd each independently represent a Ci-3 alkyl group, or together represent azetidine, pyrrolidine, piperidine, or sputum well). [Step 1]: Compound 63 can be produced by reacting compound 63 with furfural, polyfurfural or the like in the presence of an amine reagent such as piperidine or dinonylamine in a suitable solvent or without a solvent according to a general method. 65. The reaction is carried out in the presence of an acid such as acetic acid or hydrochloric acid, as the case may be. Alternatively, it can be produced by reacting a commercially available dimercaptoalkylphosphonium iodide salt (Me2N+=CH2r) with compound 63. [Step 2]: by reacting the compound 65 with a dentate alkyl group such as mercapto iodine in a suitable solvent or without a solvent according to a general method, and a metal hydride such as sodium hydride such as sodium hydride or an alkali metal carbonate such as potassium carbonate. Manufactured by reaction of a reagent such as a potassium acid face metal reagent such as potassium phosphate or an organic reagent such as triethylamine, a metal hydroxide (hydrogen 199 323256 201206906, etc.), or a metal oxide oxide (potassium tert-butoxide) Compound 64. The reaction can be reported by Tetrahedr〇n

Asymmetry, 2000, 1217-1225., etc., or by methods based on these standards. Specific examples of the solvent for each reaction in the production method X are selected depending on the type of the raw material compound, and the like, and examples thereof include dihalomethane, trichlorodecane, dihaloethane, tetrahydrofuran, and 1,4-dioxane. , dimethoxyethane, N,N-didecylguanamine, acetonitrile, dimercaptosulfoxide, toluene, ethyl acetate, • acetic acid, or alcohols such as decyl alcohol, ethanol, isopropanol, etc. It can be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is generally -4 (TC to 20 (TC, preferably (TC, 15 (TC, depending on the case) can be reacted under pressurized conditions. The raw material compound of the formula Y] L is not -S (=0) 2 - is produced by the following production method.

(In the formula, the Ar2 system is the same as the definition of item 1). The compound 66 is a known compound, or can be produced by a method using a known compound. For example, by clicking on Research 〇n

The method of Chemical Intermediates, 2009, 35, 137-144., or the like, is manufactured by the method specified herein. [Step 2]: Compounds 67 and 68 can be produced by a method using a known compound. For example, it can be recorded in accordance with J 〇rg. 323256 200 201206906

The method of Chem. 1993, 56, 4098-4112. etc. or is manufactured by the method of these standards. [Production Method Z] The raw material compound of the production method C is produced by the following production method.

(wherein, Ar2, R1, R2, R3, and R4 are the same as the definition of item 1). ♦ Compound 69 is a known compound, or can be produced by a method using a known compound. For example, by the method described in the Journal of the Chemical Society, Perkin Transactions 1 *· Organic and Bio-Organic Chemistry (1972-1999), (5), 1114-1?' 1908, or the like Manufactured for standard methods. [Step 1]: Compound 70 is a known compound, or 4 is produced by using the compound 69 as a standard, and the compound 69 is used, for example, by the method described in WO2008/8518, etc. These are manufactured by standard methods. [Step 2]: Compound 8 can be produced by urethanizing compound 7 according to a general method. For example, the reaction is carried out in a suitable solvent or under a non-permeating agent. In the case of a hydrogenation metal reagent such as sodium hydride, a metal reagent such as potassium carbonate or the like, an alkali metal phosphate reagent such as potassium acid, or an organic test sword such as triethylamine, fluorine In the presence of a halogenated alkali metal reagent such as iron, a metal hydroxide (sodium hydroxide or the like), a greece oxide (potassium third potassium oxide, etc.), etc., the compound 7 is reacted with an isocyanate compound ( ArLkOO) is produced by reaction. Further, the compound 8 can be produced by reacting the compound 70 with a reactive derivative (e.g., a reactive urethane or the like) by reacting with a compound derivative (e.g., a reactive urethane or the like) according to the method of the genus. (Reference Reference Example 27) &quot; Specific examples of the solvent for each reaction in the production method Z are selected according to the type of the raw material compound, and the like, and examples thereof include di-methane, trichloropyrene, and dioxane. Tetrahydrooxan, 1,4-dioxane, dimethoxyethane, N,N-dimethylformamide, acetonitrile, dimercaptosulfoxide, acetic acid, or methanol, ethanol, isopropanol ·Alcohols, etc., can be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the starting material compound and the reagent to be used, and is usually 40C to 200 C, preferably 0C to 150C, and the reaction can be carried out under pressure conditions as the case may be. [Production Process Aa] In the formula (I), R2 represents a compound of a C,-3 alkyl group substituted with a halogen atom [the compound of the following formula 72], and R2 represents a group selected from the group consisting of a thiol group and a fluorene group.

And a compound of the Cl_3 alkyl group substituted with a substituent of the group of -C(=0)RaK [the compound of the following formula 73] is produced by the following production method.

(wherein, Ar1, Ar2, L, R°, R1, R3, and R4 are the same as defined in the item 1, broadly indicating an unsubstituted C»-3 alkyl group, and R2b represents a Ci-3 substituted by a halogen atom. The base ' R2c represents a light base, -NRcRd, -0Ra&amp;-0C(=0)Ra(Rc,

Rd and 1^ are the same as item 1) and are substituted for (^_3 alkyl). 202 323256 201206906 [Step 1]: Compound 72 can be produced by performing halogenation of Compound 71 in accordance with a general method. For example, the reaction is carried out by reacting a brominating agent such as bromine, N-bromosinium iodide or iodine in a suitable solvent or without a solvent. (Refer to Examples 128 and 129) [Step 2]: Compound 72 and a metal hydroxide such as sodium hydroxide can be used in a suitable solvent or in the absence of a solvent in the presence or absence of a base according to a general method. Compound 73 is produced by reacting a metal alkoxide such as sodium oxyhydroxide or an acid such as chlorpyrifos or an amine such as dimethylamine. (Reference Example 130 to 133) Specific examples of the solvent for each reaction of the production method Aa should be selected according to the type of the raw material compound, for example, methylene chloride, trichloromethane, and dichlorobenzene. Ethane, tetrahydrofuran, 1,4-dioxane, dimethoxyl, Y,N-N-mercaptoamine, acetonitrile, dimethyl sulphur, smudge, ethyl acetate or sterol Alcohols such as ethanol and isopropyl alcohol may be used singly or as a mixed solvent. The reaction temperature varies depending on the type of the raw material compound and the reagent to be used, etc., and is generally _40 C to 200 C ', preferably 〇 ° C to 15 ° ° C, and the reaction may be carried out under pressure, as the case may be. When the compound of the present invention represented by the formula (I) has a functional group in the middle product or a raw material compound thereof, a substituent introduction reaction or a functional group conversion reaction or the like can be carried out according to a general method of the present invention as needed. These methods are described in "Experimental Chemistry Lecture (Medical Society of Japan, Maruzen)" or "Comprehensive Organic Transformations,!?. C. Larock, "VCH Publishers, Inc., 1989". For example, as the functional group conversion reaction, a carbon-carbon bond formation reaction, a reductive amination reaction or an amine alkane such as a Friedel-Crafts 203 323256 201206906 reaction and a Wittig reaction can be exemplified. Carbon-nitrogen bond formation reaction, oxidation or reduction reaction, and the like. Further, when the compound of the present invention represented by the formula (I) or an intermediate product thereof has a functional group such as an amine group, a thiol group, a hydroxyl group or a pendant oxy group, it may be protected or deprotected as necessary. As a suitable protecting group, a protective method, and a deprotecting method, § Sheep is described in "Protective Groups in Organic Synthesis 2nd Edition (J〇hn Wiley &amp; Sons, Inc.; 1990)" and the like. Further, in the structure of the compound of the present invention represented by the formula (I), the intermediate product or the structure of the reaction compound, when two or more halogen atoms are present, the difference in reactivity of the halogen atom at the bonded position is utilized, and The type of the halogen atom that has been bonded is changed, and the position of the reaction can be determined by the specific atom. Further, when the compound of the present invention represented by the formula (I) has a functional group in L, a substituent introduction reaction or a functional group conversion reaction or the like can be carried out according to a general method used by those skilled in the art. These can be found in the "Experimental φ Lecture (Medical Society of Japan, Maruzen)" or "Comprehensive Organic Transformations, R.C. Larock, VCH Publishers,

Inc., 1989", etc. For example, as the functional group conversion reaction, a carbon-carbon bond formation reaction such as a Friedel-Crafts reaction and a Wittig reaction, a coupling reaction, a reductive amination reaction or an amine can be exemplified. Carbon-nitrogen bond formation reaction, oxidation or reduction reaction, etc., such as a home reaction. (Reference Example 155) The compound of the present invention having a functional group at L in the formula (I) can be produced by using a raw material or an intermediate product having a functional group on L. (Reference Example 204 323256 201206906 119) The compound of the formula (I) produced by the above respective production methods can be isolated/purified by a general method such as chromatography, recrystallization or reprecipitation. Further, the compound of the formula (I) or a pharmaceutically acceptable salt thereof may have an axial chirality or a substituent containing an asymmetric carbon, and such a compound has an optical isomer. The compounds of the present invention contain a mixture of such isomers and the individual. As a method of obtaining such an optical isomer purely, an optical resolution method, a preferential crystallization method, or a non-image isomer method by a chromatography using an optically active column can be exemplified. And optical analysis. When the compound of the present invention or an intermediate product thereof has an functional group, it is an inert solvent (for example, an alcohol solvent such as decyl alcohol, ethanol or 2-propanol, an ether solvent such as diethyl ether, or acetic acid). An ester-based solvent such as ethyl ester, an aromatic hydrocarbon solvent such as benzene or the like, acetonitrile or the like, and a mixed solvent thereof can form an optically active acid (for example, phenylglycolic acid, N-benzoquinoxyalanine, and milk φ). a monocarboxylic acid such as an acid such as tartaric acid, o-isopropyl tartaric acid or malic acid; and a sulfonium and a salt such as camphorsulfonic acid or molybdenum. X 'the compound of the present invention Or an intermediate product thereof having an acidic substituent such as a carboxyl group, can form an optically active amine (for example, α-phenethylamine, quinine, qUinidine, cinchonidine; cinchonidine) , Cinchonine, organic amines such as strychnine) ° As the temperature at which the salt is formed, a range from room temperature to the boiling point of the solvent is exemplified. Temperature up to solvent boiling 205 323256 2 The range of from about 0.5 to about 2.0 equivalents, preferably in the range of from about 0.5 to about 2.0 equivalents, based on the amount of the optically active acid or amine, relative to the substrate. The range of about 1 equivalent is suitable, and it is crystallized in an inert solvent as needed (for example, an alcohol solvent such as decyl alcohol, ethanol or 2-propanol, an ether solvent such as diethyl ether or an ester solvent such as ethyl acetate; , an aromatic hydrocarbon solvent such as toluene, acetonitrile or the like and a mixed solvent thereof to be recrystallized to obtain a high-purity optically active salt. The obtained salt is treated with an acid or a base in a usual manner as needed to obtain a free The compound of the formula (I) can be obtained by a free base or an acid addition salt form by the type of the functional group present in the structural formula, the selection of the starting compound, and the reaction treatment conditions, and can be converted into a general method. The compound of the formula (I). On the other hand, the compound of the formula (I) can be converted into an acid addition salt by treatment with various acids according to a general method. The dihydropyrimidinone derivative of the present invention is as described later. Powerful The inhibitory activity of neutrophil elastase is expected to have an inhibitory activity against neutrophil Φ protease, and/or may be expected to be a pharmaceutical for diseases requiring it. Administration as a compound of the present invention The route may be administered by oral administration, parenteral administration or intrarectal administration, and the dosage of one day varies depending on the type of the compound, the administration method, and the symptom/age of the patient. In the case of oral administration, the human or mammal usually has a weight of about 0.01 to 3000 mg per lkg of body weight, and more preferably about 0.1 to 500 mg is divided into 1 to several administrations. Or the mammal usually has a weight of about 0.01 to 500 mg per lkg of body weight, and more preferably about 1 to 100 mg is divided into 1 to several administrations. / 206 323256 201206906 When used in the medical use as described above, the compound of the present invention is usually administered in the form of a preparation prepared by mixing with a carrier for preparation. As the carrier for the preparation, a non-toxic substance which is usually used in the field of preparation and does not react with the compound of the present invention can be used. Specifically, for example, citric acid, face acid, glycine, lactose, inositol, glucose, mannitol, dextran, sorbitol, cyclodextrin, starch, and partial chemistry may be mentioned. Starch, white sugar, methyl paraben, propyl paraben, magnesium metasilicate aluminate,

Synthetic oxalic acid, crystalline cellulose, sodium carboxymethyl lysate, hydroxypropyl starch, calcium carboxymethyl averaging, ion exchange resin, methyl vesin, gelatin, gum arabic, polytriglucose ( Pullulan), hydroxypropyl vesin, low-substituted hydroxypropyl averaverin, hydroxypropyl decyl vesyl, polyethylene oxime oxime, polyethylene glycol, alginic acid, sodium alginate, light Rocky acid anhydride, magnesium stearate, talc, tragacanth, bentonite, VEEGUM carboxyvinyl polymer, cerium oxide, sorbitan fatty acid hydrazine, laurel, glycerin, fatty acid Glycerin, refined lanolin, sweet/gelatin, polysorbate, macrogol, vegetable oil, wax, propanol, ethanol, stupid methanol, gasified sodium, sodium hydroxide, hydrochloric acid, water, etc. . The dosage form' may, for example, be a key agent, a capsule, a granule, a powder, a saccharide, a suspension, an injection, a suppository, an eye drop, an ointment, a coating agent, a human or the like. These preparations can be prepared in a conventional manner. Further, when it is dissolved, it may be dissolved or suspended in water or other suitable medium, and the granules may be coated by a known method ((3) ating). The agent can contain other ingredients that are therapeutically valuable. ΨΗ 四 四 四 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 323 The agents are administered in combination. Specific examples of the therapeutic or prophylactic agent that can be used in combination are shown below. As a short-term or long-term type of muscarine receptor (subtype M1, M2 and M3) antagonist, for example, ipratbrium bromide, eptobromide can be exemplified. Money (tiotropium bromide), etc., as a short-term or long-term type of receptor (sub-type cold 1, / 3 2, / 5 3 and 10,000) inflammatory agents, for example, can be cited F enotero 1 hydrobromide, salbutamol sulfate, salmeterol xinafoate, formoterol fumarate, etc., as inhaled or oral steroids, For example, fluticasone propionate, beclometasone propionate, budesonide, etc., as a combination of a agonist and an inhaled steroid "for example" can be exemplified by A compounding agent of trosthenate and oxycapine propionic acid vinegar, etc., as a phosphodiesterase (PDE) inhibitor, for example, 'theophylline, the aminophyl line Xanthan gum (methylxantha) Nine) and other PDE4 inhibitors, as an antispasmodic agent, for example, 'exemplified by carbocysteine, etc., as an antibiotic', for example, erythromycin and clarithromycin (clari let r〇mycin), etc. . (Embodiment) Hereinafter, the present invention will be described more specifically by way of Reference Examples, Examples and Test Examples. However, the present invention is not limited thereto. Furthermore, the identification of the compound 208 323256 201206906 is by elemental analysis value, mass spectrometry, high performance liquid chromatography mass spectrometer; LCMS, infrared absorption spectrum (IR spectra), nuclear magnetic resonance spectrum (R spectrum), high performance liquid layer Performed by HPLC (HPLC). In order to simplify the description of the specification, the abbreviations shown below are used in the tables in the reference examples, the examples, and the test examples. As abbreviations used as a substituent, Me means a methyl group, Et means an ethyl group, Ph means a phenyl group, CN means a cyano group, and N〇2 means a nitro group. As a sign for NMR, s means a single peak, d means a doublet, dd • an Italian doublet, a t is a peak, td means a doublet, q means a quadruple, and quin means five. Heavy peak, sextet means sixfold, m means multiple peak, br means wide, brs means wide single peak spectrum, brd means wide double peak spectrum, brt means peak spectrum, and J means coupling constant. The measurement conditions of NMR are as follows.

Measurement conditions 1: 300 MHz, CDCh measurement condition 2: 300 MHz, DMSO-de measurement condition 3 = 300 MHz, cd3〇d measurement condition 4: 400 MHz, CDCh measurement condition 5: 400 MHz, DMSO-de measurement condition 6: 400 MHz, CDaOD high-efficiency liquid The phase chromatography mass spectrometer; the measurement conditions of LCMS are as follows (measurement conditions 7 and 8), and the value of the mass analysis observed [MS (m/z)] is represented by MH+, and the retention time is represented by Rt (minutes). Measurement conditions: Test equipment: LC/MS-2010EV (manufactured by SHIMAZU Co., Ltd.) 209 323256 201206906 HPLC: LC/MS-2010C HT (manufactured by SHIMAZU Co., Ltd.) Column: CAPCELL PAK, C18 MGIKSHISEIDO (S-3em, 4) 6x35ram) solution: solution A; acetonitrile, solution B; 0. 05% trifluoroacetic acid / water dissolution conditions: 0. 0 to 5.0 (minutes); A: B = 10: 90-99: 1 5. 0 To 7. 0 (minutes); A: B = 99 : 1 7. 0 to 10. 0 (minutes); A : B = 99 : 1-&gt; 10 : 90 . Flow rate: 0.35 ml / minute UV : 220 nm tube Column temperature: 40 ° C Measurement conditions 8 : MS Detection machine: Waters micromass ZQ HPLC : Waters 2790 separations module Column: Impact Cadenza CD-C18 2. 0mmx20mm φ Flow rate: 1 · 0ml / minute Measurement wavelength: 254nm Moving layer: A liquid ; water B liquid; acetonitrile C solution; 2% citric acid acetonitrile solution dissolution conditions: 〇 · 〇 to 0. 1 (minutes); A liquid: B liquid: C liquid = 95 : 2 : 3 〇. 1 to 3. 1 (minutes); A liquid: B liquid: C liquid = 95 : 2 : 3 - 1: 96 : 3 3. 1 to 3.5 (minutes); A liquid: B liquid: C liquid = 1: 96 : 3 210 323256 201206906 Reference Examples 1 to 3:

[Step 1] Reference Example 1

a solution of propargylaldehyde diethyl acetal (1. 〇g), hexyl decylphosphoric acid triamide (1.5 ml) in tetrahydrofuran (30.0 ml), at -78 ° C, n-butyl lithium (3. Lml) After the dropwise addition, the mixture was heated to room temperature and stirred for 30 minutes, and then became _78 ° C. Then, propylene oxide (1.4 g) was added dropwise, and the mixture was warmed to room temperature, and the mixture was stirred for 18 hours. After a saturated aqueous solution of chloroacetic acid (30 ml) was added to the mixture, ethyl acetate (50 ml, twice). The organic layer was washed with water (30 ml), EtOAc (EtOAc) . • H-NMR CCDCh: 300 MHz) (5: 1. 22 (dd, 6H, J = 13. 5, 6. 9 Hz), 2. 32-2. 46 (ιη, 2H), 2. 62 (d, 3H, • J=9. 3Hz), 3. 53(q, 1H, J=6. 9Hz), 3. 56(q, 1H, J=6. 9Hz), 3. 69(q, 1H, J=6. 9Hz), 3. 72(q, 1H, J=6. 9Hz), 3. 91-4. 01(m, 1H), 5. 25(t, 1H, J=1.6Hz).

[Step 2] Reference Example 2, 3 Addition of 4-cyanobenzene to a solution of 6,6-diethoxy-4-hexyn-2-ol (4.0 g) in ethanol (30 ml) obtained in Step 1. The hydrazine hydrochloride (4. 〇g) was stirred under reflux with heating for 8 hours. After adding water (i〇〇ffli) to the reaction mixture, it was extracted with ethyl acetate (3 〇〇mi, twice). The organic layer was washed with brine (1 mL) and evaporated The residue 211 323256 201206906 was purified by silica gel column chromatography (solvent solvent hexane/ethyl acetate) to give 4-[5-(2-hydroxypropyl)-1Η-°bazol-1-yl group. Benzene nitrile 35g) and 4-[3-(2-propylidene-l-propyl-1-yl)benzonitrile (667. 8mg). ^-NMRCCDCh : 300ΜΗζ) δ : Reference Example 2 : 4-[ 5-(2-Hydroxypropyl)-111-pyrazol-1-yl]benzonitrile: 1.18 ((1,31|,] = 6. 2 Hz), 2. 18 (d, 2H, J=5. 9Hz), 4. 00-4. 〇8(m, 1H), 6. 32(brs, 1H), 7. 58(brs, 1H), 7. 60-7. 62(m, 2H), 7. 70-7. 73(m, 2H). 10 Reference Example 3: 4-(2-propylpropyl)-i Η-n ratio. Sodium-1-yl]benzoquinone.: 1. 29 (d, 3H, J=6. 3Hz), 2. 77(dd, 1H, J=15. 〇, 5. 4Hz), 2. 88(dd, 1H, J=15. 0, 3. 6Hz), 4. 15 -4. 21(m, 1H), 6. 36(d, 1H, J=2. 4

Hz), 7. 71(d, 2H, J=9. 0Hz), 7. 78(d, 2H, J=8. 7Hz), 7. 91(d, 1 H, J=2. 7Hz). Examples 4 to 6:

[Step 1] Refer to Examples 4 and 5 for 66-diethoxy-4-enohexan-2-ol (4.82 g) obtained from Reference Example 1, 4-1 phenylquinone hydrochloride (6·) 57g) N, N_ two? Hydrochloric acid (1 M aqueous solution, μ.-) was added dropwise to a solution of the amine formate (100 ml) for a period of 26 hours. After the addition of water (150 ml) 212 323256 201206906 to the reaction mixture, it was extracted with hexane/ethyl acetate = 1/1 (500 ml, 2 times). The organic layer was washed with water (aq.) and brine (150 ml), dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography on silica gel (solvent solvent / hexanes / ethyl acetate) to give (Z)-4-[2-(5-yl-2-ylhexyl)indenyl]phenylhydrazine. Nitrile (1.15 g) and (E)-4-[2-(5-hydroxy-2-subhexyl)indenyl]benzonitrile (2.76 g). 1H-NMR (CDCh: 300 MHz) 5 : Reference Example 4: Lu (Z)-4:-[2-(5-trans- 2,2-hexenyl)indenyl]benzonitrile: 1. 17 (d, 3H , J=6. 2Hz), 2. 62(dd, 2H, J=l. 6Hz), 3. 86-3. 94(m, 1H), 5. 13(brs, 1H), 6. 64(brs , 1H), 7. 25(d, 2H, J=8. 8Hz), 7. 64(d, 2H, J=8. 6Hz), 10.19(s, 1H). Reference Example 5: (E)-4 -[2-(5-Hydroxy-2-n-hexyl)indenyl]benzonitrile: 1. 16 (d, 3H, J = 6. 2 Hz), 2. 42-2. 51 (m, 2H), 3 77-3. 85(m, 1H), φ 4. 86(d, 1H, J=4. 6Hz), 7. 03(d, 2H, J=8. 4Hz), 7. 19(s, 1H ), 7. 61 (d, 2H, J = 8. 2Hz), 11.18 (s, lH).

[Step 2] Reference Example 6a N, N- of (Z)-4-[2-(5- mercapto-2-y-hexyl)-phenyl]benzonitrile (102. 4 mg) obtained in the step 1 To a solution of dimercaptomethylamine (2.5 ml), 1N hydrochloric acid (〇. 9 ml) was added, and the mixture was stirred at 140 ° C for 5 hours. After adding water (30 ml) to the reaction mixture, it was extracted with hexane/ethyl acetate = l/2 (40 ml, twice). The organic layer was washed with brine (30 ml) and dried over anhydrous sodium sulfate. The residue was purified by column chromatography 213 323256 201206906 (solvent solvent hexane / ethyl acetate) to give 4-[5~d#t propyl)-1 Η-pyrazol-1-yl] Benzoonitrile (36. Omg). j-NMRCCDCla : 300 MHz) 5 : The same as Reference Example 2. [Step 2] Refer to Example 6b for (Z)-4-[2-(5-trans-base_2-subhexyl) tillage]benzonitrile (200. Omg) of dichloropurine obtained in Step 1. In a solution of alkane (5.0 ml), tri-glycolated gold (50.4 mg) was added, and the mixture was stirred at room temperature for 14 hours. After a saturated aqueous solution of sodium hydrogencarbonate (30 ml) was added and the mixture was evaporated. After drying over anhydrous sodium sulfate, it was concentrated. The residue was purified by silica gel column chromatography (solvent solvent hexane / ethyl acetate) to give (2- propyl propyl)-1 Η _ _ ). j-NMRCCDCh: 300 MHz) 5 : The same as Reference Example 2. [Step 2] Reference Example 6c Φ Dioxethane of (E)-4-[2-(5-hydroxy-2-indolyl)indenyl]benzonitrile (220. Omg) obtained in Step 1. (6. 〇ml) In the solution, add = gold (59. 4 ml) and stir at room temperature for 15 hours. The mixture was stirred with EtOAc (EtOAc m. The solvent was purified by hexane/ethyl acetate to give (2-hydroxypropyl)-1?-pyrazol-1-yl]benzonitrile (187. Omg). H-NMR (CDCl3: 300 MHz) (5: The same as Reference Example 2. 323256 214 201206906 Reference Example 7:

a solution of 4-[5-(2-hydroxypropyl)-1H-pyrazol-1-yl]benzonitrile (278. Omg) in dichloromethane (6. 〇mi) obtained in Reference Examples 2 and 6. Add Dess-Martin reagent (570. 7 mg) and stir at 〇 °c for 2 hours. After adding a saturated aqueous solution of sodium hydrogencarbonate (5 〇m 1 ) to the reaction mixture, it was extracted with trioxane (30 ml, twice). The organic layer was washed with brine (3 mL) and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (solvent solvent hexane / ethyl acetate) to give 4-[5-d- oxypropyl)-1 Η-pyrazol-1-yl]phenylhydrazine. Nitrile (177. 6 mg). H-NMR (CDC13: 300MHz) 5 : 2. 18(s, 3H), 3. 85(s, 2H), 6. 37(d, 1H, J=l. 8Hz), 7. 52-7. 56 (m, 2H), 7. 70(d, 1H, J=l. 8Hz), 7. 74-7. 78(m, 2H). References 8 to 9:

The starting material of the above formula: 4-cyanobenzamide is produced by the method of j. 〇rg. Chem. 2009, 74, 6410-6413. [Step 1] Reference Example 8 A solution of 4-cyanobenzidine (300. 〇mg) and dimercapto amine amine dimethyl acetal (330 //1) in acetonitrile (10 ml) After stirring for 5 minutes at 5 ° C, 215 323256 201206906 was allowed to stand at room temperature, 2-hydroxy-propylamine (240//1) and acetic acid (16/zl) were added, and the mixture was stirred under heating and reflux for 4 hours. After adding water (5 ml) to the reaction mixture, it was extracted with ethyl acetate (30 ml, twice). Washed with water (_), saturated brine (3Gml), prepared with 'anhydrous sulfur _ dry, concentrated under reduced pressure { , Γ 糸 虱 methane / methanol) refined, and served to 4-[4-(2-hydroxyl Propyl)-4Η~ι 9 / η η I 2,4-triazol-1-ylbenzonitrile (112.2 mg). ^-NMRCCDCh : 300ΜΗζ) δ :

1.28 (d, 3H, J = 6.4 Hz), 3.76-3. 94 (m 9 Η, η 4, m, 2H), 4.24 - 4.32 (m, lH) 7.70-7.74 (m, 2H), 7.81 - 7.84 (m, 2H), 8l3 (slH) [Step 2] Reference Example 9 ' '4-[4-(2-P-propyl)luu'f tris-yl]benzonitrile (10).Oing) In the gas-fired (10) hydrazine solution, acridine diphosphate (197.8 mg) was added at room temperature for 3.5+. The reaction mixture was filtered through celite with chloroform. The residue was purified by silica gel column chromatography (dissolving solvent trichlorohydrazine/methanol) to give 4-[4_(2_-oxypropyl hydrazine-1,2,4-tris-yl)benzene. Nitrile (19.3 rog) LC/MS (measurement condition 8) 227 (M+H) / 1.42 (min). Reference Examples 10, 11:

323256 216 201206906 [Step 1] Reference Example 1 1,4-Difluoromethylphenylurea (13.6 g), copper chloride (i) (i. 3 g) of 1,4-dioxane (200 ml) To the solution, a solution of valeraldehyde u3 4g) in chloroform (20ml), 2-bromophenylacetone (9.5g), acetic acid (1. 〇ml), trifluoride diandiethyl hydrazine complex ( 8. 5 ml), stirred under heating and reflux for 6 hours. After the reaction mixture was added with aqueous sodium hydrogencarbonate (1 mL) and aqueous ammonia (5 ml), ethyl acetate (50 ml ' The organic layer was washed with water (5 ml) and brine (50 ml). The residue was purified by column chromatography (eluent solvent hexane/ethyl acetate) to afford 1-[2-(2-bromophenyl) 3-(Trifluoromethyl)phenyl]urea (2.0 g). W-NMRCCD· : 300MHz) (5 : 2. 06(s, 3H), 3. 48-3. 57(m, 1H), 3. 74-3. 82(ra, 1H), 4. 62(t , 1H, J=6. 8Hz), 6. 18(brs, 1H), 7. 18-7. 24(m, 3H), 7. 33-7. 46 (m, 3H), 7. 68(d , 1H, J=8. 1Hz), 7. 77(s, 1H). φ [Step 2] Reference Example 11 [2-(2-Bromophenyl)-3-side oxygen obtained from Reference Example 10 A solution of butylbutyl]-3-[3-(trifluoromethyl)phenyl]urea (1.62) in acetic acid (3. 1111) was stirred for 6 hours under reflux. Water (50 ml) was added to the mixture. The mixture was extracted with EtOAc (30 mL, EtOAc) (EtOAc) (Isolation solvent hexane/ethyl acetate) was purified to give 5-(2-bromophenyl)-6-methyl-1-[3-(trifluoromethyl)benzyl]-3, 4- · 虱 密 ° ° -2 (1H)-ketone (565. Omg) 217 323256 201206906 'H-NMRCCDCh: 300MHz) 5 : 1. 24 (t, 3H, J = l. 7Hz), 3. 96 ( Brd, 1H, J=14. 1Hz), 4. 19(brd, 1H, J=14. 1Hz), 5. 22(s, 1H), 7. 08-7. 14(m, 1H), 7. 17-7. 20 (m, 2H), 7. 24-7. 29(m, 1H), 7. 45-7. 58(m, 5H). Reference Example 12:

1-[2-(2-Bromophenyl)-3-oxobutylbutyl]-3-[3-(trifluoromethyl)phenyl] gland (194. Omg) obtained in Reference Example 10. Adding tetrakis(triphenylphosphine)le to a solution of cyanophenyl ester (332. Omg), sodium carbonate (479. Omg) in tetrahydropyrrole (5.0 ml) / water (0.8 ml). 52. 2 mg), stirred under heating and reflux for 2.5 hours. After adding water (20 ml) to the reaction mixture, ethyl acetate (10 ml, twice) was evaporated. The organic layer was washed with brine (20 ml), dried over anhydrous sodium sulfate The residue was purified by column chromatography (eluent solvent hexane/ethyl acetate) to give 1-[2-(4'-cyanobiphenyl-2-yl)-3-oxobutyl butyl. ]-3-[3-(Trifluoromethyl)phenyl]urea (53.6 mg). ^-NMRCCDCh: 300MHz) (5: 1. 79(s, 3H), 3. 50-3. 57(m, 1H), 3. 62-3. 70(ra, 1H), 3. 94(dd, 1H, J=9. 2, 4. 0Hz), 5. 16(brs, 1H), 6. 34(brs, 1H), 6. 99-7. 03(m, 1H), 7. 24-7. 37(m, 5H), 7. 42-7. 47(m, 2H), 7. 54(d, 2H, J=8. 3Hz), 7. 72(d, 2H, J=8. 3Hz). 218 323256 201206906 Reference Example 13:

A solution of 4-fluorophenylthioacetone (2.0 g acetic anhydride (2.1 ml) was heated to 60 ° C to give N,N,N,N-hexamethylene fluorenyldiamine (1.5 ml) After dropping into it, it was stirred for 10 minutes. After a saturated aqueous solution of sodium carbonate (100 ml) was added, and ethyl acetate (50 ml, twice). The organic layer was washed with saturated brine (50 ml) and dried over anhydrous sodium sulfate. The residue was purified by a silica gel column chromatography (solvent solvent hexane/ethyl acetate) to give 3-(4-fluorophenylthio)-3-butan-2-one (493.9 mg) ). R (CDC13: 300MHz) (5: 2. 40(s, 3H), 5. 21(d, 1H, J=l. 5Hz), 6. 10(d, 1H, J=l. 5Hz), 7 06-7. ll(m, 2H), 7. 41-7. 46(m, 2H). Reference Example 14: φ The same raw material compound was used, and reacted and treated in the same manner as described in Reference Example 13. After that, the compound shown below was obtained.

CI j-NMRCCDCh ·· 300MHz) 5 : 2. 37(s, 3H), 5. 94(s, 1H), 6. 15(s, 1H), 7. 13-7. 18(m, 2H), 7. 36-7. 40(m, 2H). Reference examples 15 to 16: 219 323256 201206906

[Step 1] Reference Example 15 in 1-(4-bromophenylthio)propan-2-one (300. Omg), zinc cyanide (718.4111), zinc powder (39.9111叾) 叱 1^-two To a solution of methyl decylamine (4. 1111), tetrakis(triphenylphosphine)palladium (282. Omg) was added, and the mixture was stirred at 100 ° C for 4 hours. The reaction mixture was filtered with EtOAc. EtOAc (EtOAc) The organic layer was washed with brine (20 ml) The residue was purified by EtOAc EtOAc EtOAc (EtOAc) R (CDC13: 300MHz) 5 : 2. 29(s, 3H), 3. 75(s, 2H), 7. 29-7. 32(m, 2H), 7. 51-7. 54(m, 2H).

