TW436487B - Imidazole derivatives having an inhibitory activity for farnesyl transferase and process for preparation thereof - Google Patents

Abstract

The present invention relates to a novel imidazole derivative represented by the following formula (1) which shows an inhibitory activity against farnesyl transferase: [Formula 1] or pharmaceutically acceptable salts or isomers thereof, in which A, n1 and Y are defined in the specificaiton; to a process for preparation of the compound of formula (1); to intermediates which are used in the preparation of the compound of formula (1); and to a pharmaceutical composition comprising the compound of formula (1) as an active ingredient.

Description

d364B7 at B7 V. Description of the invention (1) This invention relates to a novel oxazole derivative having inhibitory activity on farnesyl transfer SS as shown in formula (ii) below, or a pharmaceutically acceptable hydrazone Or its isomers [Formula I]

In CCH ^ -Y, A, η, and Υ are defined as follows. The present invention also has a method for preparing a compound of formula (I), an intermediate for preparing a compound of formula (I), and a turmeric composition comprising a compound of formula (I) as an active ingredient.

Fei Shufang IS The mammalian Ras protein acts as a molecular switch on matters related to cell growth and differentiation. The r * as proto-oncogene family is composed of the following three groups: M-, K-, and H-ras. Their pro-oncogenes encode four highly homologous proteins, namely: 189 residues, N- " as protein, and two isoforms of K-ras-4B and Kr · as-4 A with 188 and 189 residues, respectively. The theoretical basis of the switch mechanism and the non-activating (off) guanyl diphosphate (GDP) -bonded proteins and activated (open) guanosine triphosphate (GTP) -bonded proteins are circulated in cycles (Bourne, HR; Sanders, D. A .; McCormick. F .; Nature, 1 9 9 1, 349, 117). According to biochemical and structural studies, point mutations of residues 12, 13, and 61 located near the base of the GTP phosphatium resulted in a decrease in the activity of Magnesium Triphosphatase. Valve national standard 4 *-(CNS) Λ4 specification (210X 297 male Chu) 1 91506 (Please read the precautions on the back before filling out this page-pack--° 436487 A7 B7 V. Description of invention (2) Multiple human cancers * Especially related to pancreatic carcinoma, bladder cancer, colon cancer, etc. (Bos, JL, Cancer Res., 1989, 49, 4682) 0

When Ras protein was first synthesized, it was a cytosolic precursor. After a series of post-translational modifications, Ras protein was finally located on the cytoplasmic surface of the plasma membrane (Gibbs, J. B., Cell 1991, 65, 1). This series of chemical modifications that increase hydrophobicity by changing the state of charge or spatial structure makes Ras proteins more easily adhere to cell membranes. The first and necessary step in this series of actions is to add the farnesyl moiety to the C-terminal CAAX main structure in a reaction catalyzed by farnesyl protein transfer (FTase) (C: Cysteine; A : —Like aliphatic residues; X: any other amino acid) half (read the precautions on the back first and then fill out this page)-install 1 amino acid residues 0 This modification effect on Ra s The function is necessary • This is evidenced by the R as mutant lacking C-terminal cysteine that cannot be farnesylated, cannot be located in protoplasts, and cannot transform cultured mammalian cells (Η a η C 0 ckt J. F • 9 Mag ee, A. I., Chi Ids, J. E »Harsha 11 C. J * f Cel 1 1989, 57, 1167). Modification of post-mineral release and modification; AAX residue splitting, carboxymethylation of cysteine by fluorinated cysteine and upstream of CAAX main structure of Η- and Η-ras proteins. The cystylation of cystine »is not the membrane binding of Ras or in cells. What is necessary for the fire-transforming activity ° Interestingly, Kr as-4B is different from Η and \] N-ras, which There are multiple lysine-rich regions (known as polybasic regions) and .-r eliminates, 1 | does not have the cysteine required for predation, and is thus ribonized 1 'A ii The ra S protein is linked to the anionic lipid layer of the cell membrane. Therefore, it is suggested that the FT ase inhibitor, which catalyzes the necessary modification, as an anticancer agent for cancers that are transformed by the ras oncogene (Buses, J. Ε. Et al. Shi Qingshi_ 办 州 刺 格 ⑺㈤⑽) 31506 、-° rJ step on. IJ 4 3 6487 iJ 4 3 6487 " The Ministry of Shanghai beats £ v and, "τ,; ι, ί the combination is still '1 printed wv A7 B7 V. Description of the invention (3 ) • Chemistry & Biology, 1995, 2, 787). Recently, several FTase inhibitors have been demonstrated in vitro and in animal models. They have been shown to be effective and unique in blocking Ras farnesylation, messaging, and transformation in transformed cells and tumor cell lines. Uoh 丨 _ Ν · E · et al. Proc. Natl · A cad. S c ί · USA. 1 9 9 4, 9 1, 9 1 4 1; K oh 1, N. E.

Mature Medicine, 1995, 1 792) 0 However, most of the inhibitors mimic Ras matrix, which is essentially a peptide related to the main structure of CAAX • Becoming a hydrogen-sulfur group (USP NO, 5,141'851; Kohi, Ν · E. Et al. Science, 1993, 260, 1 9 34 ί PCT / US95 / 1 2 224, Graham et al., Sebti, S. M. et al. * J. Biol. Cheat., 1 99 5. 2 7 0, 268 02; James, G. L. et al., Science, 1993, 26.0, 1937; Bishop, WR et al.,

Biol. Chem., 1995, 270, 30611). Recently * It has been reported that there is a novel peptide mimicking inhibitor (Poulter, CD et al., J. Am. Chem. Soc., 1996, 118, 876) that mimics the catalytic step of FTase. The theoretical basis of the chemistry of this inhibitor design It is related to the catalytic reaction mechanism of the FTase. That is, * the isopentenyl transfer of the enzyme is an electrophilic substitution * and the reaction requires a (+) charge when the state is switched. However, the inhibition described by them previously The agent has limited activity and selectivity in inhibiting the carcinogenesis of the Ras protein most commonly found in human cancers, especially K-ras-AB. Therefore, there is a need for a novel compound having the ability to effectively inhibit K- "as activity Inhibitors: For restenosis K and vascular proliferative diseases, in vivo tests have shown that inhibiting cellular ras can prevent smooth muscle proliferation after vascular injury (--'· (诮 Read the precautions on the back before filling (Coincidentally on this page)

Li. Dimensions of the paper team iiU) Ten 阉 栉 栉 Φ (fNS) Λ4 specifications (2I0X297 public 浼) 3 91506 -.VI 1.'rt. I Ί—t 11. ΛΤ. · Γ. 1 / · — 4 3 6487 A7 B7 V. Description of the invention (4)

Indolfi C. et al., Nature Med., 1995, 1 (6), 541-545). This report clearly supports the role of farnesyl transfer inhibitors in this disease by inhibiting the aggregation and proliferation of vascular smooth muscle. The invention has been studied by the present inventors, and M has developed a compound having a structural characteristic that mimics the state of an intermediate in a FTase-catalyzed reaction. As a result, the imidazole derivative of the present invention can effectively inhibit the enzyme. Therefore, the object of the present invention is to provide an oxazole derivative of formula (1) which has an inhibitory effect on FTase activity, a method for producing the same, and an intermediate which can be effectively used to prepare a compound of formula (1) A hair bun composition comprising a compound of formula (1) as an active ingredient is provided. gfe The present invention aims to provide an imidazole derivative represented by the following formula (I) with a farnesyl transfer inhibitory activity, or a pharmaceutically acceptable amidine or isomer thereof:

(CH ^ np-Y where η 1 represents an integer from 1 to 4, and A represents hydrogen; any straight or branched Ci-Cio alkyl group which may be substituted by C3-C7 cycloalkyl or lower fluorenyloxy; Or select from the following groups: (# 1 Read the precautions on the back before filling out this page)-Binding paper 汴 Ruler Mei tra House (CNS) Λ4 gauge pile (210X297 mm> 4 31506 436487 A7 B7 V. Description of Invention (5

, R4 wherein Ri and Ri 'are each independently hydrogen, halogen, cyano, nitro, hydroxycarbonyl, aminocarbonyl, aminothiocarbonyl, lower alkoxy, phenoxy, phenyl, benzyloxy, or Any lower alkyl substituted with C3-Cs cycloalkyl · R2 shows hydrogen or lower alkyl, or -EP, where E is -CH2-, -C (0)-or -S (0) 2_, And F represents hydrogen; lower alkyl which may be optionally substituted with phenoxy or biphenyl; lower alkoxy which may be substituted with aryl; phenyl; benzyl: benzyloxy; or optionally lower alkyl Group, benzyl or Cs-Cs cycloalkyl substituted amine group, R3 is not hydrogen, lower alkyl or phenyl group, and r4 represents a group selected from the group: + _n2_

R7-|-(CH2):

Rto Ί ~ (〇Η3) π3

(Please read the notes on the back before copying this page).

, 1T J '·' / -ii In the Indian style, π 2 and π 3 are each independently 0, 1, 2, 3, or 4, Rs and R9 are each independently hydrogen, lower alkyl, lower alkoxy, benzene Oxygen, phenyl, hydroxy or halogen, R6 and Rs each independently show hydrogen, lower alkyl, lower alkanoyl, phenoxy Paper size is suitable for t country (SM CNS) Λ4 specification (2! 0 × 297 mm ) 5 9 1. 5 0 β 43 648 A7 B7 5. Description of the invention (6), phenyl, cyano, hydroxy or halogen | R7 shows hydrogen; lower alkyl which can be optionally substituted by C3-C6 cycloalkyl; lower Alkoxy; hydroxyl; C3-C6 cyclofluorenyl; di (lower alkyl) amino; phenylphenoxy; or halogen, Rio is hydrogen, lower alkyl or lower alkoxy, Y is selected from the group Group base:

X.

G

L (read the notes on the back of the reading, and then fill in this page) -packing ', where X shows Cl or S, B shows hydrogen or can be arbitrarily passed through hydroxyl, fluorenyl, lower alkoxy, lower alkylthio or aryl Substituted lower alkyl, C shows hydrogen or lower fluorenyl which can be optionally substituted with aryl; or shows a group selected from the group: ti 屮 if 消 / -ii

〇

Rh • 13 In the formula, each independently shows hydrogen, lower alkyl, lower alkoxy, and halogen. Paper size Xiao Chuanmin Fujian National Standard (CNS) Λ4 specification (21〇297297) 6 9150 6 ^ 1U. Τ -λμ ^ 436487 at B7 V. Description of the invention (7) Cyano, hydroxycarbonyl, amine carbonyl, amine thiocarbonyl, hydroxyl, phenyl or phenoxy ·

Rl3 and R14 each independently represent hydrogen, lower alkyl, aryl or ten (<: Η2) ηΤχ- & 5 where X has the same definition as above, (14 is an integer from 2 to 4, and R 15 is lower Alkyl * D shows an amino acid residue or a lower alkyl ester of an amino acid residue; or a group selected from the group consisting of: flat 10 sub 10 ^ Nv ^ qRo ^ n ^ Ri ° fN ^ Z ^ / ! 6

Rio 115

Among them, the definition of R 1 0 is as before, Q shows 0'S'S = 0 or S〇2 * Z shows 0, S 'S = 0, S〇2, C = 0 or C = S, or CH-R20 or N- R20 (where ho is hydrogen, lower alkyl or hydroxyl), ns is an integer of 1 to 3,

R16 and R17 each independently show hydrogen; aryl; lower alkyl which may be optionally substituted by aryl or cyanoaryl; or + Q-Rio • In the formula, Γ14, Q, and Rio are as defined above * > {18 And 1 {19 each independently show hydrogen; halogen; hydroxyl; cyano; lower alkyl; lower alkoxy; alkoxyalkyl; alkylfluorenyl; hydroxycarbonyl; aminecarbonyl {Please read the notes on the back before filling in this page)

Recognition standard of this paper: Takigawa takahashi family (CNS) Λ4 specification (210X297 mm) 7 91506 436487 A7 B7 V. Description of the invention (8) 'group; amine thiocarbonyl group; alkanethio group; alkanethioalkyl group Alkylthioalkoxy; aryl; or oxy, thio, sulfonyl, or lower alkyl substituted with aryl · ~ G represents a group selected from the group consisting of:

In the formula, * Rll and Rl2 have the same definitions as before, and I represents a lower alkoxy group, or a group selected from the following sister groups:

In the formula, ϋΐβ, R17 and Z have the same definitions as before. L represents a basis selected from the group: Ν ′

In Z is the formula but Q and H as defined previously are hydrogen 3 R and ο are not 2 η (please read the precautions on the back first / .. this page)

This paper is suitable for Sichuan and Fujian National Standards (CNS) A4 specifications (210X 297 mm) 8 9 1506 436487 A7 B7 V. Description of the invention (9) \ (2) When A is, Y is not

X Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. In particular, the compound of the present invention has a structure quite different from that of conventional farnesyl transferase inhibitors, and in particular, the compound of the present invention does not contain a fermenting moiety. In the definition of a substituent of a compound of formula (I), the term "lower fluorenyl" means a straight or branched fluorenyl group having 1 to 4 carbon atoms, and includes methyl, ethyl, isopropyl, iso Butyl and tertiary butyl. Since the compound of formula (I) according to the present invention may have an asymmetric carbon atom depending on the substituent, the compound may exist in the form of a KR or S isomer, a racemate, or a mixture thereof. Therefore, the present invention also includes all of their stereoisomers and mixtures thereof. The compound of formula (I) according to the present invention can also form a pharmaceutically acceptable hydrazone. Such hydrazones include non-toxic acid additions containing peony acceptable anions, such as hydrazones formed with inorganic acids such as osmic acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, azaiodic acid, etc., and fluorinated carboxylic acids such as tartaric acid. , Formic acid, citric acid, acetic acid, triacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, aspartic acid, etc., or with sulfonic acids such as methanesulfonic acid Plutonium formed from acids, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, etc .; sickle-added plutonium, such as plutonium with pyridine or ammonia; and metal-added anthrax, such as with alkali metals or plutonium-II I—I -In:-II--1i Shit In I (Please read the notes on the back before filling this page) The size of the paper is applicable to China National Standard (CNS) A4 (210X297 mm) 9 91506 4 3 64 8 7, A7 B7 V. Description of the invention (10) The gold of the earth is like a lithium *. Furthermore • The present invention comprises a vehicle compound * of a compound of formula (I) such as its alcoholate or hydrate. These compounds can be prepared by conventional transformation methods. Among the compounds of the present invention (1), the compounds with a higher content include those in which each substituent is defined as follows: ni represents an integer of 1 to 3, and A represents hydrogen; it may be optionally substituted with a C3-C7 cyclofluorenyl group or a lower alkoxy group. Straight or supported Ct-Cio group; or a group selected from the following groups: (Read the precautions on the back before filling this page j

Where

Ri and R " each independently represent hydrogen, halogen, aryl, nitro, hydroxycarbonyl, amine carbonyl, amine carbonyl, lower alkoxy, phenoxy, phenyl, benzyloxy, or any of C3-C6 Cycloalkyl-substituted lower alkyl> R2 represents hydrogen or lower alkyl, or -EF-, where E is -CH2-, -C (0)-or -S (0) 2-, and F is hydrogen ; Lower alkyl which may be optionally substituted with phenoxy or biphenyl; lower alkoxy which may be substituted with aryl; phenyl i benzyl; benzyloxy; or optionally lower alkyl. Or Cs-Ce cycloalkyl substituted amines. R3 is hydrogen or lower fluorenyl. * R4 is a radical selected from the following groups: Paper size tracking / 彳 丨 taker standard (CNS) Λ4 specification (2 丨OX297 male Zhao) 10 91506 A7 4 3 64 8 7 B7 V. Description of the invention (1 1) _

In the formula, Π2 and Π3 each independently show 0, 1, 2, 3 or

Rs, 1Ϊ6, R8 and R9 each independently represent hydrogen, lower alkyl, lower alkoxy, light or halogen. R7 represents hydrogen; lower alkyl which may be optionally substituted by C3-C6 cycloalkyl; lower alkoxy; hydroxyl; C3-C6 cycloalkyl; or nan, R10 represents hydrogen, methyl or methoxy, Y It is selected from the following sister groups:

Where X represents 0 or S > B represents hydrogen or a lower alkyl group optionally substituted with a lower alkoxy or aryl group, and C represents hydrogen or a lower alkyl group optionally substituted with an aryl group; Group basis: {Please read the notes on the back before filling in the clothes page)

436487 A7 B7

5. Description of the invention

Rt2 ^ 0 ~ R, 2 Rn

I N. I Rn, Ri + In the formula, min ^ and ^^ each independently show hydrogen, lower alkyl, lower alkoxy, halogen, cyano, aminocarbonyl, phenyl or phenoxy, and R13 and R14 each independently show Hydrogen, lower alkyl, aryl or ten (where X is as defined above), Π4 is 2 and Ris is lower alkyl * D shows amino acid residue or lower alkyl group of amino acid residue or optional From the bases of the following groups:

fl〇 子 iO Ν I Leather! 0, Z tN 'R, • 17 (Please read the precautions on the back before filling out this page) Binding-Ordering Department k it if i / i f ΐΐ

Rl9

N

R [s R 19

RiS Rl9 where * R i 〇 has the same definition as before, Q indicates 0 ′ S 'S = 0 or S〇2 • Z indicates 0 ′ S' S = 0, S〇2, or C = 0 or CH-R20 or N -R2〇 (where R20 is the paper's iic scale m 丨 'National Standard Engine (CNS) 8-4 specifications (2 丨 Ox297 mm) 12 91506 4 3 6487 A7 * B7 V. Description of the invention (13) hydrogen, lower alkanes Radical or hydroxy), ns represents an integer from 1 to 3,

R16 and R17 each independently show hydrogen; aryl; lower alkyl which may be optionally substituted by aryl or ^ aryl; or + (CH2) nT ^ -Ri. In the formula, the definitions of Π4, Q, and R 1 0 are as before, and R18 and R19 each independently show hydrogen; halogen: hydroxyl; gas group; lower alkyl; lower alkoxy; alkoxyalkyl; sulfanyl; Carbonyl group; amine carbonyl group; amine thiocarbonyl group; alkylsulfonyl group; alkylthioalkyl group; alkylthioalkoxy group; aryl group; or oxy group, thio group, sulfonyl group or lower alkyl group substituted with aryl group * G shows From the group of the following groups: (Please read the precautions on the back before filling this page), installed ·: 1 ·· Order

LT style *

The definitions of Rll and Rl2 are as above * I represents a lower alkoxy group, or a group selected from the following groups:

Among them, the definitions of Rl6, Rl7 and Z are the same as above. L indicates the basis selected from the following groups: 91506 Paper size 10 1 ¾ Store standard (CNS) Λ4 size (210X297 mm) A7 B7 436487 V. Description of the invention ( u \ Ή / Q— where Z and Q are defined as before, but (1) when R3 is hydrogen · η2 is not 0, in time, Y is not (please read the precautions on the back before filling ^ this page)

Β • C

X

R] '(2) When A is • N

Order ™ i

X The Ministry of Economy, Ministry of Standards and Labor of the People ’s Republic of China.

B Ή Compounds The general examples of the compounds of formula (1) of the present invention are shown in the following table 1. The paper size is applicable to Chinese National Standard (CNS) A4 (2! 〇 × 297 mm) 14 91506 • M *,

And ii .1 ·; /) 't A ii 卬 V 436487 V. Description of the invention (15 Table 1-1 A7 B7 Compound number structure Compound number structure ° \ J.. 9., 3 1 2 .Id.' N '〇 0

N

6 ^ Paper Ruler State Network China Standard (CNS) Λ4 Specification (210X297 mm) {" Read the precautions on the back before filling this page) d. / ^ 0 0

N

, N

N

* 1T

15 91506 43 6487, A7 B7 V. Description of the invention (1 6.) _ V '· Table 1-2 Compound number structure Compound number structure. Structure 7, N [:] 1 8 9 ^, KN〇r 9, 〇 / 10 .cf N〇r. 〔] N [11 12 、 0 '(" Read the precautions on the back before filling in this page) / Pack. Order' ^ 11 Zhang Xiao Xiao) 丨 11 !, Valve Country 橾((^ 5 > / \ 4Specifications (21〇 乂 297 漦) 16 91506 厶 3 6 4 8 7 A7 B7 I ---. · * ≪ · — — —- * — ..---. _— 'M —ΙΙ · II I Ι ·-| · Γ · Ι--V. Description of the invention (1 7) ^ 1-3 β " 部 屮 "' " i? ^: JB '--elimination In ^ 仂. &Quot; " ^ ·

---------1, install-tis first read the precautions on the back before filling this page)

* 1T 17

1δ

屮 柯 闽 家 标 隼 (CNS > M specification (2 丨 OX 297)) 17 91506 ^ 4 3 6 ^ 37 A7 'B7 V. Description of the invention (18) Table 1-4

& Zhang Zhishi Jrt Chinese valve national standard i CNS> Λ4 specification (210X297 mm) 18 91506 (诮 1 Read the precautions on the back and fill in the i-'g page), order r 4 3 6487 a; B7 . r _ _ __ .__, *, a _ · —---· * ^ * V. Description of the invention (1 9) Table 1-5 # ΐ: ·; Γ 部 屮 打 ifi, JvJ! T- 消# " μ. '' ξγύ

ITk recognizes Shizhou t four countries 橾 (CNS) Λ4 ^ grid (2! 0 × 297 public t) 19 9 15 06 (诮 Please read the precautions on the back before filling in this page > 装-

1T A7-B7 V. Description of the invention (2 Ο) Table 1-6

(诮 Please read the precautions on the back before writing this page) The paper size is appropriate; 丨] Ten countries in the Min family (CNS > Λ4 is present (2) 〇 × 297 mm) 20 91506

ίΐ \ 部 t if 消 j! Aii 0 'f 436487 V. Description of invention (21) Table 1-7 A7 B7

-1 II.: L: il- tn ^ 1 ^ 1., .. 11 -I (Please read the note on the back first and then fill out this page.) Λ4 specification (210x297 mm) 2 1 91506 h <.; Γ · ten iV Λ f Combined: 4 3 64 8 J V. Description of the invention (2 2 Table 1.8 A7 B7

This paper is in Shizhou 1¾ National Standard Rate (CNS) Λ4 specification (210X 297 mm) 22 91506 ------------- (Read the precautions on the back of the first cabinet and fill in this purchase) Ϋ-ϋ 4364 87 A7 B7 V. Description of the invention (23) Table 1-9 Chemical structure number Compound number • Structure ― 44 0 45 Η ^ ζχ ^ ύ / j 0 46 Η ^ < χ〇 ~ 0 0 47 Today 0 Br 48 < X ^ 〇er 0 49 0 50 < xSp 0 ch3 51 iX ^ 〇Y〇vCH3 0 52 < x ^ aCH3 0 53 0 (rNS) Λ4 specification {2I0X297 male; i) 23 91506 (谙 Read the precautions on the back before writing this page) d. Order A7 436487 B7 V. Description of the invention (24) Table 10 10 丨 Composition and assembly costs! \ mm Chess color silver 1 J. '»t structure 54 < x5a0CH! 0 55 < X ^ p 0 Cl 56 < xa ^ acl 0 57 each. 0 Cl 58 < x ^ 0 59 < χ ^ 7Ρ 0 F 60 〇3 < Xn〇 / 7cn 0 61 0 62 0 63 < χ ^ α0 ^ ° ί ------------ 2—— (诮 Please read the notes on the back before filling (This page) The size of the paper is suitable for Chuanzhongwei standard (CNS) Λ4 specification (210X297 mm) 24 91506 A7 B7 Explanation (25) Table 1-11 < J / l ^ ν. AW π—chemical profile fee 1 & structure a fc fu 1 chemical profile 鸯 ^ knot '64 < χ ^ Χκ 0 65 66 LxS ^ 0 67 ^ £ σ ° Ό 0 68 0 69 70 0 71 Knee i 0 Cl 72 j 1 i win. t O Cl 73 NC ° (诮 Please read the precautions on the back before writing this page) 'Packing. Binding paper 讥 Dimensions 州 州 十 ΝΝ 阐 家 梯 i?-(CNS) 44 specifications (2) 0 × 297297 苈25 91506 ..I; r 屮 Jk i ". Consumer IV ΐ t '4 3 64 8 7 V. Description of the invention (2 6 Table 1.12 Α7 Β7 Compound number structure 74 76 78 80 82