[Step 2] Reference Example 16 Lu 4-(2-oxopropylpropylthio)benzonitrile (130. 〇mg), aqueous furfural (178 a 1), acetic acid (9/U), piperidine (9 v 1) acetonitrile (6.0 ml) was stirred for 1 hour under reflux. The reaction mixture was concentrated under reduced pressure, and water (l········ The organic layer was washed with brine (20 ml), dried over anhydrous sodium sulfate The residue was purified by silica gel column chromatography (eluent solvent / hexane / ethyl acetate) to afford 4-(3-o-oxy-i-butene-2-ylthio)benzonitrile (57. 6mg). ^-NMRCCDCh: 300MHz)^ : 220 323256 201206906 2. 38(s,3H), 5.79(d,1H,J=0. 9Hz), 6.40(d,1H,J=0. 9Hz), 7. 39-7. 42(m, 2H), 7. 57-7. 6(m, 2H). References 17 to 21:

[Step 1] Reference Example 17 2-bromophenylacetone (298. Omg), aqueous furfural (366 // 1), acetic acid (18/^1), glutamic acid (18#1) sterol (5. 1111) The solution was stirred under heating and reflux for 2 hours. The reaction mixture was concentrated under reduced pressure. EtOAc (EtOAc) The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (eluent solvent hexane / ethyl acetate) to give 3-(2-bromophenyl)-3-buten-2-one (255.Omg). (CDC13: 300MHz) (5: φ 2. 36(s, 3H), 5. 79(s, 1H), 6, 30(s, 1H), 7. 16-7. 23(m, 2H), 7 29-7. 34(m, 1H), 7. 54-7. 58(m, 1H). Reference Examples 18 to 19: The same raw material compound was used, and reacted in the same manner as described in Reference Example 17 After the treatment, the compound shown in Table 1 was obtained. [Table 1] 221 323256 201206906 Table 1 Reference Example Structural Formula Determination Conditions! H-NMR5 (or LC-MS: [M+H]+ / Rt) 18 1 2'3 (s, 3H), 5'94 (s, 1H&gt;, 6.15 (s, 1H), 7.13-7 -13⁄4 (m( 2H), 7.36-7.40 (m, 2H) 19 1 2-2l (s, 3H), 6.18 (s, 1H), 6.40 (s, 1H), 6.43 (d-1H, J=1.8Hz), 7.52-7.56 (m, 2H), 7.65-7.69 2H), 7.71 (d, 1H, J=1.8 Hz) [Step 2] Reference Example 20 Called 3-(2-bromophenyl)-3-buten-2-one (100. 〇mg), 3-trifluorodecylphenylurea (100) .Omg), vaporized copper, boron trifluoride diethyl ether complex (113/z 1) tetrahydro π η η ( (5. 〇mi) solution, stirred under heating and reflux for 10 hours Water (20 ml) was added to the reaction mixture, and the mixture was evaporated. The residue was purified by silica gel column chromatography (solvent solvent hexane / ethyl acetate) to give 5-(2-bromophenyl) φ - fluorenyl </ br> 3, 4-Dihydro 0 唆 -2 (1H)-酉 (107.Omg). 'H-NMRCCDCh: 300 MHz) (5: same as the reference example. Reference Example 21: Using the corresponding starting compound, After reacting and treating in the same manner as in the method described in Reference Example 20, the compound shown below was obtained. 222 323256 201206906

^-NMRCCDCh: 300MHz) δ : 1· 47(t, 3H, J=l. 7Hz), 4. 20(t, 2H, J=l. 7Hz), 4.97(brs,1H), 7. 13 -7. 16(m, 1H), 7. 22-7. 25(m, 1H), 7. 36-7. 41(m, 2H), 7. 46-7. 61(m, 4H). Examples 22 to 24:

3-(2-bromophenyl)-3-buten-2-one (1. 05g), 1-methyl-3-[3-(trifluoromethyl)phenyl]urea (1.5 mg) , a vaporized copper (1) (100. lmg), boron trifluoride diethyl ether complex (0. 98ml) tetrahydrofuran (5.0 ml) solution, φ using a microwave synthesis device, at 100 ° C was stirred for 20 minutes. After adding water (30 ml) to the reaction mixture, ethyl acetate (m. The organic layer was washed with brine (30 ml), dried over anhydrous sodium sulfate The residue was purified by column chromatography (eluent solvent / hexane / ethyl acetate) to give 5-(2-bromophenyl)-3,6-didecyl-1-[3-(3) Fluorinyl)phenyl]-3,4-dihydropyrimidine-2(1H)-indole (1.43 g). j-NMRCCDCh: 300MHz) (5: 1. 28(s, 3H), 2. 98(s, 3H), 3. 95(dd, 1H, J=14. 1, 2. 1Hz), 4. 1 7 (dd, 1H, J=14. 1, 1. 8Hz), 7. 14-7. 19(m, 1H), 7. 26(d, 1H, J= 223 323256 201206906 1.8Hz), 7. 29- 7. 34 (m, 1H), 7. 45-7. 63 (m, 5H). Reference Examples 23 to 24: After reacting and treating in the same manner as in the method described in Reference Example 22 using the corresponding starting compound, The compounds shown in Table 2 were obtained.

Table 2 Reference Example X Measurement conditions lH-NMR5 (or LC-MS: [M+H]+ / Rt) 2 3 OMe 1 1-26 (t, 3H, J = 1.5 Hz), 2.90 (s, 3H), 3.72 (s, 3H) .3.88 (dd, 1H, J=14.4, 1.8Hz), 4.10 (dd, 1H, j= 14.1, 1.5Hz), 6.74 — 6.84 (ra, 3H), 7.06 — 7.27 (m _ ..4H), 7.54 (dd, 1H. i=8.1, 0.9Hz) ' 2 4 Cl 1 1.^6 (s, 3H), 2.89 (s, 3H), 3.90 (d, 1H, J=14.4Hz ).4.11 (d, 1H, J=14.1Hz), 7.09-7.30 (m, 7H) 7 56 (d, 1H, J=7.8Hz> ' ' Reference examples 25 to 26:

[Step 1] Reference Example 2 5 4 [4-(2-Sideoxypropyl 2, 4-tris-ytyl-3-yl)benzonitrile (19. Omg), formic acid·aqueous solution (25# 1), A solution of acetic acid (1 〆 1), π bottom bite (1# 1) in methanol (2.0 ml) was stirred for 3 hrs under reflux with stirring. The reaction mixture was concentrated under reduced pressure and water (l? The mixture was extracted with chloroform (2 mL, EtOAc). Butane-2-yl)-4Η~1,2 4-disial-3-yl]benzonitrile (14. 9 mg). LC/MS (measurement condition 8) 271 (M+H)/1.35 (rain) ).

[Step 2] Reference Example 26

a solution of 4-[4-(1-decyloxy-3-oxooxybutan-2-yl)24-tris-tris--3-phenyl]benzonitrile (48.0 mg) in acetic acid (1.0 mL) Mix for 3 hours. After adding water (30 ml) to the reaction mixture, ethyl acetate (20 ml, twice) was evaporated. The organic layer was washed with a saturated aqueous solution of brine (2 mL), and then purified and purified. Residue (4) m-column chromatography (dissolved solvent is trichlorosulfonium/methanol), and obtained, M _ [ 4 _ (3 _ side oxy_gong-butan-2-yl) pu 1,2 , 4-tri &amp;, 3_yl]benzonitrile (28 〇mg). ^-NMRCCDCh : 300 ΜΗζ) ά : 2. 35 (s, 3 Η), 6. 24 (d, 1 Η, J = 2 · OHz), 6. 49 (d, 1 Η, J = 2. 2 Hz), 7. 66 (s, 4H), 8. ll(s, 1H). References 27 to 30:

[Step 1] Reference Example 27 Compound of the above formula, 1-[2~methyl-4-oxoxypentane-2-yl]_3_ 225 323256 201206906 [3-(Trifluoromethyl)phenyl]urea It is manufactured according to the method described in Japanese Patent Laid-Open No. g-311026. 'H-NMRCCDCh: 300ΜΗζ)ά : 1. 42(s, 6H), 2. 15(s, 3H), 2. 93(s, 2H), 6. 67(brs, 1H), 7. 22 (d , 1H, J=8. 4Hz), 7. 33(t, 1H, J=7. 9Hz), 7. 42(d, 1H, J=8. 4H z), 7. 61(s, 1H).

[Step 2] Reference Example 28 1-[2-Mercapto-4-oxooxypentan-2-yl]-3-[3-(trifluoromethyl)luphenyl]urea (1.3 g) A solution of acetic acid (4.0 ml) was stirred for 5 hours under reflux with heating. After adding water (50 ml) to the reaction mixture, ethyl acetate (3? The organic layer was washed with water (50 ml) The residue was purified by column chromatography (eluent solvent hexane/ethyl acetate) to give 4,4,6-trimethyl-1-[3-(tri-l-mercapto)phenyl]-3 , 4-Dihydro "Bite 2-(lH)-嗣 (650.Omg) φ Li R (CDC13: 300MHz) ά : 1. 33(s, 6H), 1. 49(d, 3H, J= l. 1Hz), 4. 69(dd, 1H, J=2. 2Hz), 4. 89(brs, 1H), 7. 41(d, 1H, J=7. 7Hz), 7. 46(s, 1H), 7. 51(t, 1H, J=7. 7Hz), 7. 57(brs, 1H, J=6. 6Hz).

[Step 3] Reference Example 29, 30 to 4,4,6-trimethyl-l-[3-(trifluoromethyl)phenyl]-3,4-dihydrocarcinoma bite-2-(lH)- N-hydroxysuccinimide (392. 4 mg) was added to a solution of ketone (620. Omg) in tetrahydro-pyrene (20. 〇ml), and stirred at room temperature for 30 minutes. After a saturated aqueous solution of sodium hydrogencarbonate (30 ml), EtOAc (EtOAc) (EtOAc) The organic layer was washed with brine (30 ml) The residue was purified by a sep. column chromatography (eluent solvent hexane/ethyl acetate) to give 6-(bromomethyl)-4,4-dimethyltrifluoromethyl)phenyl]-3. 4-dihydropyrimidin-2-(1Η)-one (604. 9 mg) and 5-bromo-4,4,6-tridecyl-1-[3-(trifluoromethyl)phenyl]-3, 4-Dihydropyrimidine-2-(1Η)-one (14. Omg). W-NMRCCDCh: 300MHz) (5: Refer to Example 29 6-(bromofluorenyl)-4,4-dimercapto-1-[3-(trifluoromethyl)phenyl]-3,4-dihydro Pyrimidine-2-(1Η)-one: 1. 46(s, 6H), 3. 83(d, 1H, J=l. 5Hz), 4. 57(d, 1H, J=l. 5Hz), 4 99(s, 1H), 7. 40-7. 53(m, 2H), 7. 66-7. 72(m, 2H). Reference Example 30 5-Bromo-4, 4, 6-trimethyl -l-[3-(Trifluoromethyl)phenyl]-3,4-dihydro-ruthenium-2-(1Η)_ class: 1. 48(s, 6H), 1. 72(s, 3H), 4. 98(brs, 1H), 7. 40(d, 1H, J=7. 7 Hz), 7. 44(s, 1H), 7. 52(t, 1H, J=7. 7Hz ), 7. 60(d, 1H, J=7. 7H z). Reference examples 31 to 32:

6-(Bromoindolyl)-4,4-dimethyl-l-[3-(trifluoromethyl)phenyl]-227 323256 201206906 3' 4 Hydrogen 0-bite-2-(1Η)- 5小时。 The ketone (604. Omg) in a solution of trichloromethane (10. 〇mi), while chilling, adding bromine (1N tri-methane solution, 17 ml), stirring at a temperature of 3. 5 hours. A saturated aqueous solution of sodium hydrogencarbonate (3 mL) and a saturated aqueous solution of sodium thiosulfate (3 〇mi) were added to the mixture, and then extracted with methylene chloride (30 ml, twice). The organic layer was washed with brine (3 mL EtOAc) The residue was purified by column chromatography on silica gel (eluent solvent / hexane / ethyl acetate) to give _6_(bromomethyl)-4,4-didecyl-1-[3-( Trifluoromethyl)phenyl]_3,4-dihydropyrimidine-2-(1Η)-one (162. Omg) and 6-(dibromodecyl)-4, 4-dimercaptodione Phenyl]-3,4-dihydroindole, 2-(ih)-_ (541.4 mg). 'Η-Li R (CDC13: 300MHz) 5 : Reference Example 31 5- Desert-6-(Demoyl)-4,4-Dimercapto-1-[3-(trifluoromethyl)phenyl]- 3, 4-Dihydropyrimidin-2-(1Η)-one: • 1. 44(s, 6H), 3. 80(s, 2H), 5. 14(brs, 1H), 7. 52-7. 55(m, 3H) 7. 58-7. 63(m, 1H). Reference Example 32 6-(Dibromomethyl)-4, 4-dimercapto-l-[3-(trifluoromethyl) Phenyl]_3,4-dihydropyrimidin-2-(1Η)-one: 1. 41(s, 6H), 5. 00(s, 1H), 5. 14(d, 1H, J=l. 8Hz) , 5. 4l(s, 1H), 7. 39(d, 1H, J=7. 5Hz), 7. 44(s, 1H), 7. 51-7. 60(m, 2H). Reference 33 : 323256 228 201206906

6-(Bromoindolyl)-4, 4-dimercapto-l-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrimidin-2-(1Η)-one (150. In a solution of EtOAc (4 mL), succinate (55.7 ml) was added under ice-cooling, and the mixture was stirred at room temperature for 8 hours and then stirred at 50 ° C for 2 hours. A saturated aqueous solution of ammonium sulphate (20 ml) was added to the mixture, and ethyl acetate (20 ml, twice) was taken. The organic layer was washed with brine (20 ml) The residue was purified by silica gel column chromatography (solvent solvent hexane/ethyl acetate) to give 5-di-[,4,4,6-tridecyl-1-[3-(trifluoromethyl) )]]], 4-dihydroindole 2-3 (1 Η)-_ (96. 2 mg) 丽 R (CDC13: 300 MHz) 5 : The same as Reference Example 30. Reference examples 34 to 35:

[Step 1] Reference Example 34 at 6-(&gt; skunk based)-4,4-didecyl~1-[3-(trifluoromethyl) xiaofu 1 -3,4-^a^^- 2-(lH)-S^(611.0mg)^, af^(1〇i〇ral) solution, add bromine (IN trichloromethane solution, 14ml) under ice cooling, and mix at room temperature 3 After an hour, add Moxi (10) trichloromethane solution, 〇 4mi), and stir for 1.5 hours. A saturated aqueous solution of sodium hydrogencarbonate 323 256 229 201206906 (30 ml) and a saturated aqueous solution of sodium thiosulfate (30 ml) were added to the mixture, and the mixture was extracted with three gas (30 ml '2 times). The organic layer was washed with brine (30 mL) The residue was purified by silica gel column chromatography (solvent solvent hexane/ethyl acetate) to give 5-bromo-6-(dimethanol)-4, 4-didecyl-1-[3- (Trifluoromethyl) phenyl]-3,4-dihydroglycide-2-(lH)-g (425.0 mg). 'H-NMRCCDCh: 300MHz) (5: 1. 51(s, 6H), 5. 26(brs, 1H), 6. 87(s, 1H), 7. 47-7. 49(m, 1H), ® 7. 54-7. 60(ra, 1H), 7. 64-7. 72(m, 2H).

[Step 2] Reference Example 35 to 5-bromo-6-(dibromoindolyl)-4,4-didecyl(trifluoromethyl)phenyl]-3,4-dihydropyrimidin-2-(11 〇-_(2〇〇.〇呵) in the solution of dihydrazinyl sulfoxide (3.0 ml), adding the basal side of the sodium (μ. 〇mi), and mixing at room temperature for 2 hours. After adding a saturated aqueous solution of ammonium chloride (2 mL), ethyl acetate (20 mL, twice) was evaporated. After that, it was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (solvent solvent hexane/ethyl acetate) to give 5-bromo-4,4,6-trimethyl(trifluoromethyl)benzene. ]3, 4_ Dihydro π-Bite-2-(1Η)-one (45. 6 mg) W-NMRCCDCh: 300 MHz) 5 : The same as Reference Example 30. Reference Example 36: 230 323256 201206906

To a solution of 1-(4-cyanophenyl)-1Η-η than saliva-5-ylboronic acid (100. Omg) in tetrahydrofuran (2.0 ml), 2,3-dimercapto-2, 3- Pinacol (145. Omg) and a powder molecular sieve (180. Omg) were stirred at room temperature for 7 hours. Ethyl acetate (20 ml) was added to the mixture and filtered. Hexane (i〇mi) was added to the filtrate, and the mixture was stirred at room temperature for 1 hour. The precipitate was collected by filtration to give 4-[5-(4,4,5,5-tetramethyl-1,3, 2-Dioxaborolan-2-yl)-1Η-pyrazol-1-yl]benzonitrile (4-[5-(4, 4, 5, 5-tetramethyl-l, 3, 2 -dioxaborolane-2-yl)-lH-pyrazole-l-yl]benzonitrile) (120. Omg). • H-NMRCCDCh: 300MHz) 5 : 1. 26(s, 12H), 6. 94(d, 1H, J=l. 8Hz), 7. 76-7. 79(m, 2H), 7. 8 7 (d, 1H, J = 1.8 Hz), 7. 95-9. 98 (m, 2H). φ Example 1: 4-[5-(6-fluorenyl-2-yloxy-1-(3) -(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1Η-. Bizozol-1-yl]benzonitrile

3-Trifluorodecylphenylurea (204. Omg), 4-[5-(3-o-oxy-2-buten-2-yl)-1 fluorene-carbazole-1- obtained from Reference Example 19. Benzoquinone nitrile (95. Omg), copper chloride (1) (19.8 mg), boron trifluoride diethyl ether complex 231 323256 201206906 (130//1) tetrahydroanthracene ( 2. Qml) solution, using a microwave reaction synthesis unit, at 165. (: 1 hour of mixing. After adding water hydrazine ml to the reaction mixture), it was extracted with B16^(1〇ιη1 '2 times). The organic layer was washed with brine, dried over anhydrous sodium sulfate The residue was purified by column chromatography (eluent solvent, hexanes: ethyl acetate, EtOAc: EtOAc: EtOAc: EtOAc) -2-Sideoxy-1-(3-(difluoromethyl)phenyl)_ι,2,3,4-tetrahydropyrimidin-5-yl)-ih-mouthbiazol-1-yl]phenylhydrazine Nitrile (19.4 mg). _ ^-NMRCCDCh : 300ΜΗζ) δ : 1. 28(s, 3H), 3. 95(s, 2H), 5. 18(s, 1H), 6. 34(d, 1H, J= 1. 8Hz) , 7. 49(t, 1H, J=7. 7Hz), 7. 56(d, 1H, J=7. 5Hz), 7. 67 (d, 1H, J=l. 8Hz), 7. 72- 7. 77(m, 4H). Example 2: 4-[4-(3,6-Dimercapto-2-oxo-l-(3-(trifluoromethyl)carbonyl)-1, 2,3,4-tetrahydro'»密11定-5-yl)-4}1-1,2,4-three-degree sitting-3-yl]benzonitrile

Mercapto-3-[3-(dioxamethyl)phenyl]urea (16.7 mg), 4-[4-(3-o-oxy-1-but-2-yl) obtained from Reference Example 26 -4Η-1,2,4-triazol-3-yl]indole nitrile (14. Omg), vaporized copper (l) (〇. 6 mg), trifluoronized diethyl ether complex ( 14 &quot;1) tetrahydrofuran (i.〇mi) solution was stirred at 120 ° C for 30 minutes using a microwave reaction synthesis apparatus. After a saturated aqueous solution of sodium hydrogencarbonate (1 mL) was added to the mixture, ethyl acetate (1 ml, twice) 232 323256 201206906. The organic layer was washed with brine (1 ml) and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (solvent solvent trichloromethane / decyl alcohol) to give 4-[4-(3,6-dimercapto-2-yloxy-1-(3-) (trifluoromethyl)phenyl)-1,2,3,4-tetrahydrofuro"-5-yl)-4!^-1,2,4-tris-3-yl]benzonitrile ( 1. 8mg). 'H-NMRCCDCh: 300ΜΗζ) δ : 1. 29(t, 3H, J=l. 7Hz), 2. 92(s, 3H), 3. 85-4. 15(m, 2H), 7. 33 ( d, 1H, J=7. 5Hz), 7. 39(s, 1H), 7. 52(t, 1H, J=7. 9Hz), 7. 61 (d, 1H, J=7. 9Hz), 7. 78-7. 81(m, 2H), 7. 98-8. 01(m, 2H), 8. 20(s, 1H). Example 3: 5-(4-fluorophenylthio) -3,6-Dimethyl-l-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrimidin-2(1H)-one

Methyl-3-[3-(trifluoromethyl)phenyl]urea (i33.4 mg), 3-(4-fluorophenylthio)-3-buten-2-one obtained from Reference Example 13 1〇〇· 〇mg), vaporized copper (1) (5. Omg), boron trifluoride diethyl ether complex (120# 1) tetrahydrofuran (3.0 ml) solution, using microwave reaction synthesis device , at 1〇〇. (: stirring for 30 minutes. After adding a saturated aqueous solution of sodium hydrogencarbonate (10 ml), the mixture was extracted with ethyl acetate (1 mL, twice). The layer was dried over anhydrous sodium sulfate and evaporated, evaporated, evaporated, evaporated. -3,6-Dimercapto-1·~[3-(trifluoromethyl)phenyl]-3,4-dihydropyrimidin-2 (11〇-ketone (25.511^). j-NMRCCDCh: 300MHz) (5: 1. 83(t, 3H, J=l. 6Hz), 2. 89(s, 3H), 3. 92(d, 2H, J=l. 7HZ)} 7. 00-7. 06(m, 2H), 7. 22-7. 27(m, 2H), 7. 42(d, 1H, J=7. 9Ηζ), 7. 49(s, 1H), 7. 53(t, 1H, J=7. 8 Hz), 7. 60 (d, 1H, J=7. 9hz) Examples 4 to 6: The same raw material compound was used to react and treat in the same manner as described in Example 3. Thereafter, the compound shown in Table 3 was obtained. Example 4: 5-(4-fluorophenylthio)_3,6-dimethyl-bu [3_(trifluoromethyl)phenyl]-3,4 -dihydropyrimidin-2 (11〇-ketone Example 5: 51 fluorophenylthiomethyl-H3-(trimethylmethyl)phenyl] _3,4-dihydropyrimidin-2(1H)-ketoru Example 6: 5-(4-phenylthio)+methyl-[b-[3-(trifluoromethyl)phenyl]-34- Hydropyrimidine-2(1H)-one

323256 234 201206906 [Table 3] Table 3

Implementing Y example 4 F 5 C 1 6 CN embodiment

R

Determination conditions ^-NMR δ (or LC-MS: [M+H] + / Rt) 1.80 (s, 3H), 3.63 (s, 2H), 5.19 (s, 〇(m, 2H), 7.19-7.23 ( m, 2H), 7.40 (d, 1H, &gt; 7.9 Hz), 7.46-7.52 (m, 2H), 7.55 (d, 1H, J=7.7H, \ ' 1.77 (t, 3H, J=1.6Hz) , 2.85 (s, 3H), 3.89 (^73⁄4^ J=1.5Hz), 7.1 7.15 (m, 2H), 7.22-7.25 (m, '2H)' 7.38 (d, 1H, J=7.7Hz), 7.44 (s, 1H), 7.48 (d, ^ H, J=7.7Hz), 7.56 (d, 1H, J=8.3Hz) ' I. 75 (t, 3H, J=1.6Hz), 2.89 (s, 3H), J=1.7Hz)&gt; 7.23-7.26 (τη, 2H), 7.36-7.54 (m/ 6H>* —: 4~[5~(4, 4, 6-trimethyl-2-side oxygen) 1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)_1Η_β-pyrazole-丨-yl] 5-[4-, 4,6-tridecyl-1-[3~(:fluoromethyl)phenyl]~3,4-dihydro-2-(1Η)-one (60. Omg) , 4-[5-(4, 4, 5, 5-tetramethyl-1,3,2-dioxapentan-2-yl)-1Η-pyrazole obtained in Reference 36 -1-yl]benzonitrile (145 〇mg), phosphoric acid (210.0mg), water (20&quot;1) in 1,4-dioxane (2.〇mi) solution, crying and sputum 1 1 - bis(monophosphinyl) Ferrocene (II) · Dioxane (2.7 mg) was stirred at 110 ° C for 6 hours. After adding water (20 ml) to the reaction mixture, ethyl acetate (20 ml ' 2 times) The organic layer was washed with EtOAc EtOAc (EtOAc) (EtOAc) 4-(5-(4,4,6-trimethyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine is obtained. -5-yl)-1Η-°bazol-1-yl]benzonitrile (24.9 mg) 〇^-NMRCCDCh: 300 MHz) 5 : 1. 24 (s, 3H), 1. 28 (s, 3H), 1. 46(s,3H),6·53(d,1H, J=l. 8 Hz), 7. 49-7. 55(m, 2H), 7. 62-7. 73(m, 2H) , 7. 79-7. 85(m, 3H), 7. 91-7. 95(m, 2H). Example 8: 2'-[6-fluorenyl-2-yloxy-1-(3) -(trifluoromethyl)phenyl)-1,2,3,4-tetrahydrobutyrate-5-yl]biphenyl-4-carbonitrile

5-(2-Bromophenyl)-6-mercapto-1-[3-(trifluoromethyl)phenyl]-3,4-dihydromethane-2 (1H) obtained in Reference Example 20. a solution of ketone (460. Omg), 4-cyanophenylboronic acid (658. Omg), sodium carbonate (950. Omg), water (2 ml) in 1,4-dioxane* (10 ml), add four (Triphenylphosphine)|β(129π^), stirred at 100 ° C for 3 hours. After adding water (20 ml) to the reaction mixture, ethyl acetate (20 ml, twice) was evaporated. The organic layer was washed with brine (20 ml) The residue was purified by silica gel column chromatography (solvent solvent hexane / ethyl acetate) to give 2'-[6-mercapto-2-oxoyl-1-(3-(trifluoromethyl) Phenyl)-1, 2, 3, 4- 236 323256 201206906 Tetrahydro 0-bend-5-yl]biphenyl-4-indene nitrile (362 mg). ^-NMRCCDCh: 300MHz) 5 : 1. 12(s,3H),3·75(brd,1H,J=14. 1Hz), 4. 04(brd,1H,J=l4

1 Hz), 4. 83 (s, 1H), 7. 26-7. 52 (m, 8H), 7 · 60 (brd, 1H, J = 8. iH z), 7. 69 (brd, 2H, J =8. 3 Hz), 7. 78 (brd, 1H, J = 8. 1 Hz). Examples 9 to 18: Using the corresponding starting compounds, after reacting and treating in the same manner as described in Example 8, a table was obtained. Compound shown in 4. • Example 9: 5-(4'-chlorobiphenyl-2-yl)-6-methyl-1-[3-(trifluoromethyl)phenyl 3,4-dihydropyrimidine-2 (11〇 - Ketone Example 10: 6-methyl-5-(4'-nitrobiphenyl-2-yl)-1-[3-(trifluoromethyl)phenyl]_ 3,4-dihydro shout -2(1H)-ketone Example 11: φ 6-methyl-[4'-(indolylsulfonyl)biphenyl-2-yl]-bu[3-(trifluoromethyl)phenyl]- 3, 4_dihydrol] n--2 (1H)-酉 Example 12: 6-fluorenyl-5-[4'-(trifluoromethyl)biphenyl-2-yl]trifluoromethyl) Phenyl]-3,4-dihydropyrimidin-2 (11〇-ketone Example 13: 2-methyl-2 -[6-methyl-2-oxo-l-(3-(trifluoro)) Phenyl) phenyl 1,1,3,4-tetrahydropyrimidin-5-yl]biphenyl-4-carbonitrile Example 14: 323256 237 201206906 5-[4'-Chloro-2'-(trifluoro Methyl)biphenyl-2_yl]-6-methyltrifluoromethyl)phenyl]-3,4-dihydro-biti-2(1 H)-one Example 15: 5~[2, 4-dihydrobiphenyl-2-yl]_6_mercapto-[[3-(trifluoromethyl)phenyl) 3,4-dihydropyrimidin-2(1H)-one Example 16: ^33' Chlorobiphenyl-2_yl]_6_methyl_1_[3-(trifluoromethyl) stupid

Di-hydropyrimidin-2(1H)-one Example 17: Bismuth bauxite, 2, pendant oxy-1-(3-(trifluoromethyl)phenyl == gas, 5-based TM] B. -LO-T base, 9 7 tetrahydro terminal Coxy + yl] biphenyl-4-indene nitrile

Eight % 323256 238 201206906 [Table 4-1] Table 4 Example LA r 2 Measurement conditions 'H-NMR δ (or LC-MS: [Μ+Η]+ / Rt) 9 1 1.14 (t, 3H, J= 1.6H2), 3.75 (d, 1H, J=14.7Hz), 3.98 (d, 1H, J=13.9Hz), 4.95 (s, 1H), 7.20-7.26 (m, 5H), 7.29-7.38 (m, 5H), 7.42-7.50 (m, 2H) 10 V 1 1.22 (s, 3H), 3.81 (d, 1H, J=14.9Hz), 4.10 (d, 1H, j =14.7Hz), 4.85 (s, 1H ), 7.23-7.30 (m, 3H), 7.32-7.4 0 (m, 2H), 7.41-7.49 (tnr 2.5H), 7.51-7.55 (m, 2; 5H), 8.29-8.33 (m, 2H) 11 ^sosMe 1 1.20 (s, 3H), 3.13 (s, 3H), 3.78 (d, 1H, J=14.3Hz), 4.07 (d, 1H, J=13.8Hz), 4.88 (s, 1H), 7.31- 7.37 (m, 2H), 7.40-7.47 (m, 3H), 7.50-7.58 (τη, 3H), 7.61-7. 68 (m, 2H), 7.99-8.03 (m, 2H) 12 V 1 1.08 (d , 3H. J=1.7Hz), 3.81 (d, 1H, J=14.5Hz), 4.04 (d, 1H, J=14.3Hz), 4.88 (s, 1H); 7.13 (d, 1H, J=7.7 Hz ), 7.20-7.50 (m, 9H), 7.65 (d, 2H, J=8.1Hz) 13 1 1.19 (s, 1.5H), 1.33 (s, 1.5H), 2.12 (s, 3H), 3.28-3 40 (in, 0.5H), 3.65-3-.90 (m, 1.5H), 5.07 (brs, 0.5H), 5.18 (brs, 0.5H), 7.10-7.19 (m, 2H), 7.25-7.38 (m, 5H), 7.42-7.54 (m, 4H) 14 1 1.39 (s, 3H), 3.35 (brd, 1H, J=15.5Hz), 3.67 (brd, 1 H, J=15.9Hz), 4.79 (s, 1H), 7.05-7.15 (m, 1H ), 7.2 1-7.38 (m, 6H), 7.45-7.55 (m, 3H), 7.71 (brs, 1H)

239 323256 201206906 [Table 4-2] Continued Table 4 Example LA r 2 Measurement conditions Ή-NMR 8 (or LC-MS: [M+H]+ / Rt) 15 1 ^•31 (s, 3H), 3.65 -4.00 (m, 2H), 4.86 (brs, 0.5H), 4.99 (brs, 0.5H), 7.02-7.18 (m, 1H), 7.24-7.51 ( m, l〇H) 16 1 1-19 (t , 3H, J=1.6H2), 3.70 (d, 1H, J=14.3Hz), 3. 93 (d, 1H, &gt;13.9Hz), 4.94 (s, 1H), 7.13 (d, 0.5H , J =2.2Hz), 7.16 (d, 0.5H, J=2.2Hz), 7.22-7.35 (m, 6H), 7.40 (d, 1H, J=2.0Hz), 7.46 (d, 2H, J=8.3H z 7.50 (d. 1H, J=8.0Hz) 17 1 114 (s, 3H), 3.82 (s, 2H). 3.87 (d, 1H, J=15.0Hz) .4.06 (d, 1H, J=15.7 Hz), 4.89 (s, 1H), 7.16 (brs, 1H), 7.29-7.54 (m, 11H) 18 1 ^&gt;50 (s, 3H), 4.27 (s, 2H), 5.28 (s, 1H) , 7.26-7.3 〇(m, 1H), 7.43 (s, 1H), 7.47-7.52 (m, 3H), 7.54-7-56 (m, 2H&gt;, 7.60 (d, 1H, J=7.9Hz), 7.66 (d, 2H, J = 8.3 Hz), 7.73 (d, 2H, J = 8.3 Hz) Example 19: 5-(4'- gasbiphenyl-2-yl)-3,6-dimethyl- L-[3-(Trifluoromethyl)phenyl]-3,4-dihydropyrimidine_2(1H)-one

5-(2-Bromophenyl)-3,6-dimercapto-1-[3-(difluoroindolyl)phenyl]-3,4-dihydropyrimidine-2 (Reference Example 22) 1H)-ketone (50.0 mg), 4-nitrophenylboronic acid (55.2 mg), sodium carbonate (71. 〇mg), water (〇. 2 ml) in 1,4-dioxane (2 ml) Tetrakis(triphenylphosphine)palladium (13.5 mg) was added and stirred at 100 C for 5 hours. After adding water (2〇1111) to the reaction mixture, it was extracted with ethyl acetate (20 ml &apos; twice). The organic layer was washed with brine (2 mL). The residue was purified by column chromatography (eluent solvent hexane/ethyl acetate) to give 5-(4'-chlorobiphenyl-2-yl)-3,6-didecyl-1-[ 3-(Trifluoroimethyl)phenyl]-3,4-dihydro σ-Bite-2(1H)-S is the same as (27. 8). Leg R (CDCh: 300MHz) 5 : 1. 22(t, 3H, J=l. 6Hz), 2. 78(s, 3H), 3. 65(d, 1H, J=13. 6Hz), 3. 94(d, 1H, J=14.7 Hz), 7. 27-7. 31(m, 4H), 7. 33-7. 42(m, 6H), 7. 46(t, 1H, J=7 7 Hz), 7. 52 (d, 1H, J = 7.9 Hz). • Examples 20 to 21: Using the corresponding starting compounds, after reacting and treating in the same manner as described in Example 19, Table 5 was obtained. The compound shown. Example 20: 5-(4'- gasbiphenyl-2-yl)-3,6-dimethyl-1-(3-phenylphenyl)-3,4-dihydro-β-bite-2 (1H )-ketone Example 21: φ 5-(4'-azabiphenyl-2-yl)-3,6-dimethyl-1-(3-decyloxyphenyl)-3,4-diazo定定-2 (1Η)_国241 323256 201206906

[Table 5] Table 5 Example X Measurement conditions 'H-NMR δ (or LC-MS: [Μ+Η]+ / Rt) 2 0 C1 1 1.15 (s, 3H), 2.73 (s, 3H), 3 · 59 (d, 1H, J = 14.1 Hz), 3.92 (d, 1H, J = 14.1 Hz), 6.89-6.91 (m, 1H), 6.96 (brs, 1H), 7.19-7.22 (m, 2H), 7.28-7.37 (m, 4H&gt;, 7.42 (d, 2H, J=8.1Hz), 7.68 (d, 2H, J=8.1 Hz) 2 1 OM e 1 1.19 (t, 3H, J=1.5Hz), 2.79 (s&gt; 3H), 3.66 (d, 1H, J=14.7Hz), 3.7 5 (s, 3H>, 3.98 (d, 1H, J=14.1Hz), 6.54 (t, 1H, J=2_4Hz)., 6.79 ( dd, 1H, J=2.1, 0.6Hz), 6.82 (d, 1H, J=2.7Hz). 7.19 (t, 1H, J=8.1 Hz), 7.30-7.43 (m, 4H), 7.47 (d , 2H, J = 8.1 Hz), 7.71 (d, 2H, J = 8.4 Hz) Example 22: 2'-[6-fluorenyl-2-yloxy-bu (3-(trifluoromethyl)) Phenyl)-1,2,3,4_tetrahydropyrimidin-5-yl]biphenyl-4-indrene

1-[2-(4'-Cyanobiphenyl-2-yl)-3-oxobutylbutyl]-3-[3-(trifluoromethyl)phenyl]urea obtained in Reference Example 12 (53 〇), a solution of benzene (5. 〇1111) for benzoic acid (4.51^), at 1〇5. (The mixture was stirred for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (solvent solvent hexane / ethyl acetate) to give 2, _[6-methyl-2 Side oxy-1-(3-(tri-Imethyl)phenyl H,2,3,4-tetrahydropropylene-yl] phenyl 4-carbonitrile (12. 8 mg). 323256 242 201206906 ^- NMRCCDCh: 300 MHz) (5: same as in Example 8. Example 23: 2' - [3,6-didecyl~·2-o-oxy-1-(3-(trifluoromethyl)phenyl) -1,2,3,4-tetrahydropyrimidin-5-yl]biphenyl-4-carbonitrile

2'-[6-Methyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine-derived from Example 8 To a solution of 5-yl] hydrazin-4-indene nitrile (6.0 mg) in tetrahydrofuran (0.5 ml), sodium hydride (0.7 mg) was added under ice cooling for 5 minutes, and then bismuth iodide was added (2 &quot;1 ), disturbed at room temperature for 1.5 hours. After a saturated aqueous solution of ammonium sulfate (i?mi) was added to the mixture, the mixture was extracted with ethyl acetate (10 ml, twice). The organic layer was washed with brine (i?mi) and dried over anhydrous sodium sulfate. The residue φ was purified by column chromatography (eluent solvent hexane/ethyl acetate) to give 2'-[3,6-dimercapto-2-yloxy-1-(3-(3) Fluorinyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]biphenyl-4-indolecarbonitrile (2.8 mg). • H-NMRCCDCh: 300MHz) (5: 1. 14(s, 3H), 2. 74(s, 3H), 3. 61(brd, 1H, J=14. 6Hz), 3. 94(b rd, 1H, J=14. 6Hz), 7. 19-7. 22(m, 2H), 7. 26-7. 33(m, 2H), 7. 35-7. 39(m, 2H), 7. 41-7. 50(m, 4H), 7. 68(d, 2H, J=8. 3Hz). Examples 24 to 28: Using the corresponding starting compound 'with the method described in Example 23 323256 243 201206906 After the reaction and treatment of the sample, the compound of Example 24: ! Table 6 was obtained. 2-[5_(4 _Alia-based phenyl group) Benzene) 2 3 —yl)-4-methyl-2- Sideoxy-3-(3-(trifluoro:yl)benyl (1)-:hydrogen(10) Example 25: 2 [3 butyl 6 methyl '2' pendant oxy-b (3-(trifluoro) Methyl)phenyl)-1,2,3,4-tetrahydrofuran+yl]biphenyl+carbonitrile Example 26: 2'-[6-diyl+-oxyl'3' (4, 4, 4-Tri-I butyl)+(3-(trimethylmethyl)phenyl)-1,2,3,4-tetrahydrogen_5_yl]biphenyl_4_methine Example 27: 2? [diyl-2-oxooxy, 3-phenylyl)+(3_(trifluoromethyl)-based H' 2' 3' 4-tetrahydro-nose ~5_yl] Nitrile Example 28: 4-[5-(4'-Cyanobiphenyl-2,yl)+indolyl-2-sideoxy_3_(3_( Trimethyl sulfhydryl)phenyl)-2,3-dihydropropionate 1,3-(圏-yl)butyrate ethyl ester 323256 244 201206906