NC

NC

〇 NX) This paper describes the claw valve Minjiao grass (CNS > Λ4 size (210X 297 male 1)) according to the size. Compound No. 75 77 79 81 83

26 91506 A7 ^,-. ¾ 屮 —K η; Α ′ · 5 ^ and Μ. ^ 印 4 3 6 4 8 7 B7 2 7 V. Description of the invention () 'Table 1-13 Compounds and toughness 7 Structure compound number Structure-.84 0 85 CK 0 86 0 '.87 0 S8 < V ^ OH: 0 89 < χ ^ 〇 " 3 0 90 Η 中 < χ ^ ο 0 91 0 92 | ί < χ £ σ ° j 0 93 Ύ \ < Χ ~ u〇H 0 i --------— ^.} ¾— · ---- ·. (诮 Please read the notes on the back before filling in this tile) The paper ruler passes through the Sichuan-Fujian national rate (CNS) Λ4 is present (2 丨 0 X 297 mm) 2 7 9 1 5 0 6 4 3 64 8 7 a? The 'B7 Five' invention i 28) Table 1-14-Α " ίν ^ :; ίί-.; νί ^^ Works ··

Compound No. Structure Compound No. m m 94 0 95 <N h3 0 96 0 97 0 98 0 99 Γ. cC ". 100 NC 101 NC Ά r &gt; Y ^ C〇: s 102 NC 103 1 NC Ά rj rC ^ co'-H i Paper size, Shizhou, 丨, CNS Λ4 size (2! 0 × 297)尨) 28 91506 {Please read the notes on the back before filling out this page) 装--* 29 il- ； / ί /. 43648. V. Description of the invention (Table M5 A7 B7

This paper recognizes the national standard (CNS) in the claws and describes the national standard (CNS) Λ4 specifications (2 [OX 297 公 f) 29 9 1506 ---: ---- ^ ---} equipment-〆ί \ {诮 尤 Read the back Note for refilling this page) l1T. A7 4 3 6487 B7 V. Description of the invention (30) Table 1-16 Compound number structure cold 丨 Compound number — Structure 114 〇115 iSw 0 116 aSw 0, · 117 0 118 H, C 0 119 0 120 0 121 CU ^ rl〆0 122 1 f 123 1 0 (诮 Please read the precautions on the back before filling in this page): Packing _ Booklet and Paper Ruler Escape 丨] China Valve Country Standard (['Yang] / \ 4 specifications (210/297 mm) 30 91506 64 87 A7 B7 V. Description of the invention (31 I) 1 · 部 ， kf A 卬

Size of this paper j'un 1 W W Jia Jia Bei (CNS) Λ4 specification (2Ι0 × 297 mm) 3 1 91506 (please read the precautions on the back before writing the page on this page) Binding. Order

V. Description of the invention (3 2) Table ι-is Compound number structure 编号 134 135 Nine t κό 0 \ 136 x6 'q 137 0 138 ζ &gt; ο 139 NC 140 141 (诮 Please read the note on the back first Matters need to be refilled on this page) Binding. Binding—The paper team ’s standard speed regulation valve national standard (CNS) Λ4 specification (2 丨 0X297 mm) 4 3 648 7. A7 B7 V. Description of the invention (33) Table 1- 19 Compound No. Structured Na No. Structure 142 Βο143 0〇olxH χ ^ —ο / 144 Q〇 like brother 145 \ ς〇CU ^: — 146 Qo CM 147 ^ 〇D CLrk— 1. 〆 148 ^ 0〇 &lt; xrH 149 I Ch 03 CU ^ 〇 (Please read the precautions on the back before transferring this buttercup). Binding. The size of the paper is stated in the national standard 4M CRS. Λ4 specification (2I & X 297 male) 33 91506 ^ 4 3 64 37 · 'A7 B7 V. Description of the invention (34) Table 1-20

&gt;, Paper 汍 standard iM CNS 追 4 size (210X2W public 牦) 34 91506 (Read the precautions on the back before filling out this page)-Pack · * 17 35 units 屮

j.i.T Consumer f A 436487 V. The invention is not clear (Table 1-21 A7 B7

(Please read the precautions on the back first and then write each page.) Pack. 1 &quot;! Σ This paper size j′un Ten internal valve house standard 丨 (CNS) Λ4 specification (2 丨 0 × 297 male) 35 91506 436487 A7 B7 5. Description of the invention (36) Another object of the present invention is to provide a method for producing an imidazole derivative of the formula (1) as defined above. According to the present invention, the imidazole derivative of the formula (1) can be produced by the following methods. The special advantages of these methods are: (a) The compound represented by the following formula (2) is in a solvent. 3) The compound shown is reacted, and then the trityl · K in the product thus obtained is removed in the presence of trifluoroacetic acid to obtain a compound represented by the following formula (la): Reaction formula 1 (诮 Please read the precautions on the back before Fill ^: this page) ^ ^ (CH2) nrCl · HC1 + HN '/ (2)

Solvent TFA D m

HN B '(CH ^ npH (la)

DX,-口 屮. 央 ίΐri; or (b) reacting a compound represented by the following formula (4) in a solvent with a compound of the formula (3) in the presence of a base * to obtain a compound represented by the following formula (lb) : Reverse membrane 忒 2

AN, solvent 7 A N- ^. '.- (_ η 「α.Ηα + Η \ Χ ^ 轮 J- (CH2) nrNs D C4) (3) X N- J1 ·· A i'i; or ( c) The compound represented by the following formula (5) is reacted in a solvent * with a compound of the formula (3) in the presence of a base * in the presence of triacetic acid to remove the trityl product thus obtained. (6) Compounds shown * followed by hydrogenation reaction. Paper size 琏 川 | 丨, Jia Jia Gu leather (CNS) Λ4 size (210X 297 mm) 36 9 1506

4.36 ^ 37 a? B7 V. Description of the invention (3 &gt; 7 to produce a compound represented by the following formula (lc): Reaction formula 3

Or (d) hydrolyze a compound represented by the following formula (7) to obtain a compound represented by the following formula (8) * Then, in the presence of a coupler, react with a compound represented by the following formula (9) to obtain the following formula (Id) Compound: (诮 Please read the precautions on the reverse side, and then go to this page) Reaction 忒 4

Or (e) In the presence of a vulcanizing agent, the carbonyl group in the compound represented by the following formula (le) is converted into a thiocarbonyl group to obtain a compound represented by the following formula (If): Reaction formula: 5 1. CNS Standard Λ4 Specification (2! 0X297 mm) 37 9 15 0 6 436487 A7 B7 5. Description of Invention (3) 8

B

B 3h (CH2) nrN () e)

D vulcanizing agent. 0

+ HCH2) n 「: CH2) nrN GO

D

Or (8) coupling a compound represented by the following formula (lg) with a compound represented by the following formula (10) in a solvent to obtain a compound represented by the following formula (lh):

R2—Τ (10) Solvent

D --------.-- 1J clothing-(诮 Read the precautions on the back first and then fill out this I) -3 or; (s) Make the compound shown by the following formula (11) ring in an inert solvent Into a compound represented by the following formula (1 i):

Or (h) convert the amido group in the compound of formula (11) to thiosamino group 1 M to produce a compound represented by the following formula (12), and then cyclize the paper in an inert solvent and store it at an appropriate scale House standard (CNS &gt; Λ4 specification (210X297 mm) 38 9 15 0 6 A7 B7 436487 V. Description of the invention (such as to produce the compound represented by the following formula (Π)

, N cij)

〇; or (i) A compound represented by the following formula (13) in a solvent is reacted with a compound represented by the following formula (14a) * to obtain a compound of the following formula (lj): Inverted tendon 9 {&quot; Read the note on the back first Matters are refilled on this page), order * order

A

Ν S 03) NH2

Cl Ο

+ G- y, I 〇 solvent (14a) 〇; or (J) reacting a compound of the following formula (13) with a compound of the following formula (14b) in a solvent to prepare a compound of the following formula (lk):忒 H) k \ N, ί

XT (13) Ο Ο ct (Mb) A i M Solvent

CH, (lk); or paper-size national sample apple (CNS) Λ4 specification (210X297 male) 3 9 9 1506 A7 3_6 4 8_7 V. Description of the invention (40) (k) Let the following formula ( 11) The compound shown is hydrolyzed in the presence of a base, and the product thus obtained is in a solvent * reacted with a compound represented by the following formula (15) in the presence of a coupling agent to prepare a compound of the following formula (lm):

Or U) reacting a compound represented by the following formula (16) in a solvent with a compound represented by the following formula (17) in the presence of a base to prepare a compound of the following formula (In): trans_formula 1 2

(Please read the precautions on the back before filling in this page.) Install ·; or (m) make the compound of formula (18) below in a solvent | in the presence of a base, react with a compound of formula (17), and then deprotect it In order to obtain the compound represented by the following formula (10), and then combined with the compound represented by the following formula (19), the compound represented by the following formula (lp) is prepared: Reverse formula: 1: ¾ The paper scale is suitable for Sichuan Due to the national standard (CNS) Λ4 specification (2) 0 × 297 males) 40 9 15 0 6 4 3 6 4 8 7 V. Description of the invention A7 B7, 41

Cbz

+ H-N

Η

T—E-F (19)

(诮 Read the precautions on the back before filling the page j 'pack. · Ί &gt;;ί; 屮,' J; iV η j: l'i f: · A 中 In the above reaction formula, A, ni, B , C, X, D, R16 Λ Ri7, R2, G, I, L, B, and F have the same definitions as above, I ′ represents a lower alkoxy group, and I ”has the same definition as I, but does not include a lower alkoxy group * T indicates a radical or a reactive leaving group, preferably halogen * Tr indicates a tribenzylmethyl group, CbZ indicates a benzyloxycarbonyl group, and the definitions of the symbols throughout the text are the same. However, the compounds according to the present invention can be combined by Any method designed by various synthetic methods known in the art can be easily produced, and the combination can be easily performed by those skilled in the art. The methods (a) to (m) are described in more detail below. In the methods (a) to (e) of the compound of the present invention, any inert solvent can be used as long as it does not adversely affect the reaction. The preferred solvent is one or more selected from dimethylformamide and dimethyl. A group consisting of acetamide, ethanol, water, digasmethane, chloroform, tetrahydrofuran and N-methylpyrrolidine. As for tritium, it can be described One or more types selected from sodium hydride, potassium hydroxide, paper, and paper towels, 1¾, family standard (CNS), Λ4 size (2IOX, 297 mm) 41 9 1506 A7 Λ 3 6 厶 8 7 Β7 ^ 卬 Λ 'V. Description of the Invention (42) 1 i Ν Potassium carbonate, third potassium butoxide, ammonium bis (trimethylsilyl) II, ammonium sodium and bis (trimethylsilyl ammonium potassium ammonium potassium) For the group, it is better to mention sodium oxide or potassium hydroxide in 1 I. As for the method used in this method «using a coupling agent for reacting a compound of formula (8 read 1 1 first i) with a compound of formula (9) is 1-Hydroxybenzitriazole and 1 1 1 or more mixtures selected from the following materials, which can be selected from 1 1 by ISS m Diimide such as dicyclohexylcarbodiimide (DCC ), 1-Ethyl-3-(Italian j-based item 1-3 1-Dimethylaminopropyl) carbodiimide (EDC) Ψ 1-1 -dicarbonyldioxazole (again. 1-·!) CD I), etc., and inorganic dehydrating agents such as tetrachloropolysiloxane. Among them, 3 is particularly preferred. (3-Dimethylaminopropyl) carbodiimide (EDC) and 1 &quot; Hydroxybenzotriazole water 1 i mixture 0 1 1 I for S Formula (1 e) Compound Preparation Formula (1 η The compound's vulcanizing agent contains 1 1 order 2,4-bis (phenylthio) -1,3 di-2,4-diphosphate (ph 〇SP ha tane)-1, 2, 4-disulfide, Rowanson's (L a Ve es so η 'S Re age η t) and 1 1 P4 Si 0. It is best to use 2,4-bis (benzylsulfur) ~ 1,3-di-m-2,4-diphosphate 1 1 alkane-2,4-disulfide 4 :. : i in method (f)-using a compound of the formula (lg) as a starting material, 1 I can be reacted to tite 1 1 1 compound by protecting at the position of the hydrogen pyridine moiety -1 hydroxybenzyloxycarbonyl Made for protection. The deprotection reaction can be performed by the application of the conventional reaction I 1 I condition, which is preferably under a hydrogen gas garden »in a fermentation solvent» using 1 1 Pd (OH) 2 / C or Pd / Cifi. The compound of formula (1 s) thus obtained is contained in the anthracite solvent described in the first 11 above. • If necessary in the presence of a tertiary amine base »is combined with a compound of formula (10) i 1 to obtain a compound of formula (1 h). The compound of formula (1 g) is reacted with the dwarf: acid-derived shuttle (τ = 0H) in the presence of the coupling agent described in Method 1 1 * to obtain a compound of formula (lh) of 1 I amine form 〇 1 i Paper size Chasing ;!) 屮 Minhu family brown standard (CNS) 8 4 specifications (2.0 × 297 mm) 42 91506 厶 3 Μ 8 7 Α7 Β7 V. Description of the invention (43) In the manufacture of compounds (li) and (lj) In the cyclization reactions (U) and (h), any inert solvent may be used, but one or more selected from the group consisting of tetrahydrofuran and acetic acid is preferably used. As for the vulcanizing agent used in the conversion step of converting amidine to 1 into thiamine in method (h), 2,4-bis (phenylthio) 1,3-diqu-2, 4 may be mentioned -Alkane diphosphate-2,4-disulfide, Rowanson's agent or P4Si0, preferably Rowanson's agent. In the methods (i) and (j) for producing compounds (U) and Uk) by reacting a compound of formula (13) with a compound of formula (14a) or (14b) *, one selected from ethanol and isopropanol can be used Of one or more solvents. Furthermore, in the method (k) for preparing a compound of the formula (lm) by subjecting the compound of the formula (U) to hydrolysis, and then reacting with the compound of the formula (15), a general hydrazone can be used, such as selected from One or more of the groups consisting of lithium hydroxide, sodium hydroxide and potassium hydroxide. As the coupling agent, those described in method (d) can be used. In the methods (1) and U), any inert solvent may be used as a solvent, but it is preferred to use one or more selected from dimethylformamide and dimethylacetamide, and use selected from sodium hydride One or more of the groups consisting of sodium sulfonamide, sodium bis (trimethylsilyl) sulfonamide and potassium bis (trimethylsilyl) sulfonamide are used as bases. The deprotection reaction in method (m) can be performed under conventional deprotection reaction conditions, and is preferably performed in the presence of * Pd / C or Pd (0H) 2 / C in a hydrogen atmosphere. Furthermore, a coupling agent for coupling a compound of the formula (10) with a compound of the formula (19) is the same as that described in the method (d). According to the present invention, the compound of formula (3) which is used as the main intermediate of the methods (a) to (c) for producing the compound of formula (1) is itself a neofluoride compound. Therefore, another object of the present invention is to provide a compound of formula (3). As explained below, in the test paper, one of the interpreters in the test state refers to the (_CNS_) A4 specification (210X297 gong) ^ 43 91506 (诮 Please read the precautions on the back before filling out the supplier's page).

1T A7 B7 X3 6_4 _B 7 — __ 5. Description of the invention (44) The compounds of formula (3) according to formulae 14 to 1δ can be prepared by the following method, which is characterized by the following formula (20) The compound shown in the solvent is reacted with the compound represented by the following formula (21) in the presence of a coupling agent; the chemical compound of formula (20) is in a solvent and reacts with the subunit in the presence of dimethylformamide (DMF) Thiochlorine is reacted to prepare a compound represented by the following formula (20a), and then the compound of the formula (20a) thus obtained is reacted with a compound of the formula (21) in a solvent; A compound of formula (3b) is obtained. Arbutin 1 4

B

DH (20 Couplings (3) (Please read the notes on the back before ^ 荇 this page) Order Reverse film 1 5

S〇CI2

DH (21) Solvent (3) Λ Department 屮 Elimination Reaction 忒 1

H-N

B

B

〇 · 〇 This paper is based on the National Standards of China (CNS) in Shizhou Λ4 (210 × 297); i) 44 91506 4 3 6487 A7 B7: in 屮 '1'. Lose Cen X.j /-

A 5. Description of the invention 45) 1 | In the above-Λ reverse ate formulas 14 ^ 15 and 16, the definitions of B, (:, and D are as ί, and Q a shows S or 1 1 I 〇-V is used in the above. In the reaction formulas (1 4 &gt; to U6) for the production of compound (3), please read it first. Note 1 1 i Any inert solvent can be used 3, but the best choice is g dimethyl l ~ i ~ f Jfcti Methylamine &gt; 1 dimethyl ethyl. One such as tetanine dichloromethane tetrahydrofuran and 1 2--dichloroethane 1 1 or more as the solvent. As for the couple in reaction formula 14 Mixture t can refer to a mixture of 1-hydroxybenzotriazole and __. One or more of the following substances are selected, and they are filled in by J Liang.% This page 1 substances are made of diimines such as dicyclohexyl Carbodiimide (DCC) \ I 1 -ethyl-3- (3-dimethylaminopropyl) carbodiimide and other groups selected from the group of _-1 | Among them, the best is 1- Ethyl-3 (3 &quot; dimethylaminopropyl) carbodicarbonate Mixture of imine 1 1 I (EDC) and 1-hydroxybenzotriazole hydrate &gt; The amount of catalyst used in the formula 1 of the reaction formula (15) is 1 g. It is better to use benzoic acid as a hydrogenating agent in the process of ordering. However, 1 1, coupling agent 9 oxidant solvent catalyst can be selected in addition to those mentioned above i 1 Μ appropriately selected 1 as long as the reaction can be completed It can be large. The reaction conditions include the reaction temperature. The reaction temperature and reaction time of the reactant can be determined by the person skilled in the art depending on the specific reactant. 1 I ϊ Since it is used in method (d) as A compound of formula (8), which is a 1 1 intermediate used to produce a compound of formula (Id), is like a compound of formula (3) —a novel 1 i compound »Another aspect of the present invention— * i is to provide formula ( 8) Compound. The 1 compound can be prepared by hydrolyzing a compound of formula (7). 1 1 On the other hand 1 The starting material used in the above method can be prepared by the specific method described in the following inverse 1 Ι nte according to formulas 17 to 2 〇 First ι is protected by the following reaction 17 And halogenation reaction can produce 1 1 氺 paper music scale. Speed;! 1 Chinese valve national standard (CNS) Λ4 specifications (2IOX297 mm) 45 9 1506 4 3 6487 A7 B7 V. Description of the invention (46 formula (2) Compound. Look back: 1 7

_d0H << N &gt; (CH2) nrOH 1〇 邙 .τ /, (2) • HCI where A is a 4-cyanobenzyl compound of formula (4) can be protected and tritiated as described in reaction formula 18 below , Coupling, deprotection and halogenation. Compound (4) is more often obtained by reacting an amine compound with dihydroxypropane to obtain a mercaptoimidazole derivative, followed by desulfurization and halogenation as described in Reaction Formula 19 below. Detailed reaction conditions can be referred to similar reactions detailed in J. Med. Chem., 33, 1312-1329, 1990. Inverted tendon palate 1 «

TrCl (Please read the notes on the back before writing this page} A. .1 -5

(CH2) n-OH • HCI

DMF / TEA .N, _ Ac-, 0-(CH2) nf &lt; 3H-: ~ &gt; Bft 卩 Tr << (CH2) nf 〇Ac

TFA CH2Ct

K2C03 (CH2) nr〇Ac MeOH

2 ^ (CH2) n-OH SOCl2

(CH.JnpCI

, CN

HCI paper scales pass through the Chuan'bu Hoon Min family standard (CNS) Λ4 specifications (210X297 mm) 46 91506 4 3 6487 5. Description of the invention (47 A7 B7 〇

KSCN H0.

.OH ANH. ^ Cl '

NaN02 hno3

N

H SOCl ·, A used in reaction formula A shows 1- (benzyloxycarbonyl) and hexahydropyridine-4-ylmethyl amine compounds. It is synthesized by the protection, benzyloxycarbonylation reaction and deprotection described in 20. (Please read the note i on the back before filling this page)

i) CbzCI Guangjiacui benzaldehyde toluene

Js ii) KHS04 'f nh2 In the above reaction formula 20, CbzCl represents benzyl benzoate, and the symbol is defined throughout the specification. The compound of formula (5) can be synthesized by esterification, protection, selection, and halogenation reaction as described in reaction formula 21 below.

I

CbzN

Reaction 忒; η meaning :) -t; / i fi. 合 ii

ΌΗ

HCI

MeOH

OMe

TrCl / ΓΕΑ N DMF

OMe

SOC1-,-»CHCb

This paper is a literary scale of the State Ten-Valve Solid Family Standard (CNS) Λ4 specification (210X297 mm) 47 915 0 6 4 a G4 37-A7 B7. 5. Description of the invention (4 8) In the above reaction formula 21, DIBAL shows hydrogenation Diisobutyl aluminum. (Please read the precautions on the back of the pin, and then fill in the {: ii page.) In addition, in the above reaction formula 21, the alcohol compound obtained before the final chloride is produced can be obtained by conventional methods. ~ Chlorine reaction to prepare a compound of formula (2) in which niS 3 is prepared. The compound of the formula (20) used as a starting material for preparing the intermediate of the formula (3) can be prepared according to, for example, the method described in the following reaction formula 22 (a method starting from naphthaldehyde). In particular, the intermediate of formula (3) in which D is 1-naphthyl can be easily synthesized according to the reactions of reaction formulae 23 and 24 below.

Recognition of the scale of this paper It 1 ¾ ¾ family size (CNS) Λ4 specifications (2! OX 297 mm) 48 9 1506 436487 A7 B7 V. Description of the invention (49 Reaction Formula 2 4

i) n-BuLi a

sO

hdc / hobt / r13runh ii) 1 Ηι) ΒΤ

NR13R14

TosMIC / t-BuOK

In the method (g), using the compound of the formula (n) as a starting material, the phosphonium acid of the glycine ester derivative and the phosphonium acid of 4-oxazoleacetic acid can be obtained by the following 逑 Reaction Formula 25 Made by coupling. As for the coupling agent *, those described in method (d) can be used. The compound of formula (13) used in method U) can be prepared according to the procedure described in the following reaction formula 26 * using the chloride derivative obtained in reaction formula 19 as a starting material. Reverse film type 2 5

f Mixture HCI. Solvent (please read the precautions on the back before writing this page) ..-¾ t i?

CI

'G

NH2 Paper size 10 12 National Standard (CNS) Λ4 specification (2 丨 0 &gt; &lt; 297 publicly available) 49 91506 A7 B7 V. Description of the invention (δ〇) Used in methods U) and ii) of compounds (14a) and (14b) can be prepared according to the following reaction formulas 27 and 28, respectively. First, a compound of the formula &lt; 14a) can be synthesized by reacting an aldehyde derivative with methyl dichloroacetate in the presence of potassium third butoxide. The compound of formula (14b) in which I is 1 ′ can be synthesized by reacting a ketone derivative with a dialkyl carbonate in the presence of hydrazone: sodium sulfide, and then reacting the product thus obtained with a thiocarbazone. .

G, H 〇 C1.