[Table 6] Table 6 Example-R 0 - R 1 Measurement conditions 'H-NMR δ (or LC-MS: [Μ+Η]+ / Rt) 2 4 1 HI (s, 3H), 3.75 (brd, 1H, J=14.5Hz), 3. 97-4.06 (m, 3H), 4.95 (brs, 2H), 7.19-7.23 (ra, 2H), 7.27-7.31 (m, 2H), 7.35-7.38 (m , 2H), 7.40-7.51 (m, 4H), 7.69 (d, 2H, J= 8.1Hz) 2 5 1 0.88 (t, 3H, J=7.2Hz), 1.18-1.39 (m, 7H), 3.15 (t , 2H, J=7.4Hz), 3.62 (d, 1H, J=14.3 Hz), 4.00 (d, 1H, J=15.0Hz), 7.28-7.43 (m, 6H), 7.46-7.51 (m, 4H) , 7.72 (d, 2H, J=6 .9Hz) 2 6 1 1.19 (s, 3H), 1.55-L72 (m, 2H), 1.90-2.06 (m, 2H), 3.04-3.31 (rn, 2H), 3.59 (d, 1H, J=14.4Hz), 3.96 (d, 1H, J=14.7Hz), 7.23-7.57 (m, 10H), 7.69 (d, 2H, J=8.7Hz) 2 7 1 1.34-1.42 (m, 2H), 1.46-1.61 (ra, 5H), 2.5 5 (t, 2H, J=7.5Hz), a.05-3.24 (m, 2H), 3.5 7 (d, 1H, J=13.8Hz ), 3.93 (d, 1H, J=13.8H z>, 7.08-7.14 (m, 3H), 7.2 7.56 (m, 12H), 7.63 (d, 2H, J=8.4Hz) 2 8 1 1.13 (s , 3H), 1.17 (t, 3H, J=7_2Hz), 1.69 ( quin., 2H, J=7.2Hz), 2.22 (t, 2H, J=6.9Hz), 3.05-3.12 (m, 1H), 3.22 -3.32 (m, 1H), 3. 66 (d, 1H, J=14.4Hz), 3.97-4 .08 (m, 3H), 7.22 (brs, 1H), 7.27-7.49 (m, 9H), 7.69 (d , 2H, J = 8.7 Hz) Examples 29 to 30: Using the corresponding starting compounds, The compound shown in Table 7 was obtained in the same manner as in Example 1 and 245 323256 201206906. After the reaction and treatment of the sample, Example 29: -1-(3-(trifluoromethyl)phenyl)-pyrazol-1-yl]benzonitrile-10-[5-(3,6-dimethyl Base-2_sideoxy 1,2,3,4-tetrahydropyrimidinyl)_1H Example 30: 4-[5-α 4' 4,6-tetramethyl{sideoxy+(3_(three gas) Methyl) stupid) 1,2, 3,4 four-street bite _5_base) one ιη_0 than 嗤_ι_基] benzonitrile

[Table 7] Table 7 Example R3 R4 Determination conditions 'H-NMR δ (or LC-MS: [M+H]+ / Rt) 2 9 RS=H r4=h 1 1.27 (s, 2H), 1.93 ( s, 1H), 2.83 (s. 2H), 3.18 ( s, 1H), 3.87 (s, 1.3H), 3.98 &lt;s, 0.7H), 6.31 (d, 0.4H, J=1.8Hz), 6.35 (d, 0.6H, J=1.8Hz), 7.29-7.38 (m, 2H), 7.44-7.56 (m, 2.5H), 7.60 (s, 0.5 H), 7.63 (s, 0.3H), 7.66 (d , 0.4H, J=1.8Hz), 7.6 8 (d, 0.6H, J=l.8Hz), 7.73 (s, 2.7H) 3 0 R3 = Μ β R4 ^ Μ © 1 1.00 (s. 3H), 1.22 (s, 3H), 1.37 (s, 3H), 2.89 (s, 3H), 6.31 (d, 1H, J=1.7Hz), 7.34 (d, 1H, J=7.8Hz), 7.39 (s, 1H), 7.49 (t, 1H, J = 7.8 Hz), 7.6 8-7.71 (m, 3H), 7.77 (brd, 2H, J = 9.0 Hz) Example 31: 2,-[3-ethenyl- 6-mercapto-2-yloxy-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydrocarcinoma-5-yl]biphenyl-4-indrene 246 323256 201206906

2' _[6_mercapto_2_sideoxy_ι — (tris-decyl)phenyl)-1'2'3'4~tetrahydrofuran _5_ obtained in Example 8 Base] Lianqi, 4-jia guess a〇mg) tetrahydrogen humming (〇._ solution, add nitriding month 眷 (〇·7) under ice cooling, stir for 1 minute, then add methyl iodide (2 / / 丨), stirring at room temperature for 3 hours. After adding a saturated aqueous solution of ammonium hydroxide (i〇mi), the mixture was extracted with ethyl acetate (10 ml '2 times). The layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. EtOAc EtOAc EtOAc EtOAc 'H-NMRCCDCh: 300ΜΗζ) δ : • 1. 22(s, 3H), 2. 40(s, 3H), 4. 06(brd, 1H, J=15. 8Hz), 4. 45(b rd,1H,J=15. 8Hz) , 7. 24-7. 31(m, 4H), 7. 35-7. 40(m, 4H), T. 49(t, 1H, J=8. 2Hz), 7. 56(d, 1H, J = 8.1 Hz), 7. 66 (d, 2H, J = 8.3 Hz). Examples 32 to 35: using the corresponding starting compounds to The method of Example 31 the compound contained in the reaction with the sample was treated to afford the embodiment shown in Table 8. Example 32: 247 323256 1 (4-nitrobiphenyl '2-alkyl)-4-mercapto-2-yloxy-3-(3-(trifluoromethyl 201206906)phenyl)-2, 3 -dihydropyrimidin-1 (6H)-carboxylic acid phenyl ester Example 33: 5-(4'-cyanobiphenyl-2-yl)-4-methyl-2-oxo-3-(3- (Trifluoromethyl)phenyl)-2,3-dihydropyrimidin-1(6H)-carboxylic acid 4-nitrophenyl ester Example 34: 5-(4'-cyanobiphenyl-2-yl) 4-methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidine-K6H)-carbenamide Example 35: 5-(4' -cyanobiphenyl-2-yl)-N,N,4-trimethyl-2-yloxy-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidine- 1(6H)-nonylamine

Table 8 Example - Π1 Determination conditions H-NMR δ (or LC-MS: [M+H]+ / Rt) 3 2 8 5 5 4 (M+H) /5 . 0 9 (min) 3 3 8 5 9 9 (M+H) /4.97 (min) 3 4 ~nh2 1 1.12 (s, 3H), 4.17 (brd, 1H, J=I5.8fiz), 4.61 (brd, 1H, J=15.8Hz)&gt; 5.05 (brs, 2H), 7.23-7.31 (m, 4H), 7.34-7.39 (m, 4H), 7.49 (t, 1H, J = 7.8 Hz), 7.56 ( d, 1H, J = 8.2 Hz), 7.67 (d, 2H, J=8.4Hz) 3 5 V, 1 1.24 (s, 3H), 2.89 (s, 6H), 3.85 (brs, 1H), 4.14 ( brd, 1H, J=14.7Hz), 7.23- 7.31 (m, 4H), 7.34-7.53 (m, 6H), 7.67 (d, 2H, J = 8.2 Hz) 2' -[3-mercapto-6-methyl-2- oxo-1- (3-(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl]biphenyl-4-indenecarbonitrile 248 323256 201206906

2, _[6-mercapto-2-indolyl-(3-(difluoroindolyl)phenyl)~1,2,3,4-tetrahydropyrimidine-obtained in Example 8 5-Alkyl] benzylidene _4-indenenitrile (1.7g) in a solution of squirrel (5 〇mi), sodium hydride (194 mg) was added under ice cooling for 5 minutes, and phenyl chloroformate (905 /U) was added. The mixture was stirred at room temperature for 1 hour, and N,N-didecylguanamine (l〇mi) was added, and it was stirred at (10) for 1.5 hours. After a saturated aqueous solution of ammonium sulfate (3 〇mi) was added to the mixture, ethyl acetate (20 ml, twice) was applied. The organic layer was washed with water (2 mL ml) and brine (20 ml) and dried over anhydrous sodium sulfate. The residue was purified by silica gel column chromatography (dissolved solvent was calcined / acetic acid acetate) to obtain 2'-[3-methyl-branched-6-fluorenyl-2-ylidene_h3_ (three IL) Mercapto)phenyl)-1,2,3,4-tetrahydropyrimidinyl]biphenyl-4-indenecarbonitrile (687.6 mg). φ 'H-NMRCCDCh : 300MHz)d :

1· 23(d,3H,J=l. 8Hz), 4. 02(d,1H,J=i6. 3Hz), 4.43(d,1H,J=16 9Hz), 7. 29-7 37(m, 4H), 7. 40-7. 46(m, 4H), 7. 55(t, 1H, J=8. 4Hz), 7. 63(d, 1H, J=8. 1Hz) 7. 70-7. 74(m, 2H), 9. 25(s, 1H). Examples 37 to 38: After reacting and treating in the same manner as described in Example 1, using the corresponding starting compound, The compound shown in Table 9 was obtained. Example 37: 323256 249 201206906 5-[ 1-(4-Cyanophenyl)-1 Η-α than 嗤-5-yl]-4,6,6-trimethyl-2-oxooxy-3 -[3-(Trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6Η)-carboxylic acid phenyl ester Example 38: 5-[1-(4-cyanophenyl)-1Η -0 峻-5-yl]-4-methyl-2-oxo[3-(trifluoromethyl)phenyl]_2,3-dihydropyrimidin-1(6Η)-carboxylic acid phenyl ester

Table 9 Example L R3 R4 Determination conditions W-NMR δ (or LC-MS: [Μ+Η]+ / Rt) 3 7 RS = H R4 = H 1 1.57 (s, 3H), 4.36 (d, 2H, J=1.7Hz), 6.46 (d, 1 H, J=1.8Hz), 7.08-7.14 (m, 4H), 7.33-7.42 (m, 4H), 7.52-7.55 (m, 2H), 7.66-7.81 ( m, 4H) 3 8 R 3 = Μ β R 4 — Μ β 1 1.19 (s, 6H), 1.34 (d, 3H, J=2.9Hz)·, 6,36 (d, 1 H, J=1.3Hz ), 7.05 (d, 2H, J=8.3Hz), 7.13 (d, 2 H, J=8.3Hz), 7.26-7.35 (in, 4H), 7.48 (s, 1H), 7.55 (t, 1H, J = 7.7 Hz), 7.62 (d, 1H, J = 7.5 Hz), 7.73-7.83 (m, 3H) Example 39: 4-[5-(4'-Cyanobiphenyl-2-yl)-4- Methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-1-decylamine]ethyl butyrate

2,-[6-Mercapto-2-yloxy-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine-5 obtained in Example 8 -Based on a solution of biphenyl-4-phthalonitrile 250 323256 201206906 (200.0 mg) in N,N-dimethylformamide (5 〇ml), adding sodium hydride (24. Omg) under ice cooling for 5 minutes. Ethyl 4-isocyanatobutyrate (135 &quot;l) was added and stirred at room temperature for 2 hours. After adding a saturated aqueous solution of ammonium sulphate (2 〇mi) to the reaction mixture, it was extracted with ethyl acetate (20 ml s). The organic layer was washed with EtOAc (EtOAc)EtOAc. The residue was purified by column chromatography on silica gel eluting solvent (hexanes / ethyl acetate) to give 4-[5-(4'-cyanobiphenyl-2-yl)-4-indolyl-2 -Phenoxy-3-indole-3-(3-(difluoromethyl)phenyl)-1,2,3,6-tetrahydropilot-1-carboxamide]ethyl butyrate (181·3 mg). 'H-NMRCCDCh: 300ΜΗζ) δ : 1. 13(s, 3H), 1. 17(t, 3H, J=7. 1Hz), 1. 73-1. 83(m, 2H), 2. 28 ( t, 2H, J=7. 5Hz), 3. 19-3. 26(m, 2H), 4. 04(q, 2H, J=7. 1Hz), 4. 15(brd, 1H, J=16 1Hz), 4. 60(brd, 1H, J=16. 1Hz), 7. 22-7. 32(ra, 4H), 7. 36-7. 40(m, 4H), 7. 48(t , 1H, ]=1. 7Hz), 7. 56 φ (d, 1H, J=7. 7Hz), 7. 66(d, 2H, J=8. 4Hz), 8. 66(brs, 1H). Examples 40 to 44: The compounds shown in Table 10 were obtained by the same reaction and treatment as in the method described in Example 39 using the corresponding starting compound '. Example 40: 5-(4'-Cyanobiphenyl-2-yl)-N-ethyl-4-indolyl-2-ylidene-3-[3-(trifluoromethyl)phenyl] -2,3-Dihydro- lysole-1 (6H)~methylamine Amine Example 41: 5-(4'-Cyanobiphenyl-2-yl)-4-mercapto-2-yloxy- N-propyl-3-[3- 251 323256 201206906 (trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)-nonylamine Example 42: N-butyl-5- (4'-Cyanobiphenyl-2-yl)-4-mercapto-2-oxo-3-[3-(trifluoromethyl)phenyl]-2,3-dihydro σM0 -1(6H)-decylamine Example 43: 2-[5-(4'-Cyanobiphenyl-2-yl)-4-methyl-2-oxo-3-(3-(3) Ethyl fluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidin-1-ylamine] Example 44: 3-[5-(4'-cyanobiphenyl-2- 4-mercapto-2-oxooxy-3-(3-(trimethylsulfonyl)phenyl)-1,2,3,6-tetrahydropyrimidin-1-indenylamine]propionic acid ester

252 323256 201206906 [Table 10] Table 1 ο Example - R1 Measurement conditions 'H-NMR δ (or LC-MS: [Μ+Η]+ / Rt) 4 0 1 1.06-1.16 (m, 3H), 1.18 ( t, 3H, J=1.6Hz), 3.22-3 .31 (m, 2H), 4.23 (brd, 1H. J=15.5Hz), 4.63 (brd, 1H, J=15.5Hz), 7.25-7.44 (m , 8H), 7.53 (t, 1H, J=7.7Hz), 7.60 (d, 1H, J=8.4Hz), 7.71-7.68 (m, 2 H), 8.58 (brs, 1H) 4 1 1 0.86 (t , 3H, J=7.4Hz), 1.13 (s, 3H), 1.43-1.53 (m , 2H), 3.11-3.18 (m, 2H), 4.18 (brd, 1H, J=16.0H z), 4.58 (brd , 1H, J=16.0Hz), 7.23-7.31 (m, 4H), 7.34-7.40 (m, 4H), 7.48 (t, 1H, J=7.7Hz), 7.56 ( d, 1H, J=7.9Hz) , 7.65 (d, 2H, J=8.4Hz), 8.59 (brs ,1H) 4 2 1 1.12 (s, 3H), 1.17-1.32 (m, 5H), 1.39-1.46 (m, 2 H), 3.15- 3.22 (m, 2H), 4.17 (brd, 1H, J = 16.1 Hz), 4.60 (brd, 1H, J = 16.1 Hz), 7.23-7.31 (m, 4H), 7. 34-7.40 (m, 4H) , 7.48 (t, 1H, J=7.7Hz), 7.56 (d, 1H, J=7.9Hz&gt;, 7.65 (d, 2H, J=8.1Hz), 8.57 (brs, 1H) 4 3 ^〇〇2έχ 1 1.14 (s, 3H), 1.21 (t, 3H, J=7.1Hz), 3.95 (d, 2H, J=5.5Hz), 4.11-4.20 (m, 3H), 4.56 (brd, 1H, J=1 5.5 Hz), 7.23-7.31 (m, 4H), 7.33- 7.39 (m, 4H), 7. 47 (t, 1H, J=7.8Hz), 7.55 (d, 1H, J=8.1Hz), 7.67 (d, 2H, J=8.3Hz), 9.00 {brs, 1H ) 4 4 ^»^C02Et 1 1.17 (s, 3H), 1.22 (t, 1.5H, J=7.1Hz), 1.24 (t, 1. 5H, J=7.1Hz), 2.53 (t, 2H, J= 6.4 Hz), 3.51 (dd, 2H, J = 12.5, 6.2 Hz), 4.08-4.22 (m, 3H), 4.64 (d, 1H, J = 16.3 Hz), 7.24-7.29 (m, 2H), 7.32- 7.36 (m, 2 H), 7.39-7.44 (m, 4H), 7.51 (t, 1H, J=8.1Hz), 7. 59 (d, 1H, J=7.9Hz), 7.71 (d, 2H, J =7.9Hz), 8.91 (t, 1H, J=6.0Hz)

Examples 45 to 46: Using the corresponding starting compounds, the compounds shown in Table U were obtained by the same reaction and treatment as described in the Example 39. Example 45: 5-[1-(4-Cyanophenyl)-ιη-pyrazol-5-yl]-oxime-ethyl-4-mercapto-2-yloxy-3-[3-( Trifluoromethyl)phenyl]_2,3-dihydropyrimidin-1(6H)-formamide 253 323256 201206906 Example 46: 2-[5-(l-(4-Cyanophenyl)-1Η- °Bizozol-5-yl)-4-methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-1-methyl Ethylamine

Table 1 Example - R 1 Measurement conditions • H-NMR δ (or LC-MS : [Μ + Η] + / Rt) 4 5 1 1.08 (t, 3H, J = 7.2 Hz), 1.33 (s, 3H) , 3.17-3.26 (m , 2H), 4.40 (d, 2H, J=1.5Hz), 6.37 (d, 1H, J=1.8 Hz), 7.37 {d, 1H, J=8.1Hz), 7.42 (s, 1H), 7.54 (t , 1H, J = 7.8 Hz), 7.60-7.63 (m, 3H), 7.68-7.73 (ra, 3H), 8.54 (brs, 1H) 4 6 1 1.26 (t, 3H, J= 7.1 Hz), 1.41 (t, 3H, J=L5Hz), 3.9 8 (d, 2H, J=5.7Hz), 4.22 (q, 2H, J=7.1Hz), 4.44 (d, 2H, J=1.5Hz ), 6.41 (d, 1H, J=1.8Hz), 7.44 (d, 1H, J=8.1Hz), 7.48 (s, 1H), 7.59 (t, 1H, J=8.1H z), 7.64-7.67 ( m, 3H), 7.73 (d, 1H, J = 1.8 Hz), 7.7 7-7.80 (m, 2H), 9.01 (t, 1H, J = 5.3 Hz) Example 47: 5-(4'-Cyano Biphenyl-2-yl)-N-[4-(didecylamino)propyl]_4_methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-2 , 3-dihydropyrimidine-K6H)-formamide

254 323256 201206906 5-(4'-Cyanobiphenyl-2-yl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl obtained from Example 32 -2,3-Dihydro 0-Mec0 -1 (611)-sodium benzoic acid Benzene (6.〇11) acetonitrile (1.〇1111) solution, 3-dimethylamino group added Propylamine (5/z 1) was stirred at 50 ° C for 2 hours. It was concentrated under reduced pressure in the reaction mixture. The residue was purified by a silica gel column chromatography (solvent solvent hexane/ethyl acetate) to give 5-(4'-cyanobiphenyl-2-yl)-N-[4-(dimethyl Amino)propyl]-4-mercapto-2-oxo-3-[3-(trifluoromethyl)phenyl]-2,3-dipyrimidine-1 (61〇-formamide) 4.11^). _ j-NMRCCDCh : 3G0MHz) 5 : 1. 17(s, 3H), 1. 62-1. 72(m, 2H), 2. 18(s, 6H) 2. 29(t, 2H , J= 7. 2Hz), 3. 24-3. 31(m, 2H), 4. 20(brd, 1H, J=16. 5Hz), 4. 66 (brd, 1H, J=16. 5Hz) , 7. 26-7. 36(m, 4H), 7. 40-7. 44(m, 4H), 7. 53(t, 1H, ]=Ί. 6Hz), 7. 60(d, 1H, J = 7. 9 Hz), 7. 70 (d, 2H, J = 8. 3 Hz), 8.73 (brs, 1H). Examples 48 to 77: φ using the corresponding starting compound, and the method described in Example 47 After the same reaction and treatment, the compound shown in Table 12 was obtained. Example 48: 5-(4'-Cyanobiphenyl-2-yl)-indole, 4-dimethyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-2 , 3-dihydropyrimidine-K6H)-guanamine Example 49: 5-(4'-cyanobiphenyl-2-yl)-indole-isopropyl-4-indolyl-2-yloxy- 3-[3-(Trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6Η)-decylamine Example 50: 255 323256 201206906 5-(4'-Cyanobiphenyl-2 -yl)-N-cyclohexyl_4-methyl-2-oxooxy-3_[3-(trifluoromethyl)phenyl]_2,3-dihydropyrimidin-1(6H)-carbenamide Example 51: N-Azainyl-5-(4'-cyanobiphenyl-2-yl)-4-mercapto-2-yloxy-3-[3-(difluoroindolyl)phenyl]- 2,3-Dihydro-penetration-1(6H)-decylamine Example 5 2: 4-[5-(4-Disylbiphenyl-2-yl)-4-methyl-2-oxooxy -3-[3-(Trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyrimidin-1-carboxamide]piperidine-1-ethylate •Example 53 : 5- (4 '-Cyanobiphenyl-2-yl)-N-(3-methoxypropyl)-4-mercapto-2-oxo-3-[3-(trifluoromethyl)phenyl]- 2,3-Dihydropyrimidin-1(6H)-guanamine Example 54: 5-(4'-Cyanobiphenyl-2-yl)-N-(3-hydroxypropyl)-4-methyl -2-Sideoxy-3-[3-(trifluoro Base)], 3-dihydropyrimidine-l(6H)-nonylamine Example 5 5: N-[3-(bis(2-hydroxyethyl)amino)propyl]-5 -(4, _cyanobiphenyl-2-yl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-2,3-dihydro-β -1(6H)-carbamide Example 56: 5-(4-cyanobiphenyl-2-yl)-4-mercapto-2-yloxy-N-[3-(° ratio 17 each 0 Ding-1-yl)propyl]-3-[3-(trifluoromethyl)phenyl]- 2,3-dihydropyrimidin-1(6H)-carbenamide Example 57: 256 323256 201206906 5- (4'-Cyanobiphenyl-2-yl)-4-methyl-2-oxo-N_[3-indolepyridin-1-yl)butyl]-3-[3-(trifluoro Methyl)phenyl]-2,3-dihydroglycine _ -1(6H)-carbenamide Example 58 : 5-(4'-cyanobiphenyl-2-yl)-4-fluorenyl -N-[3_(4_methyl 口 井-1-yl) propyl]-2- oxo-3-[3-(trifluoromethyl)phenyl]_2, 3-dihydropain -1(6H)-carbamide Example 59: _ 5-(4'-cyanobiphenyl-2-yl)-4-indolyl-N-(3-(N-morphinyl)propyl) -2-Phenoxy-3-[3-(trifluoromethyl)phenyl]-2,3-dihydromethane-1 (6H)-cartoamine Example 60: 3-[5-(4 '-Cyanobiphenyl-2-yl)-4-mercapto-2-yloxy-3-(3-( Trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-1-decylamine] propylamine decanoic acid tert-butyl ester φ Example 61: 5-(4'-cyano group Biphenyl-2-yl)-4-mercapto-2-yloxy-N-[3-(2-o-oxyoxazolidin-1-yl)propyl]-3-[3-(trifluoro Methyl)phenyl]-2,3-dihydropepine-1(6H)-guanamine Example 62: 5-(4'-cyanobiphenyl-2-yl)-4-methyl-2 -Sideoxy-n-[3-(2-o-oxaoxaridin-1-yl)ethyl]-3-[3-(trifluoromethyl)phenyl]_2, 3-dihydro-snap -1(6H)-carbamamine Example 63: , 257 323256 201206906 5-(4,-Cyanobiphenyl-2-yl)-N-isobutyl-4-indolyl_2_sideoxy_ 3-[3-(Tricycle decyl)phenyl]-2'3-dihydroanthracene] (10) _ anthraquinone Example 64: 5-(4'-cyanobiphenyl-2-yl)|(2 , propyl)+methyl-2-oneoxy 3 [3-(difluoromethyl) phenyl]-2,3, dihydro chlorinated amine 65: 5-(4'-cyanide Benzyl-2-yl)_N_(cyclopropylmethyl)+methyl-2_oxy 3 [3_(difluoroindolyl)phenyl]-2,3-dihydrogen _1 (6H)曱醯 曱醯 实施 Example 66: 5_(4'-cyanobiphenyl-2-yl)|(cyclohexylfyl)_4_mercapto_2_sideoxy 3-[3-(two Fluoromethyl)phenyl bromide 2,3__diaza(tetra)_m(6Η)_cartoamine Example 67: 5-(4-cyanobiphenyl-2-yl)|[2-(dimethylamino) Ethyl]-4-mercapto-2-oxooxy-3-[3-(tri-indenyl)phenyl]_2,3-dihydro as 4(10))_ guanamine ruthenium Example 68 : 5_(4 -cyanobiphenyl-2-yl)-n-[2-(didecylamino)butyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)benzene A 2,3-dihydropyrimidin-1 (61}) monoamine A. Example 69: 5-[5-(4'-Cyanobiphenyl-2-yl)- 4-fluorenyl_2_ Ethyloxy_3_(3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidin-1-decylamine]ethyl valerate Example 70: 5-(4'-cyanide Benzyl-2-yl)- 4-methyl-2_sideoxy_N_[2_(2_ side oxygen 258 323256 201206906 carbimidin-1-yl)ethyl]-3-[3-( Trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)-carbenamide Example 71: N-(l-Ethylpiperidin-4-yl)-5-(4' -Cyanobiphenyl-2-yl)-4-indolyl 2 flavonyl-3-[3-(difluoroindolyl)phenyl]-2,3-diazepine bite-1(6H)_ 曱Indoleamine Example 72: 3-[(5-(4'-Cyanobiphenyl-2-yl)-4-mercapto-2-yloxy-3_[3-(trisulfanyl)phenyl) ]-1, 2,3,6-tetrahydrocarban-1-carboxamide)methyl]indole-bucarboxylic acid (R)-t-butyl ester Example 73: 5-(4'-cyanobiphenyl- 2-yl)-4-mercapto-N-[2-(nonylsulfonyl)ethyl]-2-yloxy-3-[3-(trifluoromethyl)phenyl]- 2, 3- Dihydropyrimidine-l(6H)-decylamine Example 74: φ 5-(4-cyanobiphenyl-2-yl)-4-mercapto-2-yloxy-N-(amine hydrazino) Ethyl)-3-[3-(trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)-carbenamide Example 75: 5-(4 -murine conjugate-2 -yl)-N-[3-(2-(yl)methyl)pyrene-oxime_ι_yl)propyl]-4-mercapto-2-yloxy-3-[3-(trifluoro Benzo)phenyl]- 2,3-dihydro-bite-1 (6H)-guanamine Example 76: 5-(4'-cyanobiphenyl-2-yl)-N-(cyanomethyl ))-4-mercapto~2-o-oxy-3-[3-(trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)~nonylamine 323256 259

201206906 Example 77: 5-(4'-Cyanobiphenyl-2-yl)-N-cyclopropyl-4-mercapto-2-oxo-3-[3-(trifluoromethyl)benzene 2,3-dipyrimidine-1(6H)-carboxamide

[Table 1 2 - 1] Table 1 2 Example - R1 Measurement conditions ^-NMR 6 (or LC-MS: [Μ+Η]+ / Rt) 4 8 'Me 1 1.17 (t, 3H, J=1.5 Hz ), 2.82 (d, 3H, J=4.8Hz), 4.23 (brd, 1H, J=16.0Hz), 4.65 (brd, 1H, J=16 • 1Hz), 7.27 (brd, 1H, J=7.9Hz) , 7.32-7.36 (m, 3H), 7.41-7.44 .(m, 4H), 7.52 (t, 1H, J=7.9H z), 7.60 (brd, 1H, J=8.3Hz), 7.68-7.72 (m , 2H ), 8.52 (brs, 1H) 4 9 1 1.10 (t, 6H, J=6.3Hz), 1.14 (s, 3H), 3.82-3.9 3 (m, 1H), 4.17 (brd, 1H, J= 16.0 Hz), 4.56 (br d, 1H, J = 16.0 Hz), 7.24-7.34 (m, 4H), 7.36-7. 39 (m, 4H), 7.49 (t, 1H, J = 7.8 Hz), 7.56 (d, 1 H, J=8.1Hz), 7.65 (d, 2H, J=8.2Hz), 8.59 (brs ,1H) 5 0 1 1.14-1.29 (m, 9H), 1.55-1.75 (m, 2H) , 1.80-1. 95 (ra, 2H), 3.50-3.59 (m, 1H), 4.19 (brd, 1H, J = 15.9Hz), 4.53 (brd, 1H, J = 15.9Hz), 7.27-7 .31 (m, 4H), 7.35-7.40 (m, 4H), 7.47 (t, 1H, J=7.8Hz), 7.55 (d, 1H, J=7.9Hz), 7.65 (d, 2H, J=8.4Hz) , 8.53 (d, 1H, J=10.5Hz) 5 1 /0© 1 1.11 (s, 3H), 4.20 (brd, 1H, J=15.4Hz), 4.37 C dd, 2H, J=12.5, 6.8Hz) , 4.63 (brd, 1H, J=15.4 Hz), 7.06-7.31 (m, 9H), 7. 36-7.39 (m, 4H), 7.46 (t, 1H, J=7.8Hz), 7.53-7.64 (m, 3H), 8.97 (brs, 1H) 260 323256 201206906

[Table 1 2 - 2] Performance Table 12 Example 1 R 1 Measurement conditions 'H-NMR δ (or LC-MS: [Μ+Η]+ / Rt) 5 2 ϊ 1 0.78 (t, 3H, J= 7.1 Hz), 1.15-1.21 (m, 5H), 1.8 0-1.90 (m, 2H), 2.84-2.96 (m, 2H), 3.76-3.80 (m, 1H), 3.82-3.98 (m, 2H), 4.05 (t, 2H, J = 7.1Hz), 4.16 (brd, 1H, J = 15.8Hz), 4.51 (brd, 1H, J = 15.8Hz), 7.26-7.32 (m, 4H), 7.36-7.40 (m , 4H), 7.50 (t, 1H, J=7.7Hz), 7.57 (d, 1H, J=7.7Hz), 7.66 (d, 2H, J=8.1Hz>, 8.64 (d, 1H, J=7.3Hz 5 3 1 1.13 (s, 3H), 1.70-1.77 (m, 2H), 3.24 (s, 3H), 3.26-3.31 (ra, 2H), 3.36 (t, 2H, J=6.1Hz), 4 . 16 (brd, 1H, J=16.3Hz), 4.60 (brd, 1H, J=16. 3Hz), 7.22-7.31 (m, 4H), 7.36-7.40 (m, 4H), 7.48 (t, 1H, J =7.9Hz), 7.55 (d, 1H, J=7.9Hz), 7.66 (d, 2H, J=8.4Hz), 8.69 (brs, 1H) 5 4 Λχν^ΟΗ 1 1.16 (s, 3H), 1.60- 1.68 (m, 2H), 2.68 (brs, 1 H), 3.31-3.38 (m, 2H), 3.57 (brs, 2H), 4.18 ( brd, 1H, J=16.4Hz), 4.57 (brd, 1H, J =16.4Hz), 7.22-7.32 (m, 4H), 7.37-7.41 (m, 4H), 7.49 (t, 1H, J=7.7Hz), 7.56 (d, 1H, J=7.1Hz), 7.67 (d , 2H, J=8.3Hz), 8.73 (brs, 1H) 5 5 Γ°Η 1 1.17 (s, 3H), 1.79-1.82 (m, 2H), 2.68-2.76 (tn, 6H), 3.28-3.36 (m, 2H), 3.64-3.68 (m, 4H), 4.15 (brd , 1H, J=15.6Hz), 4.51 (brd, 1H, J = 15.6Hz), 7.25-7.32 (m, 4H), 7.35-7.40 (m, 4 H), 7.49 (t, 1H, J=7.8Hz ), 7.57 (d, 1H, J=8, l Hz), 7.76 (d, 2H, J=8.4Hz), 8.74 (brs, 1H) 261 323256 201206906

[Table 1 2 - 3] Continued Table 12 Example - R 1 Measurement conditions 'H-NMR 5 (or LC-MS: [M+H] + / Rt) 5 6 1 1'12 (s, 3H), 1.65 -1.70 (m, 4H), 1.89-1.98 (m , 2H), 2.41-2.44 (m, 6Hz), 3.21-3.28 (m, 2H), 4.15 (brd, 1H, J=15.6Hz), 4.61 (brd , 1H, J=1 5.8Hz), 7.23-7.31 (m, 4H), 7.34-7.40 (m, 4H), 7.47 (t, 1H, J=7.8Hz), 7.55 (d, 1H, J=8.3Hz ), 7.66 (d, 2H, J=8.3Hz), 8.71 (brs, 1H) 5 7 1 1.26 (s, 3H), 1.45-1.60 (m, 6H), 1.73-1.82 (m , 2H), 2.04 ( Brs, 4H), 3.05-3.26 (m, 4H), 4.1 9 (brd, 1H, J = 15.8 Hz), 4.37 (brd, 1H, J = 15.8 Hz), 7.21-7.44 (ra, 8H), 7.48- 7.59 (m, 2H), 7. 68 (d, 2H, J=7.0Hz), 8.62 (brs, 1H) 5 8 1 1.15 (s, 3H), 1.64 (t, 2H, J=6.6Hz), 2.28 (s, 3H), 2.39 (t, 2H, J=6.6Hz), 2.49-2.70 (m, 8H), 3.20-3.28 (m, 2H), 4.16 (brd, 1H, J=16.6Hz), 4.58 ( Brd, 1H, J=16.6Hz), 7.21-7.32 (m, 4H), 7.36-7.40 (m, 4H), 7.46-7.58 (in, 2H), 7.66 (d, 2H, J=7.9Hz), 8.79 (brs, 1H) 5 9 1 1.14 (s, 3H), 1.60-1.70 (m, 2H), 2.37 (brs, 6 H), 3.21-3.28 (m, 2H), 3.65 (brs, 4H), 4.15 ( Brd,' 1H, J=16.3Hz), 4.58 (br d, 1H, J=16.3Hz), 7.22-7.31 (m, 4H), 7.36-7.40 (m, 4H), 7.48 (t, 1H, J=7.9Hz), 7.56 (d, 1H, J=7.9Hz) ), 7.6 6 (d, 2H, J=8.4Hz), 8.70 (brs, 1H) - 262 323256 201206906