Cl

Cl ο

t-BuOK / t-BuOH G〆 Ya, I 0 (14a) (诮 Read the precautions on the back before filling this page) 'Load' Reactive formula 2ft,-= 5

O A

NaH / r2CO q o o S02Cb 1,2-dichloroethane σ

Finally, in methods (1) and (m), * G represents 1-naphthyl, and L represents N-methyl-N- (2-methoxyethyl) amino. The reactant of formula (17) * The following formula is reaction formula 29, which is prepared from buprofenal. Other compounds of formula (17) having different substituents can also be prepared by referring to Reaction Formula 29. Reverse film type: 29 papers X degree Shizhou national valve standard (CNS), \ 4 size (2ί〇 × 297 mm) 5 0 91506 A7 B7 V. Description of the invention (51)

+ -NH—

Η

{Please read the notes on the back before filling this page) Order The compound of formula (1) prepared according to the above method has inhibitory activity on farnesyl transferase, so it can be effectively used as an anticancer agent. Therefore, the present invention also provides a pharmaceutical composition comprising the novel compound of formula (1) as defined above or a medically acceptable hydrazone or its isomer as an active ingredient and a pharmaceutically acceptable drug. Agent. In particular, the compound of formula (1) is very effective for treating cancer, restenosis, atherosclerosis, and infections caused by &lt; 5 M hepatitis and related viruses. When the active compound of the present invention is used for clinical use | It is preferably administered in an amount of 10 mg to 100 mg per kg body weight per day. Single-day source doses can be administered in single or divided doses. However, the specific dosage of the patient can be adjusted according to the paper standard in the state of Shizhou (CNS) Λ4 now (210X297 mm) 5 1 9 1506 4 3 6 4 8-, A7 B7 Mi &quot; 梠 i? -x, Ju V. Description of the invention (5Σ)-1 I Specific compounds for use 9 Patients' weight and sex% of treated patients Hygiene conditions Soft food 1 I, Dosage time or method% Excretion rate * Mixture ratio of Cai agent 1 Medical treatment 1 1 I The severity of the disease varies, etc. 0 1 1 Read! I The compound of the present invention can be administered in the form of K-li injection or 0 eye preparation. 0 no read \ 1 read 1 | Or the oily suspension can be prepared according to the conventional 1 | 1 1 Step 1 Use a suitable dispersant, wetting agent or suspending agent to prepare it. Note that car 1 The solvent for preparing injections contains water Ringer's (R i η ger 'S) Liquid and Na C 1 and 1 4 (Solution 0 In addition to -4ur M bacteria fixed oil (F 1 X ί η g 0 1 1) can be advantageously used as a JT i as a solvent or suspension medium. Any Λαιm Fixed oils containing mono or di 1 | glycerides »can be used for this purpose 0 fatty acids such as oleic acid can also be used as 1 1 I injections 0 1 I As for solid preparations for P administration can be mentioned capsules, tablets N Drugs [pills &gt; powders and granules, etc. t are preferably capsules and lozenges. 0 recording agents and pills are adjusted [[formulated into enteric coating agents are also desirable 0 solid preparations can be made by using as in the present invention 1 (1) The active compound of the formula (1) is grouped with at least 1 species of inactive diluent (such as sugarcane powder, lactose m powder, etc.), lubricants such as magnesium stearate, disintegrants, and binders. The selected carriers are mixed to obtain 0 1 1 The examples illustrate the present invention in more detail. However, rthr should understand the following 1 1 The examples are only used to illustrate the present invention and should not be used to limit the scope of the present invention. 1 i is used to make the starting material of the compound of formula (1) Preparation method · Also prepared in the following 1 I prepared ftir Example Aozhong JM detailed description! 1 I S_ 1-barrel L. (3 cases, 4 丄 -methoxydioxybenzyl)-5- Synthesis of 1-based hydrazone-imidazolium sulfonium 1 1 1 1-1) 1-(3,4-methoxydioxybenzyl) -5 -hydroxyyear | yl- 1H -oxazole using di 1 1 paper Standards in this state 屮 ragu family (CNS) Λ4 specifications (2.0 × 297 male f) 52 91506 436? 81 ^ Five 'invention description (53) hydroxypropane dimer and piperonylamine as starting materials, By J. Med.

Chein ·, 33, 1312, 13 2 9, 1990 was carried out in an improved method. 1.37 g (10 mmol) piperonylamine, 1.08 g (5.5 mmol) dihydroxyS acetone dimer and 1.15 g (11 Millimoles) cyanide was introduced into 10 ml of propionate | Next, 2 ml of acetic acid was added thereto, and the mixture was reacted at room temperature for 48 hours. The reaction mixture was washed with 5 ml of isopropyl alcohol (x2) and 5 ml of water (x2) as the remaining solids thus obtained. The filtered solid was added to 12.5 ml of a 10% aqueous solution of nitric acid, and the resulting solution was cooled to ο. After adding 10 mg of sodium nitrite to the reaction solution in portions, the mixture was reacted at room temperature for 1 hour. This water was dissolved in 10 ml of ethyl acetate, washed with alkali, and then recrystallized to obtain 1.16 g (yield 50%) of the title compound. NMR (CDCb) δ 4.45 (3, 2Η), 5.13 (s, 2H), 5.97 (s, 2H), 6.70 (m, 2H), 6.78 (d, 1H), 6.95 (s, 1H), 7.45 (s , 1H) FAB 233 (M + H), C12H12N2O3 1- 2) (3, 4-methyldioxybenzyl) -5-chloromethyl-1H-imidazolium, 233 mg (1 mmol) Preparation Example 1-1) The compound prepared was dissolved in 3 ml of aerosol *, and then 355 mg (3 mmol) of sulfurous acid was slowly added dropwise thereto at 0 ° C. After 2 hours of incubation, the solvent was distilled off under reduced pressure, and the residual osmic acid * was removed to obtain the title compound in a yield of 95%. The product thus obtained was used directly in the next reaction without purification. Preparation Example 2: Synthesis of 1- (naphthalene-butylmethyl) -5-chloromethyl-1H-oxazolium sulfonium acid 2- 1) 1- (naphthalene-1-ylmethyl) -5-hydroxymethyl -1H-imidazole -------- J} 'Pack II (Please read the precautions on the back before filling this page) 55 This paper is suitable for ten valve country standards (C'NS) / \ 4 Specifications (210X297) 9 53 9 1506 —43 64 8 7 a? B7 V. Description of the invention (54) Follow the same steps as in Preparation Example 1-1) * to obtain the title compound in 65% yield, but use the dihydroxy group Propylene dimer and (ch-1-ylmethyl) amine were used as starting materials. ~ JH NMR (CDC13) ^ 4.44 (3, 2H), 5.42 (s, 2H), 6.78 (d, 1H), 6.85 (s, 1H), 7.25 (111, 1H), 7.35 (s, 1H), 7.43 (m, 2H)? 7.65 (d, 1H), 7.68 (d3 1H), 8.02 (d, 1H) FAB 239 (M + H), Ci5Hi4N20 2- 2) 1- (naphthalene-1 -ylmethyl)- 5-Chloromethyl-1H-oxazolidine hydrazone was prepared in the same manner as in Preparation Example 1-2i * using the compound obtained in Preparation Example 2-1) to obtain the title compound in a yield of 90%. The product thus obtained was used directly in the next reaction without purification. Preparation Example 3: Synthesis of l-((R) -ct-methylbenzyl) -5-hydroxymethyl-1H-oxazolium sulfonium acid 3- 1) 1-((1〇-«-methylbenzyl ) -5-hydroxymethyl-111-oxazole was prepared in the same manner as in Preparation Example 1-1) to give the title compound in 60% yield, but using dihydroxypropanidine dimer and (R)-(+)- ct-methylbenzylamine was used as the starting material. NMR (CDCb) 5 I · 73 (d, 3H), 4.28 (s, 1H), 4.43 (d, 1H), 5.60 (m, 1H), 6.75 (s, 1H), 7.04 (d, 2H)} 7.23 (m, 3H), 7.42 (s, 1H)

FAB 203 (M + H), C12H14N2O 3-2) l-((R) -a -methylbenzyl) 5-aminomethyl-1H-imidazolium phosphonium compound prepared using Preparation Example 3-1), Following the same steps as in Preparation Example 1-2), the title compound was obtained in a yield of 90%. The product thus prepared can be straight _ this paper size Yichuan 屮 Min national jujube (CNS) / \ 4 specifications (210X297 public trend) 54 91506 {Please read the precautions on the back before filling (¾ page), install Order A7 436 ^ 87 V. Hairpin description (55) was used for the next reaction * without purification. Preparation Example 4: l-((S) -ct-methylbenzyl) -5-aminomethyl-1H-oxazosinic acid (read the precautions on the back before reading &quot; write this page) 合成 的 合成 4- 1) 1-((S) -ct-methylbenzyl) -5-hydroxymethyl-1H-oxazole was prepared in the same manner as in Preparation Example 1-1), but using dihydroxyacetone dimer and (S) -(+)-ct-methylbenzylamine was used as a starting material to obtain the title compound in a 55% yield. lH NMR (CDC13) 5 1.73 (d, 3H), 4.28 (s, 1H), 4.43 (d7 1H), 5.60 (m, 1H), 6.75 (s, 1H), 7.04 (d, 2H), 7.23 (m , 3H), 7.42 (s, 1H)

FAB 203 (M + H), C12H14N2O 4- 2) l- (S) -ct-methylbenzyl) -5-chloroprimer-IH-imidazolium acid, according to the same steps as in Preparation Example 1-2), use Preparation Example 4-1) * The title compound was obtained in a yield of 94%. The product so prepared can be used directly in the next reaction without purification. Preparation Example 5: Synthesis of 1-phenethyl-5-ylmethyl-1,1-imidazolium hydrazone, 5- 1) 1-phenethyl-5-hydroxymethyl-1,1-imidazolium Preparation Example 1-1) Same procedure "but using dihydroxyacetone dimer and phenethylamine as starting materials, the title compound was obtained * yield 70%. * H NMR (CDC13) ^ 3.08 (t, 2H), 4.27 (t, 2H), 4.47 (s, 2H), 6.89 (s, 1H), 7.05 (d, 2H), 7.26 (m, 3H), 7.44 (s, 1H) FAB 203 (M + H), Ci2Ht4N20 5-2) 1-benzyl-5--5-methyl-1H-oxazolium acid, paper standard, follow national standards ((-&gt; ^) / \ 4 specifications (210 '/ 297 mm) 55 91506 (4-36487 a7 B7 V. Description of the invention (56) Use the compound prepared in Preparation Example 5-1) according to Preparation Example 1-2). By the same procedure, the title compound was obtained in a yield of 90%. The product thus obtained does not need to be passivated and is directly used in the next reaction. Preparation Example 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4- (naphthalene-1 -yl) -1） -pyrrole synthesis 6-1) 3- (naphthalene- 1-yl) -ethyl acrylate 22.4 (0.10 mole) triethylphosphine phosphonium acetate dissolved in 500 ml of acetonitrile * Slowly add 30.4 g (0.2 mole) of 1,8-diacylbicyclo [5.4.0] Undecyl-7-ene (1,5-5) (0810 to it. 15.6 g (0.10 mole) of 1-naphthaldehyde was dissolved in 20 ml of a tetrahydrofuran solution and the solution was slowly added, and the mixture was stirred for 8 hours. The organic solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed twice with M water, dehydrated with magnesium sulfate, and concentrated, followed by silica gel column chromatography (solvent: n-hexane / ethyl acetate = 95). / 5, ν / ν) to obtain 20.3 &lt; * g (0.090 mol, 90% yield) of the title compound.! H NMR (CDCl3) S 1.33 (t, 3H), 4.10 (q, 2H ), 6.75 (q, 1H), 7.50 (m5 3H), 7.73 (d, 1H), 7.85 (m, 2H), 8.10 (d, 1H), 8.21 (d, 1H) FAB 227 (M + H) 6 -2) 3- (Ethoxycarbonyl) -4- (naphthalene-1-yl) -lΗ-larole 4.3 g (1δ.9 mmol) The 3- (naphthalene- 1-based)-ethyl acrylate with 3.68 g (18.9 mmol) paraben Methyl isobutyl cyanide dissolved in 100 ml of tetrahydrofuran. To this solution was slowly added a solution of 2.55 g (22.7 mmol) of a third potassium butoxide solution in 100 ml of tetrahydrofuran. * The mixture was refluxed for 30 minutes. Add 100 ml of water to the reaction solution to stop the reaction. The paper size conforms to the Chinese National Standards (CNS) Λ4 grid (2) 0 X 2M mm. „56 91506 (Please read the precautions on the back first, then the moth-&quot; this page} --1, —"}.

, 1T -D 'Α7 Β7 5. Description of the invention (5 7) The solvent should be removed under reduced pressure. The reaction solution was extracted with diethyl ether. K sodium chloride aqueous solution was washed * and then magnesium sulfate was dehydrated. Reduce the solvent and remove the solvent. The obtained residue was subjected to silica gel column chromatography (eluent: ethyl acetate / n-hexane = 1/3, \ / 〇, to obtain 3.35 g of the title compound (14.5 millitores, 77% yield). * H NMR (CDC13) 3 l-27 (t, 3H), 4.07 (q, 2H), 6.76 (s, 1H), 7.28-7.47 (m, 5H), 7.59 (s, 1H), 7.82 (m , 2H), 9.99 (s, 1H) FAB 266 (M + H). 6-3) 3-Hydroxycarbonyl-4- (naphthalene-1-yl) -lH-nth Preparation of 2.64 g (10 mmol) The compound obtained in Example 6-2) was dissolved in 50 ml of 50% ethanol, and 2.24 g (40 mmol) of potassium hydroxide was added thereto. The reaction mixture was refluxed for 7 hours, cooled to room temperature, adjusted to pH 4-5, extracted with ethyl acetate, and dehydrated with sodium sulfate. Removal of the solvent under reduced pressure * gave 1.90 g (8.1 mmol, 81% yield) of the title compound. The product thus obtained was used directly in the next reaction without purification. ! H NMR (CDC13) ^ 6.60 (s, 1H), 7.32-7.49 (rn, 5H), 7.54 (s, 1H), 7.84 (m, 2H), 9.92 (s, 1H) FAB 238 (M + H) 6-4) 3- [N- (2-Methoxyethyl) -N-methyl] aminomethyl-4- (naphthalene-phenyl- 1-pyrrole) 234 mg (1 mmol) The compound prepared in Example 6-3) was dissolved in 2 liters of dimethylformamide, followed by 230 mg (1.2 mmol) of EDC. 101 mg (1 mmol) of triethylamine and 162 mg (1.2 (No mol) Η0ΒΤ to it>, paper scales described in the state of Central and South China (椋, Can) eight 4 specifications (2) 0 &gt; &lt; 297 citizenship) ~ 7ΤΤ7Ί 57 91506 ------ 1 attack ------ 、 Order ------ (诮 Please read the notes on the back before filling in this page} &quot; 4 3 6487 67. B7 V. Description of the invention (5 8) (诮 Read the first on the back Please note this page again}. The resulting mixture was stirred in Ot: 5 minutes. To the reaction solution was added 124 mg (1 millole) of N- (2-methoxyethyl) -N-methylamine sulfonate, Then search at room temperature for 5 hours. Remove the solvent under reduced pressure, and then add 10 ml of potassium carbonate 16 solution to the residue. The resulting solution was extracted with 20 ml of ethyl acetate and M 10 ml of 1H aqueous acid. Liquid washing, followed by washing with sodium carbonate aqueous solution and water * dehydration with sodium sulfate and concentration • to obtain 246 mg of the title compound (0.79 millitors, yield%) 4 NMR (CDCb) accounted for 2.46 (s, 2Η), 2.80-3.40 (m, 8Η), 3.40 (s, 1Η), 6.80 (s, 1H), 7.00 (s, 1H), 7.42 (m, 4H), 7.73 (d, 1H), 7.81 (d, 1H) , 8.17 (d, 1H), 10.66 (s, 1H) FAB 309 (M + H) Preparation Example 7: Synthesis of 3- (morpholin-4-yl) carbonyl- 4- (naphthalene-1-ylrole) 234 mg (1 millimolar) The compound prepared in Preparation Example 6-3) was dissolved in 2 ml of dimethylamidamine, and then 230 mg (1.2 mmol) of EDC and 162 mg (1.2 mmol) were added to The resulting mixture was stirred for 5 minutes in Ot. 87 mg (1 mmol) of morpholine was added to the reaction solution, followed by stirring at room temperature for 5 hours. The solvent was removed under reduced pressure, and 10 ml of a saturated solution of potassium carbonate was added to the residue. The resulting solution was extracted with ethyl acetate, washed with 10 ml of a 1N aqueous solution of acetic acid | washed with an aqueous solution of sodium chloride and water, dehydrated with sodium sulfate and condensed to obtain 243 mg of the title compound (0.8 millimolar • Yield 80% ). (H NMR (CDC13) 5 2.13-3.52 (br, 8H), 6.54 (S) 1H), 7.31-7.5l (m, 5H), 7.53 (s, 1H), 7.8l (m, 2H), 9.93 ( s, 1H) FAB 307 (M + H) Original paper Na UH, sample (called exposure (Don't x war magic 58 ^ 43 6487 A7 • B7 V. Invention? Dui Ming (5 9)) Preparation Example 8: 3-U-甲Hexahydropyridine-1-yl) carbonyl-4- (naphthalene-1-yl)-1 Η -pyrrole synthesis (please read the precautions on the back before filling in this 萸) The same as in Preparation Example 6-4) Procedure, but using the compound prepared in Preparation Example 6-3) and 4-methylhexahydropyrrolium as starting materials, the title compound was obtained (yield 75%). NMR (CDC13) 3 l-15 (br, 2H), 1.87 (br, 2H), 1.92 (s, 3H), 2.96 (brf 2H), 3.41 (br, 2H), 6.83 (s, 1H), 7.09 ( s, 1H), 7.36-7.42 (m, 4H), 7.73 (d, 1H), 7.75 (d, 1H), 8.10 (d, 1H), 10.52 (s, 1H) FAB (M + H): 320 Preparation Example 9: Synthesis of 3- {N- (2- (H, N-dimethylamino) ethyl] -H-methyl) aminomethyl-4- (naphthalene-1-yl) -1Η-pyrrole Using the compound prepared in Preparation Example 6-3) and N, N, N'-trimethyl-ethylenediamine in the same manner as in Preparation Example 6-4), the title compound was obtained (yield 82%). ! H NMR (CDC13) $ 1.89 (br, 3H), 2.18 (br, 4H), 2.44 (br, 2H), 2.75 (5, 1H), 2.98 (br, 1H), 3.36 (br, 2H), 6.84 (s, 1H), 7.07 (s, 1H), 7.38-7.43 (m, 4H), 7.74 (d, 1H), 7.83 (d, 1H), 8.13 (b, 1H), 10.14 (br5 1H) FAB ( M + H): 322 Preparation Example 10: Synthesis of 4- (naphthalene-1-yl) -3- (thiomorpholin-4-yl) carbonyl-1H-pyrrole 234 mg (1 mmol) in Preparation Example 6 -3) The compound prepared in -3) was dissolved in 2 ml of dimethylformamide, and then 230 mg (1.2 mmol) of EDC and 162 mg (1.2 mmol) of OBT were added thereto. The resulting mixture was stirred at 0¾ for 5 minutes. Add 87 mg (1 millimolar) of thiomorpholine to the reaction solution, and then follow the paper standard (CNS) Λ4 specification (2ίΟΧ297 公 #) Λ one 59 91506 4 3 6 4 8 7 A7 B7 V. Description of the invention (60) Stir at room temperature for 5 hours. The solvent was removed under reduced pressure, and 10 ml of potassium carbonate and the solution were added to the residue. The resulting solution was extracted with ethyl acetate, washed with 10 ml of a 1H aqueous solution of acetic acid, and then washed with an aqueous sodium hydroxide solution and water, dehydrated with sodium sulfate, and concentrated to obtain 258 mg of the title compound (10.8 mmol, yield 80%). 1H NMR (CDCb) 5 1.35 (br, 2Η), 2.14 (br, 2Η), 3.21 (br, 2Η), 3.41 (br, 2H), 6.91 (s, 1H), 7.21 (s, 1H), 7.31-7.51 ( m, 4H), 7.80 (d, 1H), 7.87 (d, 1H), 8.11 ((1, 1H), 10.69 (s, 1H) FAB 323 (M + H) Preparation Example 11: 3- (1,1 -Dioxothiomorpholine-4-yl) carbonyl-4- (naphthalene-1-yl) -1 hydrazone-pykal Synthesis 323 mg (1 mmol) The compound obtained in Preparation Example 10 was dissolved in 5 ml Dichloromethane, 430 mg (1.5 mmol) of 60% 3-chloroperbenzoic acid (MCPBA) was added thereto, and then the mixture was stirred at room temperature for 1 hour. 3 ml of 10% sodium thiosulfite was added to the mixture To remove excess 3-nitroperbenzoic acid, the resulting mixture was stirred at room temperature for 30 minutes. After adding 10 ml of a saturated solution of sodium carbonate to it, the mixture was extracted with methylene chloride, washed with a saturated solution of sodium chloride and water, and Sodium sulfate was dehydrated and concentrated to obtain 264 mg (0.75 mmol, 75% yield). The title compound: lH NMR (CDCl3) δ 1.50-2.30 (br, 4H), 3.65 (br, 4H), 6.92 (s, 1H), 7.20 (s, 1H), 7.32-7.54 (m, 4H), 7.81 ( d, 1H), 7.88 (d, 1H), 8.12 (d, 1H), 10.69 (s, 1H) FAB 355 (M + H) Preparation Example 12: 3- [N- (2-methylthioethyl)- Synthesis of N-methyl] aminomethyl-4- (naphthalene-1-yl-1H-diphenyl) _ ^ Paper size: State Minzhou National Minute (CNS) Λ4 specification (210X 297 mm) 60 91506 (诮 Please read the precautions on the back before filling in this page) Pack 'Order A7 436487 B7 V. Description of the invention (61) 234 mg (1 millimolar) in compound 6-3) dissolved in 2 ml Dimethylmethanamine · Then 230 mg (1.2 mmol) of EDC. 101 mg (1 mmol) of triethylamine and 162 mg (1.2 mmol) of HOBTi were added. The resulting mixture was stirred at 0 ° for 5 minutes. 140 mg (1 mil) of N- (2-methylthioethyl) -N-methylaminophosphonium acid was added to the reaction solution, followed by searching at room temperature for 5 hours. The solvent was removed under reduced pressure. 10 ml of a saturated solution of potassium carbonate was added to the residue. The resulting solution was extracted with 20 ml of ethyl acetate, washed with 10 ml of 1N aqueous acetic acid solution, washed with aqueous sodium chloride solution and water, dehydrated with sodium sulfate, and concentrated to obtain 243 mmol of the title compound (0.75 mmol). Yield 75% ) 0] H NMR (CDC13) 5 1.98 (s, 3H), 2.13 (br, 2H), 2.46 (br; 2H), 2.65 (brf 1H), 2.95 (br, 1H), 3.29 (br, 1H), 6.81 (s, 1H), 7.02 (s, 1H), 7.43 (m, 4H), 7.72 (d, 1H), 7.82 (d, 1H), 8.18 (d, 1H), 10.65 (s, 1H) FAB 325 (M + H) Preparation Example 13: Synthesis of 3-hydroxycarbonyl-5 -methyl- 4- (naphthalene-1-ylrole 13-1) 3 -ethoxycarbonyl-5-methyl- 4- (naphthalene -1-yl) -1Η-larrole 4.3 g (18.9 milli-chills) in Preparation Example 6-1 &gt; 3- (naphthalene-butyl) ethyl acrylate and 3,95 g (18.9 milli-moles) ct -Methyl-p-toluenesulfonylmethyl isocyanide (disclosed by AM van Leusen et al.,