[Table 1 2 - 4] Continued Table 12 Example - R 1 Measurement conditions 1H-NMR δ (or LC-MS: [M+H]+ / Rt) 6 0 1 1.15 (s, 3H), 1.36 (s, 9H), 1.56-1.65 (m, 2H), 3.04-3.12 (m, 2H), 3.20-3.27 (m, 2H), 4.14 (brd, 1H, J=16.9Hz), 4.58 (brd, 1H, J= 16.9Hz) , 4.82 (brs, 1H), 7.23-7.31 (m, 4H), 7.37-7.4 0 (m, 4H), 7.48 (t, 1H, J=7.7Hz), 7.56 (d, 1 H, J =7.7Hz), 7.67 (d, 2H, J=8.3Hz), 8.66 (brs ,1H) 6 1 1 1.18 (s, 3H), 1.65-1.70 (m, 2H), 1.92-2.00 (m ,2H) , 2.28-2.34 (m, 2H), 3.16-3.34 (m, 6H), 4.17 (brd, 1H, J=16.2Hz), 4.49 (brd, 1H, J= 16.2Hz), 7.28-7.31 (tn, 4H ), 7.35-7.41 (m, 4H ), 7.48 (t, 1H, J=7.9Hz), 7.55 (d, 1H, J=9.2H z), 7.67 (d, 2H, J=8.4Hz), 8.69 ( Brs, 1H) 6 2 1 1.18 (s, 3H), 1.96-2.02 (m, 2H), 2.33 (t 2H, J=8.1Hz), 3.39-3.44 (in, 6H), 4.18 (brd, 1H, J =16.3Hz), 4.62 (brd, 1H, J=16.3Hz), 7.30-7.3 6 (rn, 4H), 7.39-7.44 (m, 4H), 7.52 (t, 1H, J = 8.1Hz), 7.60 ( d, 1H, J=8.1Hz), 7.72 (d, 2H, J=8.3Hz), 8.76 (brs, 1H) 6 3 1 0.85 (d, 6H, J=6.6Hz), 1.13 (s, 3H), 1.68-1.7 7 (m, 1H), 2.98-3.04 (m, 2H), 4.19 (d, 1H, J = 15.6Hz), 4.59 (d, 1H, J = 15.6Hz), 7.25-7.31 (m, 4H), 7.36-7.40 (m, 4H), 7.48 (t, 1H) , J=7. 9Hz), 7.56 (d, 1H, J=8.3Hz), 7.65 (d, 2H, J= 8.1Hz), 8.65 (s, 1H) 263 323256 201206906

[Table 1 2 - 5] Continued Table 12 Example - R1 Measurement conditions 1H-NMR δ (or LC-MS: [M+H]+ / Rt) 6 4 \〇H 1 1.12 (d, 3H, J=6.4 Hz), 1.15 (s, 3H), 2.34 (brs, 1H), 3.06-3.15 (m, 1H), 3.28-3.37 (m, 1H), 3.82-3.90 (m, 1H), 4.17 (d, 1H, J=17.0Hz), 4.58 (d, 1H, J=16.0Hz), 7.23-7.32 (m, 4H), 7.35-7.41 (m, 4H), 7.48 (t, 1H, J=7.8Hz), 7.56 (d, 1H, J=7.7Hz), 7.65-7.68 (m, 2H), 8.88 ( brs, 1H) 6 5 1 1.12 (d, 3H, J=6.4Hz), 1.15 (s, 3H), 2.34 (fars, 1H), 3.06-3.15 (m, 1H), 3.28-3.37 (m, 1H), 3.82-3.90 (m, 1H), 4.17 (d, 1H, J=17.0Hz), 4.58 (d, 1H) , J=16.0Hz), 7.23-7.32 (m, 4H), 7.35-7.41 (m, 4H), 7.48 (t, 1H, J=7.8Hz), 7.56 (d, 1H, J=7.7Hz) , 7.65-7.68 (m, 2H), 8.88 ( brs, 1H) 6 6 1 0.80-0.94 (m, 3H), 1.16 (t, 3H, J=1.5Hz), 1.2 2-1.30 (m, 3H), 1.60-1.74 (m, 5H), 3.07 (t, 2H, J=6.2Hz), 4.22 (d, 1H, J=14.5Hz), 4.65 ( d, 1H, J=17.2Hz), 7.28-7.36 (m , 4H), 7.40-7. 45 (m, 4H), 7.53 (t, 1H, J=7.7Hz), 7.60 (d, l H, J=7.9Hz), 7.68-7.71 (ra, 2H), 8.68 (brs, 1 H) 6 7 νΤ'ν, 1 l. 11 (s, 3H), 2.17 (s , 6H), 2.37 (t, 2H, J=6.3 Hz), 3.31 (dd, 2H, J=11.6, 6.3Hz), 4.15 (d, 1 K, J=16.0Hz), -4.59 (d, 1H, J=15.8Hz), 7.22-7 .31 (ra, 4H), '7.35-7.39 (m, 4H), 7.47 (t, 1H, J=7.9Hz), 7.55 (d, 1H, J=7.7Hz) , 7.64-7.67 ( m, 2H), 8.68 (brs, 1H) 264 323256 201206906

[Table 1 2 - 6] Continued Table 12 Example - R1 Measurement conditions 'H-NMR 5 (or LC-MS: [Μ+Η]+ / Rt) 6 8 1 1.13 (s, 3H), 1.60-1.70 ( m, 4H), 2.16 (s, 6H), 2.16-2.24 (nx, 2H)( 3.16-3.22 (m, 2H), 4.16 (d, 1H, J=17.1Hz), 4.60 (d, 1H, J= 16.5Hz), 7. 20-7.31 (m, 4H), 7.36-7.40 (m, 4H), 7.48 (t, 1H, J=7.9Hz), 7.56 (d, 1H, J=8.8Hz), 7.66 ( d, 2H, J=8.3Hz), 8.62 (brs, 1H) 6 9 C02Et 1 1.13 (s, 3H), 1.17 (t, 3H, J=7.1Hz), 1.45-1.62 (m, 4H), 2.24 ( t, 2H, J=7.2Hz), 3.20 (dd, 2 H, J=12.6, 6.7Hz), 4.04 (q, 2H, J=7.1Hz), 4.1 5 (d, 1H, J=16.3Hz), 4.60 (d, 1H, J = 17.2 Hz), 7.22-7.32 (m, 4H), 7.34-7.40 (m, 4H), 7.48 (t, 1H, J = 7.9 Hz), 7.56 (d, 1H, J= 7.7Hz), 7.66 (d, 2H, J=7.0Hz), 8.63 (s, 1H) 7 0 1 1.13 (s, 3H), 3.24-3.46 (m, 8H), 4.14 (d, 1H, J=16.0) Hz), 4.35 (brs, 1H), 4.59 (d, 1H, J=15.8Hz), 7.24-7.31 (m, 4H), 7.36-7.40 (m, 4H), 7.47 (t, 1H, J=8.1 Hz), 7.55 (d, 1H, J=8.1Hz), 7.67 (d, 2H, J=8.1Hz), 8.73 (brs, 1H) 7 1 1 1.24 (s, 3H), 1.25-1.38 (m, 2H ), 1.80-1.98 (m , 2H), 2.01 (s, 1.5H), 2.03 (s, 1. 5H), 2.73-2. 83 (m, 1H), 3.08-3.18 (m, 1H), 3.61-3.80 (m, 2H), 4.13-4.22 (m, 1H), 4.29-4.56 (m, 2H), 7.25-7.33 (m, 4H), 7.35-7.41 (m. 4H), 7.50 ( t, 1H, J=6.9Hz), 7.57 (d( 1H, J=7.1Hz), 7.66 (t, 2H, J= 8.3 Hz), 8.62 (brd, 0.5H, J = 7.8 Hz), 8.67 (brd, 0.5H, J = 7.8 Hz) 265 323256 201206906 [Table 1 2 - 7] Continued Table 12 Example - R 1 Measurement conditions ' H-NMR δ (or LC-MS: [M+H]+ / Rt) 7 2 1 1.20 (s, 3H), 1.42 (s, 9H), 1.53-1.63 (m, 1H), 1.90-2.00 (ra , 1H), 2.30-2.44 (m, 1H), 2.90-3.05 (m, 1H), 3.20-3.54 (m, 5H), 4.19 (d, 1H, J = 16.7Hz), 4.64 (d, 1H, J = 15.8 Hz), 7.28-7.3 6 (m, 4H), 7.40-7.45 (m, 4H), 7.54 (t, 1H, J = 7.8 Hz), 7.61 (d, 1H, J = 7.5 Hz), 7.71 ( d, 2H, J=8.1Hz), 8.80 (brs, 1H) 7 3 ^.S〇2Me 1 1.21 (s, 3H), 2.91 (s, 3H), 3.20 (t, 2H, J=6.5 Hz), 3.65-3.72 (m, 2H), 4.11 (d, 1H, J=14.7H z), 4.47 (d, 1H, J=16.3Hz), 7.27-7.33 (m, 4H), 7.36-7.44 (m, 4H) ), 7.49 (t, 1H, J=8.3Hz), 7.56 (d, 1H, J=7.5Hz), 7.66-7.71 (m, 2H), 8.9 6 (t, 1H, J=5.7Hz) 7 4 &lt;^/s〇2nh2 1 1.20 (s, 3H), 3.21-3.26 (m, 2H), 3.50-3.72 (rn , 2H), 4.18 (d, 1H, J=16.0Hz), 4.42 (d, 1H, J = 15.2Hz), 5.00 (brs, 2H), 7.26-7.33 (m, 4H ), 7.35-7.41 (m, 4H), 7.49 (t, 1H, J = 7.8 Hz), 7.56 (d, 1H, J = 7.5 Hz), 7.68 (d, 1H, J = 8.3 Hz), 8.8 8 ( t, 1H, J=5.5Hz) 7 5 1 1.14 (d, 3H, J=4.0Hz), 1.65-1.80 (m, 6H), 2.1 0-2.20 (m, 1H), 2.25-2.35 (m, 1H) ), 2.50-2.60 (m, 1H), 2.75-2.90 (m, 1H), 3.15-3.25 (m, 2 H), 3.30-3.40 (m, 2H), 3.56-3.64 (m, 1H), 4. 16 (d, 1H, J=16.0Hz), 4.56 (d, 1H, J=15.0Hz), 7.23'(d, 1H, J=7.9Hz), 7.28-7.31 (m, 3H), 7.35-7.40 ( m, 4H), 7.47 (t, 1H, J=7.8Hz), 7.5 5 (d, 1H, J=7.7Hz), 7.66 (d, 2H, J=7.5Hz), 8. 77 (brs, 1H) 266 323256 201206906 [Table 1 2 - 8] Continued Table 12 Example - R1 Measurement conditions ^-NMR 5 (or LC-MS: [Μ+Η]+ / Rt) 7 6 /s^CN 1 1.15 (s, 3H ), 4.05-4.18 (m, 3H), 4.63 (d, 1H, J = 15.1Hz), 7.22-7.25 (m, 2H), 7.28-7.32 (m, 2H), 7.36-7.41 (m, 4H), 7.50 (t, 1H, J=7.7H z), 7.58 (d, 1H, J=8.1Hz), 7.68 (d, 2H, J=8.1 Hz), 9.09 (t, 1H, J=5.4Hz) 7 7 1 0.40-0.46 (m, 2H), 0.64-0.70 (m, 2H), 1.12 (t , 3H, J=1 .5Hz), 2.58-2.66 (m, 1H), 4.17 (d, 1H, J=16.0Hz), 4.59 (d, 1H, J=16.0Hz). 7.19-7.24 (in, 2H), 7.28-7.31 ( m, 2H), 7.34-7.39 (m, 4H), 7.47 (t, 1H, J=7.7Hz), 7.55 (d, 1H, J = 7.9Hz), 7,64-7.67 (m, 2H), 8.52 (s, 1H) Examples 78 to 79: The compounds shown in Table 13 were obtained by reacting and treating in the same manner as described in Example 47 using the corresponding starting compound. Example 78: 5-[1-(4-Cyanophenyl)-111-indolazole-5-yl]-4-mercapto-2-oxoyl-[3-(咐•r-pyridine- 1-yl)propyl]-3-[3-(trifluoromethyl)phenyl]-2,3-dihydrohydrogenate-1 (6H)-cartoamine Example 79: 5-[1_( 4 nitrogen basic ratio. sit-5-yl]-4-methyl-2_sideoxy-N~ [3-(2-sidedoxy)pyrrolidinyl-yl)propyl;|_3- [3_(Trifluoromethyl)phenyl]-2,3-dihydropyrimidine_ι(6Η)_Metformamide

267 323256 201206906 [Table 1 3] Table 1 3 Example - R 1 Measurement conditions] H-NMR δ (or LC-MS: [Μ+Η]+ / ) 7 8 1 1-33 (s, 3Η), 1.68-1.76 (ra, 6H), 2.48-2.54 (m, 6 H), 3.25 (dd, 2H, J=12.5, 6.6Hz), 4.39 (d, 2H, J = 1.5Hz), 6.37 (d, 1H , J=1.8Hz), 7.37 (d, 1H, J=8 1Hz), 7.42 (s, 1H), 7.54 (t, 1H, J=8.〇Hz)&gt; 7.60-7-63 (m, 3H ), 7.68 (d, 1H, J=1.8Hz), 7.70-7.73 (m. 2H); 8.73 (brs, 1H) 7 9 1 1-40 (s, 3H), 1.62-1.71 (m, 2H), 1.90-2.00 (m, 2 H), 2.33 (t, 2H, J=8.2Hz), 3.14-3.21 (m, 2H), 3. 24-3.35 (m, 4H), 4.33 (s, 2H), 6.36 (d, 1H, J=l. 7Hz), 7.42-7.45 (m, 2H), 7.54 (t, 1H, J=8.0Hz), 7.60-7.64 (m, 3H), 7.68 (d, 1H, J= L-7Hz), 7.73-7 •76 (m, 2H), 8.67 (brs, 1H)

Example 80: 4-[5-(4'-Cyanobiphenyl-2-yl)-4-indolyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1 ,2,3,6-tetrahydropyrimidin-1-decylamine]butyric acid

4-[5-(4'-Cyanobiphenyl-2-yl)-4-indolyl-2-oxo-3-(3-(trifluoromethyl)benzene obtained in Example 39 a solution of 1,1,2,3,6-tetrahydropyrimidine-1-carboxamide, ethyl butyrate (Π· 〇mg) in ethanol (10. 〇mi), 1N aqueous sodium hydroxide solution under ice cooling (3 〇 / / 〇, after stirring for 5 hours at 5 ° C. The reaction mixture was neutralized with hydrochloric acid, and then extracted with chloroform (10 ml, 2 times). After drying the organic layer with anhydrous sodium sulfate Concentration under reduced pressure. The residue was purified by silica gel column chromatography (solvent solvent tri-methane / 268 323256 201206906 alcohol) to give 4-[5-(4'-cyanobiphenyl-2-yl) -4-mercapto~2~ oxo-3-(3-(Tritonyl)phenyl)-1,2,3,6-tetrahydrofuran 0-methyl guanidine]butyric acid (8. Lmg). • H-NMR CCD Ch: 300 MHz) (5: 1. 14 (s, 3H), 1. 75-1. 81 (m, 2H), 2. 32 (t, 2H, J = 7. 3 Hz), 3. 2l -3. 28(m, 2H), 4. 15(brd, 1H, J=16. 3Hz), 4. 59(brd, 1H, J= 16. 3Hz), 7. 22-7. 31 (m, 4H), 7. 34-7. 40(m, 4H), 7. 48(t, ^ J=7. 8Hz), 7. 56(d, 1H, J=8. 1Hz), 7. 66(d, 2H, J=8. 3Hz), • 8.71 (brs, lH). Examples 81 to 84: The compounds shown in Table 14 were obtained by the same reaction and treatment as in the method described in Example 8 using the corresponding starting compounds. Example 81: 2- [5 -(4'-cyanobiphenyl-2-yl)-4-methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1,2,3,6-tetra Hydropyrimidin-1-decylamine]acetic acid φ Example 82: 3-[5-(4'-cyanobiphenyl-2-yl)-4-indolyl-2-oxo-3-(3- (Trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-1-decylamine]propionic acid Example 83: 5-[5-(4'-cyanobiphenyl-2 -yl)-4-methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-1-1-carbamimidyl]pentanoic acid Example 84: 2-[5-(1-(4-Cyanophenylbisazol-5-yl)-4-methyl-2-oxo-3-yloxy-3-(3-(trifluorofyl)benzene Base)-1,2,3,6-tetrahydropyrimidine-1-carboxamide]B 269 323256 201206906 Acid

[Table 1 4] Η 实施 Example L Ρ Measurement conditions Ή-NMR δ (or LC-MS: [M+H]+ / Rt) 8 1 1 3 1.18 (s, 3H), 3.96-3.98 (m, 2H ), 4.34 (brd, 1H, J = 15.8 Hz), 4.60 (brd, 1H, j = l5.2 Hz), 7.40-7.50 (m, 6H), 7.54-7.58 (m, 2H), 7.62 (t, 1H) , J=7.4 Hz), 7.68 (d, 1H, J=8.1Hz), 7.80-7.83 (m, 2H), 9·08 (brsf 1H) 8 2 2 3 l. 05 (s, 3H), 2.48- 2.56 (m, 2H), 3.47-3.54 (m, 2H), 4.02 (d, 1H, J = 14.1Hz), 4.30 (d, 1H, J=15. 2Hz), 7·27 (s. 1H), 7.32 (d, 1H, J=7.9Hz), 7.4 2-7.46 (m, 4H), 7.53-7.62 (m, 4H), 7.82-7.87 ( m, 2H) 8 3 4 3 1.24 (s, 3H), 1.52-1.68 (m, 4H), 2.33 (t, 2H, J = 6.8Hz), 3.21-3.27 (m, 2H), 4.27 (d, 1H, J=16. OHz), 4.51 (d, 1H, J =17.2Hz), 7.40-7.52 (m, 6H), 7.55-7.70 (m, 4H), 7.78-7.81 (m 〇u\ ' 8 4 1 3 1.39 (s, 3H), 3.90 (s, 2H), 4.50 (s 2H) 6 62 (d, 1H, J = 1.8 Hz), 7.60-7.83 (m&gt; 7 '' (m, 2H), 8.22 (brd, 0.3H, J=8. Example 85: 5 -(4'-cyanobiphenyl-2-yl)-4-methyl 4-(methylamidido)-4-oxobutylbutyl]-2-oxo-3-[3-(three Fluoromethyl) phenylene^ 2,3-dihydro" dense bite-1 (6H)-A Amine

4-[5-(4,-Cyanonaphthalen-2-yl) 323256 270 201206906 -4-methyl-2-oxo-3-(3-(disindolyl)phenyl) Addition of triethylamine to a solution of -1,2,3,6-tetrahydropyrimidine-1-carboxamide]butyric acid (Π.Omg) in N,N-dimethylformamide (0.5 ml) (5/z 1), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (13.8 mg), 1-hydroxy-7-azabenzotriazole (15. 9 mg After stirring with methylamine (2M tetrahydrofuran, 62//1), it was stirred at room temperature for 2 hours. After a saturated aqueous solution of sodium hydrogencarbonate (10 ml) was added, and ethyl acetate (1 ml, twice). The organic layer was washed with water (1 〇mi) and brine (10 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by a silica gel column chromatography (solvent solvent tri-trimethylbenzene / decyl alcohol) to give 5-(4'-cyanobiphenyl-2-yl)-4-mercapto-N-[4 -(decylamino)-4-oxobutyl]-2-oxo-3-[3-(trifluoromethyl)phenyl]-2,3-difluorene- 0-bit-1 6H) - guanamine (5.6 mg). j-NMRCCDCh: 300MHz) &lt;5 : 1. 19(s, 3H), 1. 80-1. 87(ra, 2H), 2. 19(t, 2H, J=7. 0Hz), 2. 78 (d, 3H, J=4. 8Hz), 3. 23-3. 34(m, 2H), 4. 20(brd, 1H, J=16. 3 φ Hz), 4. 58(brd, 1H, J=16. 3Hz), 6. 00(s, 1H), 7. 29-7. 37(m, 4H), 7. 41-7. 45(m, 4H), 7. 54(t, 1H, ]=1. 8Hz), 7. 62(d, 1H, J = 8. 4Hz), 7. 71(d, 2H, J=8. 3Hz), 8. 73(t, 1H, J=4. 8Hz Examples 86 to 97: The compounds shown in Table 15 were obtained by the same reaction and treatment as in the method described in Example 85, using the corresponding starting compound. Example 86: N-(2-Amino-2-oxoethyl)-5-(4'-cyanobiphenyl-2-yl)-4-indolyl-2-oxo-3- [3-(Trifluoromethyl)phenyl]-2,3-dihydropyrimidine 271 323256 201206906 -1(6H)-carbenamide Example 87: 5~(4'-cyanobiphenyl-2-yl )-N_[2-(decylamino)_2_sideoxyethyl]-4-methyl-2-oxooxy_3_[3_(trifluoromethyl)phenyl]-2, 3-di Hydropyrimidine-1(6H)-carboxamide Example 88: 5-(4'-Cyanobiphenyl-2-yl)-N-[2-(didecylamino)_2-side oxyethyl ]-4-methyl-2-oxooxy-3-[3-(trifluoromethyl)phenyl;|_2,3-dihydro®pyrimidine-1(6H)-carbenamide Example 89: 5 -(4'-cyanobiphenyl-2-yl)-4-mercapto-2-yloxy-N-[2-o-oxy-2-(pyrrolidin-1-yl)ethyl]-3- [3-(Trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)-carbenamide Example 90: 5-(4'-cyanobiphenyl-2-yl)-N -[2-(2-(Dimethylamino)ethylamine φ))-2-oxoethyl]-4-methyl-2-oxooxy-3_[3-(trifluoromethyl) Phenyl]-2,3-dihydrocarbimate_1(6H)-carbenamide Example 91: 5-(4'-cyanobiphenyl-2-yl)-4-mercapto-N- [3-(decylamino)-3-side oxygen Propyl]-2-oxo-3-[3-(trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)-guanamine Example 92: N-(4 -amino-4-ylideneethyl)-5-(4'-cyanobiphenyl-2-yl)-4-methyl-2-oxo-3-[3-(trifluoromethyl) Phenyl]-2,3-dihydropyrimidine 272 323256 201206906 -l(6H)-decylamine Example 93: 5-(4,-Cyanobiphenyl-2-yl)-N-[4-(dimethyl Amino)-4-oxobutylbutyl]_4_mercapto-2-oxo-3-[3-(di-mercapto)phenyl]-2,3-dihydropyrimidine-1 (6H - decylamine Example 94: 5-(4,-Cyanobiphenyl-2-yl)-N-[4-(ethylamino)-4-oxobutyl]-4-indolyl -2-Sideoxy-3-[3-(trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)-guanamine Example 95: 5~(4'-cyano Biphenyl-2-yl)-4-methyl-2-oxo-N-[4-o-oxy-4-(pyrrolidin-1-yl)butyl]-3,[3-(trifluoro Methyl)phenyl]-2,3-dihydropyrimidin-1(6H)-carbenamide Example 96:

N-[4-(azetidine-fluorenyl)-4-yloxybutyl]_5-(4,-cyanobiphenyl-2-yl)-4-methyl-2-oxo- 3-[3-(Trifluoromethyl)phenyl]_2,3-dihydropyrimidin-1(6H)-carbenamide Example 97: =4 -murinebiphenyl-2_yl)_N_[4_( Isopropylamino side butylbutane 4 methyl 2 oxo (trimethyl) phenyl chloroformin-1 (6H)-formamide 323256 273. 201206906

[Table 1 5 - 1] Table 1 5 Example P - Z Measurement conditions 'H-NMR 5 (or LC-MS: [M+H] + / Rt) 8 6 1 ^νη2 1 1.19 (s, 3H), 3.87 (d, 2H, J=5.9Hz), 4.15 (d, 1H, J=15.2Hz), 4.54 (d, 1H, J=17.1Hz), 5.41 (brs, 1 H), 5.88 (brs, 1H) , 7.25-7.32 (m, 4H), 7.35-7.40 (m, 4H), 7.49 (t, 1H, J=7.7Hz), 7.57 (d, 1H, J= 8.1Hz), 7.66-7.68 (m, 2H ), 9.02 (t, 1H, J=5.7Hz) 8 7 1 Η 1 1.16 (s, 3H), 2.75 (d, 3H, J=4.8Hz) J 3.85 (d, 2H, J=5.9Hz), 4.12 (d, 1H, J=16.0Hz), 4.60 (d, 1H, J=16.7Hz), 5.96 (brs, 1H), 7.22-7.32 (ra, 4H), 7.3 5-7.40 (m, 4H), 7.49 (t, 1H, J=7.6Hz), 7.57 (d, 1H, J=8.1Hz), 7.66-7.68 (m, 2H), 9.00 (t, 1H, J= 5.9Hz) 8 8 1 1 1.19 (s , 3H), 2.92 (s, 3H), 2.93 (s, 3H), 4.00 (d, 2H, J=4.4Hz), 4.19 (d, 1H, J=16.0Hz), 4.43 (d, 1H, J= 16.0Hz), 7.26-7.40 (m, 8H), 7.46 (t, 1H, J = 8.1Hz), 7.53 (d, 1H, J=7.9Hz), 7.64-7.67 (m, 2H ), 9.17 (brs, 1H) 8 9 1 〆〇1 1.21 (s, 3H), 1.77-1.83 (m, 2H), 1.88-1.94 (m, 2 H), 3.30-3.37 (m, 2H), 3.41-3.46 (m, 2H ), 3.93 ( d, 2H, J=4.6Hz), 4.19 (d, 1H, J=14.9Hz), 4. 44 (d ,1H, J=16.7Hz), 7.26-7.40 (m, 8H), 7.46 (t, 1H, J=8.2Hz), 7.53 (d, 1H, J=7.9Hz), 7.64-7.68 (m , 2H), 9.13 (brs, 1H) 274 323256 201206906

[Table 1 5 - 2] Continued Table 15 Example P - Z Measurement conditions 'H-NMR δ (or LC-MS: [M+H] + / Rt) 9 0 1 1 1.17 (s, 3H), 2.14 ( s, 6H), 2.33 {t, 2H, J=6.0Hz), 3.28 (q, 2H, J=5.7Hz), 3.85 (d, 1H, J=5.5Hz), 3.86 (d, 1H, J =5.5Hz), 4.13 (d, 1H, J=17.1Hz), 4.6 1 (d, 1H, J=16.1Hz), 6.30 (brs, 1H), 7.19-7.31(m, 4H), 7.34-7.39 ( m, 4H), 7.47 (t( 1H, J=7.9z), 7. 55 (d, 1H, J=8.1Hz), 7.67 (d, 2, J=8.3Hz), 9.02 ( t, 1H, J =5.6Hz) 9 1 2 1 1.10 (s, 3H), 2.30-2.42 (m, 2H), 2.72 (d, 3H, J= 4.8Hz), 3.26-3.34 (in, 1H), 3.48-3.58 (m , 1H), 3. 72 (d, 1H, J=14.5Hz), 4.07 (d, 1H, J=14.1Hz), 6. 03 (brs, 1H), 7.19-7.55 (m, 10H), 7.68 ( d, 2H, J = 8.4Hz) 9 2 3 ^nh2 1 1.18 (s, 3H), 1.74-1.84 (m, 2H), 2.20 (t, 2H, J=7, 3Hz), 3.22-3.28 (m, 2H), 4.16 (d, 1H, J=16.5Hz), 4.53 (d, 1H, J=16.3Hz), 5.71 (brs, 1H), 6.04 (b rs, 1H), 7.15-7.32 (m, 4H) , 7.37-7.41 (m, 4H), 7.49 (t, 1H, J=7.7Hz), 7.57 (d, 1H, J=7.9Hz), 7.6 5*7.68 (m, 2H), 8.70 (t, 1H, J=5.5Hz) 9 3 3 5〆1 1.13 (s, 3H), 1.76-1.85 (m, 2H), 2.28 (t, 2H, J=7 .4Hz), 2.86 (s, 3H), 2.91 (s, 3H), 3.20-3.28 (ra, 2H), 4.14 (d, 1H, J = 15.8Hz), 4.60 (d, 1H, J = 15.8 Hz) , 7.23-7.31 (m, 4H), 7.34-7.40 (m, 4H), 7.48 (t, 1H, J=7.7Hz) J 7.56 (d, 1H, J=7.9Hz), 7.65-7 .67 (m , 2H), 8.64 (t, 1H, J=5.5Hz) 275 323256 201206906 [Table 1 5 - 3 I Connection Table 15 Example

P

Z Determination conditions 'H-NMR δ (or LC-MS: [M+H]+ / Rt) 9 4 1.06 (t, 3H, J = 7.2 Hz), 1.17 (s, 3H), 1.73-1.83 (ra, 2H), 2.12 (t, 2H, J=7.0Hz), 3.16-3.26 (m, 4H), 4.16 (d, 1H, J=15.6Hz), 4.53 (d, 1H, J=15.6Hz), 5.87 ( Brs, 1H), 7.15-7.32 (m, 4H), 7.37-7.41 (m , 4H), 7.49 (t, 1H, J=7.7Hz), 7.57 (d, 1H, J=7.9 Hz), 7.65-7.68 (tn, 2H), 8.66 (t, 1H, J=5.8Hz) 9 5 3 1.13 (s, 3H), 1.71-1.90 (m, 6H), 2.23 (t, 2H, J=7 • 4Hz), 3 , 21-3.39 (ra, 6H&gt;, 4.14 (d, 1H, J=15.0Hz), 4.60 (d, 1H, J=16.3Hz), 7.22-7.31 (tn, 4H), 7.3 4-7.40 (m, 4H), 7.48 (t, 1H, J=7.7Hz), 7.56 (d, 1H, J=7.9Hz), 7.65-7.67 (m, 2H), 8.64 (t, 1H, J= 5.6Hz) 9 6 3 1.14 (s, 3H), 1.74-1.82 (m, 2H), 1.91-1.97 (m, 2 H), 2.03 (t, 2H, J = 7.2 Hz), 3.19-3.25 (m, 2H), 3. 93 (t, 2H, J=8.0Hz), 4.04 (t. 2H, J=7.4Hz), 4.15 (d, 1H, J=15.2Hz), 4.59 (d, 1H, J=15.9Hz)&gt; 7.2 3 -7.31 (m, 4H), 7.35-7.40 (m, 4H), 7.48 (t, 1H, J=7.1Hz), 7.56 (d, 1H, J=7.1Hz), 7.65-7.68 (ra, 2H), 8.64 (brs, 1H) 9 7 3 Λ l. 07 (d, 6H, J=6.4Hz), 1.17 (s, 3H), 1.72-1.82 ( m, 2H), 2.1 0 (t, 2H, J=7.3Hz), 3.22 (q, 1H, J=6. 4Hz), 3.93-4.40 (ra, 1H), 4.17 (d, 1H, J=15.2Hz), 4.53 (d, 1H, J=15.6Hz), 5.69 (brs, 1H), 7.23-7. 32 (m, 4H), 7.37-7.40 (m, 4H), 7.49 (t, 1H, J=7. 7Hz), 7.57 ( d, 1H, J = 8.3 Hz), 7.66 (d, 2H, J = 8.1 Hz), 8.64 (s. 1H) Example 98: 4-[5-(4'-Cyanobiphenyl-2-yl) 4-mercapto-2-oxooxy-3-(3-(fluoroindolyl)phenyl)-2,3-dihydropyrimidin-1(6H)-yl]butyric acid

02Et

276 323256 201206906 In the solution of ==8 _ of 4|(4, _ secret benzene ^ (3' ^ tetrahydrogen (5)), Γ: Γ: sodium bismuth solution (1 〇 (4), at room temperature Scramble

〃彳 Aqueous sodium hydroxide solution (5 Ν, 25//1) was added under ice-cooling, and the mixture was stirred at room temperature for 3 g minutes. After that, I ate the cake for 3 hours. After adding water (2Gml) n JE (2) ml) to the reaction mixture, the water layer is made acidic by potassium hydrogen sulfate (1) 11 about 3). The organic layer is washed with saturated brine (1〇1111). The aqueous layer was extracted with MgSO4 (3 EtOAc). The residue was purified by preparative thin layer chromatography (solvent solvent trichloromethane / decyl alcohol) to give 4-[5-(4'-cyanobiphenyl-2-yl)-4-methyl- 2-Phenoxy-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidin-1(6H)-yl]butyric acid (8.9 mg). 'H-NMRCCDaOD: 300ΜΗζ)δ 〇· 90(t, 2Η, J=5. 4Hz), 1. ll(s,3Η), 1. 76(t, 2H, J=6. 6Ηζ),

2. 25(t, 2H, J=6. 3Hz), 3. 91(d, 1H, J=H. 1Hz), 4. 19(d, 1H, J = 13. 5Hz), 7. 31-7 42(ra, 3H), 7. 42-7. 47(m, 5H), 7. 54-7. 62 (m, 3H), 7. 55(d, 2H, J=8. 7Hz). Example 99: 4, [5-(4'-cyanobiphenyl-2-yl)-4-mercapto-2-oxo-3-(3-(trimethylmethyl)phenyl)-2, 3-dihydropyrimidin-1(6H)-yl]-N-methylbutyramine 323256 277 201206906

4-[5-(4'-Cyanobiphenyl-2-yl)-4-indolyl-2-oxo-3-(3-(tri-l-indenyl)benzene obtained in Example 98 a solution of N,N-dimethylformamide (0.5 ml) in a solution of -2,3-dihydro- dimethyl hydrazide-1 (6H)-yl]butyric acid (8.9 mg), 0- (7-azabenzotriazol-1-yl)-N, fluorene, Ν', Ν'-tetradecyl-urea hexafluorophosphate (0-(7-benzotriazol-l-yl)-N, Ν,Ν',Ν'-tetramethyluronium hexafluorophosphate) (14.6mg), 1-hydroxy-7-azabenzotriazole (5.3mg), triethylamine (50# 1), decylamine hydrochloride After (6. 2 mg), the mixture was stirred at room temperature for 62 hours. Ethyl acetate (30 ml) was added to the mixture, and the mixture was evaporated. The residue was purified by preparative thin layer chromatography (solvent solvent trichloromethane/methanol) to give 4-[5-•(4'-cyanobiphenyl-2-yl)-4-indolyl- 2-Sideoxy-3-(3-(trifluoromethyl)indolyl)-2,3·~~虱~0~-1(6Η)-yl]-Ν-mercaptobutylamine (1. 7mg). ^-NMRCCDsOD : 300ΜΗζ) δ : 1. 13(s, 3H), 1. 61-1. 75(m, 2H), 2. 07(t, 2H, J=6. 6Hz), 2. 69 (d , 3H, J=4. 5Hz), 2. 98-3. 07(m, 1H), 3. 27-3. 36(m, 1H), 3. 63 (d, 1H, J=14. 1Hz) , 4. 04(d, 1H, J=14.1Hz), 6. ll(brs, 1H), 7. 22(brs, 1H), 7. 28-7. 56(m, 9H), 7. 68( d, 2H, J = 8. 1 Hz). Example 100: N-(3-Aminopropyl)-5-(4,-cyanobiphenyl-2-yl)-4-indolyl-2-sideoxy 278 323256 201206906 -3-[3-(Trifluoromethyl)phenyl]-2,3-dihydropyrimidin-1(6H)-carbenamide hydrochloride

3-[5-(4,-Cyanobiphenyl-2-yl)-y-4-mercapto-2-oxo-3-(3-(trifluoromethyl) group obtained in Example 60 Phenyl)-1,2,3,6-tetrahydropyrimidine-1-carboxamide] propylamine decanoic acid tert-butyl ester (2〇. 〇mg) in ethanol (2.〇1111) solution, added 41 ^ hydrochloric acid / ethanol (48 / / 1) solution, at 9 〇.搅拌 Stir for 2 hours. The reaction mixture was concentrated under reduced pressure. N-(3-Aminopropyl)-5-(4,-cyanobiphenyl 2) 4-indenyl 2-oxo-3- as a solid obtained by azeotropy with tri-methane/hexane [3-(Trifluoromethyl)phenyl]- 2,3-dihydropyrimidin-1 (6H)-decylamine hydrochloride (16.4 mg).匪R(CD3〇D : 300MHz) ά :

J = 8. 4 Hz), 8. 83 (brs, 1H). Example 101:

Example 101: Methyl-2-oxooxy-N-(〇比洛 bite(S)-5-(4'-cyanobiphenyl-2-yl)~4, 323256 279 201206906 -3-ylindene 3-(3-(trifluoromethyl)phenyl]-2,3-dihydropyrimidine-K6H)-nonylamine hydrochloride

^-NMRCCDaOD : 300MHz) 5 : 1. 33(s, 3H), 1. 68-1. 79(m, 1H), 2. 10-2. 20(m, 1H), 2. 53- 2. 63 (ra, 1H), 2. 92-3. 00(m, 1H), 3. 31-3. 41(m, 5H), 4. 24(d, 1H, J=15. 4Hz), 4. 39 (d, 1H, J=15. 8Hz), 7. 38-7. 41(m, 1H), 7. 46-7. 52(m, 4H), 7. 57-7. 61(m, 3H) , 7. 65(t, 1H, J=7. 8Hz), 7.71(d, 1H, J=8.11Hz), 7. 78-7. 82(m, 2H). Example 102: N- (3-acetamidopropyl)-5-(4,-cyanobiphenyl-2-yl)-4-mercapto-2-oxo-3-[3-(trifluoromethyl) Base]-2, 3-dihydro-u-bite _1(6Η)~·甲甲胺