Tetrahedron Letter, 1975, 40, 3487) was dissolved in 100 ml of tetrahydrofuran. Add 2.55 g (22.7 mmol) of tertiary potassium butoxide in 100 ml of tetrahydrofuran to the above solution. • The mixture is refluxed for 30 minutes. 6 1 {Please read the precautions on the back first, and then refer to this page D-s The scale of the paper music is appropriate; the family standard (C'NS) Λ4 specification (2 丨 0〆297 male; t) 9 1506 屮-'' 'i? M': il; v '^' hc n ;;; ' fal_ 印 〆4 3 6487 A7 B7 5. Description of the invention (6 2). 100 ml of water was added to the reaction solution to stop the reaction, and the solvent was removed under reduced pressure. The residue was extracted with ether and washed with a saturated solution of sodium chloride, followed by dehydration with magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was subjected to silica gel column analysis / using a solvent mixture of ethyl acetate / n-hexane (1/3, ν / ν) as an eluent. 3.50 g of the title compound (12.5 mmol) was obtained Yield 66%). FAB 2 80 (Μ + Η) 13-2) 3-Transyl-5 -methyl-4, (Cha_1-yl) -1 Bupi blind 280 g (10 millitorles) Preparation Example 13-1 The prepared compound was dissolved in 50 ml of 50% ethanol, and 2.24 g (40 mmol) of potassium hydroxide was added to the reaction mixture. The reaction mixture was refluxed for 7 hours. • Cooled to room temperature * adjusted to ρΗ 4-5 μM ethyl acetate extraction. , Dehydrated by sodium sulfate. The solvent was removed under reduced pressure to obtain 2.02 g (8.1 m ?, 81% yield) of the title compound. FAB 252 (Μ + Η) Preparation Example 14: Synthesis of 5 -methyl- 3- (morpholin-4-yl) carbonyl-4- (naphthalene-1-yl) -1 propyrrole 248 mg (1 millitorr) ) The compound prepared in Preparation Example 13-2) was dissolved in 2 ml of dimethylformamide, and then 230 mg (1.2 mmol) of EDC and 162 mg (1.2 mmol) of OBT were added thereto. The resulting mixture was stirred in Ot: 5 minutes. Add 87 mg (1 mole) of morpholine to the antipyretic solution, then search for 5 hours at room temperature. The solvent was removed under reduced pressure. 10 ml of a saturated solution of potassium carbonate was added to the residue. The resulting solution was extracted with ethyl acetate, washed with 10 ml of 1N aqueous solution of acid, washed with sodium chloride aqueous solution and water, dehydrated with sodium sulfate and condensed to obtain 224 mg of the title compound (10.7 mmol, yield 70%). . (诮 Please read the precautions before ^ 艿 this page) Ding___________ -ΰ ί— J —Is this paper ί / i size this state towel S National Standard (CNS) Λ4 specifications (210X 297 公 #) 6 2 9 15 06 436487 V. Statement of invention (6 3 kl B7 lH NMR (CDCb) stone 2.12 (s, 3H), 2.80-3.40 (br, 8H), 7.01 (s, 1H), 7.30- 7.50 (m, 4H ), 7.75-7.95 (m, 3H), 10.60 (br, 1H) FAB 321 (M + H) ^ {: j .T Aii Example 1: 3-U-2-methoxyethyl) N-methyl] Carboxamidine-l- [l- (3,4-methoxydioxybenzyl) -1Η-oxazol-5-ylmethyl] -4 (Cai-1-yl) -1Η-pyrrole (1 ) Synthesis 62 mg (0.2 millilitres) The compound prepared in Preparation Example 6 was dissolved in 2 mL of dimethylformamide, and 26.4 mg (0.66 millitors) of sodium hydride (60%) was added to it. Then, the mixture was stirred for 5 minutes. To this mixture was added 50 mg (2.2 mmol) of the compound prepared in Preparation Example 1. The entire mixture was searched at room temperature for 3 hours. Remove the solvent by subtractive distillation and add 3 ml of water to the residue. The mixture M was extracted twice with 10 liters of ethyl acetate * dehydrated with anhydrous sodium sulfate, concentrated, and subjected to silica gel column chromatography (eluent: dichloromethane / formic acid = 95/5, ν / ν). 78 mg (product Rate 75%) of the title compound. * H NMR (CDC13) § 2.40 (m, 2H), 2.72 (m, 1H), 2.91 (s, 3H), 3.09 (m, 2H), 3.32 (br, 1H), 4.09 (br, 1H), 4.89 (s, 2H), 4.95 (s, 2H), 5.S9 (s, 2H), 6.45 (s, 1H), 6.62 (d, 1H), 6.63 (s, 1H), 6.70 (d, 1H), 7.0 (s, 1H), 7.16 (s, 1H), 7.3l (t, 1H), 7.41 (ιη, 3H), 7.66 (s, 1H), 7.73 (d, 1H), 7.8l (d, 1H) , 8.03 (d, 1H) FAB (M + H) 523, C31H30N4O2 Example 2: l- [1- (3,4-dimethoxybenzyl) -lH-oxazol-5-ylmethyl-3- Synthesis of (morpholin-4-yl) carbonyl-4- (naphthalene-1-ylrole (2) (&quot; Read the precautions on the back first, and then go to the top of this page to install ------, τ -55 The paper and the description of the Sichuan ten storehouse (C'NS) M specifications (210X 297 feet) 63 91506 A7 436487 B7 V. Description of the invention (64) 62 mg (0.2 millimolar) in Preparation Example 7 The obtained compound was dissolved in 2 ml of dimethylformamide, and in Ot: 26.4 mg (0.66 mmol) of sodium hydride (60%) was added thereto, and then the mixture was stirred for 5 minutes. 50 mg was added to the mixture ~ (2.2 millimoles) The compound obtained in Preparation Example 1. The entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure * and 3 ml of water was added. The residue was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, shrinkage, and subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 9 5/5 * v / v) to obtain 70 mg (67% yield) of the title compound. NMR (CDCl3) (5 2.36 (br, 2H), 3.06 (br, 4H), 3.33 (br, 2H), 5.23 (s, 2H), 5.33 (s, 2H ), 5.96 (s, 2H), 6.65 (s, 1H), 6.70-6.85 (m, jH), 7.18-7.50 (m, 7H), 7.79 (d, 1H), 7.81 (d, 1H), 7.94 ( d, 1H) FAB (M + H) 521, C31H28N4O4 Example 3: l- [l- (3,4-methyldioxybenzyl) -lH-imidazol-5-ylmethyl] 3- (4- Synthesis of methylhexahydrol-1-yl) phile-4- (naphthalene-1-yl) -1Η-pyrrole (3) 64 mg (0.2 mil) was dissolved in the compound prepared in Preparation Example 8 In 2 ml of dimethylformamide • 26.4 mg (0.66 mmol) of sodium oxide (60%) was added to the solution, and the mixture was stirred for 5 minutes. Leave in the mixture for 5 minutes. To this admixture was added 50 mg (2.2 mils) of the compound obtained in Preparation Example 1 * and the entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10 · ν / ν) * 73 mg (yield 67%) of the title compound. i Paper scales Chuan 1 National Standards (CNS) Λ4 specifications (2i0x 297) ~ ~ 64 91506 (1 note on the back of the book, then work hard, 3: binding 436487 A7 — 'B7 V. Description of the invention (6 5) (Notes on the first reading and reading on this page, and then on this page)! H NMR (CDCb) δ 2.18 (s, 3Η), 2.30-2.60 (br, 4H), 3.10-3.30 (br, 4H), 4,98 (s, 2H), 5.05 (s, 2H), 5.95 (s, 2H), 6.44 (s, 1H), 6.53 (d, 1H), 6.70 (d, 1H), 6.73 (d, 1H), 7.14 (d, 1H), 7.20-7.40 (m, 3H), 7.50 (m, 3H), 7.8l (d, 1H), 7.83 (d, 1H), 7.88 ( d, 1H) FAB (M + H) 534, C32H31N5O3 Example 4: 3- [H- [2- (H, N-dimethylamino) ethyl] -N-methyl} aminomethyl-1- [1- (3,4-methoxydioxybenzyl) -1 oxazol-5-ylmethyl: Synthesis of 1-4 * · (Cai-1-yl slightly (4) 64 mg (0.2 mmol) Ear) The compound obtained in Preparation Example 9 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 millirales) of sodium hydride (60%) was added thereto, and the mixture was then searched and stirred for 5 minutes. 50 mg (2.2 millimoles) of the compound prepared in Preparation Example 1 was added to the mixture, and the entire mixture was stirred at room temperature for 3 hours. The solution was distilled off under reduced pressure, and 3 ml was added to the residue. The mixture K was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90 / 10, v / v) to obtain 7δ mg (71% yield) of the title compound. NMR (CDC13) δ 1.87 (π, 1Η); 2.01 (m, 2H), 2.14 (br, 6H), 2.36 (br , 2H), 2.50-3.00 (br3 1H), 3.29 (br, 2H), 4.87 (s, 2H), 4.95 (s, 2H), 5.89 (s, 2H), 6.45 (s, 1H), 6.50 (4 1H), 6.63 (d, 1H), 6.72 (d, 1H), 7.00 (s, 1H), 7.l8 (s, 1H), 7.31 (br, 1H), 7.35-7.47 (m. 3H), 7.54 (s? 1H), 7.73 (d, 1H), 7.8l (d, 1H), 8.01 (br, 1H) FAB (M ten H) 536, C32H33N5O3 Example 5: 3- [N- (2-methoxyethyl ) -M-methyl] carbamate- 4- (naphthalene-1-ylnaphthalene-1-ylmethyl) -1Η-imid-5-ylmethyl] -1H-pykal (5 &gt; Paper dimensions are described in the National Standards (CNS) Λ4 specification (210X297 male Zhao) ~ 65 91506 A7 436487 B7 V. Description of the invention (66)) 62 mg (0.2 millitorles) compound prepared in Preparation Example 6 Dissolved in 2 ml of dimethylformamide, add 26.4 mg (0.66 mmol) of sodium vaporized (60%) to Op , Then the mixture was stirred for 5 minutes. To this mixture was added 58 mg (2.2 millitorles) of the compound prepared in Preparation Example 2, and the entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture M was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, and concentrated * and then subjected to silica gel column chromatography (eluent: methane / methanol = 95/5, v / v) to obtain 79 mg (yield 75%) of the title compound. lH NMR (CDC13) δ 2.37 (br5 2H), 2.72 (br, 1H), 2.99 (br, 3H), 3.00 (br, 2H), 3.31 (br, 1H), 3.71 (br, 1H), 5.06 (s , 2H), 5.48 (s, 2H), 6.62 (d, 1H), 6.91 (d, 1H0, 7.03 (d, 1H), 7,27 (d, 2H), 7.2S-7.55 (m, 6H), 7.58 (s7 1H), 7.69 (d, 1H), 7.75 (d, 1H), 7.81 (d, 2H), 7.87 (d, 1H), 8.00 (d, 1H) FAB (M + H) 529, C34H32N4O2 Examples 6: 3- (morpholin-4-yl) carbonyl-4- (naphthalene-butyl) -bu [1- (naphthalene-1-ylmethyl) -1） -oxazol-5-ylmethyl] -1H -Synthesis of pyrrole (6) 62 mg (0.2 mmol) The compound prepared in Preparation Example 7 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60 Ii) To this, the mixture was stirred for 5 minutes. To this mixture was added 58 mg (2.2 mmol) of the compound prepared in Preparation Example 2. The entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 ml of water to the residue. The mixture was extracted twice with M10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (solubility solution: dichloromethane / methanol = 95/5, v / v). To give 76 mg (72% yield) of the title compound ------- ^ --- -Ϊ 装-(Dian first read the note on the back and then copy the book) The size of the paper is suitable for the national standard in the flood season (CNS) Λ4 Specification (2I0X2W (Mm) 66 9 1506 ^ 1.3 64 8 7 A7 • B7 V. Description of the invention (67) (诮 read the precautions before reading &quot; '荇 this page) lU NMR (CDCl3) $ 2.38 (br, 2H) , 3.06 (br, 4H), 3.30 (br, 2H), 4.99 (s, 2H), 5.42 (s, 2H), 6.5S (d, 1H), 6.80 (d, 1H), 7.00 (s, 1H) , 7.17 (d, 1H), 7.25 (s, 1H), 7.26-7.54 (m, 6H), 7.69 (d, 1H), 7.71-7.81 (m, 3H), 7.85 (d, 1H), 7.91 (d , 1H) FAB (M + H) 527, C34H30N4O2 Example 7: 3- (4-methylhexahydropyrine-1-yl) hydroxy-4- (naphthalene-1-yl) -l- [1- (Cai -Bulkyl) -1Η-oxazol-5-ylmethyl] -1H ~ Synthesis of pyrrole (7) 62 mg (0.2 mmol) The compound obtained in Preparation Example 8 was dissolved in 2 ml of dimethyl To methylformamide, 26.4 mg (0.66 mmol) of sodium hydride (60%) was added thereto, and the mixture was stirred for 5 minutes. To this mixture was added 5 δ mg (2.2 mmol) of the compound prepared in Preparation Example 2, and the entire mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure, and 3 ml of water was added to the residue. The mixture M was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, and then subjected to shrinkage, and then subjected to silica gel column chromatography (solvent: dichloromethane / methanol = 90/10, ν / ν, to obtain 75 mg (product Yield 69%) of the title compound. LH NMR (CDCb) &lt; 5 1.07 (br, 2H), 1.77 (d, 2H), 1.85 (s, 3H), 2.84 (br, 2H), 3.27 (br, 2H), 4.99 (s, 2H), 5.42 (s, 2H), 6.58 (d, 1H), 6.80 (d, 1H), 7.01 ((1, 1H), 7.16 (d, 1H), 7.25 (s, 1H), 7.31-7.60 (m, 6H), 7.68 (d, 1H), 7.69-7.83 (m, 3H), 7.85 (d, 1H), 7.94 (d, 1H)

FAB (M + H) 540, C35H33N5O Example 8: 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-1- [1-((R) paper scale 4 ^ 4:!; ^-(C'NS) Λ4 ^ (21 OX 297 ^ ¾) 6 7 9 1 5 06 A7 436487 B7 V. Description of the invention (68) -0C -methylbenzyl) -1Η-oxazole Synthesis of -5-ylmethyl] -4- (naphthalene-1-yl) -1H -pyrrole (8) (-ifl first read the precautions on the back &quot; nitrate copy irc 62 mg (0.2 mmol) The compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60%) was added thereto, followed by stirring the mixture for 5 minutes. To this mixture was added 50 mg (2.2 mmol) of the compound prepared in Preparation 3, and the entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate. After dehydration and shrinkage with anhydrous sodium gallate, silica gel column chromatography was performed (eluent: dichloromethane / methanol = 95/5, v / v to obtain 70 mg (yield 71%) of the title compound. 1K NMR (CDC13 ) ^ 1.78 (d, 3H), 2.28 (3, 1H), 2.40 (br, 2H), 3.02 (br, 3H), 3.09 (br, 2H), 3.32 (br, 2H), 4.7l (d, 2H), 4.92 (d, 2H), 5.12 (qf 1H), 6.59 (d, 1H), 7.00 (m, 3H), 7.18 (s, 1H), 7.20 -7.39 (ιη, 4H), 7.40-7.62 (m? 3H), 7.74 (m, 2H), 7.82 (d, 1H), 8.04 (d, 1H) FAB (M + H) 493, C31H32N4O2 Example 9: 1 -[1-((R)-ct -methylbenzyl) -1 H -imidazol-5-ylmethyl] -3- (morpholin-4-yl) carbonyl-4- (naphthalene-1-yl) (9) Synthesis 62 mg (0.2 mmol) The compound prepared in Preparation Example 7 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60 To it, and then the mixture was stirred for 5 minutes. To this mixture was added 50 mg (2.2 mmol) of the compound prepared in Preparation Example 2. The entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure. Add 3 milliliters of water to the paper standard (CNS) Λ4 specification &lt; 2 丨 0Χ 297 公 #) 68 91506 A7 B7 43 6487 V. Description of the invention (6 9) (诮 Read the precautions on the back first桢 βτ page) residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated and dehydrated with anhydrous sodium sulfate, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 95/5, v / v, to obtain 1 mg (yield 72) the title compound. 'NMR (CDC13) δ l · 81 (4 3H), 2.28 (br, 2H), 3.06 (br, 4H), 3.29 (br, 2H), 4.65 (d, 1H), 4.96 ( d, 1H), 5.14 (q, 1H), 6.62 (d, 1H), 7.01 (d, 2H), 7.04 (s, 1H), 7.20 (s, 1H), 7.23-7.36 (m, 5H), 7.39 -7.50 (m, 3H), 7.76 (3, 1H), 7.78 (d, 1H), 7.84 (d, 1H), 8.00 (d, 1H) FAB (M + H) 491, C3lH3〇N4〇2 Example 10 : l- [l-((R) -ct-methylbenzyl) -lH-oxazol-5-ylmethyl]-3- (4-methyl-hexahydropyridine-butyl) carbonyl-4 Synthesis of-(naphthalene-1-yl) -1 fluorene-pyrrole (1 0) 64 mg (0.2 mmol) The compound obtained in Preparation Example 8 was dissolved in 2 ml of dimethylformamide, 26.4 mg (0.66 mmol) of sodium hydride (60 舛) was added thereto, followed by stirring the mixture for 5 minutes. 50 mg (2.2 mmol) of the compound obtained in Preparation Example 3 was added to the mixture, and the entire mixture was at room temperature. Stir for 3 hours. Remove the solvent by distillation under reduced pressure and add 3 ml of water to Residue. The mixture was extracted twice with K10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10, v / v, to obtain 73 mg (product Yield 73 bar) of the title compound.! H NMR (CDC13) ^ 1.09 (br? 2H)? 1.77 (d, 3H), 1.83 (s, 3H), 1.70-1.90 (br, 2H), 2.90 (br , 2H), 3.31 (br, 2H), 4.73 (d, 1H), 4.92 (d, 1H), 5.14 (q, 1H), 6.60 (d, 1H), 7.01 (m, 3H), 7.17 (s, 1H), 7.20-7.35 (m, 4H), 7.45 (m, 3H), 7.73 (m, 2H), 7.80 (d, 1H), 8.00 (d) 1H)

FAB (M + H) 504, C32H33N5O Standard of this paper: Shuzhou Ten Valves (CNS) Λ4 specification (210 × 297 mm) 6 9 9 1506 1 ^ 7 / l · 1 ^ _1,. Ϊ- yt —1r 7J -Γ Λ A7 ________4 3 64 8 7 ________________ π? ________ V. Description of the invention (7 o) Example 11: 3- [N- (2-methoxyethyl) -N-methyl] amine formamidine-l- Synthesis of [l-((s) -α-methylbenzyl) -1Η-oxazol-5-ylmethyl] -4- (naphthalene-1-yl) -1 Η-Bttrole (1 1) ~ 62 mg (0.2 mmol) of the compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and Ot: 26.4 mg (0.66 mmol) of sodium hydride (except 60) was added thereto, and then The mixture was stirred for 5 minutes. To this mixture was added 50 mg (2.2 mmol) of the compound prepared in Preparation Example 4, and the entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture M10 ml was extracted twice with ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 95/5, v / v) to obtain 75 mg (yield 75 Known) The title compound. lH NMR (CDC13) § 1.78 (d, 3H), 2.28 (s, 1H), 2.40 (br, 2H), 3.02 (br, 3H), 3.09 (br, 2H), 3.32 (br, 2H), 4.72 ( d, 2H), 4.93 (d, 2H), 5.12 (q3 1H), 6.59 (4 1H), 7.00 (π, 3H), 7.18 (s, 1H), 7.20-7.39 (m3 4H), 7.40-7.62 ( m, 3H), 7.74 (m, 2H), 7.82 (d, 1H), 8.04 ((1, 1H) FAB (M + H) 493, C31H32N4O2 Example 12: l- [l-((S) -a- Synthesis of methylbenzyl) -lH-oxazol-5-ylmethyl] -3-methyl-4-yl) hydroxy-4- (naphthalen-1-yl) -1Η- € (12) 62 mg (0.2 millimolar) The compound obtained in Preparation Example 7 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60 mil) was added thereto at 0¾, followed by stirring the mixture 5 minute. 50 mg (2.2 millimoles) of the compound prepared in Preparation Example 4 was added to the mixture, and all of the compounds were mixed in the paper size 迤 州 中 围 丨 翌 家 榇 准 (CNS) Λ4 specification (210X297) _ Λ „, r Λ ^ fυ 91506 (Notes on the back of Chi You, read again-Ti? This page)

--- 1 ---- ： ---- 4 ------- IT A7 B7 436487 V. Description of the invention (70 (Please read the precautions on the back before filling this page) The compound is at room temperature Stir for 3 hours. Remove the solvent by distillation under reduced pressure, add 3 ml of water to the residue. The mixture is extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and subjected to silica gel column chromatography (eluent: dichloromethane). 'Hane / formase = 95/5, v / v, 73 mg (73% yield) of the title compound was obtained.! H NMR (CDC13) d 1.81 (4 3H), 2.28 (br, 2H), 3.06 (br, 4H), 3.29 (br, 2H), 4.64 (d, 1H), 4.95 (d, 1H); 5.14 (q, 1H), 6.62 (d, 1H), 7.01 (d, 2H), 7.04 (s, 1H ), 7.20 (s, 1H), 7.23-7.36 (m, 5H), 7.39-7.50K 3H), 7.76 (s, 1H), 7.78 (d, 1H), 7.84 (d, 1H), 8.00 (d, 1H) FAB (M + H) 491, C31H30N4O2, Example 13: l- [l-((S) -〇t-methylbenzyl) -lH-oxazol-5-ylmethyl]-3- ( 4-methylhexahydropyridine-butyl) carbonyl- 4- (naphthalene-butyl) -1 hydrazone-pyrrole (1 3) printed by S4 mg (0.2 mil) ) The compound prepared in Preparation Example 8 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.6 6 millitorr) sodium hydride (60 〆), and then the warm compound was searched and stirred for 5 minutes. 50 mg (2.2 millimolar) of the compound obtained in Preparation Example 4 was added to the warm compound, and the whole mixture Stir at room temperature for 3 hours. Remove the solvent by distillation under reduced pressure, add 3 ml of water to the residue. The mixture M is extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and subjected to silica gel column chromatography (solubilization). Solution: dichloromethane / methanol = 90/10, ν / ν), to obtain 75 mg (yield 75 涔) of the title compound. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 91506 43 648 7 b7 V. Description of the invention (72) 'H NMR (CDC13) ^ 1.09 (br, 2H), 1.77 (d, 3H), 1.83 (s, 3H), 1.70-1.90 (br, 2H), 2.90 (br, 2H ), 3.31 (br, 2H), 4.74 (d, 1H), 4.93 (d, 1H), 5.14 (q, 1H), 6.60 (d, 1H), 7.01 (m, 3H), 7.17 (Sj 1H), 7.20-7.35 (m, 4H), 7.45 (m, 3H), 7.73 (m, 2H), 7.80 (d, 1H), 8.00 (d, 1H)