Indole-(3-aminopropyl)-5-(4,-cyanobiphenyl-2-yl)-4-methyl-2-oxo-3-[3] obtained in Example 100 -(Trifluoromethyl)phenyl]- 2,3-dihydropyrimidine-U6H)-nonylamine hydrochloride (5. 〇mg), triethylamine (4 #1) dioxane ( 0.5 ml) in the night, add ethyl hydrazine d /1) under ice cooling, stir for 5 minutes, and stir at room temperature for 6 hours. After 280 323256 201206906, a saturated aqueous solution of sodium hydrogencarbonate (10 ml) was added, and then extracted with chloroform (1 mL, twice). The residue was purified by silica gel column chromatography (solvent solvent chlorobenzene / methanol) to give N-(3-ethylaminopropyl)-5-(4,-cyanobiphenyl-2-yl) 4--4-mercapto-2-oxooxy-3-[3-(trifluoromethyl)phenyl]-2,3-dihydropyrimidine-1 (61〇-formamide (2.1呃). H-NMRCCDCh: 300 ΜΗζ) δ : 1. 20(s, 3H), 1. 62(t, 2H, J=6. 5Hz), 1. 91(s, 3H), 3. 18-3. 26 φ 4H ), 4. 17(brd, 1H, J=15. 2Hz), 4. 48(brd, 1H, J=15. 2Hz), 6. 06(s, 1H), 7. 27-7. 33(m , 4H), 7. 37-7. 41(m, 4H), 7. 49(t, 1H, J=7. 8Hz), 7. 57(d, 1H, 1=7. 9Hz), 7. 67 (d, 2H, J = 8. 1 Hz), 8. 69 (brs, 1H). Examples 103 to 104: After reacting and treating in the same manner as described in Example 1〇2, using the corresponding starting compound, The compound shown in Table 16 was obtained. Example 103: • 5-(4'-Cyanobiphenyl-2-yl)-4-methyl-N-[3-(indolylsulfonylamino)propyl]_2-sideoxy-3- [3-(Trifluoromethyl)phenyl;|_2, 3-dihydropyrimidine-1(6H)-carboxamide Example 104: (R)-N-[(l-Ethylpyrrolidine-3 -yl)indenyl]-5-(4,-cyanobiphenyl-2-yl)-4-methyl-2-oxooxytrifluoromethyl)phenyl]_2,3_dihydro shout Guanamine 281 323256 201206906

[Table 1 6] Table 1J_ Example-R 1 Measurement conditions 'H-NMR δ (or LC-MS: [Μ+Η]+ / Rt) U 1.19 (s, 3H), 1.66-1.71 (in, 2H) , 2.S8 (s, 3H), 3.05-3.12 (m, 2H), 3.09 (dd, 2H, J=12.8, 6.6Hz 10 3 1 ), 4.14 (brd, 1H, J=16, lHz>, 4.51 (brd, 1H, J=1 X 6.1Hz), 7.23-7.33 (m, 4H), 7.35-7.41 (in, 4H), 7.50 (t, 1H, J=7.9Hz), 7.58 (d, 1H, J =8.4Hz), 7.67 (d, 2H, J=8.1Hz), 8.71 (brs, 1H) 1.17 (s, 3H), 1.50-1.67 (m, 2H), 1.95 (s, 1.5H), 1.97 (s, 1.5H), 2.30-2.46 (m, 1H), 3.03-3.09 (m, 1H), 3.12-3.65 (m, 5H), 4.13 (d, 0.5H, J=1 10 4 1 5.9Hz) , 4.18 (d, 0.5H, J = 15.9Hz), 4.44 (d, 0.5H, J = 15.9Hz), 4.55 (d, 0.5H, J = 15.9Hz), 7.24-7.3 2 (m, 4H). 7.35-7.40 (m, 4H), 7.50 (t, 1H, J=7. 7Hz), 7.57 (d, 1H, J=7.4Hz), 7.64-7.67 (m, 2H) one.. , 8.72-8.80 ( m, 1H) Φ Example 1〇5 ' 2 -[3-(ΙΗ-味°坐-1-基牛牛)-β__曱基_2_sideoxy-1-(3-(trifluoro Mercapto)phenyl)_丨,2,3,4_tetrahydropyrimidin-5-yl]biphenyl-4-indrene

2, -[6-methyl-2-indolyl (trimethylsulfonyl)phenyl)_1,2,3,4-tetrahydrop-bist-5-yl] obtained from Example 8 Stupid_4_甲猜323256 282 201206906 (50.0mg) in N,N-dimercaptocaramine (1.5ml) solution, add sodium hydride (6. lmg) under ice ^ stir for 5 minutes 'add 1 1, - Continued brewing base two flavor saliva (34.3 mg) was stirred for 1 hour. After a saturated aqueous solution of chlorinated water (10 ml) was added to the mixture, ethyl acetate (10 m) was applied. The organic layer was washed with water and brine (20 ml), dried over anhydrous sodium sulfate and evaporated. The residue was purified by gel column chromatography (the solvent was dissolved in ethyl acetate) to give 2,-[3-(1Η-σ米π圭-1-基基基基)甲美-2- The pendant oxy-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydro-bine _5_yl]biphenyl-4-indenecarbonitrile (26.5 mg). 'H-NMR CCD Ch: 300 MHz) 5 : 1. 23 (s, 3H), 4. 19 (d, 1H, J = 14. 3 Hz), 4. 48 (d, 1H, J = i 3. 9 Hz), 6. 95-6.m (m, 1H), 7. 22-7. 31(m, 4H), 7. 33-7. 5〇(m, 6H), 7. 55(d, 1H, J=17. 7 Hz), 7. 71-7. 73(m, 2H), 7. 93(s, 1H). Example 106: 5-(4-Fluorophenylsulfinyl)-3,6-dimethyl -i-[3-(Trifluoromethyl)phenyl]-3,4-dihydropyrimidin-2(1H)-one

5-(4-Fluorophenylthio)~3,6-dimercaptodimethylmethyl)phenyl]-3,4-diaza 11 sigma sigma" obtained from Example 3 &quot;*2 (1 Η)__ (24. Omg) in dichloromethane (2. 〇ml) solution, m-chloroperoxybenzoic acid (16.2 mg) was added under ice cooling, and stirred for 30 minutes. After adding water (10 ml) to the reaction mixture, it was extracted with chloroform (i?mi, twice). After drying the organic layer with anhydrous sodium sulfate 283 323256 201206906, it was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (solvent solvent chloroform / methanol) to give 5-(4-fluorophenylsulfinyl)-3,6-didecyl-1-[3- (Trifluoromethyl)phenyl]_3,4-dihydropyrimidine_2 (11〇-嗣 (13.7111 hydroxy). ^-NMRCCDCh: 300MHz) 5 : 1. 97(t, 3H, J=l. 4Hz) , 2. 81(s, 3H), 3. 38(dd, 1H, J=13. 8, 1. 6Hz), 4. 08(dd, 1H, J=13. 8, 1. 3Hz), 7. 17-7. 23(m, 2H), 7. 35(d, 1H, J=7. 7Hz), 7. 42(s, 1H), 7. 50-7. 55(m, 3H), 7. 61 W (d, 1H, J=7. 7 Hz). Examples 107 to 108: The compounds shown in Table 17 were obtained by the same reaction and treatment as in the method described in Example 1〇6 using the corresponding starting compounds. . Example 107: 5-(4-Chlorophenylsulfinyl)-3,6-diamidino-i-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrimidine-2 (1) fluorenone-ketone φ Example 1 〇 8 : 4_[3,6-dimethyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1, 2, 3, 4-tetrahydropyrimidin-5-ylsulfonyl]benzonitrile

323256 284 201206906 [Table 1 7] Table 1 7 Example Υ -R°-R 1 Measurement conditions 'H-NMR δ (or LC-MS: [Μ+Η]+ / Rt) 10 7 Cl Μ· e 1 1.97 (t, 3H, J=1.3Hz), 2.82 (s, 3H), 3.37 ( d, 1H, J=13.9Hz), 4.08 (d, 1H, J=13.9Hz), 7.35 (d, 1H, J= 9.1 Hz &gt;, 7.42 (s, 1H), 7.48 (s, 4H), 7.52 (t, 1H, J = 7.5 Hz), 7.61 (d, 1 H, J = 7.3 Hz) 10 8 CN Me 1 2.00 (s , 3H), 2.81 (s, 3H), 3.32 (dd, 1H, J=13.8, 1.5Hz), 4.07 (d, 1H, J=13.8 Hz), 7.36 (d, 1H, J=7.7Hz) &gt; 7.42 (s, 1H), 7.53 (t , 1H, J = 7.8 Hz), 7.62 (d, 1H, J = 7.2 Hz), 7.6 7 (d, 2H, J = 8.3 Hz), 7.80 (d, 2H, J=8.1Hz)

Reference Examples 37 to 40 In Reference Examples 10 and 20 to 24, the urea derivatives used in Examples 1 to 3, 109 to 120 were synthesized by the following methods.

Reference Example 37: 3-(trimethylhydrazino)phenyl isocyanate (10. g) was dissolved in ethyl acetate (150 ml) and cooled to 0. 5小时。 The solution was immersed in a solution of isopropylamine (13. 73 ml) in ethyl acetate (25 ml). The precipitated solid was collected by filtration and washed with ethyl acetate. Further, the filtrate was concentrated, hexane was added, and the precipitated solid was collected by filtration and washed with hexane to obtain 1-isopropyl-3-(3-(trifluoromethyl)phenyl)urea (12.82 g). W-fiMRUOOMHz, CDCh, 5 ppm): 1. 20(d, 6H, J=6. 5Hz), 3. 99(q, 1H, J=6. 5Hz), 6. 57(brs, 1H)

, 7.28(d, 1H, J=8. 1Hz), 7. 38(t, 1H, J=8.11Hz), 7. 53(d, 1H, J 285 323256 201206906 =8. 1Hz), 7 61 (s, 1H). The following compounds (Reference Examples 38 to 40) were synthesized by the same reaction and treatment as in the method described in Reference Example 37 using the corresponding starting compound.

Reference Example 38: 1-ethyl-3-(3-(trifluoromethyl)phenyl)urea, j-NMRUOOMHz, CDCh, 6 ppm): 1. 18 (t, 3H, J = 7. 2 Hz), 3 31(ςι,1H,J=7· 2Hz), 6.69(brs,1H), 7.28(d, 1H, J=8. 1Hz), 7. 39(t, 1H, J=8. 1Hz), 7. 54(d, 1H, J = 8. 1Hz), 7. 60(s, 1H).

• Reference Example 39: 1-isopropyl-3-carbazinyl urea 1H-NMR (400 MHz &gt; CDCh &gt; δ ppm): 1. 15 (d, 6H, J = 6. 5 Hz), 2. 28 (s, 3H), 3. 98(q, 1H, J=6. 5Hz), 6. 86(d, 1H, J=7. 5Hz), 6. 89(brs, 1H), 7. 07(d , 1H, J=7. 7Hz), 7. ll(s, 1H), 7. 15(t, 1H, J=7. 7Hz). Τ(Λ Reference 40 : 1 -isobutyl-3-( 3-(Trifluoromethyl)phenyl)urea 323256 286 201206906 匪R (400MHz, CDC13, 6 ppm):

0. 88(d, 6H, J=6. 7Hz), 1. 72 (sept, 1H, J=6. 7Hz), 3· 08(d, 2H, J=6. 7Hz), 5. 66(brs , 1 (1), 7. 7. 58(s, 1H), 7. 60(brs, 1H). Reference Examples 41 to 42 In Reference Examples 10, 20 to 24, the urea derivatives of Examples 1 to 3, 109 to 120 can be borrowed The following methods are synthesized. [Step 1] Reference Example 41 will be described by the literature (J. Med. Chem. 1995, 38, 49-57).

The 3-(difluoromethyl)aniline hydrochloride (325 mg) obtained by the method was suspended in THF (5 ml), and then, at 0 ° C, phenyl chlorophenyl phthalate (〇·35 ml) and triethylamine # (0. 63 ml), stirring for 1 hour, 1 M hydrochloric acid was added to the reaction mixture, and extracted twice with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated. The residue was chromatographed on a silica gel column (eluent solvent &amp; EtOAc/ethyl acetate) to afford &lt;RTIgt;&lt;/RTI&gt; iH-NMRUOOMHz, CDC13, (5 ppm): 6. 63 (t, 1H, J = 56.3 Hz), 7. 05 (brS, 1H), 7·2 〇 (dd, 2H, j=i. 2 7 7Hz), 7. 24-7. 29(m,2H)' 7. 39-7. 45(m,3H), 7. 54_7 melon, 1H), 7. 68(s, 1H). * 323256 287 201206906 [Step 2] Reference Example 42 3_(dioxadecyl) phenylamine phthalic acid benzene vinegar (42 〇mg) obtained in Reference Example 41 was dissolved in acetonitrile (5 ml), and methylamine was added. GM THF solution, 1.6 ml), stirred at room temperature for hrs. Saturated brine was added to the reaction solution, and extracted with acetic acid (10) 2: owed. After the sulphur-free sulphur secret money layer, the decompression is concentrated. The residue was purified by a silica gel column chromatography (eluent solvent hexane / ethyl acetate) to afford (3-(difluoromethyl)phenyl)_3-methyl (2) 6 mg). 1H-NMR (400MHz » CDCh » δ ppm): 2. 64(d, 3H, J=4. 6Hz), 6. 08(q, 1H, J=4. 5Hz), 6. 95(t, 1H, J= 56. 0Hz), 7. 〇5(d, 1H, J=7. 6Hz), 7. 34(dd, 1H, J=7. 8, 7. 9Hz), 7. 44(dd, 1H, J=l. 〇, g. 2Hz), 7. 72(s, 1H), 8. 75(s, 1H). Reference Examples 43 to 48 Reference Examples 8, 9, and 26 can be synthesized by the following methods.

[Step 1] Reference Example 43 4-cyanobenzidine (12. g) was dissolved in DMF (120 ml), and n, n-dimethyl decylamine dimethyl acetal (14 95 ml) was added. The mixture was stirred at 50 ° C for 50 min. 1-amino-2-propanol (8. 62 ml) and acetic acid (60 ml) were added dropwise to the reaction mixture and stirred at 120× for 2 hr. Trichloromethane (3 〇mi) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour, and then a solid was collected by filtration. To the obtained solid was added trichloromethane (30 ml), and the mixture was allowed to stand for 30 minutes under heating and reflux. 〇. After hydrazine, the solid was collected by filtration to give 4_[4_ 288 323256 201206906 (2-propylpropyl)-4Η-1,2,4-tris-indolyl-3-benzonitrile (11. ggg) j-NMRUOOMHz, DMS0-d6, ¢5 ppm): 1. 01 (d, 3H, J = 5. 9 Hz), 3. 83-3. 92 (m, 2H), 4. 10 (dd, 1H, J = 2. 5, 13. 3 Hz), 5. 12 (d, 1H, J = 4. 6 Hz), 7. 95 (dd, 2H, J = l 8 6. 5 Hz), 8. 12 (dd, 2H) , J = l. 8, 6. 5 Hz), 8. 67 (s, 1H). The following compounds were synthesized and treated in the same manner as in the method described in Reference Example 43 using the corresponding starting compound. Reference example 44).

Reference Example 44: 4-(4-(2-carboxybutyl)-411-1,2,4-trix»yt-3-ylphenylphthalonitrile j-NMRMOOMHz, CDCh, 5 ppm) · 1. 01 (t, 3H, J=7. 4Hz), 1. 52-1. 60(ra, 2H), 3. 89-4. 00(m, 2H) , 4. 05(dd, 1H, J=l. 6, 13. 1Hz), 7. 78(dd, 2H, J=l. 9, 6. 7Hz), • 7. 87(dd, 2H, J=l. 8, 6. 6Hz), 8. 61( s, 1H).

[Step 2] Reference Example 45 4-[4-(2-Hydroxypropyl)-4H-1,2,4-triazol-3-yl]benzonitrile (11·83 g) obtained in Reference Example 43 The mixture was stirred at room temperature for 1.5 hours. The mixture was stirred at room temperature for 1.5 hours. Isopropyl alcohol (10 ml), water (10〇1111), and saturated brine (10〇1111) were added to the mixture, and ethyl acetate (200 ml×l, 100 ml×l8) was extracted. The organic layer was dried over anhydrous magnesium The solid obtained was filtered with ethyl acetate (55 ml) to give 289 323 256 </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Further, the filtrate was concentrated, and the residue was purified by silica gel column chromatography (eluent solvent, tri-methane/methanol), and the obtained solid was filtered with ethyl acetate and combined with the previous filter. 4-[4-(2-Polyoxypropyl)-4Η-1,2,4-triazol-3-yl]benzonitrile (7.39). R (400MHz, CDC13, (5 ppm): 2. 27 (s, 3H), 4. 93 (s, 2H), 7. 66 (Mountain 2H, J = 8. 4Hz), 7. 80 (d, 2H, J = 8.4 Hz), 8.35 (s, 1H). The following compounds were synthesized and treated in the same manner as in the method described in Reference Example 45 using the corresponding starting compound (Reference Example 46).

Reference Example 46: 4-(4-(2-Sideoxybutyl)-xian-1,2,4-triazol-3-yl)benzonitrile φ 匪R (400 MHz, DMSO-cU, (5 PPm) ): 0. 91(t, 3H, J=7. 3Hz), 2. 51(q, 2H, J=7. 3Hz), 5. 28(s, 2H), 7. 76(d, 2H, J =8. 2Hz), 7. 98(d, 2H, J=8. 2Hz), 8. 52(s, 1H).

[Step 3] Reference Example 47 4-[4~(2-Sideoxypropyl)-4H-1,2,4-triazol-3-yl]benzonitrile obtained in Reference Example 45 (7.39 g) The solution was dissolved in acetonitrile (150 ml), EtOAc (35% aqueous solution, 3.23 ml), piperidine (0·32 ml), and acetic acid (0.11 ml) were added and the mixture was stirred overnight under reflux. After cooling to room temperature, an anhydrous sulfuric acid meter (5 g) was added and the mixture was stirred for 1 minute and then filtered. The sputum is reduced by 290 323256 201206906. The residue was purified by silica gel column chromatography (solvent solvent trichloromethane/methanol) to give 4-[4-(3-s-oxy-1-but-2-yl)-4? 2,4-Triazol-3-yl]benzonitrile (4.82 g). 1H-NMR (400MHz j CDCI3 5 δ ppm): 2. 41(s, 3H), 6. 28(d, 1H, J=2.1 Hz), 6. 54(d, 1H, J=2.1 Hz) , 7.73(s, 4H), 8. 19(s, 1H).

The following compound (Reference Example 48) was synthesized by the same reaction and treatment as in the method described in Reference Example 47 using the corresponding starting compound. Reference Example 48: 4-(4-(3-Phenoxy-1-penten-2-yl)-4Η-1,2,4-triazol-3-yl)benzonitrile 1H-NMR (400 MHz &gt ; CDCh » δ ppm): 1. 06(t, 3H, J=7. 2Hz), 2. 73(q, 2H, J=7. 2Hz), 6. 29(d, 1H, J= • 1. 9Hz), 6. 55(d, 1H, J=l. 9Hz), 7. 74(s, 4H), 8. 28(s, 1H). Reference examples 49 to 51

Reference Example 49: In a solution of 4-(5-(2-hydroxypropyl)-1H-.bazol-1-yl)benzonitrile (1.18 g) in acetic acid (10 ml) After dropping &gt; odor (0.40 ml) at room temperature, it was allowed to stand at room temperature for 1 minute. Add 1% aqueous sodium thiosulfate solution (20 ml) to the reaction mixture and drop 3 〇 323256 291 201206906 minutes at room temperature. The reaction mixture was diluted with ethyl acetate (150 ml), and evaporated. The residue was purified by silica gel column chromatography (solvent solvent hexane / ethyl acetate) to give 4-(4-di--5-(2-propylpropyl)-111-〇 〇 - - 1-based) benzoquinone guess (1.41 舀). j-NMRCSOOMHz, CDC13, (5 ppm):

1.19(d,3H,J=6. 0Hz), 2.84(d,2H,J=6. 6Hz), 4.17(sextet, 1H, J=6. 6Hz), 7. 64(s 1H), 7.72 (s, 4H). The following compounds were synthesized and treated in the same manner as in the method described in Reference Example 7 using the corresponding starting compound (Reference Example 50).

Reference Example 50: 4-(4-Bromo-5-(2-o-oxypropyl)-1Η-«bazol-1-yl)benzonitrile

j-NMRCSOOMHz, CDC13, (5 ppm): 2. 25(s, 3H), 3. 85(s, 2H), 7. 53(d, 2H, J=8. 7Hz), 7. 71(s, 1H), 7. 76 (d, 2H, J = 9. 0 Hz). The following compounds were synthesized and treated in the same manner as in the method described in Reference Example 47 using the corresponding starting compound (Reference Example 51). .

292 323256 201206906

-1-yl)benzonitrile W-NMRQOOMHz, CDC13,5 ppm): 2. 25(s, 3H), 6. 29(s, 1H), 6. 64(s, 1H), 7. 52(d , 2H, J=8.

Hz), 7.67 (d, 2H, J = 8.4 Hz), 7.73 (s, 1H). Examples 109 to 120 Example 109: 4-(4-(3-isopropyl-6-fluorenyl-2-) Sideoxy-1 fluoroindolyl)-1,2,3,4-tetrahydropyrimidin-5-yl 2, *-triazol-3-yl) carbonitrile

4-(4-(3-Oxyl-1-butene-2-yl)-4H-1,2,4-triazol-3-yl)benzonitrile (3.0 g) obtained in Reference Example 47 And 1_isopropyl-3-(3-(trifluoromethyl)phenyl)urea (6.20 g) obtained in Reference Example 37 was suspended in propionitrile (150 ml), and titanium tetrachloride was added ( 5小时。 1M: chloromethane solution, 25.2ml), stirred under heating and reflux for 8.5 hours. After cooling to room temperature, saturated sodium bicarbonate water was added to the reaction mixture, and the solid was filtered through Celite. Ethyl acetate was added to the filtrate to extract (15 mL), and the organic layer was washed with EtOAc. The residue was purified by silica gel column chromatography (eluent solvent ethyl acetate / methanol), and then purified by silica gel column chromatography (solvent solvent chloroform/methanol) to obtain a solid; In the ester (2〇mi), hexane ("丨") was added for crystallization, 293 323256 201206906 to give 4-(4-(3-isopropyl-6-methyl-2- oxo-1-(3) -(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4Η-1,2,4-triazol-3-yl)benzonitrile (2. 09g Li R (400MHz, DMSO-de, &lt;5 ppm): 0. 96(brs, 3H), 1. 07(brs, 3H), 1. 15(s, 3H), 3. 94(brs, 1H), 4. 10(brs, 1H), 4. 44(q, 1H, J=6. 8Hz), 7. 58(d, 1H, J=7. 8Hz), 7. 62(s, 1H) , 7. 66(t, 1H, J=7. 8Hz), 7. 74(d, 1H, J=7. 8Hz), 8. 06(s, 4H), 8.83(s, 1H). The starting compound was reacted and treated in the same manner as in the method described in Example 109, and the following compounds (Examples 110 to 120) were synthesized.

Example 110: (R) 4-(4-(3-(l-pyridyl-2-yl)-6-methyl-2_ oxo-l-(3-(trifluoromethyl)) Phenyl)-1,2,3,4-tetrahydro σ-Bist-5-yl)-4Η-1,2,4-triazol-3-yl)benzoquinone^-NMRCSOOMHz * CDCI3 » S ppm) · 1.18-1. 30(m, 6H), 1. 93(brs, 1H), 3. 44-3. 80(m, 3H), 4.11 (brs, 1H), 4. 51(brs, 1H), 7. 36(d, 1H, J=8. 1Hz), 7. 43(s, 1H), 7. 51(t, 1H, ]=7. 5Hz), 7. 60(d, 1H, J=7 . 9Hz), 7. 76-7. 80 (m, 2H), 8. 03(d, 2H, J=8. 6Hz), 8. 19(s, 1H). 294 323256 201206906

Example 111: 4-(4-(6-Mercapto-2-yloxy-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropainidine- 5-yl)-4H-1,2,4-trisyl-3-yl-3-phenylhydrazide j-NMRMOOMHz, DMSO-de, ά ppm):

1. 06(s, 3H), 3. 30(brs, 1H), 4. 08(brs, 1H), 4. 14(brs, 1H), 7. 54(d, 1H, J=7. 8Hz) , 7. 57(s, 1H), 7. 65(t, 1H, J=7. 8Hz), 7. 73(d, 1H, J=7. 8Hz), 8. 05-8. 09(s, 4H), 8. 84(s, 1H).

φ Example 112: 4-(4-(6-Methyl-2-oxo-l-l-tolyl-1,2,3,4-tetranitroxanth-5-yl)-4Η-1 , 2, 4-tris-based) Benzene 1H-NMR (400 MHz &gt; CDCh &gt;&lt; 5 ppm): 1. 36 (s, 3H), 2. 39 (s, 3H), 4. 13 (brs, 1H), 4. 28(brs, 1H), 5. 14(s, 1H), 6. 99(s, 1H), 7. 01(d, 1H, J=7. 7Hz), 7. 22(d, 1H, J = 7. 7Hz), 7. 34(t, 1H, J=7. 7Hz), 7. 86(d, 2H, J=8. 4Hz), 8. l〇(d, 2H, J=8.4Hz), 8. 28(s, 1H). 295 323256 201206906

Example 113: 4-(4-(3-Ethyl-6-methyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetra Hydropyrimidin-5-yl)-411-1,2,4-triazol-3-yl)benzonitrile R (400MHz, CDC13, (5 ppm): 1. 05 (ΐ, 3Η, ]=1. 1Hz), 1. 08(s, 3H), 3. 30(q, 2H, J=7. 1Hz), 4. 14(brs, 1H), 4. 24(brs, 1H), 7. 56(d , 1H, J=7. 8Hz), 7. 58 (s, 1H), 7. 66(t, 1H, J=7. 8Hz), 7. 73(d, 1H, J=7. 8Hz), 8 04-8. 09(m, 4H), 8. 86(s, 1H).

Example 114: 4-(4-(3-isopropyl-6-mercapto-2-oxo-l-m-tolyl-1,2,3,4-tetrahydropain-5-yl) -4Η-1, 2, 4-tridec-3-yl)benzonitrile 1H-NMR (400MHz » CDCh &gt; δ ppm): 0. 96-1. 20(m, 6H), 1. 13(s , 3H), 2. 30(s, 3H), 3. 92(brs, 1H) , 4. 08(brs, 1H), 4. 44(q, 1H, J=6. 8Hz), 7. 00( d, 2H, ]=1. 8Hz ), 7. 16(d, 1H, ]=1. 8Hz), 7. 28(dt, 1H, J=3. 0, 7. 8Hz), 8. 02 (dd , 2H, J=l. 9, 6. 7Hz), 8. 09(dd, 2H, J=l. 9, 6. 7Hz), 8. 83(s 296 323256 201206906

Example 115: 4-(4-(3-Isobutyl-6-methyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2,3, 4- Tetrahydropyrimidin-5-yl)-4Η-1,2,4-triazol-3-yl)benzonitrile R (400MHz, DMS0-d6, (5 ppm): 0. 81(d, 6H, J =6. 6Hz), 1. 15(s, 3H), 1. 80(sept, 1H, J=6. 9Hz ), 3. 02-3. 08(ra, 2H), 4. 00(brs, 1H ), 4. 20(brs, 1H), 7. 56(d ,1H, J=8. 1Hz), 7. 60(s, 1H), 7. 67(t, 1H, ]=T. 8Hz), 7. 74(d, 1H, J=7. 8Hz), 8. 05(s, 4H), 8. 83(s, 1H).

Example 116: 4-(4-(6-ethyl-3-methyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2,3, 4-tetra Hydropyrimidin-5-yl)-4Η-1, 2,4-triazol-3-yl)benzonitrile\j-NMRUOOMHz, DMS0-d6, 5 ppm): 0. 63(t, 3H, J=7 5Hz), 1. 78(q, 2H, J=7. 5Hz), 2. 98(s, 3H), 4. 00(d, 1H, J=14. 3Hz), 4. 20(d, 1H , J=14. 4Hz), 7. 46-7. 53( m, 2H), 7. 60(t, 1H, J=7. 8Hz), 7. 67(d, 1H, J=7. 9Hz) , 7. 88(d 297 323256 201206906 d, 2H, J=l. 8, 6. 8Hz), 8. 13(dd, 2H, J=l. 8, 6. 8Hz), 8. 39(s, 1 H).

Example 117: 4-(4-(3,6-Diethyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydrol] σ定-5-yl)-4Η-1, 2, 4-tridec-3-yl) benzoquinonitrile 1H-NMR (400MHz 5 CDCh &gt; δ ppm): 0. 62(t, 3H, J=7 5Hz), 1. 15(t, 3H, J=7. 2Hz), 1. 79(q, 2H, J= 7. 4Hz), 3. 43(q, 2H, J=7. 2Hz), 3 94(d, 1H, J=14.7 Hz), 4. 23 (d, 1H, J=14. 3Hz), 7. 49-7. 54(m, 2H), 7. 59(t, 1H, J=7. 8Hz ), 7. 66(d, 1H, J=7. 8Hz), 7. 86(dd, 2H, J=l. 6, 8. 3Hz), 8. 14( dd, 2H, J =1.9,6. 7Hz), 8. 36(s, 1H).

Example 118: 4-(4-(1-(3-(Trifluoromethyl)phenyl)- 3,6-dimethyl-2-oxooxy-1,2,3,4-tetrahydro Bite base) -4Η-1,2,4-tris(β)-3-yl)benzonitrile; Η-ΝΜΡ (400ΜΗζ » DMSO-de ? δ ppm) · 1. 05(s, 3H), 2. 85 (s, 3H), 4. 19(brs, 1H), 4. 21(brs, 1H), 323256 298 201206906 7. 05(t, 1H, J=55. 7Hz), 7. 37-7. 40( m, 2H), 7. 54-7. 57(m, 2H), 8.05(s, 4H), 8.86(s, 1H).

LT N Me

Example 119: 4-(4-Bromo-5-(3-isopropyl-6-methyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2, 3,4-tetrahydropyrimidin-5-yl)-1 fluoren-1-ylbenzonitrile 1H-NMR (400 MHz &gt; CDCh &lt;&lt; 5 ppm): 0. 88 (d, 3H, J =6. 9Hz), 1. ll(d, 3H, J=6. 6Hz), 1. 36(s, 3H), 3. 55(d,1H,J=14· 1Hz), 3. 98(d , 1H, J=12. 6Hz), 4. 61(quin, 1H, J=6. 9Hz), 7. 42(d, 1H, ]=1. 5Hz), 7. 47(s, 1H), 7 53(t, 1 H, J=7. 5Hz), 7. 59(d,1H, J=7. 5Hz), 7.74(s, 1H), 7.78(d,4H φ ,J= 3.3Hz)

Example 120: 4-(5-(3-Isopropyl-6-mercapto-2-oxoyl-1-(3-(trifluoromethyl)phenyl)-1,2,3, 4- Tetrahydropyrimidin-5-yl)-1Η-oxazol-1-yl)benzonitrile 299 323256 201206906 1H-NMR (400MHz ^ CDCh &gt; (5 ppm): 0. 99(d, 6H, J=6. 9Hz), 1. 36(s, 3H), 3. 77(s, 2H), 4. 59(quin ,1H, J=6. 9Hz), 6. 38(d, 1H, J=l. 8Hz) , 7. 33-7. 44(m, 2H), 7. 51(t, 1H, J=7. 8Hz), 7. 58(d, 1H, J=7. 8Hz), 7. 72(d, 1H, J = 1.5 Hz), 7.77 (s, 4H). Examples 121 to 127 Example 121. 5_(3_(4~V-phenyl)-411-1, 2,4_3° all-4- -N,4-dimethyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-2, 3-•dipyrimidine-K6H)-carboxamide

4-(4-(6-Methyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine) obtained in Example 111 -5-yl)-4Η-1,2,4-φ triazol-3-yl)benzonitrile (178 mg) was suspended in THF (7mi), and sodium hydride (55% in mineral oil) was added at 〇 °c , 20 mg) was stirred for 30 minutes. To the reaction mixture was added phenylamine decanoate and stirred for 30 minutes. 20% citric acid water and saturated brine were added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 ml×2). The organic layer was dried over anhydrous magnesium The residue was purified by column chromatography (eluent solvent ethyl acetate / methanol). The obtained solid was dissolved in ethyl acetate (1.5 ml), and hexane (3mi) was added to carry out crystallization to give 5-(3-(4-cyanophenyl 2, 4-triazin-4-yl)- N,4-dimercapto-2-oxo-3-(3-(difluoromethyl)phenyl)_2,3-dihydropyrimidin-1 (cation)-3 〇〇323256 201206906 guanamine 164mg). lH-NMR (400MHz » CDCla » d ppm): 1. 35(t, 3H, J=l. 5Hz), 2. 88(d, 3H, J=4. 4Hz), 4. 65(brs , 2H), 7.42 (d, 1H, J=7. 8Hz), 7. 50(s, 1H), 7. 65(t, 1H, J=7. 8Hz), 7. 74(d, 1H , J=7. 8Hz), 7. 84(dd, 2H, J=l. 6. 7Hz), 7. 95(dd , 2H, Jl. 9, 6. 7Hz), 8. 30(s, 1H) 8. 57 (d, J = 4 4 Hz) Using the corresponding starting compound, the following compounds were synthesized and treated in the same manner as in the method of Example 121 (Examples 122 to 127).

NC

Example 122: 5-(3-(4-Cyanophenyl^, hydrazine, 2,4-triazole-4-yl)-N,4-didecyl-2-oxo-3-ylidene Stupid 乂3_diazepine pyridine φ-1(6H)-guanamine 'i-NMRMOOMHz, CDC13, &lt;5 ppm): 1. 35(s,3H), 2. 41(s,3H) , 2.86 (d, 3H, h4. 5Hz), 4. 62 (brs, 2H), 6. ^, 1Η, Ι--7.7Ηζ), 7.01 (3,1Ηχ 7 26(ά&gt;1Η)Ι_. 7&gt;Ί Hz), 7. 37(t, 1H, J=7. 7Hz), 7. 83(d, 2H, j,8 3Ηζχ 7 96(d>, H, J=8.3Hz), 8.32 (brs , lH), 8.69 (d, lH, j = 4.5 Hz). 323256 301 201206906

Example 123: 5-(3-(4-Cyanophenyl)-4H-i,2,4-triazol-4-yl)-N-(2-methoxyethyl)-4-methyl- 2-Phenoxy-3-indolylphenyl-2,3-dihydropyrimidin-1(6H)-carboxamide 1H~NMR (400MHz » DMS〇-d6 » d ppm)

1. ll(s, 3H), 2. 33(s, 3H), 3. 23(s, 3H), 3. 30-3. 34(m, 2H), 3. 37-3. 41(m, (2), 4. 34(t, 1Ή, J=8. 0Hz), 8. OKs, 4H), 8. 81(t, 1H, J=5. 3Hz), 8. 88(s, 1H).

Example 124: 5-(3-(4-Cyanophenyl)-4H-l, 2,4-triazol-4-yl)-4-methyl-2-oxo-N-(pyridine- 2-ylindenyl)-3-indolylphenyl-2,3-dihydropyrimidine-K6H)-carboxamide-Li R (400MHz, DMS0-d6, 6 ppm): 1. ll(s, 3H) , 2. 34(s, 3H), 4. 49(d, 2H, J=4. 5Hz), 4. 50(brs, 1H), 4. 62(brs, 1H), 7. 11-7. 14 (m, 2H), 7. 18-7. 25(ra, 2H), 7. 33-7. 36(m, 2H), 7. 74-7. 77(m, 1H), 8. 00-8 06(m, 4H), 8. 49-8. 52(m, 1H), 8. 89(s, 1H), 9. 40(t, 1H, J=5. 4Hz). 302 323256 201206906

NC

Example 125: 5-(3-(4-Cyanophenyl)-411-1,2,4-tris(yt-4-yl)-4-indolyl-2-yloxy-N-( Acridine-3-ylindenyl)-3-m-phenylphenyl-2,3-dihydropyrimidine-U6H)-carboxamide 4-Li (400 MHz, DMSO-de, 6 ppm):

1. 09(s, 3H), 2. 32(s, 3H), 4. 38(d, 2H, J=3. 8Hz), 4. 51(brs, 1H), 4. 59(brs, 1H) , 7. 08-7. 11 (in, 2H), 7. 18-7. 23(m, 1H), 7. 31-7. 36(m, 2H), 7. 64-7. 70(m, (H), 8. 1H), 9. 17

(t, 1H, J=5. 4Hz).