FAB (M + H) 504, C32H33N5O Example 14: 3- [H- (2-methoxyethylmethyl] aminomethylamidino- 4- (naphthalene-bu * ylbenzylethyl) -1Η-imidazole-5 -Methyl-1H-pyrrole (1 4) Synthesis 62 mg (0.2 mmol) The compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg was added at 0.7 0.66 mmol) of sodium hydride (60%), followed by stirring the mixture for 5 minutes. To this mixture was added 50 mg (2.2 mmol) of the compound prepared in Preparation Example 5, and the entire mixture was stirred at room temperature for 3 minutes. Hours. The solvent was removed by evaporation under reduced pressure, and 3 ml of water was added to the residue. The warm compound K10 ml of ethyl acetate was extracted twice, dehydrated with anhydrous sodium sulfate, concentrated, and subjected to silica gel column chromatography (eluent: methylene chloride / Methanol = 95/5, v / v), yielding 7 7 mg (yield 78 标题) of the title compound. NMR (CDC13) d 2.38 (br, 2H), 2.70 (111 , 1H0, 2.80 (ζ 2H), 2.90 (m) 3H), 3.00 (br, 2H), 3.31 (br7 1H), 3.41 (br, 1H), 4.03 (ζ 2H), 4.77 (s, 2H), 6 '66 (d, 1H), 6.97 (d, 1H), 7.06 (d, 1H), 7.22 (m, 3H), 7,30-7.60 (m, 5H), 7.75 (d, 1H), 7.80 (d, 1H), 8.04 (d, 1H) FAB (M + H) 493, C31H32N4O2 Example 15: 3- (morpholin-4, yl) hydroxy-4- (naphthalene-1 -Glybenzyl) i degree applies Chinese National Standard (CNS) A4 specification (2IOX297 mm) 91506 (Please read the precautions on the back before filling out this page) 7 2 436487 A7 B7 V. Description of Invention 73 -1H-imidazole Synthesis of 5--5-methylmethyl] -IΗ-Bttrole (15) 62 mg (0.2 mmol) of the compound prepared in Preparation Example 7 was dissolved in 2 ml of dimethylformamide, and in Ot: 26.4 was added Mg (0,66 mmol) of sodium hydride (60 〆) was added thereto, followed by stirring the mixture for 5 minutes. 50 mg (2.2 mmol) of the compound obtained in Preparation Example 5 was added to the mixture, and the entire mixture was Stir at room temperature for 3 hours. Reduce the solvent by steaming and add 3 ml of water to the residue. Mixture 10 ml of ethyl acetate was taken twice, dehydrated and concentrated by anhydrous sodium sulfate, and then subjected to silica gel column chromatography (dissolution and separation). Solution: dichloromethane / methanol = 95/5, ν / ν) to obtain 79 mg (yield: 80%) of the title compound. Please read the cautions on the reverse side and fill in r page lH NMRfCDCb) S 2.28 (br, 2H), 2M (t , 2H0, 2.S3 (br, 4H), 3.21 (br, 2H), 4.07 (t, 2H), 4.78 (s, 2H), 6.68 (d, 1H), 6.99 (d, 1H), 7.10 (d , 2H), 7.10 (4 2H), 7. Do not (m, 3H), 7.30 (d, 1H), 7.50 (m, 3H), 7.67 (s, 1H), 7.77 (d, 1H), 7.82 (d , 1H), 8.00 (d, 1H) FAB (M + H) 491, C31H30N4O2 Printed by the Consumer Cooperatives of the Workers' Union Central Bureau of the Ministry of Economic Affairs Example 16: 3- (4-methylhexahydropyrazine-1-yl) carbonyl Synthesis of -4- (cha-1-yl) -bu [bu (phenethylbu 1H-imidazol-5-ylmethyl) -1 吡 -pyrrole (16) 62 mg (0.2 mmol) in Preparation Example 8 The obtained compound was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60%) was added thereto, and the mixture was then searched and stirred for 5 minutes. To this mixture was added 50 mg (2.2 millirales) of the compound prepared in Preparation Example 5, and the entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The warm compound M is extracted twice with 10 ml of ethyl acetate, and subjected to anhydrous sodium sulfate. The paper size is applicable to the Chinese National Standard (CNS) A4 (2 丨 0 X 297 mm) 73 91506 A7 B7

5. Description of the invention (74) Dehydration, concentration, and silica gel column chromatography (eluent: dichloromethane / methanol = 90/10 / v), 75 mg (yield 75) of the title compound are obtained. NMR (CDC13) d 1.06 (br, 2H), 1.90-2.00 (br, 2H), 2.05 (s; 3H), 2.80 (t, 2H), 3.37 (br, 4H), 4.04 (ζ 2H), 4.77 ( s, 2H), 6.69 (d, 1H), 6.99 (m, 2H), 7.09 (d, 2H), 7.20-7.56 (m, 8H), 7.78 (d, 1H), 7.83 (d, 1H), S .00 (d, 1H) FAB (M + H) 504, C32H33N5O Preparation Example 15: Synthesis of 1- (2-methoxy) benzyl-5-fluoromethyl-in-imidazolium phosphonium 15-1 1- (2-methoxy) phenethyl-5-hydroxymethyl-1H-imidazole was prepared in the same manner as in Preparation Example 1-1), but using dihydroxyacetone dimer and 2-methoxyphenethylamine As a starting material, the title compound was obtained in a yield of 65 ° F. NMR (CDC13) § 3.03 (t, 2H), 3.75 (s, 3H), 4.16 (t, 2H), 4.47 (s, 2H), 4.75 (s, 1H), 6.74 (s, 1H), 6.75-7.00 (m, 3H), 7.13-7.30 (m, 1H) FAB 233 (M + H), C13H16N2〇2 (M) Please read the note on the back of ik © item and then 1 '

iT 〇 f II, printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, "J. Oxygen 2 A 1 2-Example-(Preparation 1) Ethyl ethylbenzene stepwise in-phase M ^ acid to make azole T 眯15 H-Example 7 The preparation of the base used for making nails makes the pure and necessities incompatible, and the problem should be reversed! Preparation &gt; The combination of materials and materials will make the chemical conversion rate tE 0. — / For example, made of 1-methyl 4-methyl chloride- 5-methylethoxybenzyl VI / oxazolium oxybenzoate, which is made of formazan- 4-f. The paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 9 1506 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 4 3 64 8 7_ b7_ V. Description of the Invention (75) 16-1) 1- (4-methoxy) phenethyl-5-hydroxymethyl-1H -Oxazole according to the same procedure as in Preparation Example 1-1), but using dihydroxypropane dimer and 4-methoxyphenethylamine as starting materials, a standard green poplar compound was obtained in a yield of 60 ^ 〇lR NMR (CDCb) ^ 2.91 (t, 2H), 3.68 (s, 3H), 4.09 (t, 2H), 4.36 (s, 2H), 6.70 (d, 2H), 6.77 (s, 1H), 6.87 (d , 2H), 7.13 (s, 1H) FAB 233 (M + H), Ci3Hi6N2〇2 (M) 16- 2) 1- (4-Methoxy) phenethyl-5-aminomethyl-1H-oxazosinic acid was converted to the compound prepared in Preparation Example 16-1) according to the same procedure as in Preparation Example 1-2) to obtain 摞The title compound (yield S9〆). The product thus obtained was used directly in the next reaction without purification. Preparation Example 17: 1- (2-fluoro) phenethyl-5-chloromethyl-1H- 眯Synthesis of pyrazolate 17-1) 1- (2-fluoro) phenethyl-5-hydroxymethyl-1 Η-oxazole according to the same procedure as in Preparation Example 1-1), but using dihydroxyacetone dimer And 2-fluorophenethylamine as a starting material to obtain the title compound, yield 68% Ο lH NMR (CDC13) $ 3.12 (t, 2H), 3.50 (br, 1H), 4.23 (t, 2H), 4.52 (s, 2H), 6.82 (s, 1H), 7.02 (m, 3H), 7.20 (m, 2H) FAB 221 (M + HX Ci2Hl3N2〇F (M) 17-2) 1- (2-fluoro) Phenethyl-5-aminomethyl-1H-imidazolium acid was prepared according to the same steps as in Preparation Example 2), using Preparation Example 17-1) (Please read the precautions on the back before filling this page) Paper size applies Chinese National Standard (CNS) Λ4 specification (210X 297 mm) 75 9 1506 436487 V. Description of the invention (76) compound to obtain the title compound (yield 89〆 ). The product thus obtained was used directly in the next reaction without purification. Preparation Example 1δ: Synthesis of 1- (2-Hydroxy) phenethyl-5 -lanemethyl-1H-oxazolidine'acid '18 (1) (1-Chloro) phenethyl-5-hydroxymethyl The same procedure as in Preparation Example 1-1) was performed on the base -1H-oxazole, but using the dihydroxyacetone dimer and 2-gas phenylethylamine as starting materials, the title compound was obtained in a yield of 71 pellets. 0 ln NMR ( CDC13) ^ 3.13 (tf 2H), 3.34 (br, 1H), 4.18 (t, 2H), 4.42 (s) 2H), 6.79 (s, 1H), 6.94 (d, 1H), 7.03-7.20 (πι, 3H), 7.29 (d, 1H) FAB 237 (M + H), CI2H, 3N20C1 (M) 18- 2) 1-(2-chloro) phenethyl-5-chloromethyl-1H-oxazosinamidine Following the same procedure as in Preparation Example 1-2) and using the compound obtained in Preparation Example 18-1), the title compound was obtained (yield: 89%). The product thus obtained was used directly in the next reaction without box purification. Preparation Example 19: 1- (3-chloro) phenethyl-5-chloromethyl-1H-imidazolium pyrene printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) -° ★: The same procedure for the synthesis of 19-1) 1- (3-chloro) phenethyl-5-hydroxymethyl-1H-oxazole according to Preparation Example 1-1), but using dihydroxyacetone dimer And 3-chlorophenylethylamine as the starting material, the title compound was obtained with a yield of 72. The paper size is applicable to the Chinese National Standard (CNS) A4 specification (2) 0X297 mm. 76 9 1506 A7 B7 436487 V. Description of the invention (7 7 lH NMR (CDC13) &lt; 5 2.95 (t, 2H), 3.90 (br, 1H), 4.10 (t, 2H), 4.37 (s, 2H), 6.74 (s, 1H), 6.85 (〇1 , 1H), 6.98 (s, 1H), 7.10 (m, 3H) FAB 237 (M + H), C12H13N20C1 (M) 19- 2) 1- (2-chloro) phenethyl-5 -chloromethyl- According to the same procedure as in Preparation Example 1-2) using 1H-pyrazole oxalic acid, the compound obtained in Preparation Example 19-1) was used to obtain the title compound (yield: 91′〆). The product thus obtained was used directly in the next reaction without purification. Preparation Example 20: Synthesis of 1- (3-phenyl) propyl-5-chloromethyl-1H-imidazolium hydrazone 20-1) 1- (3-phenyl) propyl-5-hydroxymethyl-1H -Imidazole was prepared according to the same procedure as in Preparation Example 1-1), but using dihydroxypropanidine dimer and 3-phenylpropylamine as starting materials to obtain the title compound, yield 73. Please read the notes Xiang Zai ▲ Write this page and order the employee's cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. Consumers' cooperatives. Chloromethyl chloride-5 propyl propyl. -1 2 3 Prepare as basic system. A with ㈠ ㈠ 〆. -Make 1. 5 9 b-Step 霈 The same thing is not the same as the base and the 2- is changed, 2) The problem should be 1-marked. The first example is obtained: the system is prepared under -1, and the naphthyl group is prepared according to the use case. The paper size of Jiachenghe applies to the Chinese National Standard (CNS) A4 (2I0X297 mm) 77 91506 1 E NMR (CDC13) ^ 2.11 (m, 2H), 2.61 (t, 2H), 3.98 (t, 2H), 2 4.25 (br, 1H), 4.53 (s, 1H), 6.76 (s, 1H), 7.10-7.60 (ιη, 6H) 3 FAB 217 (M + H), C13H [sN20 (M) 4 3 64 8 7 A7 1 B7 V. Description of the invention (78) 21-1) Same steps as 1- (naphthalene-2-yl) methyl-5-hydroxymethyl-1H-oxazole according to Preparation Example 1-1), but using two Hydroxyacetone dimer and (naphthalene-2-yl) methylamine as starting materials to obtain the title compound ', yield 5 8 ^ 〇lK NMRfCDCb) δ 4.36 (s, 2H), 5.28 (s, 2H), 6.89 (s7 1H), 7.17 ((1, 1H), 7.35 (m, 2H), 7.4l (s, 1H), 7.50 (s, 1H), 7.65 (m, 1H), 7.69 (m, 2H) FAB 239 (M + H), Ci5HI4N20 (M) 21- 2) 1- (naphthalene-2-yl) methyl-5-chloromethyl-1H-imidazolium acid, according to the same procedure as in Preparation Example 2), using the preparation The compound obtained in Example 21-1) gave the title compound (yield: 87%). The product thus obtained was used directly in the next reaction without purification. Preparation Example 22: Synthesis of 1- [2- (naphthalene-1-yl) ethyl] -5-chloromethyl-1H-oxazolium sulfonium sulfonium 22-1 ] -5-hydroxymethyl-1H-imidazole was prepared according to the same procedure as in Preparation Example 1-1), but using dihydroxyacetone dimer and (naphthalene-1-yl) ethylamine as starting materials to obtain the title compound, Printed by the Workers' Cooperative of the Shiyang Standards Bureau of the Ministry of Economic Affairs NMR (CDCb) s 3.44 (t, 2H), 4.23 (t, 2H), 4.38 (s, 2H), 6.79 (s, 1H) , 7.07 (d, 1H), 7.17 (s, 1H), 7.24 (t, 1H), 7.32-7.48 (m, 2H), 7.62 (d, 1H), 7.74 (d, 1H), 7.92 (d, 1H ) FAB 253 (M + H), CieHieNaO (M) 22-2) l- [2- (naphthalene M-yl) ethyl-5-chloromethyl-1H-imidazolium hydrazone. The paper dimensions are applicable to Chinese national standards ( CNS) A4% grid (210X297 mm) 78 91506 Printed by the Consumers' Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs 4364 87 A7 _B7_ V. Description of the invention (79) Follow the same steps as in Preparation Example 2), using Preparation Example 22-1 ) To obtain the title compound (yield 87%). The product thus obtained was used directly in the next reaction without purification. '' Preparation Example 23: Synthesis of 1- (4-bromo) benzylethyl-5-chloromethyl-1H-imidazolium phosphonium 2 3-1) 1- (4-bromo) phenethyl-5-hydroxymethyl -1H-Panzole was prepared according to the same procedure as in Preparation Example 1-U, but using dihydroxytriose dimer and 4-bromophenylethylamine as starting materials to obtain the title compound. Yield: 72〆0'H NMR ( CDC13) 2.94 (t, 2H), 3.76 (br, 1H), 4.11 (t, 2H), 4.37 (s, 2H), 6.74 (s? 1H); 6.S5 (d, 2H), 6.84 (d, 2H), 7.12 (s5 1H), 7.29 (d, 2H) FAB 281 (M + H), Ci2H13N2OBr (M) 23-2) 1- (4-bromo) phenethyl-5-chloromethyl-1H- The oxazolium oxalate was prepared in the same manner as in Preparation Example 1-2) using the compound prepared in Preparation Example 23-1) to obtain the title compound (yield: 91%). The product thus obtained was used directly in the next reaction without purification. Preparation Example 24: Synthesis of 1- (4-fluoro) phenethyl-5-chloromethyl-1H-oxazosinamidine sulfonium 24-1) 1- (4-bromo) phenethyl-5 -hydroxymethyl- 1H-oxazole according to the same steps as in Preparation Example 1), but using dihydroxypropanidine dimer and 4-p-phenylethylamine as starting materials, the title compound was obtained in a yield of 72〆 (please read the back first (Notes for refilling this page)

The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (2! 0X297 mm) 7 9 9 1506 4 3 6 4 8 7_b7_ V. Description of the invention (8o) 'h NMR (CDC13) s 2.99 (t, 2H), 3.76 (br, 1H), 4.15 (t, 2H), 4.45 (s, 2H), 6.80-7.20 (m) 5H), 7.26 (s, IH) FAB 221 (M + H), Ci2Hi3N2OF (M) 1 24 -2) 1- (4-Fluoro) phenethyl-5-chloromethyl-1H-imidazolium acid was obtained according to the same procedure as in Preparation Example 1-2), using the compound obtained in Preparation Example 24-1) to obtain The title compound (91 yields). The product thus obtained was used directly in the next reaction without purification. Preparation Example 25: 1- (4-methyl) phenethyl-5-chloromethyl-1H-imidazolium acid Anonymous Synthesis 25-1) 1- (4-methyl) phenethyl-5-hydroxymethyl -1H-oxazole was prepared according to the same procedure as in Preparation Example 1-1), but using dihydroxyacetone dimer and 4-methylphenethylamine as starting materials to obtain the title compound, yield 72 4 NMR (CDC13) (5 3.02 (t, 2H), 2.99 (1 :, 2H), 3.76 (br, IH), 4.19 (t, 2H), 4.47 (s, 2H), 6.83 (s, IH), 6.94 (d, 2H ), 7.06 (d, 2H), 7.28 (s, IH) FAB 217 (M + H), Cl3Hi6N20 (M) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling in k-this Page) 25-2) 1- (4-Methyl) phenethyl-5-chloromethyl-IH-imidazolium acetic acid was obtained in the same manner as in Preparation Example 2) using the compound obtained in Preparation Example 25-1) The title compound was obtained (91 yield). The product thus obtained was used directly in the next reaction without purification. Example 26: Synthesis of 1- (4 -Amo) phenethyl-5-ammomethyl-1H-imidazolium hydrazone This paper is sized to Chinese National Standards (CNS &gt; A4 size (2! 0X297 mm) 80 9 1506 4 3 64 87 ^ B7 V. Description of the invention (81) 26-1) 1- (4-Chloro) phenethyl-5-hydroxymethyl-1H-oxazole according to the same procedure as in Preparation Example 1-1) However, using the dihydroxyacetone dimer and 4-aminophenethylamine as starting materials, the title compound was prepared with a yield of 73%. NMR (CDC13) S 3.04 (t, 2H), 4.18 (t, 2H ), 4.48 (3, 2H), 6.79 (5, 1H), 6.96 (d, 2H), 7.20-7.40 (m, 3H) FAB 237 (M + H), Ci2H13N2OC1 (M) 26- 2) 1- ( 4-Chloro) benzyl-5-chloromethyl-1H-imidazosinic acid: According to the same procedure as in Preparation Example 2), using the compound obtained in Preparation Example 26-1), the title compound was obtained (yield: 91%) ). The product thus obtained was directly used in the next reaction without purification. Preparation Example 27: Synthesis of 1- [2- (naphthalene-2-yl) ethyl] -5-chloromethyl-1H-oxazolium sulfonium acid 27-1) 1- [2- (naphthalene-2-yl) Ethyl-5-hydroxymethyl-1H-imidazole was prepared according to the same procedure as in Preparation Example 1-1), but using dihydroxyacetone dimer and 2- (naphth-2-yl) ethylamine as starting materials. The title compound was obtained, and the printing rate of employees' cooperatives of the Central Standards Bureau of the Ministry of Industry and Economy was 58%. lR NMR (CDC13) 3.22 (t, 2H), 4.28 (t, 2H), 4.48 (s, 2H), 6.84 (Sj 1H), 7.19 (d, 1H), 7.24 (d, 2H), 7.44 (m) 2H), 7.52 (s, 1H), 7.76 (m, 3H) FAB 253 (M + H), C16HI6N20 (M) 27-2) [2- (naphthalene-2-yl) ethyl 5-chloromethyl Based on the same steps as those in Preparation Example 1-2), the paper size prepared in Preparation Example 27-1) is applicable to the Chinese National Standard _ (CNS) A4 Specification (210X297 mm) 9 15 06 ( Read the notes on the back before filling in this page) 8 1 136 ^ 87 A7 B7 V. Description of the invention (82) The compound was obtained as the title compound (yield 88 涔). The product thus obtained was directly used in the next reaction. Without purification. (Please read the precautions on the back before filling this page) Example 17: 3- [N-methoxyethyl) -N-methyl] aminomethyl-1--1- [1 ·-(2-methoxy ) Phenethyl-1 乙基 -imidazol-5-yl] methyl 4- (naphthalene-1-ylbu 1H-pyrrole (17) Synthesis 62 mg (0.2 mmol) Compound prepared in Preparation Example 6 Dissolved in 2 ml of dimethylformamide and added Ot: 26.4 mg (0.66 mmol) of sodium hydride (60 F) to it, and then stirred the mixture for 5 minutes. To this mixture was added 63 mg (2.2 mmol) Mol) The entire mixture of compound t obtained in Preparation Example 15 was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 · ml of water was added to the residue. The mixture was extracted twice with 10 liters of ethyl acetate. Anhydrous sodium sulfate was dehydrated, concentrated, and then subjected to silica gel column chromatography (solubilizing solution: dichloromethane / methanol = 95/5, v / v, to obtain 78 mg (yield 75%) of the title compound. NMR (CDC13) δ 2.39 (s, 2H), 2.71 (br, 1H), 2.90 (t, 2H), 2.95-3.15 (m, 5H), 3.31 (br, 1H), 3.52 (br, 1H), 3.76 (s, 3H), 4.06 (t, 2H), 4.83 (s, 2H), 6.68 (s, 1H), 6.75-6.95 (m, 3H), 7.23 (s, 1H), 7.25 (s, 1H), 7.2 l (t, 1H ), 7.30 -7.48 (m, 4H), 7.50 (s, 1H), 7.75 (d, 1H)} 7.81 ((1, 1H), 8.06 (d, 1H) FAB 523 printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ( M + H), C32H34N4O3 (M) Example 18: l-[(2-methoxy) phenethyl-1H-oxazol-5-yl] methyl- 3- [4-methylhexahydropyridine- Benzyl] hydroxy-4- (Cha-1-ylrole (18) Synthesis 62 mg (0.2 mmol) The compound prepared in Preparation Example 8 was dissolved in 2 ml of dimethyl methylamine and in Ot: Add 26.4 milligrams (0.66 millimolars) of hydrogenated paper. This paper applies Chinese national standards. (CNS) A4 size (210 X 297 mm) 91506 8 2 4 3 64 8 7 A7 B7 V. Description of the invention (83) (please first Read the notes on the back and fill in this page again) Sodium (60〆) into it, and then stir the mixture for 5 minutes. To this mixture was added 63 mg (2.2 millitorles) of the compound prepared in Preparation Example 15, and the entire mixture was placed in a chamber. Stir for 3 hours. Distill the solvent under reduced pressure, add 3 ml of water to the residue. Extract the mixture twice with 10 ml of ethyl acetate, dehydrate it with anhydrous sodium sulfate, shrink it, and perform silica gel column chromatography. Methyl chloride / methanol = 95/5, v / v, 75 mg (70% yield) of the title compound. * H NMR (CDCb) δ l-〇9 (br, 2H), 1.70-2.10 (br + s, 5H), 2.85 (t, 2H), 2.99 (br3 2H), 3.40 (br, 2H), 3.76 ( s, 3H), 4.04 (t, 2H), 4.85 (s, 2H), 6.69 (d, 1H), 6.80-6.92 (ra, 3H), 7.04 (s, 1H), 7.08 (s, 1H), 7.25 (t, 1H), 7.30 (d, 1H), 7.35- 7.50 (m, 4H), 7.77 (d, 1H), 7.80 (d, 1H), 8.02 (d, 1H) FAB 534 (M + H), C33H34N5O2 (M) Example 19: 3- [N- (2-methoxyethyl) -N-methyl] aminomethylamidino-bu 1: 1- (4-methoxy) phenethyl-1H-fluorene Synthesis of azole-5-yl] methyl-4- (Cai-1-yl) -1) -pyrrole (19). Which Central Bureau of Standards Consumer Cooperative printed 62 mg (0,2 mmol) in preparation The compound prepared in Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60 °) was added to the solution, and the mixture was then stirred for 5 minutes. To this mixture was added 63 mg (2.2 mmol) of the compound prepared in Preparation Example 16, and the entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture M was extracted twice with ethyl acetate (10 ml), dehydrated and concentrated through anhydrous sodium sulfate, and then subjected to silica gel column chromatography (solvent: dichloromethane / methanol = 95/5, ν / ν) to obtain 83 mg (yield 80) Boli compound. This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 8 3 91506 _8 6 4 8 7 _b7_ V. Description of the invention (84) lH NMR (CDC13) δ 2.33 (br, 2Η), 2.72 (t, 2H); 2.85-3.15 (m, 7H), S.Slfbr, 1H), 3.72 (s, 3H), 3.97 (t, 2H), 4.78 (s, 2H), 6.69 (d, 1H), 6,77 (d, 2H), 6.85 (d? 2H), 7.03 (s, 1H), 7.06 (s, 1H), 7,24-7,50 (m, 5H), 7.73 (d, 1H), 7.82 (d , 1H), 8.05 (d, 1H) FAB 523 (M + H), C32H34N4O3 (M) Example 20: l- [l- (4-methoxy) phenethyl-1H -oxazol-5-yl] Synthesis of methyl-3- [4-methylhexahydropyridine-1-yl] carbonyl-4- (naphthalene-1-yl) -1Η-pyrrole (2 0) 62 g (0.2 mol) The compound obtained in Preparation Example 8 was dissolved in 2 ml of dimethylformamide, and Ot: 26.4 mg (0.66 mmol) of sodium hydride (60 to 60) was added thereto, and then the mixture was searched and mixed for 5 minutes. To this mixture was added 63 亳 g (2.2 mils) of the compound obtained in Preparation Example 16, and the entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 95/5, ν / ν) to obtain 83 mg (yield 78 ii) the title compound. Printed by 1H NMR (CDCb) 3 l-〇5 (br; 2H), 1.70-2.10 (br + s, 4H), 2.24 (br, 1H), 2.72 (t, 2H) , 2.89 (br, 2H), 3.30 (br, 1H), 3.73 (s) 3H), 3.98 (t, 2H), 4.79 (s, 2H), 6.69 (d, 1H), 6.76 (d, 2H), 6.86 (d, 2H), 7.08 (m, 2H), 7.30-7.50 (m, 5H), 7.74 (d, 1H), 7.80 (d) 1H), 8.00 (d, 1H) FAB 534 (M + H) , C33H35N5O2 (M) Example 21: l- [l- (2-fluoro) phenethyl-1H-imidazol-5-yl] methyl This paper size applies to the Chinese national standard (CNS) A4 Zhuge (2: 0X297 public (Centi) 84 9 15 08 A7 B7 436487 V. Description of the invention (85) 2-methoxyethyl) -N-methyl] methylformyl-4- (naphthalene-butyl) -1H-pyrrole (2 1) Synthesis (Please read the precautions on the back before filling this page) 62 mg (0.2 millitorr) The compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.64) was added to 0¾ 6 millimoles) of sodium hydroxide (60%), and the mixture was stirred for 5 minutes. To this mixture was added 61 mg (2.2 mmol) of the compound prepared in Preparation Example 17, and the entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The warm compound was extracted twice with 10 ml of ethyl acetate, dehydrated and dried under anhydrous sodium sulfate, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 95/5, v / v) to obtain 7δ mg. (77% yield) of the title compound. '! H NMR (CDC13) ^ 2.38 (br, 2H), 2.70 (br, 1H), 2.81 (ΐ, 2H), 2.90-3.38 (π, 7Η), 4.03 (t, 2Η), 4.91 (s, Td ), 6.71 (d, 2H0, 6.92 (m, 1K) 3 6.95-7.12 (m) 4H), 7.19 (ιη, 1H), 7.30-7.65 (m, 4H), 7.73 (4 1H) 3 7.80 (d, ! H), 8.05 (4 1H) FAB 511 (M + H), C3iH3iN402F (M) Example printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 22: Bu [1- (2-fluoro) phenethyl-1H-imidazole Synthesis of 5--5-yl] methyl-3- [4-methylhexahydropyrine-1-yl] hydroxy-4- (naphthalene-1-yl) -1Η-pyrrole (22) 62 mg (0.2 mmol) Ear) The compound prepared in Preparation Example 8 was dissolved in 2 ml of dimethylformamide, and Ot: 26.4 mg (0.66 mmol) of sodium hydride (60 涔) was added thereto, and then the mixture was stirred for 5 minutes. To this mixture was added 61 mg (2.2 mmol) of the compound prepared in Preparation Example 17, and the entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added. CNS) A4 specification (2 丨 0X297 mm) 85 9 1506 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 436487_B7 V. Description of the invention (86) to The mixture was extracted twice with M10 ml of acetic acid acetate, dehydrated and dehydrated with anhydrous sodium acetate, and then subjected to silica gel column chromatography (eluent: dichloromethane / formase = 95/5. V / v, 78 mg was obtained. (Yield 75 points) Title Compound α NMR (CDC13) $ 1.04 (br, 2H), 1.70-2.10 (br + s, 5H), 2.81 (m, 2H), 3.90 (br, 2H), 3.32 (br, 2H), 4.05 (t, 2H), 4.93 (s, 2H), 6.72 (d, 1H), 6.90 (t, 1H), 6.95-7.05 (m, 2H), 7.10 (d, 2H), 7.20 (m , 1H), 7.25 ^ 7.50 (m, 4H), 7.75 (d, 1H), 7.82 (d, 2H), 8.00 (d, 1H) FAB 522 (M + H), C32H32N5OF (M) Example 23: 1- [1_ (2-Amo) phenethyl-1H-oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4--4-methyl Naphthalene-1-yl) -1H-pyrrole (23) i Synthesis 62 奄 g (0.2 mmol) The compound obtained in Preparation Example 6 was dissolved in 2 liters of dimethylformamide, and 26.4 was added at 0¾ Milligrams (0.66 millimoles) of sodium hydride (60 Torr) was added thereto, followed by stirring the warm mixture for 5 minutes. To this mixture was added 64 mg (2.2 millirales) of the compound prepared in Preparation Example 18, and the entire mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated and concentrated with anhydrous sodium sulfate, and subjected to a silica gel column analysis (eluent: dichloromethane / methanol = 95/5, v / v) to obtain 75 grams (yield). 71X) title compound. NMRCCDCb) ^ 2.39 (br) 2H), 2.71 (br, 1H), 2.90-3.38 (m, 9H), 4.06 (t, 2H), 4.87 (3, 2H), 6.71 (s, 1H), 6.87 (m , 1H), 7.00 ^ 7.20 (m, 4H), 7.30-7.60 (m, 6H), 7.73 (d, 1H), 7.89 (d, 1H), 8.06 (d, 1H) FAB 527 (M + H), C3iH3iN403Cl (M) The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (2! 0X297 mm) 8 6 9 1 50 6 (Please read the precautions on the back before filling this page) Λ · A7 B7 436487 V. Description of the Invention (37) (Please read the precautions on the back before filling this page) Example 24: 1- [1- (2-Amo) benzylethyl-1H-oxazol-5-yl] methyl-3- [ 4-methylhexahydropyridine-; l-yl] carbonyl-4- (naphthalene] -yl) -1H-pyrrole • (24) Synthesis 62 mg (0.2 millitorr) was prepared in Preparation Example 8 The compound was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60 〆) was added thereto at 01C, followed by stirring the mixture for 5 minutes. To this warm compound was added 64 mg (2.2 millimoles) of the compound prepared in Preparation Example 18, and the entire mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 95/5, v / v) to obtain 84 mg (product Rate 78%) of the title compound. lH NMR (CDC13) § 1.04 (br? 1H), 1.70-2.10 (br + s, 5H), 2.35 (br3 1H), 2.92 (ti-br, 4H), 3.32 (br, 2H), 4.08 (t, 2H), 4.88 (s, 2H), 6.7l (s, 1H), 6.87 (mv 1H), 7.09 (m, 3H), 7.18 (m, 1H), 7.30-7.55 (m, 6H), 7.75 (d , 1H), 7.8 l (d, 1H), 8.0 l (d, 1H) FAB 538 (M + H), C32H32N5OCI (M) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Example 25: l- [l- ( 3-chloro) phenethyl-1H-oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -fluoren-methyl] aminomethylthio- 4- (naphthalene-bu -Synthesis of pyrrolyl (25) 62 mg (0.2 mmol) The compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride was added to Ot. (60 F) to it, and then the mixture was stirred for 5 minutes. In this mixture, I added δ 4 mg (2.2 mmol) to the compound obtained in Preparation Example 19. All of the _ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 8 7 9 15 0 6 4 3 64 87 A7 _B7_ V. Description of the invention (88) The mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of acetic acid acetate, dehydrated with anhydrous sodium tellurate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / formaldehyde = 95/5, v / v, 80 mg ( Yield 76〆) The title compound. ^ NMRCCDCI3) δ 2.37 (br, 2H), 2.71 (111, 3H), 2.90-3.20 (m, 6H), 3.30 (br, 1H), 3.99 (t, 2H), 4.86 (s, 2H), 6.69 (d, 1H), 6.81 (d, 1H): 7.00 (s, 1H), 7.05- 7.20 (m, 5H), 7.30-7.50 (m, 4H), '.74 ( d, 1H), -1H), 8.04 ((1, 1H) FAB 527 (M + H), C3iH3! N4〇2C1 (M) Example 26: l- [l- (3-chloro) -l-ethyl-1H -Imidazol-5-yl] methyl-3- [4-methylhexahydropyrine-1-yl] carbonyl- 4- (naphthalene-1-yl) -1Η-pyrrole (26) Central Standard for the Ministry of Synthesis Bureau-Industrial and Consumer Cooperatives Yinfan (Please read the precautions on the back before filling out this page) 62 mg (0.2 mmol) &gt; The compound prepared in Preparation Example 8 was dissolved in 2 ml of dimethylformamide, and Add 26.4 mg (0.66 mmol) of sodium hydride (60 涔) to it, and then stir the mixture for 5 minutes. To this mixture was added 64 mg (2.2 mmol) of the compound prepared in Preparation Example 19, and the entire mixture was placed in a chamber. Stir at room temperature for 2 hours. Remove the solvent by distillation under reduced pressure, add 3 liters of water to the residue. Extract the mixture with 10 ml of ethyl acetate twice, extract it with anhydrous sodium sulfate, concentrate, and perform silica gel column chromatography (eluent: dichloromethane). / Methanol = 95/5, ν / ν), to obtain 85 mg (yield 79 涔) of the title compound. The paper size applies the Chinese National Standard (CNS) A4 specification (2ί0χπ7 mm) 88 91506 436487 A7 __._ B7_ 5 Description of the invention (8 9) lH NMR (CDCb) ^ 1.05 (br, 2H), 1.70-2.10 (br + s, 5H); 2.69 (t, 2H), 2.90 (br, 2H), 3.32 (br, 2H ), 3.98 (t, 2H), 4.87 (s3 2H), 6.70 (d, 1H ;, 6.79 (d, 1H), 6.98 (s, 1H), 7.05 ^ 7.21 (m, 3H), 7.30-7.50 (m : 6H): 7.74 (d; 1H), 7.82 (d, 1H), 7.99 (d, 1H) FAB 538 (M + H), C32H32N5OCI (M) Example 27: 3- [N- (2 -methoxyethyl) Yl) -N-methyl'yl] aminocarbamyl-4- (naphthalene-1-yl) -1- [1- (3-benzyl, etc.) propyl-1H-imidazol-5-yl] methyl-1H -Synthesis of pyrrole (2 7) 62 mg (0.2 millitorr) The compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and at 0Ϊ: 26.4¾ g (0.66 millier) was hydrogenated Na (60 涔) to it, The mixture was stirred for 5 minutes granted. To this mixture was added 62 mg (2.2 millitorles) of the compound prepared in Preparation Example 20. The entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dried over anhydrous sodium sulfate, and concentrated. Silica gel column chromatography (eluent: dihydromethane / methanol = 95/5, v / v) was obtained to obtain 76 mg (yield 75 i) the title compound. ! H NMR (CDC13) ^ 1.91 (m, 2H), 2.24 (t, 2H), 2.56 (m, 5H), 2.90- 3.07 (m, 4H), 3.18 (br, 1H), 4.03 (t, 2H) 5.12 (s, 2H), 6.57 (s, 1H), 6.90- 7.20 (m, 8H), 7.21-7.52 (m, 3H) 1.66 (0, 1H); 7,72 (d, 1H), 7.89 ( d, 1H). 8.06 (br, 1H) FAB 507 (M + H), C32H34N4O2 (M) (Please read the notes on the back first and then fill in # (this page) Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 89 9 15 06 4364 87 A7 __B7 V. Description of the invention (90) Example 28: 3- [4 -methylhexahydropyridine M-based ] Synthesis of 4- (naphthalenyl-phenyl) -1- [1- (3-benzyl) propyl-1H-oxazol-5-yl] methyl-1H-pyrrole (28)-Please read first Note on the back, please fill in again, write this page 62 mg (0.2 mmol) of the compound prepared in Preparation Example δ is dissolved in 2 ml of dimethylformamide, 26.4 mg (0.66 mmol) ) Sodium hydride (60 known), and then search the mixture for 5 minutes. To this mixture was added 62 mg (2.2 millirales) of the compound obtained in Preparation Example 20, and the entire mixture was placed in a chamber. Stir for 2 hours. Remove the solvent by distillation under reduced pressure, add 3 ml of water to the residue. Extract the mixture K10 ml of ethyl acetate twice, dehydrate with anhydrous sodium sulfate, concentrate, and perform decantation on a silica gel column (eluent: dichloromethane / Methanol = 95/5, v / v), 77 g (yield 74%) of the title compound were obtained.! H NMR (CDC13) 8 l-〇l (br, 2H), 2.80-2.01 (s + br + m , 6H), 2.30 (br, 1H), 2.55 (t, 2H), 2.86 (br, 2H), 3.30 (br, 2H), 3.79 (t, 2H), 5.00 (s, 2H), 6.58 (s, IK), 7.00-7.20 (111, 8H), 7.36 (m? 1H), 7.41 (m, 2H), 7.50 (s, 1H), 7.74 (d, 1H), 7.80 (d, 1H), 8.00 (d , 1H) FAB 318 (M + H), C33H35N50 (M) Printed by the Consumer Cooperatives of the Central Standards Bureau, Ministry of Economic Affairs, Example 29: 3- [N- (2-methoxyethyl) -K-methyl] amine methylamine Synthesis of fluorenyl-4- (naphthalene-1ylnaphthalene-2-yl) methyl-1H-fluoren-5-yl] methyl-1H-pyrrole (29) 62 mg (0.2 mmol) in the preparation example The compound obtained in 6 was dissolved in 2 ml of dimethylformamide, and 26.4 g (0.66 mmol) of sodium hydride (60 μm) was added to the solution, and the mixture was stirred for 5 minutes. To this mixture was added 65 mg (2.2 millimolars) of the compound prepared in Example 21, and all the paper sizes were in accordance with China National Standard (CNS) A4 (210X297 mm) 90 91506 4 3 64 8 7 A7 __ '' _B7_ V. Description of the invention (91) The mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated and concentrated with anhydrous sodium tellurate, and then subjected to silica gel column chromatography (eluent: dihydromethane / methanol = 95/5, v / v) to obtain 85 mg (product Rate 80 allowed) Title Bei compound. ! H NMR (CDC13) δ 2.36 (br, 2H), 2.72 (br, 1H), 2.98 (br, 3H), 3.02 (br, 2H), 3.31 (br; 1H), 3.73 (br, 1H), 5.1 〇 (s, 2H), 5.47 (s, 2H), 6.58 (s, 1H), 7.03 (s, 1H), 7.08 (d, 1H), 7.15 (d, 1H), 7.2l (s, 1H), 7.34-7.53 (m, 7H), 7.60 (s, 1H), 7.70-7.83 (m, 4H), 7.97 (d, 1H) FAB 529 (M + H), C34H30N4O2 (M) Example 30: 3- (4 -Methylhexahydropyridin-1-yl] carbonyl-4- (naphthalene-1-yl) -1- [1- (ban-2-yl) methyl-1H-imidazol-5-yl] methyl- 1H -Pyrrole (30) printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Synthetic Economy (Please read the precautions on the back before writing this page) 62 mg (0.2 mil) of the compound prepared in Preparation Example 8 In 2 ml of dimethylformamide, 26.4 mg (0.66 mmol) of sodium hydride (60 mol) was added thereto, followed by stirring the mixture for 5 minutes. To this mixture was added 65 mg (2.2 mmol) of the compound prepared in Preparation Example 21, and the entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure ^ 3 ml of water was added to the residue. Mixed with 10 ml of ethyl acetate and extracted twice, dehydrated with anhydrous sodium sulfate, concentrated, and analyzed by silica gel column (eluent: dichloromethane / methanol = 95/5, v / v) to obtain 74 mg (yield 69 Ii) the title compound. This paper size applies Chinese National Standard (CMS) A4 specification (210X297 mm) 9 1 9 1506 A7 B7 436487 V. Description of the invention (9 2) 'H NMR (CDC13) s 0.98 (br, 2H), 1.70- 2.00 (s + br, 5H), 2.81 (br, 2H), 3.37 (br, 1H), 4.88 (s, 2H), 5.10 (s, 2H), 6.57 (s, 1H), 7.02 (s, 1H) Please read the note φ- on the back before filling in this page 7.08 (d, 1H), 7.16 (d, 1H), 7.21 (s, 1H), 7.34-7.52 (tn, 7H), 7 60 (s 1H) 7.70-7.83 (m, 4H), 7.97 (d, 1H) 'FAB 540 (M + H), C35H33N5O (M) Example 31: 3- [N- (2-methoxyethyl) -H-methyl] Carbamidyl-4- (naphthalene-butyl) -1- {1-[[2- (naphthalene-1-yl) ethyl] -1H-oxazol-5-yl} methyl-1H-pyrrole ( 31) Synthesis 62 mg (0.2 millimolar) The compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and in Ot: 26.4 g (0.66 mol) of sodium chloride (60 Ii) Into it, then stir the mixture for 5 minutes. To this mixture was added 68 mg (2.2 mol) of the compound prepared from 钶 22, and the entire mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / formase = 95/5, v / v) to obtain 77 mg (yield 71 ii) the title compound. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs! H NMR (CDC13) d 2.34 (br, 2H), 2.68 (br, 1H), 2.80-3.20 (m, 5H), 3.23 (t, 2H), 3.29 (br , 2H), 4.12 (t, 2H), 4.45 (s, 2H), 6.43 (d, 1H), 6.84 (d, 1H), 6.97 (m, 2H), 7.21-7.52 (m, 10H), 7.72 ( d, 1H), 7.78-7.85 (m, 2H), 8.0 l (d, 1H) FAB 543 (M + H), C35H34N4O2 (M) Example 32: 3- [4 -methylhexahydropyrine-1- Yl] carbonyl-4- (naphthalene-1-yl) -1- (1- [2- (naphthalene-butyl) Zyl] -1H-imidazol-5-yl} methyl-1H- This paper is applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 92.91506 A7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 436487 B7 V. Description of the invention (93) Synthesis of pyrrole (3 2) 62 mg (0.2 mmol) Ear) The compound obtained in Preparation Example 8 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 millitors) of sodium hydride (60X) was added to the solution, followed by stirring the mixture for 5 minutes. To this mixture was added 68 mg (2.2 mmol) of the compound prepared in Preparation Example 22. The entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / formase = 95/5, v / v) to obtain 83 mg (yield 75) The title compound. NMR (GDC13) $ 1.01 (br, 2H), 1.70-2.00 (br + s, 5H), 2.89 (br, 2H), 3.27 (t, 2H), 3.40 (br, 2H), 4.16 (t, 2H), 4.50 (s, 2H), 6.45 (d, 1H), 6.90 (d, 1H), 6.97 (d, 1H), 6.99 (s, 1H), 7.25-7.55 (m? 8H) , 7.73-7.95 (m, 5H), 8.00 (d, 1H) FAB 554 (M + H), C36H35N5O (M) Example 33: l- [l- (4-bromo) benzylethyl-1H-imidazole-5 -Methyl] methyl-3- [N- (2-methoxyethyl) -fluoren-methyl] aminomethylfluorenyl-4- (naphthalene-phenyl) -1fluorene-pyrrole (3 3) Synthesis 62 mg (0.2 millimolar,) The compound obtained in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 millimolar &gt; sodium hydride (60)) was added thereto, followed by The mixture was stirred for 5 minutes. To this mixture was added 74 mg (2.2 millirales) of the compound obtained in Preparation Example 23. The entire mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 liters of water was added to the residue. The mixture was extracted twice with K10 ml of ethyl acetoacetate. Lithium anhydrous sulfuric acid> This paper applies the Chinese national standard (〇 奶) 八 衫 见 格 (210>> 297 mm) 91506 (Please read the precautions on the back first ig ..., write this page)