Example 126: 5-(3-(4-Cyanophenyl)-4H-l,2,4-triazol-4-yl)-4-methyl-2-oxo-N-0-pyridinium -4-ylmethyl)-3-m-decylphenyl-2,3-dihydropyrimidine-l(6H)-decylamine!Η-ΝΜΡ(400ΜΗζ » DMSO-de » δ ppm): 1. l〇 (s, 3H), 2. 33(s, 3H), 4. 39(brs, 2H), 4. 51(brs, 1H), 4. 59(brs, 1H), 7. 10-7. 12( m, 2H), 7. 22(d, 1H, J=7. 7Hz), 7. 27(d, 2H, J=6. 0Hz), 7. 34(dd, 1H, J=7. 9, 8 . 1Hz), 8. 00- 303 323256 201206906 8. 06(m, 4H), 8. 50(dd, 2H, J=l. 6, 4. 4Hz), 8. 89(s, 1H), 9. 17 (t, 1H, J=6. 1Hz).

Example 127: 5-(3-(4-Cyanophenyl)-4H-l, 2,4-triazol-4-yl)-N-ethyl- 4-indolyl-2-yloxy-3 -(3-(Trifluoromethyl)phenyl)-2, 3-# Dihydropyrimidin-1(6H)-decylamine 1H-NMR (400MHz » DMS0~d6 » δ ppm) · 1. 〇5( t, 3H, J=7. 1Hz), 1. 10(s, 3H), 3. 14-3. 21(m, 2H), 4. 51 (brs, 1H), 4. 59(brs, 1H) , 7. 65-7. 74(m, 2H), 7. 77(s, 1H), 7. 79(d,1H,J=7· 7Hz), 7. 99(dd, 2H, J=l. 8, 6. 6 Hz), 8. 06 (dd , 2H, J = 1. 9, 6. 7 Hz), 8. 62 (t, 1H, J = 5. 5 Hz), 8. 90 (s, 1H). Reference Examples 51 to 54 The amine phthalate systems used in Examples 122 to 126 were combined in the following manner.

Reference Example 51 To a solution of phenyl chlorodecanoate (0. 87 ml) in THF (10 ml), diisopropylethylamine (2. 59 ml) and 2-methoxyethylamine were added and stirred. 2 hours. Water was added to the reaction mixture to extract with ethyl acetate (50 ml x 2). The organic layer was dried over anhydrous magnesium sulfate and evaporated. The residue was purified by chromatography on EtOAc EtOAc EtOAc. W-NMRUOOMHz, CDC13, (5 ppm): 3. 40 (s, 3H), 3. 44-3. 48 (m, 2H), 3. 53 (t, 2H, J = 4. 6Hz), 5. 42 (brs, 1H), 7. 11-7. 15(m, 2H), 7. 20(dd, 1H, J=7. 4, 7. 8Hz), 7. 33-7. 38(m, 2H The following compounds were synthesized and treated in the same manner as in the method described in Reference Example 51 using the corresponding starting compounds (Reference Examples 52 to 54).

Cr Reference Example 52: Pyridin-2-ylmercaptoamine phenyl phthalate R (400 MHz, CDC13, &lt; 5 ppm): 4. 60 (d, 2H, J = 5. 3 Hz), 6. 33 (brs , 1H), 7. 14-7. 27(m, 4H), 7. 33 -7. 39(m, 3H), 7. 68-7. 72(m, 1H), 8. 59(d, 1H , J=4. 4Hz).

LX) Reference Example 53: Phenyl-3-ylmethylamine decanoate, H-NMR (400 MHz &gt; CDCh &gt; 5 ppm): 4. 48 (d, 2H, J = 6. 1 Hz), 5. 59(brs, 1H), 7. 13(d, 2H, J=7. 7Hz), 7. 21(ΐ, 1H, J=7. 4Hz), 7. 30-7. 39(m, 3H), 7. 74(d, 1H, J-7. 7Hz), 8. 57(d, 1H, J=4.11Hz), 8. 63(s, 1H).

305 323256 201206906 Reference Example 54: Pyridine-4-yldecylamine decanoic acid phenyl ester 1H_NMR (400MHz * CDCI3 » S ppm) ^ 4. 47(s, 2H), 5. 69(brs, 1H), 7. 15 (d, 2H, J=8. 1Hz), 7. 22(t, 1H, J=7. 4Hz), 7. 26-7. 29(m, 2H), 7. 27(dd, 2H, J= 7. 3, 7. 4 Hz ), 8.59 (s, 2H). Examples 128 to 134 Example 128: 4-[4-(6-(bromomethyl)-3-isopropyl-2- side Oxy-l-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine-5-yl)-4Η-1, 2, 4-heap three-spot -yl]benzonitrile. Example 129: 4-[4-(6-(Dibromomethyl)-3-isopropyl-2-oxo-l-(3-(trifluoromethyl)phenyl) )-1,2,3,4-tetrahydropyrimidine-5-yl)-4Η-1,2,4-triazole-3-yl]benzonitrile

4-[4-(3-Isopropyl-6-mercapto-2-oxo-l-(3-(trifluoromethyl)phenyl)-indole, obtained in Example 109, 2, Add bromine to a solution of 3, 4-tetrahydropyrimidin-5-yl)-4H-1,2,4-tris-3-yl]benzonitrile (loo. 0 mg) in acetic acid (2. 〇ml) 0小时。 0. 32ml: 1N chloroform solution), stirred at room temperature for 1.5 hours. After adding 1% by weight aqueous sodium thiosulfate solution (1 ml), the mixture was extracted with ethyl acetate (10 ml×2×). The organic layer was washed with brine (1 mL) and dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (solvent solvent hexane / ethyl acetate) to afford 306 323256 201206906 4-[4-(6-(bromomethyl)-3-isopropyl-2- side Oxy-i_(3_(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4H-1,2,4-tris-3-yl]benzamide Nitrile (87·5 mg, Example 128) and 4-[4-(6-(dimomethyl)-3-isopropyl-2-oxo-l-(3-(trifluoromethyl)benzene) ), 2, 3, 4-tetrahydropyrimidin-5-yl)-4Η-1,2,4-triazol-3-yl]benzonitrile (2.4 mg, Example 129). ^-NMRCCDCla: 300MHz) (5: Example 128: 〇·86 (d, 3H, J=6.2 Hz), 1. 05 (d, 3H, J=5·9Hz), 3. 39 (brs, 1H) , 3. 49 (brs, 1H), 3. 64 (d, 1H, J=15. 6Hz), 4. 01(d, 1H, J=15. 5 Hz), 4. 52-4. 61 (ra, 1H), 7. 52-7. 64(m, 4H), 7. 77-7. 80(ra, 2H ), 8. 05-8. 07(m, 2H), 8. 29(s , 1H). Example 129: 〇. 78(d, 3H, J=6. 6Hz), 1. 〇2(d, 3H, J=6. 8Hz), 3. 58(d, 1H, J= 15 2Hz), 4. 00(d, 1H, J=15. 2Hz), 4. 42-4. 51(m, 1H), 5. 77(s φ , 1H), 7. 60(d, 1H, J=7. 2Hz), 7. 68(s, 1H), 7. 71-7. 78(m, 2H), 7. 77-7. 81(m, 2H), 8. 04-8. 07( m, 2H), 8. 52 (s, 1H). Example 130: 4-[4-(6-((didecylamino)methyl)-3-isopropyl-2-yloxy- 1-(3-(Trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine-5-yl)-4Η-1,2,4-triazol-3-yl]phenylhydrazine Nitrile

307 323256 201206906 4-[4-(6-(Bromoindolyl)-3-isopropyl-2-yloxy-1-(3-(trifluoromethyl)phenyl) obtained in Example 128 X,2,3,4_tetrahydropyrimidin-5-yl)-4Η-1,2,4-triazol-3-yl]benzonitrile (1 〇. 〇) acetonitrile (2.0 ml) solution The mixture was stirred for 4 hours at 80 ° C. The reaction mixture was concentrated under reduced pressure. The residue was purified by reverse phase column chromatography (solvent solvent TFA water / Purification of acetonitrile to give 4-[4-(6-((dimethylamino)methyl))-3-isopropyl-2-oxaxyloxy 1-(3-(difluoroindolyl)phenyl) -1,2,3,4-tetrahydrobine-bend-5-yl)-411-1,2,4-disial-3-yl]benzonitrile (5.8 mg). R (CDC13: 300 MHz) 6 : 1. 13(brs, 6H), 1. 68(s, 6H), 2. 38(s, 2H), 3. 93(brs, 1H), 4. 06(brs, 1H), 4. 64 -4. 73(m, 1H), 7. 41(d, 1H, J=8. 1Hz), 47-7. 52(m, 2H), 7. 59(d, 1H, J=7. 9Hz) , 7. 82(d, 2H, J=8. 3 Hz), 8. ll(d, 2H, J=8. 3Hz), 8.21(s, 1H). The corresponding raw material compound is used and described in the implementation. Example 丨3〇之方# The same reaction and treatment, the following compounds were synthesized. (Example 131). Example 131: 4-[4-(6-((Ethylamino)indolyl)- 3-isopropyl-one-tertiaryyl-1-(3-(difluoroindole) Base)), 1,2,3,4-tetrahydrogenate bite 5-yl)-4H-1,2,4-triazol-3-yl]benzonitrile

'H-NMRCCDCh: 300MHz) (5: 308 323256 201206906 0. 68(t, 3H, J=7. 1Hz), 0. 99(brs, 6H), 2. 03(q, 2H, J=6. 5Hz ), 2. 82(s, 2H), 3. 76(brs, 1H), 3. 99(brs, 1H), 4. 58-4. 67(m, 1H), 7. 53-7. 58( m, 2H), 7. 61(s, 1H), 7. 65(d, 1H, J=7. 0Hz), 7. 81(d, 2H, J=8. 3Hz), 8. 13(d, 2H, J=8. 4Hz), 8. 35(s, 1H). Example 132: 4-[4-(3-isopropyl-6-(methoxyindolyl)-2-yloxy- 1-(3-(Trifluoromethyl)phenyl)-1,2,3,4-tetradecyl-5-mercapto-5-yl)-4H-1,2,4-triazol-3-yl]benzene Nitrile

4-[4-(6-(Bromoindolyl)-3-isopropyl-2-oxo-l-(3-(trifluorodecyl)phenyl)-1 obtained in Example 128 , 2, 3, 4-tetrahydropyrimidine-5-yl]-4H-1,2,4-triazol-3-yl]benzonitrile (120. Omg) in tetrahydrofuran (5.0 ml), Add sodium decoxide (〇. 〇 96 ml: 28% 曱• alcohol solution) under ice cooling for 3 hours. Add a saturated aqueous solution of ammonium chloride (20 ml) and then extract with ethyl acetate (2 〇ml×2 times) The organic layer was washed with saturated brine (20 ml), dried over anhydrous magnesium sulfate and evaporated. [4-(3-Isopropyl-6-(decyloxyindenyl)-2-yloxy-1-(3-(trifluoromethyl)phenyl)-indole, 2, 3, 4-tetra Hydropyrimidin-5-yl)-4Η-1,2,4-triazol-3-yl]benzonitrile (22. Omg). ^-NMRCCDCh: 300MHz) (5: 〇. 75-1. 〇5( m, 6H), 2. 75(s, 3H), 3. 35(s, 2H), 3. 62(brs, 1H) 309 323256 201206906 , 3. 90(brs, 1H), 4. 50-4. 59(m, 1H), 7. 51-7. 56(m, 2H), 7. 59 -7. 62(m, 2H), 7. 76-7. 79(m, 2H), 8. 03- 8. 06(m, 2H), 8. 25(s , 1H). Example 133: Acetic acid (5-(3-(4-cyanophenyl 2, 4-tris)-4-yl)-1-isopropyl-2-oxooxy-3 -( 3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidin-4-yl)decyl ester

4-[4-(6-(Bromoindolyl)-3-isopropyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1 obtained in Example 128 , 2, 3, 4-tetrahydropyrimidine-5-yl)_4H-1,2,4-triazol-3-yl]benzonitrile (9. 〇mg) in acetonitrile (2.0 ml), Potassium acetate (4.9 mg) was added and the mixture was stirred at 80 Torr for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dissolved φ reagent system, tri-gas methane/methanol) to give acetic acid (5-(3-(4-cyanophenyl)-4H-1,2, 4- Triazol-4-yl)-1-isopropyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidin-4-yl Methyl ester (7.8 mg). ^-NMRCCDCh: 300MHz) (5: 0. 90 (brs, 3H), 1. 07 (brs, 3H), 1.72 (s, 3H), 3. 73 (brs, 1H), 4. 00-4 20(m, 3H), 4. 56-4. 63(m, 1H), 7. 44(d, 1H, J=8. 1Hz), 7. 52(d, 2H, J=7. 6Hz) , 7. 60(d, 1H, J=8. 6Hz), 7. 78-7. 81(m ,2H), 8. 01-8. 34(m, 2H), 8. 21(s, 1H) Example 134: 4-[4-(6-(hydroxyindenyl)- 3-isopropyl-2-oxo-oxo 310 323256 201206906 base_1-(3-(trifluoromethyl)phenyl)-1, 2, 3, 4-tetrazepine-5-yl)_4H_ 1'2,4 di-β--3-yl]benzonitrile

Acetic acid (5-(3-(4-cyanophenyl)-4-pyran-1,2'4-oxadiazol-4-yl)-1-isopropyl- 2_ side obtained in Example 33 Oxygen (3_(3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidin-4-yl) decyl ester (7· 〇mg) in ethanol (1.0 ml) solution 1N aqueous sodium hydroxide solution (〇.θα&quot;) was added under ice cooling, and stirred at room temperature for 30 minutes. After 1N hydrochloric acid (0. 027 ml) was added and the mixture was evaporated. The residue was purified by column chromatography on EtOAc (EtOAc/EtOAc) eluting Fluorinyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl 2,4-triazol-3-yl]benzonitrile (3.7 mg) 〇!H-Li R (CDCh: 300MHz) 5 : 0. 65-1. 00(m, 6H), 3. 15(brs, 1H), 3. 57-3. 90(m, 4H), 4. 47-4. 57(ra, 1H ), 7. 53-7. 61(m, 4H), 7. 73(d, 2H, J=8. 3Hz), 7. 99 (d, 2H, J=8. 1Hz), 8. 17(s 1H). Examples 135 to 141 The following compounds (Examples 135 to 141) were synthesized by the same reaction and treatment as in the method described in Example 47 using the corresponding starting compound. 311 323256 201206906

Example 135: N-((1H-Tesal-5-yl)methyl)-5-(4'-cyanobiphenyl-2-yl)-4-indolyl-2-oxo-3- (3-(Trifluoromethyl)phenyl)-2,3-dihydro &quot; dense-1 (6Ή)-nonylamine ^-NMRCCDCh : 300MHz) 5 : • 1. 20(s, 3H) , 4. 16(d, 1H, J=15. 4Hz), 4. 66-4. 72(m, 3H), 7. 32-7. 39(m, 3H), 7. 41-7. 47( m, 5H), 7. 54(t, 1H, J=7. 6Hz), 7.63(d, 1H, J=7. 7Hz), 7. 71-7. 74(m, 2H), 9. 38(t, 1H, J= 5. 3Hz).

-N-(3-(3-Sideoxypiped-i-yl)propyl)-3_(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidine-i(6H)-曱醯amine 'H-NMR CCDCh : 300 ΜΗζ) δ : 1. 15(s, 3H), 1. 68(t, 2H, J=6. 8Hz), 2. 44(t, 2H, J=6. 8Hz) , 2. 59(t, 2H, J=5. 4Hz), 3. 07(s, 2H), 3. 23-3. 30(m, 4H), 4. 14 (d, 1H, J=15. 8Hz), 4. 55(d, 1H, J=16. 1Hz), 5. 90(s, 1H), 7. 24 (d, 1H, J=8.1Hz), 7. 29-7. 31(m , 3H), 7. 36-7. 40(m, 4H), 7. 49 312 323256 201206906 (t, 1H, J=7. 7Hz), 7·56(d, 1H, J=8. 1Hz), 7. 66 (d, 2H, J = 8 · 3Hz), 8. 77 (brs, 1H).

Example 137: 5-(4'-Cyanobiphenyl-2-yl)-N-(2,2-difluoroethyl)-4-methyl-2-oxo-3-(3-( Trifluoromethyl)phenyl)-2,3-dihydropyrimidine•-K6H)-nonylamine j-NMRCCDCh: 300MHz) 5 : 1. 21(s, 3H), 3. 53-3. 67(m , 2H), 4. 21(d, 1H, J=16. 1Hz), 4. 62 (d, 1H, J=16. 0Hz), 5. 65(t, 0. 25H, J=4. 0Hz) , 5. 84(t, 0. 5H, J = 4. 1Hz), 6. 03(t, 0. 25H, J=4.1 Hz), 7. 28-7. 37(m, 4H), 7. 41-7. 44(m, 4H), 7. 54(t, 1H, J=7. 7Hz), 7. 62(d, 1H, J=7.99Hz), 7. 71(d, 2H, J =7. 8Hz), 8. 97(t, 1H, J=6. 1Hz).

Example 138: 2-(5-(1-(4-Cyanophenyl)-lH-indazol-5-yl)-4-indolyl-2-oxo-3-(3-(trifluoro) Benzo)phenyl)-1,2,3,6-tetrahydropyrimidin-1-indoleamine) phenyl decyl acetate 1H-NMR (CDCl3: 300MHz) 5 : 1. 35(s, 3H), 3. 99(d, 2H, J=5. 7Hz), 4. 39(d, 2H, J=l. 5Hz), 313 323256 201206906 5. 15(s, 2H), 6. 36(d, 1H, J= l. 8Hz), 7. 28-7. 31(m, 4H), 7. 38 (d, 1H, ]=1. 7Hz), 7. 43(s, 1H), 7. 54(t, 1H, J=8. 0Hz), 7. 59-7. 75(ra, 7H), 8. 98(d, 1H, J=5. 6Hz).

Example 139: 4-(5-(1-(4-Cyanophenyl)-1 H-°bazol-5-yl)-4-methyl-2-yloxy-3-(3- (trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-1-carboxamide) butyrate butyrate j-NMIKCDCh: 300MHz) 5 : 1. 32(s, 3H) , 1. 36(s, 9H), 1. 68-1. 78(m, 2H), 2. 19(t, 2H, J= 7. 5Hz), 3. 21(q, 2H, J=7. 0Hz), 4. 40(d, 2H, J=l. 5Hz), 6. 37( d, 1H, ]=2. 0Hz), 7. 36(d, 1H, ]=1. 9Hz), 7. 41(s, 1H), 7. 54(t ,1H, ]=Ί. 9Hz), 7. 59-7. 63(m, 3H), 7. 68(d, 1H, J=l. 8Hz), ^ 7. 70-7. 75(m, 2H), 8· 62(t, 1H, J=5. 6Hz).

Example 140: N-((1H-tetrazol-5-yl)indolyl)-5-(1-(4-cyanophenyl)-1Η-pyrazole-5-yl)-4-indolyl- 2-Phenoxy-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidin-1(6H)-indoleamine R (CDCh: 300MHz) (5: 314 323256 201206906 1. 31(s, 3H), 4. 48(s, 2H), 4. 67(s, 2H), 6. 59(d, 1H, J=l. 8Hz ), 7. 56-7. 72( m, 4H), 7. 76-7. 79(m, 3H), 7. 87-7. 90(m, 2H).

Example 141: 5-(1-(4-Cyanophenyl)-lH-indazol-5-yl)-N,4-dimethyl-2-oxo-3-(3-(trifluoro) Mercapto)phenyl)-2,3-dihydropyrimidine #-1(6H)-nonylamine j-miRCCDCh: 300MHz) (5: 1. 31(t, 3H, J=l. 6Hz), 2. 77(d, 3H, J=4. 8Hz), 4. 42(d, 2H, J= 1. 7Hz), 6. 37(d, 1H, J=l. 8Hz), 7. 35(d, 1H , J=7. 9Hz), 7. 40( s, 1H), 7. 53(t, 1H, J=7. 8Hz), 7. 59-7. 63(m, 3H), 7. 68(d , 1H , J=l. 8Hz), 7. 69-7. 72(m, 2H), 8. 47(brs, 1H). Examples 142 to 148 Lu use the corresponding raw material compounds, and are described in the implementation The method of Example 23 was similarly reacted and treated to 'synthesize the following compounds (Examples 142 to 148).

Example 142 ··· 2-(5-(1-(4-Cyanophenyl)-indole~π-biazole-5-yl)-4-mercapto-2-oxo-3-(3-( Trifluoromethyl)phenyl&gt;2,3-dihydropyrimidine 315 323256 201206906 -1( 6H)-yl)propionic acid third butyl vinegar ^-NMRCCDCla : 3〇〇ΜΗζ)δ ' 1. 18-1. 24(m,6Η), 1.36(s,9Η), 3.87(dd,1Η,J=16. 8, 1. 5Hz ), 4. 03(dd, 1H, J=16. 8, 1 5Hz), 4. 82(q, 1H, J=7. 5Hz), 6. 35 (d, 1H, J=l. 8Hz), 7. 32(d, 1H, J=7. 7Hz), 7 36(s, 1H), 7. 46( t, 1H, J=7. 7Hz), 7. 53(d, 1H, J=7. 5Hz), 7. 67(d, 1H, J=l. 8Hz), 7. 70-7. 79(m, 4H).

Example 143: 2-(5-(1-(4-Cyanophenyl)-lH-°bazin-5-yl)-4-mercapto-2-yloxy-3-(3-(three Fluoromethyl)phenyl)-2,3-dihydropyrimidine-K6H)-yl)ethyl propionate 匪R (CDC13: 300MHz) (5:

1. 18(t, 3H, J=l. 1Hz), 1. 27(d, 3H, J=7. 5Hz), 3. 91(dd, 1H, J = 14.1, 1. 5Hz), 4 03(dd, 1H, J=14. 1, 1. 5Hz), 4. 09(q, 2H, J= 6. 2Hz), 4. 89(q, 1H, J=7. 5Hz), 6. 36(d, 1H, J=l. 8Hz), 7. 31( d, 1H, J=7. 9Hz), 7. 36(s, 1H), 7. 46(t, 1H, J=7. 8Hz ), 7. 53 (d , 1H, J = 8. 1 Hz), 7. 67 (d, 1H, J = 1.8 Hz), 7. 71-7. 79 (m, 4H).

316 323256 201206906 Example 144: 2-(5-(3-(4-Cyanophenyl)-4Η-1,2,4-triazol-4-yl)-4-indolyl-2-yloxy -3-(3-(Trifluoromethyl)phenyl)-2,3-dihydromethane 1:1 (611)-yl) propionate ethane-[H-NMRCCDCh: 300 ΜΗζ) 5 : 1. 18 -1. 41(m, 9H), 3. 91-4. 24(ra, 4H), 4. 93(brs, 1H), 7. 28-7. 40(m, 2H), 7. 50(t , 1H, J=7. 8Hz), 7. 59(d, 1H, J=7. 9Hz), 7. 80(d, 1H, J=8. 4Hz), 8. 00-8. 15(m, 2H), 8. 22(s, 1H).

Example 145: 2-(5-(3-(4-Cyanophenyl)-4H-l,2,4-tris-4-yl)-4-methyl-2-oxo-3- (3-(Trifluoromethyl)phenyl)-2,3-dihydropyrimidine-K6H)-yl)propanoxime ^-NMRCCDCh : 300MHz) 5 : 1. 14-1. 22(m, 6H), 3. 80-4. 22(m, 2H), 4. 90(d, 1H, J=7. 2Hz), 5.33(brs, 1H), 5. 94(brs, 1H), 7. 35- 7. 45(ra, 2H), 7. 53(t, 1H, J=7. 9Hz), 7. 62(d, 1H, J=7. 9Hz), 7. 77-7. 81(m, 2H ), 7. 9 8(d, 2H, J=7. 9Hz), 8. 20(s, 1H).

Example 146: 2-(5-(3-(4-cyanophenyl)-411-1,2,4-triterpene acetate 323256 317 201206906 -4-yl)-4-mercapto-2- side Oxy-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidin-1(6H)-yl)ethyl ester IH-NMR (CDC13: 300 ΜΗζ) δ : 1. 29 (s , 3H), 1. 92(s, 3H), 3. 54(brs, 2H), 4. 10-4. 30(m, 4H) , 7. 33(d, 1H, J=7. 9Hz), 7. 39(s, 1H), 7. 51(t, 1H, J=7. 9Hz), 7. 60(d, 1H, J=7.99Hz), 7. 80(d, 1H, J=8 . 3Hz), 8. 04(d, 1H, J= 8. 3Hz), 8. 23(s, 1H).

Example 147: 4-(4-(6-Mercapto-2-yloxy-3-(pyridin-2-ylindenyl)-1 -(3-(trifluoromethyl)phenyl)-1,2 , 3, 4-tetrahydropyrimidin-5yl)-4H-1,2,4-triazol-3-yl)benzonitrile^-NMRCCDCh : 300ΜΗζ) δ : 1. 30(t, 1H, J=l 5Hz), 4. 20(brs, 1H), 4. 35(brs, 1H), 4. 54( brs, 1H), 4. 70(brs, 1H), 7. 22-7. 26(m, 1H), 7. 32(d, 1H, J= 7. 7Hz), 7. 41(d, 1H, J=7. 7Hz), 7. 48(s, 1H), 7. 56(t, 1H, J= 7. 8Hz), 7. 62-7. 70(m, 2H), 7. 73-7. 76(ra, 2H), 8. 00-8. 03(m , 2H), 8. 21( s, 1H), 8. 46(d, 1H, J=4. 8Hz).

318 323256 201206906 Example 148: 4-(4-(3-(2-methoxyethyl)-6-mercapto-2-yloxy-1_(3-(trifluoromethyl)phenyl)- 1,2,3,4-tetrahydro σ 密 0 base) _4H-1, 2, 4-trimethyl-3-yl)benzonitrile ^-NMRCCDCh : 300MHz)d : 1. 22(s, 2H) , 1. 27(s, 1H), 2. 90(s, 1H), 3. 22(s, 2H), 3. 47-3. 57(ra, 4H), 4. 11-4. 28(m , 2H), 7. 33(d, 1H, J=7. 7Hz), 7. 40 (s, 1H), 7. 47-7. 52(m, 1H), 7. 56-7. 59(ra , 1H), 7. 76-7. 80(m , 2H), 7. 97-8. 02(ra, 2H), 8. 17(s, 0. 7H), 8. 19(s, 0. 3H • Examples 149 to 150 The following compounds (Examples 149 to 150) were synthesized by the same reaction and treatment as in the method described in Example 80 using the corresponding starting compound.

Example 149: 2-(5-(1-(4-Cyanophenyl)-indole-α than oxa-5-yl)-4-mercapto-2-yloxy-3-(3-(III) Fluoromethyl)phenyl)-2,3-dihydromethane bite-U6H)-yl)propionic acid W-NMRCCDaOD-.SOOMHz:^: 1. 89(s, 3H), 2. 06(d, 3H, J=7. 2Hz), 4. 86(s, 2H), 5. 41(q, 1H , J=7. 3Hz), 7. 41(d, 1H, J=l. 7Hz), 8. 29- 8. 33(m, 2H), 8. 43( d, 1H, J=7. 8Hz), 8. 51(d, 1H, J=7. 9Hz), 8. 65(d, 2H, J=8 6 Hz ), 8.82 (d, 2H, J = 7.7 Hz), 9. 12 (s, 1H). 319 323256 201206906

Example 150: 2-(5-(3-(4-Cyanophenyl)-4Η_1,2,4-triββ-4-yl)-4-yl-2-yloxy-3-(3) -(三败曱基)phenyl)-2,3-dihydrol. Ding-1(61〇-yl)propionic acid•H-NMRCDMSO-de : 300ΜΗζ)δ : • 1. 10-1. 22( m, 6H), 4. 07(brs, 1H), 4. 31(brs, 1H), 4. 63(brd ,1H, ]=1. 2Hz), 7. 50-7. 60(m, 2H) , 7. 67(t, 1H, J=7. 7Hz), 7. 74(d, 1H, J=7. 7Hz), 8. 02-8. 10(m, 4H), 8. 81(s, 1H). Example 151: 4-(5-(1-(4-Cyanophenyl)-lH-°bazol-5-yl)-4-mercapto-2-oxo-3-(3) -(Trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidine-1-decylamine)butyric acid

4-(5-(l-(4-Cyanophenyl)-lH-indazol-5-yl)-4-mercapto-2-yloxy-3-(3) obtained in Example 139 -(Trifluoromethyl)phenyl)-l,2,3,6-tetrahydropyrimidine-l-decylamine) Butane Butyrate (32.8 mg), TFA (1· 〇 added under ice cooling Ml), stir at room temperature for 丨 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on an amine hydrazine column (eluent solvent, methylene chloride / methanol) to give 4-(5-(1-(4-cyanophenyl) 323256 320 201206906 -1H-pyrazole -5-yl)-4-methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-1,2,3,6-tetrahydropyrimidin-1-indoleamine Butyric acid (27. 5 mg). W-NMR CCDs OD: 300 MHz) &lt;5: 1. 38(s, 3H), 1. 76-1. 86(m, 2H), 2. 33(t, 2H, J=7. 4Hz), 3. 26 (t, 2H, J=6. 8Hz), 4. 41(d, 2H, J=l. 5Hz), 6. 57(d, 1H, J=2. OH z), 7. 61(t, 1H , J=7. 7Hz), 7. 66-7. 74(m, 3H), 7. 76-7. 79(ra, 3H), 7.87-7. 91(m, 2H). Example 152 ® The corresponding raw material compound was reacted and treated in the same manner as in the method described in Example 134, and the following compound (Example 152) was synthesized.

Example 152: 4-(4-(3-(2-hydroxyethyl)-6-mercapto-2-yloxy-1-(3-(trifluoromethyl)phenyl)-1,2, 3,4-tetrahydropyrimidin-5yl)-4Η-1,2,4-triazol-3-yl)benzoquinone^-NMRCCDCh: 300MHz): 1.26(s, 3H), 2.38(brs, 1H ), 3.48 (d, 2H, J = 4. 9Hz), 3. 74-3. 80(m, 2H), 4. 13(brs, 1H), 4. 29(b rs, 1H), 7. 35 (d, 1H, J=7. 7Hz), 7. 41(s, 1H), 7. 51(t, 1H, J= 7. 9Hz), 7. 60(d, 1H, J=8. 1Hz) , 7. 79(d, 2H, J=8. 3Hz), 8. 00( d, 2H, J=8.3Hz), 8.21(s, 1H). Examples 153 to 154 321 323256 201206906 Using the corresponding raw material compound After reacting and treating in the same manner as in the method described in Example 85, the following compounds (Examples 153 to 154) were synthesized.

Example 153: N-(4-Amino-4-oxobutyl)-5-(1-(4-cyanophenyl)-1Η-pyrazole-5-yl)-4-indenyl- 2-Phenoxy-3-(3-(trifluoromethyl)phenyl)-2,3-dihydroβ-mercapto-1 (6H)-bristamine•H-NMRCCDCh : 300MHz)(5 : l 37(t, 3H, J=l. 5Hz), 1. 75-1. 84(m, 1H), 2. 20(t, 2H, J=7.2 Hz), 3. 25(q, 2H , J=6. 4Hz), 4. 37(d, 2H, J=l. 7Hz), 5. 31(brs,0. 6H), 5. 87(brs, 0. 5H), 6. 37(d , 1H, J=l. 8Hz), 7. 38(d, 1H , J=7. 9Hz), 7. 42(s, 1H), 7. 55(t, 1H, J=7. 8Hz), 7 60-7. 64( m, 3H), 7. 68(d, 1H, J=l. 8Hz), 7. 70-7. 73(m, 2H), 8. 68(t, 1H , J= 6. 1Hz).

Example 154: N-(2-Amino-2-oxoethoxyethyl)-5-(1-(4-cyanophenyl)-1Η-pyrazole-5-yl)-4-indolyl- 2-Phenoxy-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidine-i(6H)-carbamimid 322 323256 201206906 ^-NMRCCDCh : 300MHz) (5 : 1 39(s, 3H), 3. 85(d, 2H, J=5. THz), 4. 36(d, 2H, J=l. 3Hz), 5. 41(brs, 0. 8H), 5 76(brs, 0. 8H), 6. 37(d, 1H, J=l. 8Hz), 7. 40(d, 1H, J=8. 0Hz), 7. 44(s, 1H), 7 56(t, 1H, J=7. 7Hz), 7. 59-7. 62(m, 3H), 7. 68(d, 1H, J=l. 8Hz), 7. 71-7. 74( m, 2H), 8. 98 (t, 1H, J = 5. 4Hz).