93 4 3 64 8 7 B7 V. Description of the invention (94) Sodium dehydration and concentration were performed on a silica gel column (eluent: digas formamidine / methanol = 95/5, v / v), 88 g (Yield 77〆) ° NMR (CDC13) i 2.38 (br, 3H), 2.67 (t, 2H), 2.90-3.23 (m, 7H), 3.30 {br, 1H), 3.97 (t, 2H ), 4.88 (s, 1H), 6.69 (d, 1H), 6.82 (d, 2H), 7.08 (d, 2H), 7.27-7.53 (ιη, 7H), 7.73 (d, 1H), 7.80 (d, 1H), S.02 (d, 1H) FAB 571 (M + H), C3iH3iN4〇2Br (M) Example 34: l- [l- (4-bromo) phenethyl-1H-oxazol-5-yl ] Methyl-3-([4-methylhexahydropyrazine-1-yl] carbonyl_4_ (Chapirago (34) Printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Synthetic Economy (please read the back first) Note: Please fill in this page again.) 62 奄 g (0.2 奄 萁 ear) The compound obtained in Preparation Example 8 is dissolved in 2ml of dimethylformamide, and 26.4 奄 g is added. &lt; 〇_66 奄 mol) Sodium hydride (60 涔), followed by mixing the mixture for 5 minutes. To this mixture was added 74 奄 g (2.2 mmol) of the compound prepared in Preparation Example 23, and the entire mixture was stirred at room temperature for 2 hours. Reduce the solvent and remove the solvent. Add 3 ml of water to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column decantation (eluent: dichloromethane / methanol = 95/5, v / v) to obtain 82 g (product Rate 70 i) The title compound. ^ NMR (CDC13) d 1.04 (br, 2H), 1.80-2.00 (br + s, 4H), 2.48 (br, 1H), 2.66 (ζ 2H), 2.90 (br, 2H), 3.31 (br , 1H), 2.96 (t, 2H), 4.88 (s, 2H), 6.70 (s, 1H), 6.82 ((1, 2H), 7.10 (d, 2H), 7.25-7.60 (m, 7H), 7.75 (d, 1H), 7.82 (d, 1H), 8.01 (d, 1H) FAB 582 (M + H), CjaHasNjOBr (M) This scale applies to China National Standard (CNS) A4 (210X297 mm) 94 91506 A7 4 3 64 8 7 V. Description of the invention (95) (Please read the precautions on the back before writing this page) Example 35: 1- [1- (4 -_) phenethyl-1H-imidazole- 5-yl] methyl-3- [N-((2-methoxyethyl) -N-methyl] aminomethylamidino, 4- (naphthalene-1-yl) -1H-pykal (35) Synthesis ~ 62 mg (0.2 mmol) of the compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.6 6 mmol) of sodium hydride (60 ash) was added thereto at 01C. Then, the mixture was stirred for 5 minutes. To the mixture was added 60 mg (2.2 millirales) of the compound prepared in Preparation Example 24. The whole mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and 3 ml of water was added to the residue. Mixture M10 ml ethyl acetate extract two After dehydration and concentration with anhydrous sodium sulfate, silica gel column chromatography (eluent: dichloromethane / methanol = 95/5, v / v) was obtained to obtain 77 g (yield 76 allowed) of the title compound.! H NMR (CDC13) § 2.34 (br, 3H), 2.70 (t, 2H), 2.90-3.20 (br, 6H), 3.30〇5r, 1H), 3.96 (1; 2H), .4.86 (3, 1H), 6.68 (d, 1H), 6.90 (m, 4H), 7.05 (s, 1H), 7.09 (s, 1H), 7.25-7.52 (m, 5H), 7.73 (d, 1H), 8.05 (d, 1H) FAB 511 (M + H), C31H31N4O2F (M) Example 36: l- [l- (4-fluoro) phenethyl-1H-oxazol-5-yl] methyl-3- [4-Ministry of Economic Central Standard Bureau's Consumer Cooperative printed 62 gram (0.2 mol) of methyl hexahydropyridin-1-yl] carbonyl- 4- (naphthalene-1-yl) -1Η- € role (36) in the preparation example The compound prepared in 8 was dissolved in 2 ml of dimethyl methylamine, and Ot: 26.4 mg (0.66 mmol) of sodium hydride was added thereto, followed by stirring the mixture for 5 minutes. To this mixture was added 60 mg (2.2 mmol) of the compound prepared in Preparation Example 24, and the entire mixture was stirred at room temperature for 2 hours. Evaporate the solvent under reduced pressure and add 3 ml of water. The paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) ~ 95 91506 436487 A7 B7. 5. Description of the invention (96) to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated and concentrated with anhydrous sodium sulfate, and subjected to silica gel column shield analysis (eluent: dichloromethane / formaldehyde (please read the precautions on the back before filling this page). 95/5, v / v) to give 78 mg (75% yield) of the title compound. ! H NMR (CDC13) s 1.05 (br, 2H), 1.70-2.00 (br + s, 4H), 2.25 (br, 1H), 2.70 (t, 2H), 2.90 (br, 2H), 3.30 (br, 2H), 3.88 (t, 2H), 4.87 (s, 2H), 6.69 (s, 1H), 6.90 (π, 4H), 7.10 (m, 2H), 7.29 (m, 2H), 7.35- 7.50 (mj 3H), 7.74 (d, 1H), 7.82 ((1, 1H), 8.00 (d, 1H) FAB 522 (M + H), C32H32N5OF (M) Example 37: 3- [N- (2- Methoxyethyl) -N-methyl] aminomethyl-l- [i_ (4-methyl) phenethyl-1H-oxazol-5-yl] methyl-4- (naphthalene-l-yl ] -1 Η-Pyrrole (37) Synthesis 62 mg (0.2 mmol) The compound prepared in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) was added to 0¾. Sodium hydride (60%) was added thereto, followed by stirring the mixture for 5 minutes. To the mixture was added 60 mg (2.2 mmol) of the compound prepared in Preparation Example 25, and the entire mixture was stirred at room temperature for 2 hours. Solvent, add 3 ml of water to the residue. Extract the mixture with 10 ml of ethyl acetate twice, and dehydrate and concentrate it through the Indian cooperative of the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs of the anhydrous sulfuric acid. Methane / methanol = 95/5, ν / ν) to obtain 78 mg (yield 80%) of the title compound. lH NMR (CDC13) s 2.02 (br, 1H), 2.28 (s, 3H), 2.38 (br, 2H), 2.70 (br, 1H) , 2.75 (t, 2H), 2.95-3.20 (m, 5H), 3.31 (br, 1H), 3.99 (t, 2H)? 4.77 (s, 2H), 6.67 (s, 1H), 6.85 (d, 2H ), 7.06 (m, 4H), 7.25-7.50 (m, 5H), 7.74 (d, 1H), 7.81 (d, 1H), 8.07 (d, 1H) FAB 507 (M + H), C32H34N4O2 (M) This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 96 91506 five 436 ^ B7__, description of invention (97) A7 B7 yellow example 38: l- [l- (4-methyl) benzyl ethyl -1H-imidazol-5-yl] methyl-3- [(Please read the notes on the back before filling this page) 4-methylhexahydropyridine-1-] carbonyl-4- (naphthalene-1-yl ) -1Η-Pyrrole (3 8) Synthesis 62 輋 g (0 * 2 mil) &gt; The compound obtained in Preparation Example 8 was dissolved in 2 ## dishenylmethoxamine, and 26.4 was added at 0! Milligrams (0.66 millimoles) of sodium hydride (60 Torr) were added thereto, followed by the mixture for 5 minutes. To this mixture was added 60 mg (2,2 mol) of the compound obtained in Preparation Example 25, and the whole was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure, and 3 liters of water g residue was added. Mix and extract twice with 10 liters of ethyl acetate. • Analyze with anhydrous sodium sulfate and water, and analyze it in a silica gel column (eluent: dichloromethane / formase = 95/5, v / v). 81 Shek (78% yield) of the title compound T. lu NMR (CDC13) δ 1.07 (br, 1H), 1.70-2.10 (br + s, 6H), 2.28 (s, 3H), 2.75 (t, 2H), 2.90 (br, 2H), 3.33 (br, 2H ), 4.00 (t? 2H), 4.78 (s, 2H), 6.72 (s, 1H), 6.86 (m, 2H), 7.04-7.23 (m, 4H), 7.25-7.60 (m, 5H), 7.75 ( d, 1H), 7.82 (soil 1H), 8.01 (4 1H) FAB 518 (M + ί), C33H35N50 (M) Central Standards Bureau of the Ministry of Economic Affairs®; Printed Example of Industrial and Consumer Cooperatives 39: l- [l- (4 -Chloro) phenethyl-1H-oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4-4- (Cai-1- Synthetic group)-1Η-pyrrole (3 9) Synthesis 62 奄 g (0.2 mmol) The compound obtained in Preparation Example 6 was dissolved in 2 ml of dimethylformamide and added to Ot; 26.4 w • 66 millimoles) of sodium hydride (60 Torr), and then the mixture was stirred for 5 minutes. To this mixture was added 64 grams (2.2 millimoles) of the compound prepared in Preparation Example 26. The good paper size of the whole: Ministry of Standards (CNS) A4 (210 X plus mm) 97 91506 A7 B7 436487 V. Description of the invention (98) The mixture was stirred at room temperature for 2 hours. The solvent was removed by distillation under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated and shrunk with anhydrous sodium sulfate, and subjected to silica gel column decantation (eluent: dichloroformamidine / formase = 95/5, v / v) to obtain 74 mg. (70% yield) of the title compound. lB NMR (CDC13) ^ 2.38 (br, 2H), 2.70 (t, 2H), 2.90-3.20 (m, 7H), 3.30 (br, 1H), 3.97 (ΐ, 2Η), 4.88 (s, 2H), 6.69 (d, 1H), 6.88 (d, 2H), 7.04 (Sj 1H), 7.09 (s, 1H), 7.19 (d, 1H), 7.24-7.50 (m, 5H), 7.75 (d, 1H), 7.81 (d, 1H)? 8.02 ((1, 1H) FAB 527 (M + H), C31H31N4O2CI (M) Example 40: 1- [1- (4-Gas) phenethyl-1H -oxazole-5- Of methyl] methyl] -3- [4-methylhexahydropyridin-1-yl] carbonyl-4- (naphthalene-1-yl) -1Η-pyrrole (40) 62 mg (0.2 mmol) The compound prepared in Preparation Example 8 was dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mmol) of sodium hydride (60%) was added thereto, followed by stirring the mixture for 5 minutes. Add 64 mg (2.2 mmol) of the compound prepared in Preparation Example 26, and stir the entire mixture at room temperature for 2 hours.> Remove the solvent by depressurizing distillation and add 3 ml of water to the residue. Extract 10 ml of acetic acid ethyl acetate Twice, dehydrated and concentrated by anhydrous sodium sulfate, and performed a silica gel column analysis (eluent: methane / methanol = 95/5, v / v) to obtain 84 mg (yield 78) of the title compound. Please first Attention after reading Re-enter. Fill in and write down the pages printed by the employees ’cooperatives of the Jiayang Standards Bureau of the Ministry of Economic Affairs. The paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) 98 9 15 0 6 4 3 6487 A7 ___B7_ V. Description of the Invention (99) lH NMR (CDC13) § 1.08 (br, 2H), 1.80 (br, 2H), 1.95 (s, 3H), 2.73 (t, 2H), 2.93 (br, 2H)} 3.35 (br, 2H), 4.00 (t, 2H), 4.90 (s, 2H), 6.71 (d, 1H), 6.91 (d, 2H), 7.13-7.60 (ra, 9H), 7.78 (d, 1H), 7.82 (d5 IE): S.01 (d, 1H) FAB 538 (M + H), C32H32N5OCI (M) Example 41: 3-U- (2-methoxyethyl) -N-shenyl] aminomethyl-4 Synthesis of-(naphthalene-1-yl) -1- {1- [2- (naphthalene-2-yl) ethyl] oxazol-5-yl) methyl-1, l-pyrrole (41) 62 mg (0.2 MM) The compound obtained in Preparation Example 6 was dissolved in 2 ml of dimethylformamide, and Ot: 26.4 mg (0.66 mmol) of sodium hydride (60 〆) was added thereto, followed by mixing Mix for 5 minutes. To this mixture was added 67 mg (2.2 mol) of the compound prepared in Preparation Example 27, and the entire mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and 3 ml of water was added to the residue. The mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 95/5, ν / ν) to obtain 79 mg (yield 71). Ii) the title compound. Central Bureau of Economic Affairs, Ministry of Economic Affairs W: Printed by the Industrial and Consumer Cooperatives {Please read the precautions on the back before writing 4.- Write this page) NMR (CDC13) § 2.96 (br, 1H), 2.39 (br, 2H), 2.71 ( br, 1H), 2.80-3.15 (m, 7H), 3.32 (br, 1H), 4.10 (t, 2H), 4.78 (s, 1H), 6.66 (s, 1H), 7.09 (m, 3H), 7.42 (m, 8H), 7.63 (m, 1H), 7.75 (m, 3H), 7.82 (d, 1H), 8.06 (d, 1H) FAB 543 (M + H), C35H34N4O2 (M) Example 42: 3 Ink [4-methylhexagas 8 ratio _-1_base] via base ink 4-(Cha_-1 _base) -1-This paper size applies to China National Standard (CNS) A4 (210X 297 mm) Θ9 91506 436487 A7 B7 V. Description of the invention (10 ^ (1- [2-naphthalen-2-yl) ethyl] -1H-oxazol-5-yl} methyl-1I-pyrrole (42) Synthesis (please Read the precautions on the back before filling in the dome page.) 62 mg (0.2 mol) of the compound prepared in Preparation Example 8 is dissolved in 2 ml of dimethylformamide, and 26.4 mg (0.66 mol) is added. Sodium hydride (60%) was added thereto, followed by stirring the mixture for 5 minutes. To the mixture was added 67 mg (2.2 mmol) of the compound prepared in Preparation Example 27, and the entire mixture was stirred at room temperature for 2 hours. Solvent, add 3 ml of water to the residue. Extract the mixture with 10 ml of ethyl acetate twice, dehydrate it with anhydrous sodium sulfate, and concentrate. Column chromatography on silica gel (eluent: dichloromethane / formase = 9 5/5, Wv) to obtain 82 mg (74% yield) of the title compound. LE NMR (CDC13) S 1.05 (br, 2H), 1.70-2.00 (s + br) 4H), 2.34 (br, 1H) 3 2.90 (t, 2H), 3.01 (br, 2H)} 3.32 (br, 2H), 4.08 (t, 2H), 4.78 (s, 2H), 6.65 (d, 2H), 7.10 (m, 3H), 7.21-7.42 (m , 7H), 7.64 (m, 1H), 7.75 (m, 3H), 7.82 (d, 1H), 8.01 (d, 1H) FAB 554 (M + H), C36H35N5O (M) Example 43: l- (l -(4-Hydroxy) phenethyl-1H-imidazol-5-yl] methyl-3 [[4-methylhexahydropyridine-1-yl] carbonyl-4 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Synthesis of-(naphthalene-1-yl) -1Η-pyrrole (43 &gt;) 53 奄 g (0.1 mmol) of the compound prepared in Example 20 was dissolved in 1 奄 liter of dichloromethane, and 75 mg (0.3 奄奄) (Ear) boron tribromide (BBγ · 3) to it, and the mixture was stirred for 3 hours. Add 1 ml of formazan to stop the reaction and remove the solvent by distillation. The residue was subjected to silica gel column chromatography (eluent: dichloromethane / formaldehyde = 20/80, v / vh to obtain 26 mg (yield 50 涔) of the title compound. This paper is in accordance with China National Standard (CNS) A4 specifications (2 ί 0 X 297 mm) 100 91506 '4 3 6487 A7 B7 _ 5. Description of the invention (101)' H NMR (CDC13) «5 1.20 (br, 2H), 1.80-2.05 (br + s, 4H) , 2.65 (t, 2H), 3.00-3,60 (br, 5H), 3.98 (t, 2H), 4.88 (Sj 2H), 6.72 (m, 5H), 7.09 (s, 1H), 7.14 (d, 1H), 7.23 (s, 1H), 7.27 (s) 1H), 7.33 (d, 1H), 7.40-7.53 (m, 3H), 7.77 (d, 1H), 7.82 (d, 1H), 7.93 (d , 1H) FAB 520 (M + H), C32H33O2N5 (M) Preparation Example 28: Synthesis of 4-chloromethyl-1-trityl-1H-oxazosinamidine 28-1) 4-hydroxymethyl- 1-trityl-1H-imidazole 3.99 g (29.6 mol) hydroxymethyl oxazolium hydrazone is dissolved in a mixture of 30% of dimethylformamide and 10% of triethylamine. Slowly add a solution containing 9.35 g (33.5 mol) of triphenylmethyl vapor in 110 ml of dimethylformamide to the base. After 2 hours, 500 ml of ice water was added to the reaction mixture to obtain a solid. This solid was recrystallized from dioxane to obtain 8.82 g (yield 87%) of the title compound. m.p .: 2 27-229 t: 28- 2) 1.50 g (4.41 mol) printed by the Consumers Cooperative of Central Standards Bureau of the Ministry of Economic Affairs Ear) The compound obtained in Preparation Example 2 and 1) was dissolved in 50 ml of chloroform, and 0.94 ml (13.2 mmol) of thionyl chloride was added to the 01C grade, and the warm mixture was stirred at room temperature for 2 hours. Hour> The organic solvent was removed under reduced pressure to obtain 1.66 g (4.2 奄 萁, yield 95 涔) of the title compound. This compound was used in the next reaction without purification. Preparation Example 29: Synthesis of 4- (5-chloromethyl-1fluorene-oxazol-1-ylmethyl) hydrazone benzylproline 29-1) 4-Ethyloxymethyl-1-trityl-1H -Imidazole. (Please read the notes on the back before filling this page) Add 100 ml pyridine to 5.00 g (14.7 奄 Mor) Preparation Example This paper size applies the Chinese National Standard (CNS) A4 ^ grid (210X297 mm) 101 9 1506 A7 43 6487 B7 V. Compounds prepared in the description of the invention (102) 28-1) and 1.65 g (16.2 millitorles) acetic anhydride, mixed (please read the precautions on the back before filling this page) The mixture was stirred at room temperature for 24 hours. The reaction solution was distilled under reduced pressure to remove pyridine, and then the residue was dissolved in 200 ml of ethyl acetate, and washed with 100 ml of a sodium chloride solution. The organic solvent was removed by distillation under reduced pressure, and the residue was subjected to column analysis (brown solution: methane / methanol = 20/1, ν / ν) to obtain 5.22 g (13.7 mmol, yield 93 fires). Compound. lR NMR (CDC13) δ '2.01 (3, 3Η), 4.95 (s, 2H), 6.88 (s, 1H), 7.08 (s, 5H), 7.27 (s, 10H), 7.45 (s, 1H) 29- 2) 4- (4-Ethyloxymethyl-1-trityl-1H-oxazole-3-ylmethyl) benzonitrile bromide 5.00 g (13.1 mmol) Preparation Example 29-1) The obtained compound was dissolved in 20 ml of dichloromethane, and 28.2 g (14.4 mmol) of 4-cyanobenzyl bromide was added thereto, and the mixture was stirred at room temperature for 60 hours. The organic solvent was removed by distillation under reduced pressure, and the residue was subjected to column chromatography (eluent: methylene chloride / methanol = 5/1, v / v) to obtain 5.31 g (9.17 mmol, yield 70) of the title compound. Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs [R NMR (CDC13 + CD3OD) $ 1.95 (s, 3H), 4.95 (s, 2H), 5.45 (s, 2H), 7.11- 7.40 (m, 18H), 7.65 (4 2H), 8.21 (s, 1H) 29-3) 4- (5-Acetyloxymethyl-1H-oxazole-butylmethyl) benzonitrile 9. 10 g (15.7 mmol) The compound prepared in 29-2) was dissolved in 500 ml of dichloromethane, and 6.06 ml (78.7 mmol) of trifluoroacetic acid and 12.5 ml (78,7 mmol) of triethyl were slowly added to 0¾. Silane was added thereto, and the mixture was stirred at room temperature for 1 hour. Scrap-removing distillation removes rubidium solvent, residue M. The paper size applies Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) 102 91506 436487 V. Description of the invention 03) K 2 C 0 3 saturated aqueous solution is adjusted to P HI 0, and M 300 ml ethyl acetate extraction. The organic solvent was removed by skimming distillation, and the residue was subjected to column analysis (using ethyl acetate as a broth) to obtain 3.60 g (14.1 mmol, yield 90 涔) of the title compound. : Η NMR (CDC13) ^ 1.90 (5, 3H)} 4.97 (s, 2H), 5.25 (s, 2H); 7.14 (d, 2H), 7.2l (d, 1H), 7.67Cs, 1H), 7.75 (d, 2H) 29-4) 4- (5-Hydroxymethyl-1H-imidazol-1-ylmethyl) benzyl The compound obtained in 4.20 g (16.5 mmol) of Preparation Example 29-3) was dissolved 'In 200 ml of formazan, add 4.50 g (32.9 mil U2CO3) to it, and stir the mixture at room temperature for 20 minutes. At room temperature, remove the organic solvent by distillation under reduced pressure. Then extract the residue with 300 liters of ethyl acetate. The extract was subjected to column chromatography (eluent: dichloromethane / methanol = 10/1, v / v) to obtain 3.19 g (15.0 mmol, 91% yield) of the title compound. LK NMR (CDCl3 + CD3OD) $ 4.28 (s, 2H), 5.18 (s, 2H), 6.84 (s, 1H), 7.12 (d, 2H), 7.42 (s, 1H), 7.55 (d, 2H) Ministry of Economy Printed by the Consumer Standards Cooperative of the Central Bureau of Standards (please read the precautions on the back before filling this page) 29-5) 4- (5-chloromethyl-1H-oxazol-1-ylmethyl) cyanonitrile sulfonic acid 3.00 G (14.1 mmol) of the compound prepared in Preparation Example 20-4) was dissolved in 40 ml of chloroform, and 5.02 ml (70.5 mmol) of thiosulfite was added at 01C, and the mixture was stirred at room temperature for 2 Time. The organic solvent was removed under reduced pressure to obtain 3.50 g (13.1 millirales, yield 93) of the title compound, which was used in the next reaction without purification. Preparation Example 30: 4- (3-chloro-1-propenyl) -1-trityl-1 甲基 -oxazole combination The paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 103 91506 43 64 87 A7 __._ B7 V. Description of the invention (〇4) to 30-1) methyl 3- (1Η-oxazol-4-yl) acrylate 500 mg (3.62 millitorles) 3- (1Η -Imidazol-4-yl) acrylic acid was added to 20 ml of methanol HC1, and the mixture was stirred at room temperature for 10 hours. The solvent was removed under reduced pressure, and then 30 ml of dichloromethane was added to the residue. The mixture was sequentially dehydrated with a saturated solution of NaHCOs, an aqueous sodium hydroxide solution, and organic cat M anhydrous magnesium sulfate, and concentrated to obtain 510 g (3.35 mol, yield 93), the title compound. This compound does not require passivation and is used directly in the bottom-reaction. 30-2) 3- (1-Tribenzylmethyl-1Η-imidazol-4-yl) acrylic acid methyl ester 350 mg (2.30 mmol) of the compound prepared in Preparation Example 30-1) and 705 mg (2.53 mmol) Mol) triphenylmethyl is dissolved in 10 ml of dimethylformamide, and 350 microliters (2.53 millimoles) of triethylamine are added to it. After 2 hours, 100 ml of ice water was added to the reaction mixture to obtain a solid. The solid was washed with osmium, acetamidine, and hexane, and then dried to obtain 810 mg (2.05 mmol, yield 87) of the title compound. HHR (CDC13) δ 3.75 (s, 3H), 6.35 (d, lH), 7.05-7.50 (a, 18H) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling in this Page) 30-3) 1-U-trityl-1H-oxazol-4-yl) propene-3-ol To 800 mg (2.03 drmol) of the compound obtained in Preparation Example 30-2) was added to 2 0 liters of anhydrous dichloromethane. After the mixture was cooled to -7 8 t: After that, 6.1 ml of diisobutylaluminum hydride (1 M solution in hexane) was added thereto. The temperature was gradually raised to room temperature, and 2 L of water was added to the mixture to stop the reaction. After adding 3 ml of 1Η NaOH, 2 ml of water was added, and the mixture was filtered through celite. The organic layer of the mash is separated and mixed with the digas methane extract from the aqueous layer. The size of the mixed paper is in accordance with the Chinese National Standard (CNS) A4 (210 X 297 mm) _ 104 91506 A7 B7 436487 V. Description of the invention "5) The compound is dehydrated by anhydrous magnesium tellurate. The rhenium solvent is removed by distillation under reduced pressure. The residue was subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 2 0/1, V / V) to obtain 671 mg (1.83 奄 mol, yield 90〆) of the title compound. '4.25 (s, 2H), 6.45 (s, 2H), 6.78 (s, 1H), read the precautions before reading this page and then leave this page * H NMR (CDC13) 7.10-7.50 (m, 16H) 30-4) 4- (3 -Aromatic propenyl) -trityl-1H-pyrazole Add 650 mg (1.77 mol) of the compound prepared in Preparation Example 30-3) to 10 ml of chloroform. In Ot :, add 135 microliters (1.9 奄 箕) to which thionyl chloride was stirred, and the mixture was stirred at room temperature for 2 hours. Under reduced pressure, the organic solvent was distilled off, and the residue was dissolved in 10 ml of ethyl acetate. The solution was washed with a saturated aqueous solution of KHaHCOs and evaporated Removal of tritium solvent, 647 mg &lt; 1.68 mmol, 95% yield) of the title compound. (R NMR (CDC13) ^ 4.22 (4 2Η), 6.40-6.55 (111, 2Η), 6.8 l (s, 1H), 7.10-7.50 (m, 16H) Preparation Example 31: 5-Anomethyl-1- Synthesis of methyloxazosinium sulfonium acid. Printed by the Consumer Cooperative of the Central Bureau of quasi-bureau of the Ministry of Economic Affairs. 