Example 155: 1-(4-Cyanophenyl)-5-(3-isopropyl-6-mercapto-2-oxoyl-1-(3-(trifluoromethyl)phenyl)- 1,2,3,4-tetrahydropyrimidin-5-yl)-1Η-pyrazole-4-carboxylic acid

4-(4-Bromo-5-(3-isopropyl-indenyl-2-oxo-l-(3-(trifluoromethyl)phenyl)-1), obtained in Example 119, 2, 3, 4-tetrahydropyrifos-5-yl)_1H-pyrazol-1-yl)benzonitrile (40. 2 mg) in dioxane / water = 4 Λ (2 ml) solution, add four (three Phenylphosphine)palladium (85.3 mg) and N,N-diisopropylethylamine (13y 1) were stirred with heating under a stream of carbon monoxide at 100 ° C for 3 hours. The reaction mixture was diluted with EtOAc (EtOAc)EtOAc. The residue was purified by silica gel column chromatography (solvent solvent trichloromethane/methanol) to give 1-(4-cyanophenyl)-5-(3-isopropyl-6-indole 323 323256 201206906 Keto-2-yloxy-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1Η-αι^β坐-4- Rebel (16. img).丽R(CDC13: 300MHz) occupies: 0. 99(d, 3H, J=6. 6Hz), 1. 15(d, 3H, J=6. 6Hz), 1. 24(d, 3H, J= 7 2 Hz), 3. 65 (d, 1H, J = 13. 5 Hz), 4. 25 (d, 1H, J = 13.8 Hz), 4. 6 5 (quin, 1H, J = 7. 5 Hz), 7. 73-7. 84(m, 9H). Inhibition of human neutrophil elastase by Test Example 1 The following shows the results of pharmacological tests of representative compounds of the present invention, but the present invention is not limited thereto. These test cases. Analytical buffer (0. 4unit/ml HNE (human neutrophil elastic egg)

White enzyme, Elastin product Company, Inc.), 200 mM HEPES

[N-(2-hydroxyethyl) piperidine-Ν'-(2-ethanesulfonic acid)], PH 7. 5, 2M NaCl, 0. 002% Bri j-35) 100 # 1, water for injection 4〇vi DMSO (dimercaptoarthracene) solution of the compound of the present invention 2〇β 1 was mixed in a 96-well plate. The solution was preincubated at 37 C for 5 minutes to prevent it from becoming 〇. .5 mM MeOSuc-AAPV-AMC (Methoxy amber thiol-propylamine hydrazino-propylamine propyl- amidinoindolyl-amine thiol group) dissolved in 1% by mass of MSO. Aminomethyl coumarin (Sigma-Aldrich Corporation) solution 40# 1 was added to the above mixed solution to start the reaction at 37. (: Pre-incubation for 5 minutes, the fluorescence intensity of AMC was measured at an excitation wavelength of 380 nm and a fluorescence wavelength of 460 nm, and the inhibition ratio was determined. With respect to the example compounds, Table 18 shows that 5 〇% of human neutrophil elastase was inhibited. The concentration of the compound required is 1 (:50 value (#) or the inhibition rate (%) at 323256 324 201206906 10#M. [Table 18]

Table 1 8 Example I Cso value (μ or inhibition rate (3⁄4) Example I C&quot; value Μ) or inhibition rate 00 Example IC 5 〇 value (β Μ) or inhibition rate (%) 1 0.168 μ Μ 40 0.009 μ Μ 75 0.016/ιΜ 2 ΟΜΟμΜ 41 0,058 μ Μ 76 0.005 ΐλ Μ 3 9.660 β Μ 42 0.010 Μ Μ 77 0.029 μ Μ 4 6.940// Μ 43 0.094μ Μ 78 0.018/ζΜ 5 1.360/ζΜ 44 0.007# Μ 79 0.005 μ Μ 6 2.440 μ Μ 45 0.007 μ Μ 80 0.009 ju Μ 7 0.082 μ, Μ 46 0.013μ Μ 81 0.009 μ Μ 8 0.965^ Μ 47 0Μ8μΜ 82 0.173μ Μ 9 1.599^ Μ 48 0.013μ Μ 83 Ο.ΟΙΟμΜ 10 0.845 β Μ 49 0.207 μ Μ 84 0.012μ Μ 11 42% 50 2.900 β Μ 85 0.010/ζΜ 12 45% 51 0.538 μ, Μ 86 0.015μ Μ 13 0.747 μ Μ 52 0.069 μ Μ 87 0.015μ Μ 14 76% 53 0.027^ Μ 88 0.015/ζΜ 15 8.363 μ Μ 54 0.023 μ Μ 89 0.017^ Μ 16 5.189^ Μ 55 0·017μ Μ. 90 0.024 μ Μ 17 5.623 μ Μ 56 0.020 ju Μ 91 0.153/ζΜ 18 8.694 μ Μ 57 0.020 μ Μ 92 0.011 ju Μ 19 1.423 μ Μ 58 0.026 μ Μ 93 Ο.ΟΙΟΜΜ 20 0.449 μ Μ 59 0.035/ζ Μ 94 0.008 μ Μ 21 6.688 μ Μ 60 0.037 μ Μ 95 0.007 μ Μ 23 0.133μΜ 61 0.006 μ Μ 96 0.010^ Μ 24 0.653 ιχ Μ 62 Ο.ΟΙδμΜ 97 0.007 μ Μ 25 0·144μΜ 63 0.036^ Μ 98 0· 104μ Μ 26 0.466 μ Μ 64 0.038 μ Μ .99 0.186 μ Μ 27 0.099 μ Μ 65 0.023 μ Μ 100 0.036 μ Μ 28 0.565 μ. Μ 66 0.021 μ Μ 101 0.018μ Μ 29 0.168/ζΜ 67 0.083 μ Μ 102 0.008 μ Μ 30 0.121/i Μ 68 0.028^ Μ 103 0.004 α Μ 31 3.575^ Μ 69 0.016μ Μ 104 Ο.ΟΙΟμΜ 32 7.666 μ Μ 70 0.009 μ Μ 105 1.283 μ Μ 34 0.082 μ Μ 71 0.032 μ Μ 106 1.075 μ Μ 35 1.477 μ Μ 72 0.004 μ Μ 107 1.062 μ Μ 36 0.149μΜ 73 0.018 μ Μ 108 0·347μΜ 39 0.025 μ Μ 74 0.007 μ Μ Test Example 2 Inhibition of human neutrophil elastase 2 325 323256 201206906 Although the results of pharmacological tests of representative compounds of the present invention are shown below, the present invention is not limited to the test examples. Analytical buffer (0.4 unit/ml HNE (human neutrophil elastase' Elastin product Company, Inc.), 200 mM HEPES [Bu (2-hydroxyethyl) piped 4'-(2-ethanesulfonic acid) )]'1) 117.5, 40〇11^ NaCl '0.2mg BSA (bovine serum albumin)) 1〇〇 From 1, water for injection 4〇β, 1% DMS0 (dimercaptosulfoxide) solution of the compound of the invention 2〇v 1 is mixed in a 96-well plate. The mixed solution is pre-incubated at 37 ° C for 5 minutes. After pre-incubation, _ in order to make it 5 mM, it will dissolve in 〇. 5% DMS0 fluorescent matrix MeOSuc -A APV-AMC (曱 醯 醯 - - 丙 丙 丙 _ _ _ _ _ _ — — — — — — — — — — — — — 40 40 40 40 40 40 40 40 40 40 40 添加 添加 添加 添加In the mixed solution, the reaction was started to be pre-incubated at 37 Torr for 5 minutes, and the light intensity of the AMC was measured at an excitation wavelength of 380 nm and a fluorescence wavelength of 46 〇 nm to determine the inhibition rate. With respect to the compounds of the examples, Table 19 shows the IC^UM) which inhibits the concentration of the compound required for the use of 5% human neutrophil elastase. 323256 326 201206906 [Table 19]

Table 1 9

(Industrial Applicability) This compound is used as a therapeutic or preventive agent for diseases related to the disease. As diseases exhibiting elastase-related pathologies, for example, chronic obstructive pulmonary disease (c〇pD), pulmonary cystic fibrosis, emphysema, adult respiratory distress syndrome (ARDS), acute lung injury (ALI), Idiopathic pulmonary fibrosis (Πρ), chronic interstitial pneumonia, chronic bronchitis, chronic respiratory infection, diffuse panbronchiolitis, bronchitis 327 323256 201206906 tube dilatation, asthma, pancreatitis, nephritis, liver Failure, chronic rheumatoid arthritis, joint stiffness, osteoarthritis, psoriasis, periodontal disease, atherosclerosis, rejection of organ transplants, early water breaks, blisters, shock, sepsis, systemic lupus erythematosus (SLE), Crohn's disease, disseminated intravascular coagulation (DIC), tissue damage during ischemia-reperfusion, formation of corneal scar tissue, myelitis, squamous cell lung cancer, lung adenocarcinoma, non-small Lung cancer such as lung cancer, breast cancer, liver cancer, bladder cancer, colorectal cancer, skin cancer, knee cancer, glioma, and the like. [Simple description of the diagram] No [Major component symbol description] No 328 323256 201206906 Sequence table &lt;110&gt; Dainippon Sumitomo Pharmaceutical Co., Ltd. &lt;120&gt; Dipyrimidinone derivative and its medical use &lt;130> 560398 &lt;;150&gt; JP 2010-149636 &lt;151&gt; 2010-06-30 I &lt;160&gt; 1 &lt;170&gt; Patentln version 3.5 &lt;210&gt; 1 &lt;211&gt; 4 &lt;212&gt; PRT &lt;213&gt;&lt;220&gt;

&lt;223&gt; The substrate of elastase, MeOjuc·peptide-AMC &lt;400〉 1

Ala Ala Pro Val 1 323256

Claims (1)

201206906 VII. Patent application scope: 1. A compound represented by the following formula (I) or a physiologically acceptable salt thereof: A "1 ^ IR4&lt; [where R represents -C(=0)NRa-, -S(=0)2NRa-, -C(=〇)〇~, -C(=0)-, -S(=〇)2 - or a single bond, R1 represents a hydrogen atom, Ci-i. An alkyl group, a C2-6 alkenyl group, which may contain from 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of one to two heteroatoms selected from the group consisting of n, hydrazine and S, or a 5- to 6-membered aromatic ring group containing 1 to 4 hetero atoms selected from the group consisting of N, hydrazine, and S, and the far-burning group of R and the dilute group at a substitutable position thereof may be selected from Substituent 1 or a plurality of substituents of the group consisting of the substituents in Table 1, the substituents are listed in Table 1: (1) via group, (2) halogen atom, (3) cyano group, (4) Ci-6 alkoxy group (The alkoxy group, at its substitutable position, may be substituted by: hydroxy, 323256 201206906 halogen atom, cyano group, -C〇0)0Rb, -C(=0)NRcRd ' may contain a selected from N a 5 to 6 membered aromatic ring group of 1 to 4 heteroatoms of the group consisting of 0 and S (the aromatic ring group, at its substitutable position, may be substituted by a hydroxyl group or a G-3 alkyl group substituted with an i atom, a G-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, an ifi atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd, - NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)nR b or -NReRd), or a 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring) a group, at a substitutable position thereof, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a 0-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, Cyano, -NRaC(=0)Rb, -NRaC(=0)NRcRd ' -NRaS (=0%Rb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy) ), (5) Cl-6 thiolthio (the alkylthio group, at its substitutable position, may be substituted by: hydroxy, halogen, cyano, -C(=0)0Rb, 323256 201206906 -C(=0)NRcRd, a 5 to 6 membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may be substituted therein) The position may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC〇 0) Rb, -NRaC(=0)NRcRd, -NRaS (=0%Rb, -NReRd), or the reference may contain a selected one selected from 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring groups of 1 to 2 hetero atoms of the group consisting of N, 0 and S (the aliphatic ring group, at the position where it can be substituted, can be Substituted: Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NReRd, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), ^(6) may contain a selected from N a 5 to 6 membered aromatic ring group of 1 to 4 heteroatoms of the group consisting of 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: a C?-3 alkyl group substituted by a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a trans group, a halogen atom, a cyano group, -NRaC(=0)Rb, 3 323256 201206906 -NRaC(= 0) NReRd, -NRaS(=0)fflRb &gt; -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd &gt; -S〇0)mRb or -NRcRd), ( 7) 3 to 6 member saturated or 4 to 6 member unsaturated aliphatic ring groups containing 1 to 2 heteroatoms selected from the group consisting of N, 0 and S (the fat) A cyclyl group, at its substitutable position, may be substituted by: Ch alkyl (the alkyl group may be via a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaC(=0)NRcRd , -NRaS (=0) mRb, -C (=0) 0Rb, -C (=0) NRcRd or -NReRd substituted), Cw alkoxy (the alkoxy group may be substituted by a hydroxyl group or a halogen atom), a hydroxyl group, ^ Halogen atom, cyano group, -NRaC〇0)Rb, -NRaC(=0)NReRd, -NRaS(=0)raRb, -C(=0)0Rb, -C(=0)NRcRd, -C(= 0) Rb, -S(=0)mNRcRd, 4 323256 201206906 -S(:0).Rb, -NReRd or pendant oxy), (8) -NRaRe, (9) -0C(=0)NRcRd, ( 10) -C(=0)Rf, (11) -S(=0)mRg, (12) mercaptan, (13) nitrate &quot; base and (14) -0Re, the 3 to 6 member of R1 is saturated or The 4 to 6-membered unsaturated aliphatic cyclic group may, at its substitutable position, be substituted with 1 or a plurality of substituents selected from the group consisting of the substituents in Listing 2, and the substituents are listed in Table 2: (1) Hydroxy group, (2) a halogen atom, (3) a cyano group, or a (4) Cl-6 group (in the place where it can be substituted, it may be substituted by: a hydroxyl group, a halogen atom, a cyano group, or may be selected From N, 0 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group consisting of S (in the place where it can be substituted, 5 323256 201206906 may be substituted by: hydroxyl group or A G-3 alkyl group substituted by a functional atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a functional atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, - a book $(=0) „^ , -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0:LRb or -NRcRd), or may contain a composition selected from N, 0 and S a 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms of the group (the aliphatic ring group, at its substitutable position, may be substituted by a G-substituted by a hydroxyl group or a _ atom 3-alkyl, Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb , -C(=0)NfTRd, -NReRd or pendant oxy)), (5) Cm alkoxy group (the alkoxy group, at its substitutable position, may be substituted by: a hydroxyl group, a halogen atom, a cyano group, a 5 to 6 membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group) In the place where it can be substituted, it may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group. , -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -SbO)# or -NRcRd instead) Or a 3 to 6 membered saturated aliphatic ring group of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group may be used in the position of 6 323256 201206906, It may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or an iS atom, a Cw alkoxy group which may be substituted by a hydroxyl group or an atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS (=0% Rb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy)), (6) Cl-6 alkylthio (the alkylthio group, Where it can be substituted, it can be substituted by: a hydroxyl group, a halogen atom, a cyano group, a 5 to 6 member aromatic group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S. a cyclic group (the aromatic ring group, at its substitutable position, may be substituted by a hydroxyl group or a halogen Substituted G-3 alkyl group, Cl-3 alkoxy group which may be substituted by a trans group or a halogen atom, a trans group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or -NRcRd), or may contain a group selected from N, 0 and S A 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms of the group (the aliphatic ring group, at its substitutable position, may be substituted by a C:- which may be substituted by a hydroxyl group or a tooth atom! 3 alkyl, Cw alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)nRb, -C(=0)0Rb, - C(=0)NReRd, -NReRd or pendant oxy)), (7) may contain 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms selected from the group consisting of N, 0 and S ( The aromatic cyclic group, at its substitutable position, may be substituted by the following: 7 323256 201206906 Anthracene-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom Base, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb &gt; -NRaS(=0)mRb &gt; -C(=0)0Rb, -C(=0)NRcRd, -S(=0) raNRcRd, -S (=0) mRb or -NRcRd), (8) may contain a 3 to 6 member saturated aliphatic ring group of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group) , where it may be substituted, may be substituted by: Ci-3 alkyl (the alkyl group may be substituted by a hydroxyl group or a halogen atom), Ch alkoxy group (the alkoxy group may be substituted by a hydroxyl group or an atom), Hydroxy group, halogen atom, cyano group, -NRaC(=0)Rb '-NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, 323256 201206906 -NRcRd or pendant oxy group), (9) -NRaRe, (10) -0C(=0)NRcRd ' (11) -C(=0)Rf, (12) -S(=0)mRg, (13) mercaptan, (14) side oxygen Base, (15) nitro, (16) -NRaC(=0)Rb, (17) -NRaC(=0)NRcRd, (18) -NRaS(=0)mRb, (19) -C(=0) 0Rb and (20) -C(=0)NRcRd, the 5 to 6 membered aromatic ring group of R1 containing 1 to 4 hetero atoms selected from the group consisting of N, 0 and S, which may be selected from Substituent group 1 consists of 1 or a plurality of substituents substituted, substituents list 3: (1) hydroxyl group, (2) halogen atom, (3) cyano group, (4) Cw alkyl group (the alkyl group) In its place to replace it, Substituted by: hydroxy, 9 323256 201206906 halogen atom, cyano group, 5 to 6 member aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S A cyclyl group, at a substitutable position thereof, may be substituted by a Cl-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a 0-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, iS Atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -SbO)# or -NRcRd), or #3 to 6 member of a saturated aliphatic ring group containing from 1 to 2 heteroatoms selected from the group consisting of N, 0 and S (the aliphatic ring group, in its replaceable position , which may be substituted by an anthracene-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ch alkoxy group which may be substituted by a hydroxyl group or an atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS (=0)»Rb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy)), (5) Cl-6 alkoxy (the alkoxy group, in The position which can be substituted can be substituted by the following: hydroxyl group, halogen atom, cyano group, and can be selected from N, 0 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group consisting of S (the aromatic ring group, at its substitutable position, may be substituted by: may be substituted by a hydroxyl group or a halogen atom a 0-3 alkyl group, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(= 0) 0Rb, 10 323256 201206906 -C(=0)NRcRd, -S(=0)mNReRd, -S(=0)mRb or -NReRd), or may contain a group selected from N, 0 and S a 3 to 6 membered saturated aliphatic ring group of 1 to 2 hetero atoms (the aliphatic ring group, at the position where it can be substituted, may be substituted by a Cl-3 which may be substituted by a hydroxyl group or a halogen atom a Cl-3 alkoxy group having a trans group or a halogen atom, a trans group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb , -C(=0)NReRd, -NReRd or pendant oxy)), (6) Cl-6-based thio group (the alkylthio group, at its substitutable position, may be substituted by: hydroxy a halogen atom, a cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (this A cyclic group, at a substitutable position thereof, may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cm alkoxy group which may be substituted by a hydroxyl group or a tooth atom, a hydroxyl group, a tooth atom, Cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)nNRcRd, -S(=0)mRb Or -NRcRd), or a 3- to 6-membered saturated aliphatic ring group of one to two heteroatoms selected from the group consisting of N, 0 and S (the aliphatic ring group, in its replaceable position , which may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ci-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC (=0) Rb, -NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy)), 11 323256 201206906 (7) may contain a selected from N, 0 and 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group consisting of S (the aromatic ring group, at its substitutable position, may be substituted by: may be substituted by a hydroxyl group or a tooth atom a Ci-3 alkyl group, a C3 alkoxy group which may be substituted by a via group or a halogen atom, a mesogen, a halogen atom, a cyano group, -NRaC(:0)Rb, -NRaS(=0)raRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or -NRcRd And I (8) may contain from 3 to 6 members of a saturated aliphatic ring group of 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group, at its substitutable position) , may be substituted by: Ch alkyl (the alkyl group may be substituted by a hydroxyl group or a halogen atom), Cw alkoxy group (the alkoxy group may be substituted by a hydroxyl group or a halogen atom), a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, 12 323256 201206906 -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NRcRd or pendant oxy), (9) -NRaRe, ( 10) -0C(=0)NRcRd, (11) -C(=0)Rf, (12) -S(=0)mRg&gt; (13) Mercaptan, (14) nitro, (15)-NRaC ( =0) Rb, (16) -NRaC(=0)NRcRd ' (17) -NRaS(=0)mRb, (18) -C(=0)0Rb, (19) -C(=0)NRH (20 -S(:0)JRcRd, R2 represents a hydrogen atom, a halogen atom, a cyano group or a Ch alkyl group (the alkyl group may be substituted by a hydroxyl group, a halogen atom, -NReRd, -0Ra, -0C〇0)Ra), R3 And R4 independently represent a hydrogen atom or a Cm alkyl group (the alkyl group may be via a hydroxyl group or a halogen group) Substituted), Ar1 represents a 5- to 6-membered aromatic ring group which may contain 1 to 3 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may be substituted at a position One position or more is substituted by a Ci-6 alkyl group which may be substituted with a hydroxy 13 323256 201206906 group or a tooth atom, an anthracene-3 alkoxy group which may be substituted by a hydroxyl group or a tooth atom, a hydroxyl group, a halogen atom, a cyano group, Nitro, phenyl, -NRaC(=0)Rh, -NRaS(=0)JRh, -NRaC(=0)NRcRd, -C(=0)NRcRd ' -C(=0)0Ra ^ -C(= 0) Ra &gt; -S(=0).NRcRd &gt; -S〇0)nRh or _NRcRd), L represents -S(=0)q-, 6 member aromatics which may contain i to 4 nitrogen atoms a ring group, Pyr-1 of the following formula, Tri-1 of the following formula or the following formula: (In each group, 'bonding 1 means bonding with a dihydropyrimidinone ring, bonding 2 means bonding with Ar2, and Z1, Z2 and Z3 respectively represent independently selected from a halogen atom, a hydroxyl group, -NRcRd, -( : (=〇) service and -C(=〇)〇Ra consists of 1 or a plurality of substituents substituted with 66 alkyl or C26 alkenyl, Halogen, -C(=0)NRcRd, -C(=〇)〇Ra, hydroxy, _NRCRd or hydrogen atom), ', here, when L is a 6-membered aromatic ring group, at its replaceable position, It may be substituted with hydrazine or a plurality of substituents selected from the group consisting of: a halogen atom, a hydroxyl group, a -NRCRd, a C(=〇)NRCRd, and a _c(=〇)(10)a Group 1 or a plurality of substituents substituted 匕-alkyl or C 2-6 alkenyl, dentate, -(χ=0)ΝΙΠΓΐ, —c(=〇)〇Ra, hydroxy, nitro and -NRaC (=0) Rb, 'A〆 denotes a 5 to 6-shell aromatic ring group which may contain a group selected from the group consisting of N, G and S to 3 hetero atoms (the aromatic ring group in which 323256 14 201206906 Substitutable position, which may be substituted at one position or more by a Ci-6 alkyl group which may be substituted by a hydroxyl group, a cyano group or a halogen atom, a Cl-3 alkoxy group which may be substituted by a hydroxyl group or a _ atom, Base, _Atom, Nitrogen, Nitrogen', -NRaC(=0)Rh, -NRaS(=0)raRh, -NRaC(=0)NReRd, -C(=0)NRcRd, -C(=0) 0Ra, -C(=0)Ra, -S(=0)mNRcRd, -S(=0)nRh or -NRcRd), Re represents a ruthenium atom, 匕-6 alkyl group (the alkyl group can be a hydroxyl group, a cyano group, a halogen atom, a C!-3 alkoxy group or a -NReRd substituent), -A, -C〇0)-A', a Cm alkylcarbonyl group (the alkyl moiety of the alkylcarbonyl group may be via a hydroxyl group, a halogen atom, a cyano group, a Ch alkoxy group or a -NReRd substituted), a C!-6 alkoxycarbonyl group (the alkyl moiety of the alkoxycarbonyl group may be substituted by a hydroxyl group or a halogen atom), -C(=0)NRcRd Or -S (=0% Rb, Rf represents a hydrogen atom, a hydroxyl group, a Cl-6 alkyl group (the alkyl group may be substituted via a thiol group, a cyano group, a halogen atom, a Cl-3 alkoxy group or a -NReRd), 0- Alkoxy (this alkoxy group may be substituted by a phenyl group, a hydroxy group, a cyano group, a halogen atom, a Cm alkoxy group or a ~NRcRd) which may be substituted with a methoxy group or a nitro group of 15 323256 201206906, ~A or -ΝΙΓΡ, Rg represents a hydroxyl group, a Cl-6 group (the alkyl group may be substituted via a thiol group, a cyano group, a tooth atom, a Ci-3 alkoxy group or a -NReRd), ~A or -嶋1, Rh Represents a Ch alkyl group which may be substituted by a hydroxyl group or a halogen atom, and P represents a hydrogen atom, a Cm alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group, a halogen atom, a Cm alkoxy group, a C3-6 cycloalkyl group or a -NReRd) ), ~A, ~C(=〇)Rb, -C(=〇)A' or Cw alkylcarbonyl (the alkyl moiety of the group may be substituted by a hydroxyl group, a tooth atom, a nitrogen group, a C-3 alkoxy group or a -NReRd), and A and A' are independently represented by A 5- to 6-membered aromatic ring group containing from 1 to 4 heteroatoms selected from the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: Cm alkyl group which may be substituted by a hydroxyl group or from an atom, 323256 16 201206906 may be cyanoguanidine 1 ' &lt; burnt-C(=0)0H or -nw), or may comprise a composition selected from N, 0 and S 1 to 3 of 6 groups of saturated or 4 to 6 members of unsaturated aliphatic cyclosolid hetero atomic ring groups, at positions where they can be substituted, may be substituted with a fatty group or a tooth atom C!-3 alkyl, may be via hydroxy or ke, rixi Cl-3 methoxy, thiol, dentate, cyano, _c(=0) 〇H, ^, or epoxide WRR r represents a hydrogen atom or may be substituted by a hydroxyl group or a tooth atom, and R6 represents a hydrogen atom, a Ci group which may be substituted by a hydroxyl group or a halogen atom, a benzyl group which is substituted by a decyloxy group or a nitro group or may be C3-6 cycloalkyl substituted by a hydroxyl atom, soil or i Rc and Rd independently represent a hydrogen atom or may be via a hydroxyl group or a halogen a sub-substituted Ci-3 alkyl group, or together form a bond containing n, and containing a group selected from the group consisting of N, 〇, and S to 2 heteroatoms, 4 to 6 members of a saturated or unsaturated aliphatic group The cyclic group (the position at which the aliphatic cyclic group may be substituted ' may be represented by a C4 group, recorded, m represents an integer of 1 or 2, η represents an integer of 0 to 2, and then Q represents an integer of 0 to 2]. A compound as described in claim 1 of the scope of the patent application, or a salt thereof, wherein 323256 17 2. 201206906 R. represents -c (=_,, - 〇 〇 ...... c(=0)0_, _C( =0)-, -S(=0)2- or a single bond, R1 represents a hydrogen atom, Cl-1. It is a r.3« ^ i'Cw alkenyl group, which may be selected from N, 0 and S 3 to 6 member saturated or 4 to 6 member unsaturated aliphatic ring groups of a hetero atom of the group formed, or 1 to 4 horses 2 which may be selected from the group consisting of n, 〇 and S 5 to 6 member aromatic ring groups of 4 heteroatoms, The base of R1 and the location where the county is substituted by the shot may be replaced by a singular or dance base selected from the group consisting of Substituent Clearing 4, Substituent Listing 4: (1) Meridian, (2) Halogen Atom, (3) cyano, (4) Cm alkoxy (the alkoxy group, at the position where t/, j is substituted, may be substituted by: base, tooth atom, cyano group, = two = an atom of the group consisting of 6 Å of a group of aromatic groups (the aromatic ring group, in which the cocoa can be substituted by: a group which can be substituted by a group or a group which is substituted by a base or a _ 1_3 silk, nitrogen base, German (bin, cargo S (, mRb, %(:; ' _ atom, -c(=0)NrRd, -s(=0) album Rd, 's(=〇)&lt; or -NrRV or 323256 18 201206906 may contain 3 to 6 membered saturated aliphatic ring groups of 1 to 2 heteroatoms selected from the group consisting of N, 0 and S (the aliphatic ring group, in its replaceable position , which may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Ch alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb , -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or a pendant oxy)), (5) (V6 alkylthio group (wherein the alkylthio group, at its substitutable position, may be substituted by a hydroxyl group, a halogen atom, a cyano group, or may be selected from N, 5 to 6 membered aromatic ring groups of 1 to 4 heteroatoms of the group consisting of 0 and S (the aromatic ring group, at its substitutable position, may be substituted by: hydroxyl or i Atom-substituted Cm alkyl group, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -C(=0)0Rb, -C( =0) NRcRd, -S(=0)mNRcRd, -S(=0)nRb or -NRcRd), or may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S to 3 a 6-membered saturated aliphatic ring group (wherein the aliphatic ring group may be substituted at the position where it may be substituted with a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be substituted by a hydroxyl group or a halogen atom G-3 alkoxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -ΝΙ^(=0)π^, -C(=0)0Rb, -C(=0)NReRd, - NReRd or pendant oxy)), (6) may contain 1 to 4 hybrids selected from the group consisting of N, 0 and S. 19 323256 201206906 Atomic 5 To a 6-membered aromatic ring group (wherein the aromatic ring group may be substituted at the position where it may be substituted: an anthracene-3 alkyl group which may be substituted by a hydroxyl group or a _ atom, may be substituted by a hydroxyl group or a halogen atom Ci-3 alkoxy group, thiol group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb ' -C(=0)0Rb, -C(=0)NRcRd ' -S (=0).NRcRd ' -S(:0)nRb4 -NRcRd), (7) 3 to 6 member saturated aliphatic group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S a cyclic group (wherein the aliphatic ring group may be substituted at the position where it may be substituted: Ci-3 alkyl (the alkyl group may be substituted by a hydroxyl group or a halogen atom), G-3 alkoxy group (the alkane) The oxy group may be substituted by a hydroxyl group or a halogen atom), a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb ' 20 323256 201206906 -C(=0)0Rb, -C(= 0) Rb, -C(=0)NReRd, -NReRd or pendant oxy), (8) -NRaRe' (9) -0C(=0)NRcRd, (10) -C(=0)Rf, (11 -S(=0)mRl (12) mercaptan, the 3 to 6 member saturated or 4 to 6 membered unsaturated aliphatic ring group of R1, at the position where it can be substituted, may be selected from the list of substituents composition Group 1 or a plurality of substituents substituted, substituents list 5: (1) via group, (2) halogen atom, (3) cyano group, (4) Ch alkyl group (the alkyl group, in its replaceable position , which may be substituted by a hydroxyl group, a halogen atom, a cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic group) A ring group, in its substitutable position, 21 323256 201206906 may be substituted by a Ci-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a 3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen Atom, cyano group, -NRaC〇0)Rb, -NRaS(=0)»Rb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0 JRb or -NRcRd), or a 3 to 6 membered saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group may be substituted therein) The position may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cw alkoxy group which may be substituted by a hydroxyl group or an iS atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC (=0) ) Rb, -NRaS(=0)nRb, -C〇0)0Rb, -C(=0)NReRd, -NtTRd or a pendant oxy)), (5) a Ci-6 alkoxy group (wherein the alkoxy group, at the position where it can be substituted, may be substituted by a group: a halogen group, a cyano group, or a group selected from N a 5 to 6 membered aromatic ring group of 1 to 4 heteroatoms of the group consisting of 0 and S (the aromatic ring group, at its substitutable position, may be substituted by a hydroxyl group or a halogen atom-substituted G-3 alkyl group, a G-3 alkoxy group which may be substituted with a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, - C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)raRb or -NRcRd), or may contain a group selected from N, 0 and S a 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms (wherein the aliphatic ring group may be substituted at the position where it may be substituted by a hydroxyl group or a halogen atom; 22 323256 201206906 Cl -3 alkyl group, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS〇0)mRb, -C(=0)0Rb , -C(=0)NReRd, -NReRd or pendant oxy)), (6) Ci-6 alkylthio group (the alkylthio group, which can be substituted a position which may be substituted by a hydroxyl group, a halogen atom, a cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (this The aromatic ring group, at the substitutable position thereof, may be substituted by a 0-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cl-3 alkoxy group which may be substituted by a via group or a halogen atom, Base, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)fflNRcRd, -S (=0)raRb or -NRcRd), or a 3 to 6 membered saturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group, The substitutable position may be substituted by a Cl-3 group which may be substituted by a hydroxyl group or a halogen atom, a Cl-3 alkoxy group which may be substituted by a via group or a halogen atom, a trans group, a halogen atom, a cyanogen group. a group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy)), (7) may be selected from 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group consisting of N, 0 and S (the aromatic ring group, at its substitutable position, can be passed down Substitution: G-3 alkyl which may be substituted by a hydroxyl group or an iS atom, 23 323256 201206906 G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a trans group, a halogen atom, a cyano group, -NRaC (=0) Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -SO0) recognize cRd, -S(=0)mRb or -NRcRd), (8) may contain A 3 to 6-membered saturated aliphatic ring group of 1 to 2 heteroatoms from the group consisting of N, 0 and S (the aliphatic ring group, at its substitutable position, may be substituted by: G -3 alkyl (the alkyl group may be substituted by a hydroxyl group or a tooth atom), Cl-3 alkoxy (the oxy group may be substituted by a via or a halogen atom), a hydroxyl group, a halogen atom, a cyano group, -NRaC (= 0) Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd ' -NRcRd or 24 323256 201206906 side oxy), (9) -NRaRe, (10) -0C (=0) NReRd, (11) -C(=0)Rf, (12) -S(=0)mRg, (13) mercaptan and (14) pendant oxy group, the content of R1 is selected from N, 0 And 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group consisting of S, may be substituted by 1 or a plurality of groups selected from the list of substituents Substituted, Substituent Listing 6: (1) via: (2) a halogen atom, (3) a cyano group, or (4) a Cw alkyl group (the alkyl group, at its substitutable position, may be substituted by: a hydroxyl group, a halogen atom, a cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may be substituted therein) The position may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or an i atom, a Ch alkoxy group which may be substituted by a hydroxyl group or an i atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC (=0) Rb, -NRaS(=0)mRb, -C(=0)0Rb, 25 323256 201206906 -C(=0)NRcRd, -S(=0)raNRcRd, -S(=0)nRb or -NRf), or a 3 to 6 membered saturated aliphatic ring group containing 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group, at the position where it can be substituted, may be as follows Substituent: Cl-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, Cl-3 alkoxy group which may be substituted by a via group or an atom, a trans group, a halogen atom, a cyano group, -NRaC(=0)Rb, - NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy)), (5) Ch alkoxy The alkoxy group, at the position where it can be substituted, may be substituted by a hydroxyl group, a halogen atom, a cyano group, and 5 to 4 hetero atoms which may be selected from the group consisting of N, 0 and S. To a 6-membered aromatic ring group (wherein the aromatic ring group may be substituted at the position where it may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, may be substituted by a hydroxyl group or a halogen atom匕-3 alkoxy group, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -S( =0) mNRcRd, -S(=0)mRb or -NRcRd), or a 3 to 6 member saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S ( The aliphatic cyclic group, at a substitutable position thereof, may be substituted by a 0-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen group. Atom, cyano, -NRaC(=0)Rb, -NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy)), 26 323256 201206906 ( 6) G-6 alkylthio group (the alkylthio group, at its substitutable position, may be substituted by: hydroxy a halogen atom, a cyano group, a 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group, in its replaceable position) , which may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cw alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a functional atom, a cyano group, -NRaC〇0)Rb, -NRaS (=0) mRb, -C(=0)0Rb, -C(=0)NRcRd, -S(=0)mNRcRd, -S(=0)mRb or -NRcRd), or may contain a selected from N a 3 to 6-membered saturated aliphatic ring group of 1 to 2 heteroatoms of the group consisting of 0 and S (the aliphatic ring group, at its substitutable position, may be substituted by: a hydroxyl group Or a 0-3 alkyl group substituted with an iS atom, a 0-3 alkoxy group which may be substituted by a hydroxyl group or a functional atom, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, -NRaS(=0)nRb, -C(=0)0Rb, -C(=0)NReRd, -NReRd or pendant oxy)), (7) may contain from 1 to 4 heteroatoms selected from the group consisting of N, 0 and S 5 to 6 membered aromatic ring group (the aromatic ring group, at its substitutable position, may be substituted by: C!-3 which may be substituted by a hydroxyl group or an ig atom Alkyl group, G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, 27 323256 201206906 cyano group, -NRaC(=0)Rb '-NRaS(=0)mRb &gt; -C(= 0) 0Rb, -C(=0)NRcRd ' -S(=0)mNRcRd, -S(=0)mRb or -NRcRd), (8) may contain a group selected from N, 0, and S. a 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms (wherein the aliphatic ring group may be substituted at the position where it may be substituted: G-3 alkyl group (the alkyl group may be via a hydroxyl group or a halogen atom substituted), a Ci-3 alkoxy group (the alkoxy group may be substituted by a hydroxyl group or a halogen atom), a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb '-Nrs(=o)raRb, - C(=0)0Rb, -C(=0)NRcRd, -NReRd or pendant oxy), (9) -NRaRe, (10) -0C(=0)NRcRd &gt; 28 323256 201206906 (11) -C( =0) Rf, (12) -S(=0)mRg&gt; (13) a thiol and (14) a nitro group, and R2 represents a hydrogen atom, a halogen atom, a cyano group or an alkyl group (the alkyl group may be via a halogen atom, -NRcRd, -01^ or -〇(:(=〇) 尺3substituted), R3 and R4 each independently represent a hydrogen atom or a Ch alkyl group (the alkyl group may be substituted by a base or a functional atom)鲁, Arl represents a benzene ring or a pyridine ring (the benzene ring and the pyridine ring are each independently, and at a position where they can be substituted, one position or more may be substituted by a C alkyl group which may be substituted by a hydroxyl group or a halogen atom; Cl-3 alkoxy group, a trans group, a halogen atom, a cyano group, a nitro group, a phenyl group, -NRaC(=0)Rh, -NRaS(=0)raRh, -NRaC(=0) substituted by a hydroxyl group or a halogen atom ) NRcRd, -C(=0)NRcRd, -C(=0)0Ra, -C(=〇)Ra, -S(=〇)nNRcRd, -S(=0)nRh or -NRcRd), _ L A 6-membered aromatic ring group having 1 to 4 nitrogen atoms, Pyr-Ι having the formula: Tri-Ι or the following formula imi-i: (In each group, the bonding 1 represents a bond with a dihydropyrimidinone ring, the bonding 2 represents a bonding with Ar2, and Z1, Z2 and Z3 respectively represent independently selected from a halogen atom, a trans group, -NRcRd, - C (= 〇) NRH-C (= 〇) 〇 lT group of 1 or a plurality of substituents substituted by Cl_e alkyl or 匕 稀 323256 29 201206906 基素, C (= 〇) nw, _c (=〇)〇Ra, hydroxy, _NRCRd or hydrogen atom), where 'L' is a 6-membered aromatic ring group, at the position where it can be substituted, can be from 1 to the group consisting of Multiple substituent substitution: a Ch-based group substituted with one or more substituents selected from the group consisting of a tooth atom, a thiol group, a -NRcRd, -C〇0)NRcRd, and -c〇〇)〇Ra Or c2-6 alkenyl, halogen, _c (= 〇) NRCRd, a c (= 〇) 〇 Ra, a hydroxyl group, a NRCRd, a nitro group and a -NRaC (= 〇) Rb, Lu A r2 represents a stupid ring or a pyridine ring (The benzene ring and the pyridine ring are each independently, and at a position where they can be substituted, one position or more may be substituted by a Cl_6 alkyl group which may be substituted by a hydroxyl group or a _ atom, and a C 3 gas which may be substituted by a hydroxyl group or a halogen atom. Base, meridine, _ atom, cyanide , Exact basis, ~ fertilizer to: (1) wide-NRaS (=0) mRh &gt; -NRaC (=0) NRcRd' -C (=0) NRcRd λ -C (=0) 〇 Ra &gt; -C (=0 )Ra, -S(=〇)nNRcRd, -S〇0)nRh or -NRcRd), Re represents a hydrogen atom, • Ci-6 alkyl group (the alkyl group can be via a thiol group, a cyano group, a _ atom, or a Ch Alkoxy or -NReRd substituted), -A ' _C(=0)-A,, Ci-e alkylcarbonyl (the alkyl moiety of the alkylcarbonyl group may be via a hydroxyl group, a halogen atom, a cyano group, a Cw alkoxy group) Or -NReRd substituted), Ci-6 alkoxy group (the alkyl group of the alkoxy group may be substituted by a via or a halogen atom), 323256 30 201206906 -C(=0)NRcRd or -S(= 0) mRb, Rf represents a hydrogen atom, a hydroxyl group, a Ch alkyl group (the alkyl group may be substituted by a hydroxyl group, a cyano group, an iS atom, a Ch alkoxy group or a -NReRd), an anthracene-3 alkoxy group (the alkoxy group) Substituted by phenyl, hydroxy, cyano, halogen, Cl-3, or -NRcRd), _A or -NRaRi, Rg represents hydroxy, G, which may be substituted by decyloxy or ruthenyl -6 alkyl (the alkyl group may be substituted by a hydroxyl group, a cyano group, a halogen atom, a Cm alkoxy group I or a hydrazine), _A or -NRT, R h represents a Cl-6 group which may be substituted by a radical or a halogen atom, and R1 represents a hydrogen atom, a Ci-6 alkyl group (the alkyl group may be via a hydroxyl group, a cyano group, a halogen atom, a Ci-3 alkoxy group or a -NReRd) Substituted), -A ' 31 323256 201206906 -C(=0)A' or Cw alkylcarbonyl (the alkyl portion of the group may be substituted by a hydroxyl group, a halogen atom, a cyano group, a G-3 alkoxy group or a -NReRd) , A and A' each independently represent a 5 to 6 membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, 0 and S (the aromatic ring group may be substituted therein) The position may be substituted by an anthracene-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, an anthracene-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a -C〇 group. 0) 0H or -NRcRd), or a 3 to 6 member saturated aliphatic ring group which may contain 1 to 2 hetero atoms selected from the group consisting of N, 0 and S (the aliphatic ring group, The position of substitution may be substituted by a G-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a G-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -C (=0)0H, -NReRd or Oxy), Ra represents a hydrogen atom or a Ci-6 alkane which may be substituted by a hydroxyl group or a halogen atom. • b R represents a hydrogen atom, a Ch alkyl group which may be substituted by a hydroxyl group or a halogen atom, or may be substituted by a decyloxy group or a nitro group. The phenylhydrazine group, Re and Rd each independently represent a hydrogen atom or a Ch alkyl group which may be substituted by a hydroxyl group or a halogen atom, or together form a bond containing N, and may contain a group selected from N, 0 and S a 4 to 6 membered saturated aliphatic ring group of 1 to 2 hetero atoms (the aliphatic ring group may be substituted with a Ci-6 alkyl group, a hydroxyl group or a halogen atom at a position where it may be substituted), and m represents an integer 1 or 2, then 32 323256 201206906 π represents the integer 〇 to 2. 3. If the compound or the physiologically-supplemented salt of the patent application or the second item is used, the towel may be replaced by one or a plurality of substituents as defined in the substituent/monthly list 4, a C2-6 alkenyl group (which may be substituted by 1 or a plurality of substituents described in the group q), and may have 3 to 2 heteroatoms of the group consisting of N, 〇 and s. Up to 6 members saturated or 4i 6 member unsaturated aliphatic ring group (the base can be 5 to 6 贞 aromatic ring groups of i to 4 hetero atoms of the group consisting of 1 N, 0 and S, substituted by 1 or a plurality of substituents as described in the list of substituents 5) It may be substituted by 1 or a plurality of substituents as shown in the list of the 6th. 4. Please refer to the compound described in any one of items 1 to 3 of the patent scope* - a salt that is allowed a 'where 'R2 means that it can be selected from the tooth atom: R, HQ (X = ()) One or a plurality of ear groups consisting of Rams are substituted (^3 filaments or hydrogen atoms). H material (4) item to item 4 towel - Gu Shuzhi compound 1: physiologically acceptable salt, wherein Arl means stupid ring or * ring (3⁄4) and bite ring are independent, in which The position of the substitution may be selected from the same or different 1 to 3 substituents of the group consisting of: = 1 or complex (4) = group selected from the group consisting of a base group and a * atom Substituted Cl-6 alkyl group, Ci 3 alkoxy group substituted by a group 1 or a plurality of substituents selected from the group consisting of light groups and (d) subgroups (4), transbasic 'poly atom cyano group, nitro group, benzene group Base, a c (= 〇) NRCRd, _C (= 〇) 〇 Ra - C (=0) Ra, a s (= 〇) nRh and - NRCRd). The compound of any one of Claims 1 to 5, or a physiologically acceptable salt thereof, wherein Ar1 represents the following formula Ai--l: (In the base, K, K, K and K4 all represent a carbon atom when Ar1 is a benzene ring, and when Ar1 is a pyridine ring, only one represents a nitrogen atom, and the others represent a carbon atom, and X represents a a Cw alkyl group substituted with 1 or a plurality of substituents of a group consisting of a hydroxyl group and a halogen atom, and a Ci-3 alkoxy group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a radical and a functional atom. Base, hydroxyl group, halogen atom, cyano group, nitro group, phenyl group, ~C(=〇)NR Rd, -C(=〇)〇Ra, -C(=〇)Ra, _s(=〇)nRh or one (10)# substituent, the substitutable position of K1 to K4, may further have the same or different 1 to 2 substituents selected from the group consisting of: a group selected from a hydroxyl group and a _ atom a group of 1 or a plurality of substituent-substituted alkyl groups, a C 3 alkoxy group substituted with i or a plurality of substituents selected from the group consisting of a hydroxyl group and a functional atom, a hydroxyl group, a tooth atom, a cyano group, a nitrate Base, -C(=0)NRcRd, -c(=〇)ORa, ~c〇〇)Ra, -S(=〇)nRh and ~NRcRd). The physiologically acceptable salt of the compound according to any one of claims 1 to 6, wherein Ar2 represents a benzene ring or a pyridine ring (the ring or the pyridine ring are each independently, at a position where they can be substituted) , may be taken from the same or different 1 to 3 substituents selected from the group consisting of the lower soul, 34 323256 201206906 generation. It may be substituted by 1 or a plurality of groups selected from the group consisting of a radical and a functional atom. a Cm alkoxy group substituted by a group of 1 or a plurality of substituents selected from a group consisting of a hydroxyl group and a halogen atom, a hydroxyl group, a halogen atom, a cyano group, a nitro group, a -C group) NRcRd, -C(=0)〇Ra, -C〇0)Ra, -S(=〇)nRh, and -NRcRd). 8. The compound according to any one of the items of the present invention, wherein the Ar2 represents the following formula Ar2-1: (In the base, 1; 12, [3 and L4, when Ar2 is a benzene ring, all represent a carbon atom, and when Ar is η than a bite ring, only one represents a nitrogen atom, and the others represent a carbon atom, Υ represents a Ci-alkyl group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a radical and a tooth atom, 1 or a plurality of substituents which may be selected from the group consisting of a hydroxy group and a halogen atom Substituted Cw alkoxy, hydroxy, dentate, cyano, nitro, _c(=〇)NReRd, -C(=0)0Ra, -C(=〇)Ra, _s(=〇)nRh or an NRCRd , the substitutable position of L to L, may further have the same or different oxime selected from the group consisting of 2 substituents: a group selected from the group consisting of a hydroxyl group and a halogen atom Or a plurality of substituent-substituted Ci-e alkyl groups, a Ci 3 alkoxy group substituted by a group or a plurality of substituents selected from the group consisting of a hydroxyl group and a tooth atom, a hydroxyl group, a halogen atom, a cyano group, and a nitrate Base, -C(=0)NRcRd, ~c(=0)0Ra, -c(=0)Ra, -S(=0)nRh 35 323256 201206906 and -NRcRd) 〇9·If the scope of patent application is 1 The compound of any one of clauses 8 to 8 or Theoretically allow the salt, wherein the formula (I) by the following formula based (Gamma]) shown: Ar1 R. ’1 (r) [In the formula, L represents a benzene ring or an n-bite ring, and the position of the ring bonded to the dihydropyrimidinone ring is adjacent to the position where the ring is bonded to the Ar 2 ring, and the 5 benzene ring and the acridine ring are respectively independent. And at a substitutable position thereof, may be substituted by one or a plurality of substituents selected from the group consisting of: a halogen atom, a hydroxyl group, -NRcRd, _c(=〇)NRCRd&amp;_c(= 〇) 〇Ra consists of 1 or a plurality of substituents substituted by Cl_6 alkyl, halogen, -C(=〇)NRcRd, -C(=〇)〇Ra, -NRcRd, nitro and ~NRaC( =〇)Rb]. 10. The compound according to any one of the preceding claims, wherein the L is an unsubstituted benzene ring or a pyridinium ring, or a physiologically acceptable salt thereof. The compound of any one of claims 1 to 8, or a physiologically acceptable salt thereof, wherein L represents pyr-i, Tri-l or Inu-1, z1, Z2 and Z3 Represents a hydrogen atom. 12. The compound of claim 36, 323256 201206906 or the physiologically glutinous salt of the salt, wherein L represents pyr-dip] or Imi-1 » Z1 ' 72 » 73 The eight knives independently represent &amp; 6 leuco, -NReRd or _ atoms which may be substituted by hydrazine or a plurality of substituents selected from the group consisting of _NRCRd and halogen. 13. The compound according to any one of claims 1 to 8, wherein the compound is a physiologically acceptable salt, wherein L represents a step, a Μ" or an Iπιi -1, and the phenotype is independently indicated. Ci-6 alkyl or _c(=〇)NRCRd substituted by -C(=〇)NRcRd. The compound of any one of the preceding claims, wherein the physiologically acceptable salt, wherein L represents a chemical, th i or broad 1 1 'z, z, and z3 are independent Representing a 6-alkyl group, a county or a 仏〇 仏〇 可 which may be substituted with one or more substituents selected from the group consisting of a thiol group and an ec'K group. : The compound described in any one of the above-mentioned claims, or the physiologically-supplemented salt thereof, wherein R1 represents 1 or a plurality of the substituents listed in the list of the substituents Substituents substituted for 2Cm ° alkyl group' or indicated at the substitutable position thereof, which may be substituted by the substituent 1 or a plurality of substituents in the substituted soil list 5, may contain a group selected from the group consisting of ruthenium and S 3 to 6 members of two heteroatoms are saturated aliphatic ring groups. 16. Please __ Item 1 to Item 15 of the article of the syllabus, or a physiologically acceptable salt thereof, wherein 〇 denotes a Cl 10 alkyl group (the base of which is replaceable) k from the group consisting of the substituents listed in Group 7 or a plurality of substituents taken from 37 323256 201206906, Substituent List 7: (1) thiol, (2) halogen atom, (3) cyano group, (4) Ci_6 alkoxy group (wherein the alkoxy group may be substituted at one or a plurality of substituents selected from the group consisting of: a base group, a halogen atom, a cyano group and It may contain a group of 3 to 6 members of a saturated aliphatic ring group selected from the group consisting of N, 0, and S to 2 heterogenes (the aliphatic ring group, which can be selected in its ambiguous position) Substituting 1 or a plurality of write-substituents of the group consisting of: a group selected from the group consisting of a halogen group and a plurality of substituents, or a substituent selected from the group consisting of幽々: The composition of the material group ^ 丨 ^ number of dance generation base take ^ burning oxygen ' 1 atom, cyano, iron (Xie, Cao S (= 〇 W - c (= 〇) 〇 R,, G (= G) NRLd to ethoxylate, = from-, thio (heterothio), at its substitutable position; substituted by group 1 or a plurality of substituents consisting of hydrazine: _ atom, cyano group and may contain From the group consisting of 0 and S, i to 2 heteroatoms 3B 323256 201206906 3 to 6 member saturated aliphatic ring group (the aliphatic ring group, at its substitutable position) may be selected from 1 or a plurality of substituents of the group consisting of: a Cl_3 alkyl group which may be substituted with i or a plurality of substituents selected from the group consisting of a hydroxyl group and a tooth atom, may be selected from a hydroxyl group and a halogen atom Composed a group of 1 or a plurality of substituents substituted with a Ci-3 alkoxy group, a transradical, a tooth atom, a cyano group, -NRaC(=0)Rb, -NRaS (=0; LRb - C(=0)0Rb, - C(=0)NRCRd, with "side oxy, There are 5 to 6 membered aromatic ring groups of i to 4 (tetra) atoms selected from the group consisting of N, hydrazine and S (the family ring group can be selected from the following: Or a plurality of (4) 1 or a plurality of 1 or a plurality of G-3 alkyl groups which may be substituted with a substituent selected from the group consisting of a hydroxyl group and a tooth atom, may be selected from the group consisting of a hydroxyl group and a _ atom. Subgroup substituted by Cl_3 alkoxy, hydroxy, dentate, cyano, -NRaC(=〇)Rb, , aS(=0)„Rb, -C(=0)〇Rb, -C(= 0) NRcRd, -S〇0) tear cRd, -S(=0)mRb and 323256 39 201206906 -NRcRd), (7) may contain 1 to 2 impurities selected from the group consisting of N, 0 and S a 3- to 6-membered saturated aliphatic ring group of an atom (the aliphatic ring group, at a position where it may be substituted, may be substituted with 1 or a plurality of substituents selected from the group consisting of: may be selected from a hydroxyl group And a C1-alkyl group substituted with one or a plurality of substituents of a halogen atom, a Cl-3 alkoxy group which may be substituted with one or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom, Hydroxyl, halogen atom, cyano group, -NRaC (= 0) Rb, -NRaS(=0)mRb, -C(=0)0Rb' -C(=0)NRcRe, -C(=0)Rb, -NReRd and side oxy), (8) -NRaRe &gt (9) -0C(=0)NRcRd ' (10) -C(=0)Rf, (11) -S(=0)raRg and (12) mercaptan. 40 323256 201206906 17.If the scope of application is The compound of any one of the items 1 to 16 or a physiologically acceptable salt thereof, wherein R1 represents an alkyl group (wherein the alkyl group may be substituted at a position selected from the following list 8 One to three substituents of the group are substituted, and the substituent is shown in Figure 8: (1) a meridine, (2) a halogen atom, (3) a cyano group, and (6) may contain a group selected from N, 0, and S. a group of 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms (the aromatic ring group, at the position where it may be substituted, may be substituted with 1 or a plurality of substituents selected from the group consisting of a Cl-3 alkyl group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom, may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom Cl-3 alkoxy, hydroxyl, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb -C(=0)0Rb, -C(=0)NRcRd, 41 323256 201206906 -S(=0)raNRcRd, -S(:0;LRb and -NRcRd), (7) may contain a selected from N, 0 and 3 to 6 member saturated aliphatic ring groups of 1 to 2 hetero atoms of the group consisting of S (the aliphatic ring group, at the position where it can be substituted, may be selected from the group consisting of the following Or a plurality of substituent substitutions: a group consisting of one or a plurality of substituents selected from the group consisting of hydroxyl groups and _ atoms, and a group selected from the group consisting of hydroxyl groups and halogen atoms One or a plurality of substituents substituted with a Cl-3 alkoxy group, a hydroxyl group, a halogen atom, a cyano group, -NRaC(=0)Rb, ^-NRaS(=0)mRb, -C(=0)0Rb, - C(=0)NRcRd, -C(=0)Rb, -NReRd and pendant oxy), (8) m (10) _C(=0)Rf. 18. The compound according to any one of claims 1 to 15 wherein the compound 42 323256 201206906 or its physiologically sulphate salt 'where 'R1 denotes a position at which it can be substituted' may be substituted by the list 5 The one or more substituents described may be substituted with a 3 to 6 membered saturated aliphatic ring group selected from the group consisting of N, 0 and S and having 1 to 2 hetero atoms. The compound according to any one of claims 1 to 15 or the physiologically acceptable salt thereof, wherein R represents a group selected from the group consisting of N, 0 and S a 3 to 6 membered saturated aliphatic ring group of 1 to 2 heteroatoms of the group (the saturated aliphatic ring group may be substituted at a position selected from the group consisting of one or more of the groups selected from the substituents in Listing 9 Substituent substitution, substituent list 9: (1) via group, (2) halogen atom, (3) cyano group, (4) Ci-6 alkyl group (the topographical group, at its substitutable position, may be selected from the following Substituting 1 or a plurality of substituents of a slightly composed group: 1 to 4 hetero atoms of the group consisting of a group consisting of a halogen group, a halogen group, a β group, and a S group, and a S group (The aromatic ring group, at the position where it can be substituted, the group of 1 or a plurality of substituents consisting of the following groups, or a group of atoms, which may be selected from the group consisting of hydroxyl groups And the composition of the tooth atom 323256 43 201206906 = group 1 or a plurality of substituents substituted oxy group, via group, tooth atom, cyano group, - Huan (Xie, s s (drink #, _c (= 〇)〇Rb, -c(4)(4), -S(=0)w, _s(|Rb and _NRCRd) and 丨 to 2 heteroatoms which may contain a group selected from the group consisting of N, 0 and S The 3 to 6-membered saturated lining group (the aliphatic ring group, at the position where it can be substituted) may be substituted by a group selected from the group consisting of or a plurality of substituents. Substituting alkoxy, hydroxyl, halogen, cyanide from one or a plurality of substituents of group i or a plurality of substituted filaments of group (4) Base, a NRaC(=〇)Rb, _NRas(=〇)niRb, _C(=0)0Rb, -C(=0)NirRd, _NRCRd and pendant oxy)), (5) Ci-e alkoxy ( The alkoxy group, at the substitutable position thereof, may be substituted with a group or a plurality of substituents selected from the group consisting of: a group, a halogen atom, a cyano group, and may contain a group selected from N, oxime and s. 5 to 6 membered aromatic ring groups of 1 to 4 hetero atoms of the group formed (the aromatic ring group, at the position where it can be substituted, may be selected from the group consisting of 1 or a plurality of substituent substitutions: one or more of a group of Cn3 alkyl groups which may be substituted with one or more substituents selected from the group consisting of a hydroxyl group and a tooth atom, and may be selected from the group consisting of a hydroxyl group and a halogen atom. Substituent Instead, Ci-3 alkoxy, hydroxy, _ atom, cyano, -NRaC(=0)Rb, -NRaS(=〇)Ab, -C(=〇)〇Rb, -C(=0)NRcRd, -s〇〇)raNRcRd, -S(=0)Jib and -NRcRd) and 44 323256 201206906 may contain 3 to 6 members of saturated fat selected from the group consisting of N, 0 and S to 2 heteroatoms a cyclocyclic group (wherein the substitutable group may be substituted with a group or a plurality of substituents selected from the group consisting of: a group selected from the group consisting of a hydroxyl group and a halogen atom; a C 3 alkyl group substituted with i or a plurality of substituents, and a C 3 alkoxy group which may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom Base, hydroxyl group, halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)nRb, -C(=〇)〇Rb, -C(=〇)NRt, _NReRd and pendant oxy)) (7) A 5- to 6-membered aromatic ring group which may contain 1 to 4 hetero atoms selected from the group consisting of N, G&amp;S (the aromatic ring group may be substituted therein) Group 1 or a plurality of substituents composed of the following a Cl. 3 alkyl group substituted with a substituent selected from the group consisting of a neon and an atom, a group of 1 or a plurality of Cl-3 alkoxy groups which may be substituted with a substituent selected from the group and the subunit , hydroxy, group 1 or a plurality of halogen atoms, cyano group, -NRaC(=〇)Rb, -NRaS(=〇%Rb, -C〇0)0Rb, -C(=0)NRcRd &gt; - S(=0)mNRcRd ' 323256 45 201206906 -S(=0)mRb and -NRcRd) &gt; (8) may contain 1 to 2 heteroatoms selected from the group consisting of N, 0 and S to 3 a 6-membered saturated aliphatic ring group (wherein the aliphatic ring group may be substituted at a position selected from the group consisting of 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom; a group consisting of 1 or a plurality of substituent-substituted Cl-3 alkyl groups, which may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom, alkoxy groups, hydroxyl groups, Halogen atom, cyano group, -NRaC(=0)Rb, -NRaS(=0)mRb, -C(=0)0Rb, -C(=0)NRcRd, -NReRd and pendant oxy), (9) - NRaRe, (10) -0C (=0) NReRd, (11) -C(=0)Rf, (12) -S(=0)mRg, and (14) side Groups. The compound of ♦, r1 is a list of substituents, or a physiologically acceptable salt thereof, as set forth in any one of claims 1 to 15, 18, and 19. The 3 or 6 membered saturated aliphatic ring group which may be substituted with ruthenium or a plurality of substituents as described in 9 and may contain a group selected from the group consisting of N, 0 and S to 2 hetero atoms, the aliphatic ring group System &amp; 6 saturated anthrax, aziridines, azetidine, pyrridine Hdine, piperididine, propylene oxide (〇xetane), tetrahydrofuran • (tetrahydrofuran) &gt; ^ (tetrahydropyran), morpholine or piperazine. The compound or physiologically acceptable salt thereof according to any one of claims 1 to 2, wherein Ra represents a hydrogen atom or may be selected from the group consisting of a hydroxyl group and a fluorine atom. a Ci 6 alkyl group substituted with 1 or a plurality of substituents, and R represents an 匕β alkyl group substituted with 1 φ or a plurality of substituents selected from the group consisting of a trans group and a fluorine atom, and R and R respectively Independently representing a hydrogen atom or may be substituted with one or more substituents selected from the group consisting of a hydroxyl group and a gas atom (^-3 or a combination of 4 to a saturated aliphatic ring group containing a bond N) (Heart-day aliphatic ring group, at its substitutable position, may be substituted by 1 or a plurality of substituents selected from the group consisting of a base group and a gas atom), and R represents a Ci-e appearance group (the base group) It may be substituted by 1 or a plurality of substituents selected from the group consisting of a hydroxyl group, a cyano group, a ruthenium atom, a Cl-3 alkoxy group and a -NReRd) H(=Q)-A', Cm 炫 base minus ( The base portion of the base 47 323256 201206906 may be subjected to one or plural groups selected from the group consisting of a hydroxyl group, a fluorine atom, a cyano 'Cw alkoxy group, and -NRcRd. Substituent substituted), -C(=〇)NRcRd or -S(=0)mRb, Rf represents a trans group, a Cl_3 alkyl group (the alkyl group may be selected from the group consisting of a hydroxyl group, a cyano group, a gas atom and a ~NReRd) Group 1 or a plurality of substituents substituted) or -NRf, Rg represents a hydroxyl group, a Cl 3 alkyl group (the alkyl group may be 1 or a plurality of groups selected from the group consisting of a hydroxyl group, a cyano group, a gas atom and a ~NReRd) Substituent • Substituted) or -NRaRi, Rh is not substituted by a group consisting of 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and a fluorine atom, and R is a Cl-6 group. The group may be substituted by one or more substituents selected from the group consisting of a fluorine atom and a group consisting of, _A, _c(=〇)_A, or a C1-6 alkylcarbonyl group (the alkyl moiety of the group may be selected from The fluorine atom and the group consisting of -NReRd are substituted by a plurality of substituents, and Lu A and A' are independently selected from a phenyl group, an imidazolyl group, a pyridyl group, and a carbazolyl group. a group consisting of xaz〇iyl), isoxazol (is〇xazolyl), pyrazollyl, thiazolyl, isoththiaz〇lyl, and tetrazolyl An aromatic cyclic group which, at its substitutable position, may be substituted by a G 3 alkyl group which may be substituted by a hydroxyl group or a tooth atom, or a 3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom. a group, a hydroxyl group, a halogen atom, a cyano group, -C(=〇)〇H or -NRt), or a compound selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyranyl, nitrogen Miscellaneous 323256 48 201206906 Cyclobutyl (61; 丨 (1丨1171), '3 to 11 each bite (mouth 71'1'〇11 to 1171), 11 base (piperidinyl), α chen 哄 ( Piperazinyl) and an aliphatic ring group of morpho 1 i ny 1 (the aliphatic ring group, at its substitutable position, may be substituted by a hydroxyl group or a halogen atom Substituted 〇3 alkyl, G-3 alkoxy group which may be substituted by a hydroxyl group or a _ atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0)0H, -NReRd or a pendant oxy group), then m represents 1 Or 2. The compound of any one of claims 1 to 21, or a physiologically acceptable salt thereof, wherein R° represents -C(=0)NRa-, _S(=0)2NRa_ , _C (=0) _, -8 (=0) 2- or single bond. The compound of any one of the above-mentioned claims, wherein the formula (I) is as follows, or a physiologically acceptable salt thereof. As shown in (Γ): Wherein L represents a benzene ring (the position at which the benzene ring and the dihydropyrimidinone ring are bonded is an ortho position to the position where the benzene ring is bonded to Ar2, and the benzene ring may be selected from a position at which it can be substituted Substituting 1 or a plurality of substituents of the group consisting of Cm alkyl, -C(=, which may be substituted by a group selected from the group consisting of a hydroxyl group and a halogen atom, 1 49 323256 201206906 or a plurality of substituents. 0) NITRd and C(_〇)〇H), or the following formula Pyr-Ι or Tri-Ι: (In each group, 'bonding 1' indicates bonding with a dihydropyrimidinone ring, and bonding 2 is bonded to Ar2, and ^2 and Z2 are independently represented by a halogen atom, a group, a NW, a -C. 0) 1 or a plurality of substituents of NRcRd and -C(=0)0H are substituted by Cl-6 alkyl, halogen, _c("Rd, _C(=0)0H, _NReRd or hydrogen atom) , R represents a Ci-u alkyl group (the alkyl group, at its substitutable position, may be 'lightly selected from 1 to 3 substituents of the group consisting of: (1) via, (2) a tooth atom, (4) a Cl-e alkoxy group (wherein the alkoxy group) may be substituted with one or a plurality of substituents selected from the group consisting of: a base, a halogen The atom, may have from 1 to 4 heteroatoms selected from the group consisting of N, 0 and S to a 6-membered ring group (the aromatic ring group, at the position where it can be substituted, may be selected from The group consisting of 1 or a plurality of substituents of the group consisting of: a group selected from the group consisting of (4) and (4), or a plurality of substituents, may be substituted by a wire selected from a wire and a tooth atom. Group 1 or a plurality of substituents substituted for &amp; Base, super group, 323256 50 201206906 halogen atom, and ~C(=〇)〇H), and 1 to 2 hetero atom oximes and aliphatic ring groups which may contain a group selected from N An aliphatic cyclic group in which one or more of the groups of the following materials can be substituted for one or more of the following: a group or a plurality of groups selected from the group consisting of a base group and a ® atom Substituted by a substituent, which may be substituted by a group selected from the group consisting of a trans group and a tooth atom, a 0-3 alkoxy hydroxy tooth atom, -C(=〇)〇 Rb, _c (= 〇) serving cRd and pendant oxy)), (6) may contain a group selected from the group consisting of N, 〇 and S to 4 impurities The 5 to 6 membered aromatic ring group of the atom (the aromatic ring group, at the position where it can be substituted) may be substituted with 1 or a plurality of substituents selected from the group consisting of: || A group consisting of 1 or a plurality of substituents substituted by a C+-3 alkyl group substituted by 1 or a plurality of substituents selected from the group consisting of a trans group and a halogen atom; Alkoxy, hydroxy, halo- and/or (C(=〇)〇Rb), (Ό may contain from 1 to 2 heteroatoms selected from the group consisting of N, 0 and S, 3 to 6 members saturated An aliphatic cyclic group (wherein the substitutable position thereof) may be substituted with one or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom; a Group 1 or a plurality of substituent-substituted Ch alkyl groups, a Cl-3 alkoxy group, a hydroxyl group, a halogen which may be substituted with one or more substituents selected from the group consisting of a hydroxyl group and a halogen group of 51 323256 201206906 An atom, -C(=0)0Rb, -C(=0)NReRd, -C(=0)Rb and pendant oxy), and (8)-NRaRe), or represents a composition selected from N and 0. 1 to 2 miscellaneous groups of the group a 3 to 6 membered saturated aliphatic ring group (the aliphatic ring group, at the position where it can be substituted, may be substituted with 1 or a plurality of substituents selected from the group consisting of: (1) (2) a halogen atom, (3) a cyano group, or a (4) Ch alkyl group (the alkyl group, at a position where it may be substituted, may be one or a plurality of substituents selected from the group consisting of a hydroxyl group and a halogen atom Substituted), (5) Cm alkoxy (the alkoxy group, at the position where it can be substituted, may be substituted with 1 or a plurality of substituents selected from the group consisting of a hydroxyl group and an atom), (9) -NRaRe , (10) -0C(=0)NRcRd ' (11) -C(=0)Rf, (12) -S(=0)mRg&amp; (14) side oxy), R0 means -C(=0) NRa-, -S(=0)2NRa-, -C(=0)-, -S(=0)2- or a single bond, R2 represents a halogen atom, -NRcRd, -0Ra&amp;-0C ( =0) Ra 52 323256 201206906 A group consisting of 1 or a plurality of substituents substituted with a Cl-3 alkyl group, R3 and R4 each independently represent a cy3 alkyl group or a hydrogen atom, and X represents 1 or a plurality of fluorine atoms. Substituted Ci-3 alkyl or nitro, Y represents a cyano group, a chlorine atom or a nitro group, and R represents a hydrogen atom or may Substituting one or a plurality of substituents consisting of a group consisting of a base group and a gas atom (^-3 alkyl group to represent a G-3 alkyl group which may be substituted by 1 to 3 fluorine atoms, Re and Rd respectively Independently denotes a Cm alkyl group or a hydrogen atom which may be substituted by a fluorine atom' or a bond N together represents a pyrrolidine or a piperidine, and Re represents a Ch alkyl group (the alkyl group may be selected from fluorine) One or a plurality of substituents of the group consisting of an atom and _NRcRd are substituted), -A, -C〇0)-A', and a Ci-e alkylcarbonyl group (the alkyl moiety of the group may be selected from a fluorine atom) And -NReRd is composed of 1 or a plurality of substituents substituted) or -S(=〇)2Rb, Rf represents a hydroxyl group or Raf, which represents a Cl-3 alkyl group, and Rh represents 1 or a plurality of fluorine atoms. Substituted Cl_3 alkyl, R represents a G-3 alkyl group (the alkyl group may be substituted by a group or a plurality of substituents selected from the group consisting of a fluorine atom and _NRCRd) or _8, A&amp;A' respectively Represents selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, decyl, azetidinyl, pyrrolidinyl, piperidinyi, pie π well base 53 323256 201206906 (pi peraz iny 1) and morpho 1 i ny 1 group of aliphatic ring groups (the aliphatic ring group, in its replaceable position, can be passed The substitution: an anthracene-3 alkyl group which may be substituted by a hydroxyl group or a halogen atom, a Cl-3 alkoxy group which may be substituted by a hydroxyl group or a halogen atom, a hydroxyl group, a halogen atom, a cyano group, -C(=0)0H, - NRcRd or pendant oxy), then m represents 2]. The compound according to any one of the preceding claims, wherein the compound or the physiologically acceptable salt thereof, wherein Z1 and Z2 represent a hydrogen atom, is a compound according to any one of the preceding claims. . 25. The compound of claim 1 or a physiologically acceptable salt thereof, wherein the compound is selected from the group consisting of: 4 (4-(3-isopropyl-methyl-2-) Phenoxy-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4Η-1,2,4-triazol-3-yl ) Benzene nitrile, (R)~4-(4-(3-(dihydroxypropane-2-yl)-6-methyl-2-yloxy (3 (monofluoromethyl)phenyl)_ι, 2 , 3,4-tetrahydropurine-5-yl)-4H-1,2,4-triazol-3-yl)benzonitrile, 4 (4-(3-isopropyl-6-methyl) 2_sideoxy_丨_meta-phenylene '3, 4 four-mouthed bite_5_yl)_4h-i, 2, 4-tris-3-yl)benzonitrile, (4 (6~B) 3-methyl-2-oxo-i-(3-(trifluoromethyl)phenyl)-1,2' 3,4-tetrahydropyrimidine _5_ kib- 丨, 2, 4_triazole_3_yl) styrene, 4(5~(3-isopropyl-6-methyl-2-oxo-l-(3-(trifluoromethyl)) 323256 54 201206906 benzene -1,2,3,4-tetrahydropyrimidin-5-yl)_1Η-β-pyrazol-1-yl)benzonitrile, 5 (3-(4-ranylphenyl)-4Η-1, 2,4-tris(s)-4-yl)-N,4-dimethyl-2-oxo-3-(3-(three Methyl)phenyl)-2,3-dihydropyrimidine-U6H)-carbenamide, 5-(3-(4-cyanophenyl)-4Η-1,2,4-triazol-4-yl )-Ν,4-dimercapto-2-oxo-3-o-tolyl-2,3-dihydropyrimidin-1(6Η)-formamide, 5-(3-(4-cyanophenyl)-4Η-1,2,4-triazol-4-yl)-indole-(2-methoxyethyl)-4-methyl-2- side Oxy-3-m-tolyl-2,3-dihydropyrimidine-1(6Η)-decylamine, 5-(3-(4-cyanophenyl)-4Η-1,2,4-triazole 4-yl)-4-methyl-2-oxo-indole-(pyridin-2-ylindenyl)-3-m-decylphenyl-2,3-dihydropyrimidine-1 (6Η)- Formamide, 5-(3-(4-cyanophenyl)-4Η-1,2,4-triazol-4-yl)-indole-ethyl_4_methyl-2-oxooxy-3 -(3-(Trifluoromethyl)phenyl)_2, 3-dione sneezing - 1(6Η)-formamide, 4-[4-(6-(hydroxymethyl)-3-isopropyl -2-Sideoxydimethicone)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl 2 4 -rat-3-yl]cyanonitrile, ,,diazole 5~( 1-(4-cyanophenyl)-lH-nbiazole-5-yl)_N,4-dimethyl-oxy-3-(3-(disindolyl)phenyl)_2,3_ Dihydrogen end i (6h = 323256 55 201206906 oxy-3-(3-(trifluoromethyl)phenyl)-2,3-di- aro-pyrimidine-1(6H)-yl) propionic acid, 2-(5 -(3-(4-cyanophenyl)-4Η-1,2,4-triazol-4-yl)-4-indolyl-2-oxo-3-(3-(trifluoromethyl) Stable base) 2,3-dihydropyrimidin-1(6H)-yl Propionic acid, 4-(5-(1-(4-cyanophenyl)-ih-indazol-5-yl)-4-methyl-2-oxo-3-(3-(tri-failed) Mercapto)phenyl)-1,2,3,6-tetrahydropyran-1-amine)butyric acid, hydrazine N-(4-amino-4-oxobutyl)-5-( 1-(4-cyanophenyl)-1Η-pyrazin-5-yl)-4-mercapto-2-oxo-3-(3-(trifluoromethyl)phenyl)-2.3- Hydropyrimidine-1 (61〇-formamide, N-(2-amino-2-yloxyethyl)-5-(1-(4-cyanophenyl)-ih_ oxazol-5- ))-4-methyl-2-oxo-3-(3-(trifluoromethyl)phenyl)-2.3- 二风嘴 bit-1(6|{)-decylamine, and 1- (4-cyanophenyl)-5-(3-isopropyl-6-methyl- 2-oxooxy_ι_ _(3~(difluoroindolyl)phenyl)-1,2, 3, 4-tetrahydropyrimidin-5-yl)-1 Η-pyrazole-4-carboxylic acid 26. A pharmaceutical composition containing as an active ingredient, any one of items 1 to 25 of the patent application scope A compound or a physiologically acceptable salt thereof and a carrier for the preparation. 27. An elastase inhibitor which comprises the compound according to any one of the above-mentioned items of claim 1 to 25 or physiologically acceptable thereof Salt as there is Ingredients. A compound for the treatment or prophylaxis of an inflammatory disease, which comprises a compound according to any one of items 1 to 25 or a physiologically acceptable salt thereof. A therapeutic or preventive agent for a disease which is required to have an inhibitory activity of elastase, which comprises the compound according to any one of claims 1 to 25 or a physiologically acceptable salt thereof. 57 323256 201206906 IV. Designated representative map: (1) The representative representative of the case is: (). (There is no picture in this case) (2) The symbol of the symbol of this representative figure is simple: (none) 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: 323256