31-1) 5-Hydroxymethyl-1-methyloxazole uses dihydroxypropanyl and methylamine sulfonium as starting materials. Following the steps described by J. M. Dener, L-H Zhang, Η. Rapoport in J. 0 rg. C hem., 1993, 58, 1159, the title compound was obtained in a yield of 32%. 4 NMR (CDCI3) δ 3.67 (S, 3H), 4.58 (s, 2H), 5.37 (brs, 1H), 6.76 (s, 1H), 7.32 (s, 1H) The paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 10591506 436487 V. Description of the invention (106) 31- 2) 5-chloroshenyl-butyrazolium oxalate according to the same steps as in Preparation Example 23-2), but using Preparation Example 3 and 1) The obtained compound was used as a starting material to obtain the title compound in a yield of 9 &. Preparation Example 3 2: Synthesis of 1-(4-bromobenzyl) -5 -aminomethyl-1 hydrazone-imidazolium sulfonium acid 32- 1) 1- (4-bromobenzyl) -5-hydroxymethyl- 1Η-imidazole uses dihydroxyacetone dimer and 4-bromobenzylamine hydrazone as starting materials, according to the procedures described by JM Dener, LH Zhang, H. Rapopor-t in Ofg. Chem ·, 1993, 58, 1159 The title compound was obtained in a yield of 50%. JH NMR (CDC13 + CD3OD) § 4.46 (s, 2H), 5.26 (s, 2H), 7.0〇Cs, 1H), 7.07 (d, 2H), 7.50 (d, 2H)} 7.65 (s, 1H) 32 -2) 1- (4-Bromobenzyl) -5-chloromethyl-1H-oxazosinic acid was prepared according to the same procedure as in Preparation Example 28-2), using the compound prepared in Preparation Example 32-1) as a starting point Substance to give the title compound (yield: 96%). The product thus obtained was used directly in the next reaction without purification. Preparation Example 33: 5-chloromethyl-1-isobutyloxazosinic acid hydrazone Synthesis 33-1) 5-hydroxymethyl-1-isobutyloxazole was prepared in the same manner as in Preparation Example 31-1), using dihydroxypropanidine and isobutylamine sulfonium acid as starting materials to obtain the title. Compound, yield 45. 'H NMR (CDC13) &lt; 5 0.90 (d, 6H), 1.76 (m, 1H), 3.62 ((1, 2H), 4.24 (brs, 1H), 4.60 (s, 2H), 6.85 (s, 1H), 7A5 (s, 1H) FAB (M + H): 155 Please read the notes at the back first and then fill in the pages printed by the Central Standards Bureau of the Ministry of Economy—Industrial and Consumer Cooperatives. This paper is printed in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 106 9 1506 4 3 6 4 8 7 π B7 V. Description of the invention (107) 33-2) 5-Chloromethyl-1-isobutyloxazosinic acid According to the same procedure as in Preparation Example 28-2), but using The compound obtained in Preparation Example 33-1) was used as a starting material to obtain the title compound. The yield was 9%. Preparation Example 34: Synthesis of 5-chloromethyl-1-cyclohexylmethyloxazolium sulfonium acid 34-1) 5-Hydroxymethyl-1-cyclohexylmethyloxazole according to the phase synchronization of Preparation Example 31-1) The title compound was prepared by using dicarboxyacetone and cyclohexylmethylaminophosphonium sulfonate as starting materials. The yield was 45 μL NMR (CDC13) 8 0.94 (m, 2H), L16 (m, 3H), 1.50- 1.70 (m, 6H), 3.65 (d, 2H), 4.24 (brs, 1H) 3 4.60 (s, 2H), 6.S5 (st 1H), 7.45 (s, 1H) FAB (M + H): 195 34-2) 5-Chloromethyl-bucyclohexylmethylimidazolium acid was converted to the same compound in Preparation Example 28-2) using the compound prepared in Preparation Example 34-1) as the starting material to obtain the title compound ( Yield: 95%). Preparation Example 35: Synthesis of 5-chloromethyl-pentylimidazolium pyrene 3 5-1) 5-hydroxymethyl-: 1-pentylimidazole Printed by the Consumers' Cooperative of Central Bureau of Quasi-Bureau of the Ministry of Economic Affairs (Please read first Note on the back page, please fill in this page again} Follow the same steps as in Preparation Example 31-1), but use dihydroxyacetone and amyl ammonium ammonium acid as starting materials to obtain the title compound with a yield of 50%. 1K NMR (CDC13) ^ 0.90 (t, 3H), 1.08 ^, 2¾. 1.30 (m; 4H), 1.45 (m, 2H), 3.64 (t, 2H), 4.24 (brs, 1Ή), 4.60 (s, 2H), 6.84 (s, 1H), 7.44 (s, 1H) FAB (M + H): 169 This paper size is applicable to China National Standard (CNS) A4 spot (210X297 mm) 107 91506 436487: V. Description of the invention (108) 35- 2) 5-chloromethyl-1-pentylimidazolium acid was converted according to the same procedure as in Preparation Example 28-2), but using the compound obtained in Preparation Example 35-1) as a starting material to obtain Title compound, yield 9G. Preparation Example 36: Synthesis of 5-ammoniummethyl-1-octyloxazoniumsulfonium sulfonate 36-1) 5-hydroxymethyl-1-octyloxazole was prepared in the same manner as in Preparation Example 31-1), using a dihydroxy group. Acetone and ammonium octylamine were used as starting materials to obtain the title compound in a yield of 52. (H NMR (CDC13) § 0.88 (t, 3H), 1.18 (brs, 2H), 1.30 (brs, 10H), 1.42 (m, 2H), 3.67 (% 2H), 4.23 (brs, 1H), 4.60 ( s, 2H), 6.84 (s, 1H), 7.44 (s) 1H) FAB (M + H): 211 36- 2) 5-Aminomethyl-1-octylimidazolium hydrazone Yiyi Preparation Example 28-2) In the same procedure, using the compound prepared in Preparation Example 36-1) as the starting material, the title compound was obtained (yield: 93%). Preparation Example 37: 5-chloromethyl-1-decyloxazolylsulfonate Printed by the Masonry Consumer Cooperative of the Central Bureau of Guidance, Ministry of Synthetic Economics (please read the precautions on the back before filling out this page) 37- 1) 5-Hydroxymethyl-1 -decyloxazolyl Preparation Example 31-1) Same procedure, but using dihydroxyacetone and decylamine sulfonium acid as starting materials, the title compound was obtained in a yield of 52% ° H NMR (CDC13) d 0.88 (t, 3H), 1.04 (brs, 2H), 1.30 (brs, 14H), 1.42 (m, 2H), 3.68 (t, 2H), 4.23 (brs, 1H), 4.60 (s, 2H), 6.84 (s, 1H), 7.44 (s, 1H ) FAB (M + H): 239 This paper size is applicable to Chinese National Standard (CNS) A4 specification (2 丨 OX297 mm) 108 91506 ^ 436487. V. Description of the invention 37-2) 5-Chloromethyl-1-decyl Preparation of base imidazolium acid 28- 2) Same steps, but using the compound obtained in Preparation Example 37-1) as a starting material, the title compound was obtained in a yield of 93%. Preparation Example 38: Synthesis of 5-Aminomethyl-1- (3-methyl) butylimidazolium pyrenesulfonate 38-1) Preparation Example of 5-hydroxymethyl-1- (3-methyl) butyloxazolyl 31-1). Using the same procedure as dihydroxyacetone and osmium isoamyl ammonium acid as starting materials, the title compound was obtained in a yield of 52 Å. lH NMR (CDC13) $ 0.90 (d, 6H), 1.32 (111, 2H), 1.65 (m, 1H), 3.67 (t, 2H), 4.23 (brs, 1H), 4.60 (s, 2H), 6.84 (s, 1H), 7.44 (s, 1H) FAB (M + H): 169 38-2) 5-Chloromethyl-1- (3-methyl) butyloxazosinacetic acid Yiyi Preparation Example 23- 2) In the same procedure, using the compound prepared in Preparation Example 38-1) as a starting material, the title compound was obtained (yield: 93%). Preparation Example 39: Synthesis of 5-Aminomethyl-1- (2-methoxy) ethyloxazoliumsulfonate, 39-1) 5-Hydroxymethyl-1- (2-methoxy) ethylimidazole Printed by the Ministry of Standards and Industry and Industrial Cooperatives in accordance with the same procedures as in Preparation Example 3 and 1), but using dihydroxyacetone and 2-methoxyethylamine sulfonium acid as starting materials to obtain the title compound in a yield of 60. Alas. ! H NMR (CDC13) 5 3.38 (s, 3H)} 3.42ft, 2H), 3.65 (t, 2H), 4.23 (brs, 1H), 4.60 (s, 2H), 6.84 (s, 1H), 7.44 ( s, 1H). FAB (M + H): 157 This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) 109 9 1506 A7 4 3 64 8 7 V. Description of the invention "l 〇) 3 9- 2) 5-Chloromethyl-: 1-(2-methoxy) ethyloxazosinamidine (Please read the precautions on the back before filling this page) Follow the same steps as in Preparation Example 28-2), but use The compound obtained in Preparation Example 39-1) was used as a starting material to obtain the title compound in a yield of 93%. Preparation Example 40: Synthesis of 5-ammoniummethyl-1- (3-methoxy) propylimidazolium hydrazone 40-1) 5-hydroxymethyl-1- (3-methoxy) propyloxazolyl In the same procedure as in Preparation Example 31-1), using the dihydroxypropanidine and the 3-methoxypropylamine sulfonium acid as starting materials, the title compound was obtained in a yield of 61.01H NMR (CDC13) «5 1.72 (m, 2H), 3.32 (s, 3H), 3.46 (t, 2H), 3.63 (t, 2H), 4.23 (brs, 1H), 4.60 (s, 2H), 6.84 (s, 1H), 7.44 (s, 1H ) FAB (M + H): 171 40- 2) 5-Aminomethyl-1- (3-methoxy &gt; propylimidazolium acetic acid, according to the same procedure as in Preparation Example 28-2), using Preparation Example 40- 1) The obtained compound was used as a starting material to prepare a standard amidine compound (yield 90%). Preparation Example 41: 5-Hydroxymethyl-bu (3-ethoxy) propyloxazosinacetate, printed by the Consumers' Cooperative of the China Standards Bureau of the Ministry of Economic Affairs 41-1) 5-hydroxymethyl-1- (3-Ethoxy) propyloxazole was prepared according to the same procedure as in Preparation Example 3b1), but using dihydroxyacetone and 3-ethoxypropylamine sulfonium phosphonium as starting materials, the title compound was obtained in a yield of 61. Alas. This paper size applies Chinese National Standard (CNS) A4 (2: 0X297 mm) 110 91506 4 3 6 4 8 7 at ___B7 V. Description of the invention "i) 'H NMR (CDC13) ^ 1.20 (ζ 3H), 1.72 (m, 2H), 3.50 (s, 4H), 3.63 (t, 2H), 4.23 (brs, 1H), 4.60 (s, 2H), 6.84 (s, 1H), 7.44 (s, 1H) FAB ( M + H): 185 'U-2) 5-Gasmethyl-1- (3-ethoxy) propyloxazosinic acid, according to the same procedure as in Preparation Example 28-2), but using Preparation Example 41-1 ) The obtained compound was used as a starting material to obtain the title compound at a yield of 90%. Preparation Example 42: Synthesis of 5-chloromethyl-1- (3-isopropoxy) propylphosphonium sulfonate 42-1) 5-Hydroxymethyl-1- (3-isopropoxy) propylimidazole was prepared in the same manner as in Preparation Example 31-1), using dihydroxyacetone and 3-isopropoxypropylamine sulfonium acid as starting materials to prepare The title compound was obtained with a yield of 61. H NMR (CDCl3) ^ l-15 (d, 6H), 1.71 (m, 2H), 3.45-3.55 (m, 3H), 3.63 (t, 2H), 4.23 (brs , 1H), 4.60 (S) 2H), 6.84 (s) 1H), 7.44 (s, 1H) FAB (M + H): 199 42-2) 5-Aminomethyl-1- (3-isopropoxy Base) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Note on the back, please fill in this page again) Follow the same steps as in Preparation Example 28-2), but use the compound prepared in Preparation Example 42-1) as the starting material to obtain the title compound. Yield Example 44: Taste (Synthetic) methylcha_1-yl) -3- (®phen-2-yl) carbonyl-lH-itt (44) Synthesis of 4 4-1) 3-(naphthalene-1 -yl) -1-( Stilbene-2 -yl) -propan-2-ene-1-_ 3.12 g (20 mmol) of 1-naphthaldehyde and 2.52 g (20 mmol) of 2-ethylfluorenylthipan in 20 ml of methanol , Yuan slowly add 800 mg (20 millimolars) of hydrogen and oxygen. The standard of this paper is applicable to Chinese National Standard (CNS) A4 (2 丨 0 X 297 mm) 1U 91506 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 43 64 8 7 A7 _ '__B7 _ V. Description of the invention "2)-Chemicals are incorporated into it. The mixture was reacted at room temperature for 8 hours. The solid thus obtained was filtered and dried. The mash was adjusted to pH 4-6 with 1M acetic acid solution, and extracted with ethyl acetate. The organic solvent was removed under reduced pressure, and the residue was subjected to column milling (eluent: hexane / ethyl acetate = 4/1, v / v) to obtain 4 '2 3 g (16 extravagance, yield 80). Iv) Blend the title compound of the filtered solid. LH NMR (CDC13) § 7.13-7.3 l (m, 2H), 7.55-7.70 (111, 3H), 7.70 (d, 1H), 7.85-7.90 (m, 4H), 8.28 (d, 1H), 8.70 (d, 1H) 44-2) 4- (Cha-1-yl) -3-¾phen-2-yl) carbonyl-1H-pyrrole 2.64 g (9.99 奄Mol) The compound obtained in Example 44-1) and 2.35 g (12.0 mmol) of p-methylbenzylsulfonium methyl isotide were dissolved in 30 liters of tetrahydrofuran. 1.35 g (12.0 mmol) Tributyrazine was added thereto, and the mixture was refluxed for 30 minutes. The solvent was removed under reduced pressure, and then 15 ml of water and 20 ml of ethyl acetate were added to the residue. The mixture was fully shaken and stirred to obtain a solid. This solid Washing with diethyl ether gave 1.97 g (6.48 mmol, 65 涔 yield) of the title compound. * H NMR (CDC13) δ 6.90 (s, lii), 7.12 (s, Ιί), 7.20-7.45 (ra, 4K 〇, 7,55 (s, 1H), 7.61 (s, 1H), 7.70-8'00 (m, 4H), 11.4 (s, 1H) 44-3) 4-(. Ca-1 * 'group) -3 -((¾phen * · 2 · yl) mine-based trityl ~ 1H -imidazol-4-yl) methyl-1-pyrrole 200 grams &lt; 0.99 millimolar) Example 44-2 &gt; The prepared compound was dissolved in 5 liters of dimethylformamide, and 95 mg (4.0 mol) of sodium hydride (50 mol) was added to the mixture. Stir for 5 minutes. 391 mg (0.99 milli-ears) {Please read the precautions on the back before you write this page) The size of the stapled paper is applicable to the Chinese National Standard (CNS) A4 ^ (210 X 297 mm) 112 91506 4 3 64 8 7 A7 B7 V. Description of the invention (1 1 3) (Please read the precautions on the back before filling in this page) Preparation Example 28-2) Add the compound obtained in the reaction solution, and search for 5 hours at room temperature. The solvent was distilled off under reduced pressure, and the residue was extracted with ethyl acetate. The extract M was dehydrated and concentrated by anhydrous magnesium sulfate, and then subjected to column chromatography (lysate: S ethane / ethyl acetate = 1/3, ν / ν) to obtain 205 mg (0.33 mmol, yield 33 ×). Compound. ! H NMRCCDCb) 5.02 (s, 2H), 6J5 (s, 1H), 6.79 (s, 1H), 6.86 (t, 1H), 7.10-7.52 (m, 23H), 7.71 (d, 1H), 7.7S (d, 1H), 7.89 (d, 1H) 44-4) 1- (1H-oxazol-4-yl) methyl-4- (naphthalene-butyl) -3- (¾phen-2-yl) Hydroxy-1 hydrazone-pyrrole 190 mg (0.304 mmol) Example 44-3) The compound prepared in Example 44-3) was dissolved in a solvent mixture of trifluoroacetic acid / dichloromethane (0.5 ml / 0.5 ml), and the solution was stirred at room temperature for 2 hours. . The organic solvent was removed under reduced pressure. The residue was dissolved in 10 ml of ethyl acetate, a saturated solution of MMa2C03 and water, and the anhydrous magnesium sulfate was dehydrated, concentrated, and subjected to column analysis (eluent: ethyl acetate to obtain 103 mg (0.269 mmol), product Rate 88〆) The title compound. NMR (CDC13) printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs «5 4.87 (s, 2H), 6.55 (s, 1H), 6.72 (s, 1H), 6.88 (t, 1H ), 7.11-7.34 (m, 7H), 7.50-7.67 (m, 3H), 7.83 (d, 1H) FAB MS: 384 (M + 1) Perform 45 to 72 according to the same steps as in Example 44. The compounds in Tables 2-1 to 2-3 are applicable to Chinese National Standards (CNS) A # see the standard (210X297 mm) 113 91506 4 3 64 87 A7 B7 V. Description of the invention (11 〇 Table 2-1 Central Ministry of Economic Affairs Consumption cooperation between employees of the Bureau of Standards, Du printed compounds, melody 'H NMR (CDC13) δ FAB MS (M + l) 45 4.85 (s, 2H), 6.5l (s, 1H), 6.67 (s, 1H), 7.06 ( s, 1H), 7.14 (s, 1H), 7.21-7.32 (m, 7H), 7.61-7.74 (m, 3H), 7.82 (d, 1H) 384 46 4.95 (s, 2H), 6.58 (s, 1H ), 6.76 (s, 1H), 7.1.3-7.35 (m, 9H), 7.61-7.68 (m, 4H), 7.91 (d, 1H) 378 47 4.92 (s, 2H), 6.61 (s, 1H) , 6.70 (s, 1H), 7.02 (d, 2H), 7.17- 7.35 (m, 9H), 7.62 (d, 1H), 7.70 (d, 1H), 7.95 (d, 1H) 456 48 5.03 (s, 2H), 6.76 (s, 1H), 6.85 (s, 1H), 7.07 (t, 1H), 7.34-7.54 (m, 9H), 7.72-7.79 (m, 3H), 7.94 (d, 1H) 456 49 5.00 (s, 2H), 6.72Cs, 1H), 6.77 (s, 1H), 7.21-7.38 (m, 11H), 7.62 (d, 1H), 7.70 (d, 1H), 7.78 (d, 1H) 456 50 2.23 (s, 3H), 5.02 (s, 2H), 6.74- 7.10 (m, 5H), 7.17-7.50 (m, 8H), 7.65 (d, 1H), 7.71 (d, 1H), 7.86 (d, 1H) 392 51: CDCI3 + CD3OD) 2.05 (3, 3H), 5.09 (s, 2H), 6.84 (s, 1H), 5.99-7.05 (m, 8H), 7.23-7.36 (m, 3H), 7.70 (d, 1H), 7.86 (d, 1H) 392 (Please read first Note on the back page, please fill in this page again), 1T ψ This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 114 91506 4 3 6487 a? __B7 V. Description of invention (h 5) Central Bureau of Standards, Ministry of Economic Affairs Printed by the Consumer Consumption Cooperative Association 2-2 j Compounding Jaw 1 f 'H NMR (CDC13) s FAB Us fM + 1) 52 2.21 (3, 3Η), 4.92 (sf 2Η), 6.62 (s, 1H), 6.83 (s, 1H), 7.14-7.35 (m, 8H), 7.61-7.73 (m, 5H), 7.88 (d, 1H) 392 53 3.66 (s, 3H), 5.04 (s, 2H), 6.85 (s, 1H), 6.82 (d, 1H), 6.90 (m, 1H), 7.12-7.17 (m, 2H) , 7.26-7.36 (m, 8H), 7.67 (t, 1H), 7.74 (d, 1H), 7.93 (d, 1H) 408 54 3.75 (s, 3H), 5.02 (5, 2H), 6.7i (m , 3H), 6.80 (t, 1H), 7.20-7.35 (m, 6H), 7.60-7.75 (m, 4H), 7.91 (d, 1H) 408 55 4.83Cs, 2H), 6.51 (s, 1H), 6.63 (s, 1H), 6.85 (m, 1H), 7.03-7.29 (tn, 10H), 7.61-7.69 (m, 2H), 7.83 (d, 1H) 412 56 5.01 (s, 2H), 6.72 (s , 1H), 6.77 (s, 1H), 7.22-7.35 (m, 11H), 7.61-7.80 (m, 3H) 412 57 4.82 (s, 2H), 6.63 (s3 1H), 6.72 (s, 1H), 7.02-7.24 (m, 10H), 7.56-7.70 (m, 3H) 446 58 4.91 (s, 2H) 3 6.65 (s, 1H), 6.77 (m, 1H), 7.20-7.3l (m, 7H), 7.6l (m, 3H), 7.81 (d, 1H) 396 59 4.92 (s, 2H), 6.45 (01, 1H), 6.71 (m3 2H), 7.20-7.32 (ra, 9H), 7.63-7.77 (m , 3H) 414 60 5.09 (s, 2H), 6.80-7.20 (m, 4H), 7.15-7.35 (m, 4H), 7.40 (d, 1H), 7.45-7.50 (m, 3H), 7.60 (m, 1H), 7.65 (d, 1H), 7.75 (d, 1H) 403 61 1.87 (s, 3H), 3.55 (s, 2H), 5.07 (s, 2H), 6.84 (s, 2H), 7.08 (d, 2H), 7.28-7.48 (m, 6H), 7.57 (d, 2XJ), 7.63 (ί, 1H), 7.71 (d, 1H), .7.90 (d, 1H) 438 62 2.03 (s, 3H), 2.74 (m, 2H), 2.91 (m, 2H), 5.00 (s, 2H), 6.67 (Sj 1H), 7.02 (d, 2H), 7.14-7.43 (m, 11H), 7.72-7. 89 (m, 3H) 452 63 L t.98 (s, 3H), 2.75 (t, 2H), 3.90 (t, 2H), 4.85 (s, 2H), 6.60-6.72 (m, tH), 7.11- 7.45 (m, 9H), 7.68-7.82 (m, 3H) 468 64:! .01 (s, 3H), 3.61 (s, 2H), 4.98 (s, 2H), 6.6l (s, 2H), 6.74 (m, 2H), M0-7.48 (m, 10H), 7.71-7.88 (m, 3H) 438 This paper size applies to China National Standard (CNS) A4 (210X297 mm), cr Λ ^ 115 9150ο (Please Read the notes on the back before filling this page) 436487 V. Description of the invention (16) Table 2-3 Hook number r Ή NMR (CDC13) s FAB MS (M + l) 65 4,92 (s, 2H), 6.62 (s, lH), 6.70 (s, lH), 7.12-7.27 (m, 14H), 7.:53· 7.62 (111, 4H) '7'81 (d, 1H) 454 66 4.97 (s, 2H ), 6.87 (d, 1H), 7.15-7.46 (m, 15H), 7.55-7.73 (m, 4H), 7.86 (m, 1H) 454 67 5.10 (s, 2H), 6.70 (t, 2H), 6.80 -6.95 (m, 4H), 7.15 (t, 1H), 7.21-7.45 (m, 7H), 7.50 (1, 1H), 7.60 (d, 2H), 7.71 (d, 1H), 7.75-7.80 (m , 2H), 7.91 (m, 1H) 470 68 3.82 (s, 2H), 4; 95 (s, 2H), 6.57 (s, 1H), 6.63 (s, 1H), 6.92 ((1, 2H), 7.04 (d, 2H), 7.20-7.32 (ra, 1GH), 7.51-7.68 (m, 4H), 7.82 (d, 1H) 468 69 4.82 (s, 2H), 6.41 (s, 1H ), 6.70 (s, 1H), 6.95 (s, 1H), 7.16-7.32 (m, 9H), 7.51 (d, 1H), 7.59 (d, IH), 7.67 (m, 3H), 7.90 (d, 1H), 8-05 ((1, 1H) 428 70 2.38 (s, 3H), 3.65 (s, 3H), 4.91 (s, 2H), 6.69 (s, 1H), 6.97 (d, 1H), 7.00 (ζ 1H), 7.04 (d, 1H), 7.10-7.16 (m, 3H), 7.19 (d, 1H), 7.34 (s, 1H), 7.42 (s, 1H), 7.57 (d, 1H), 7.67 (s, 2H) 395 71 0.61 (1, 3H), 1.02 (m, 2H), 1.25 (m &gt; 2H), 2.31 (m, 1H), 2.47 (m, 1H), 5.05 (s, 2H), 6.57 (s, 1H), 6.63 (s, 1H), 6.80 (d, 1H), 6.87 (s, 1H), 7.22-7.35 (ra, 7H), 7.61-7.72 (m, 3H) 502 72 3.71 (d, 1H), 3.85 (d, 1H), 4.85 (s, 2H), 6.61 (s, 1H), 6.73 (d, 1H), 5.92-7.41 (m, 14H), 7.62-7.73 (m, 3H) 536 Please Read the precautions of i £ r first, and then print the example from the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 73: 1-UU-cyanobenzyl) -1Η-oxazole-5-yl] methyl-4- (Cai-1- Synthesis of phenyl) -3-(«phen-2-yl) carbonyl-1H -pyrrole (73) 80 mg (0.3 mmol) of the compound prepared in Preparation Example 29-5) and 90 g (0.3 mmol) ) The compound obtained in Example 44-2) was dissolved in 2 ml of dimethylformamide, and 36 奄 g of sodium hydride (60 加) was added thereto. It was stirred for 2 hours. The solvent was removed under reduced pressure, and the residue was subjected to a column calendar. (Eluent: Erqi Huabiao Jia Guozhong used a suitable paper. Μ 公 97 116 91506 4 3 64 8 7 Α7 Β7 V. Description of the invention U7) Formazan / methanol = 10/1, v / v), 83 mg (0.17¾ mole, 56 yields) of the title compound were obtained. ! H NMR (CDC13) d 5.02 (s, 2H), 5.08 (s, 1H), 6.73 (s, 1H), 6.85 (s, 1H), 7.03 (t, 1H), 7.32-7.45 (m, 11H) , 7.63 (s, 1H), 7.75 (ά, 1H), 7.82 (d, 1H), 8.02 (d, 1H) FAB MS: 499 (M + l) The same procedure as in Example 74 to 77 M Example 73 The compounds shown in the table below. Table 3 Fana number XH 1 ^ MR (CDC13) d FAB MS (M + 1) 74 4.82 (s, 2H), 5.12 (s, 1H), 6.30 (s, 1H), 6.41 (s, 1H), 6.77 -7.〇8 (m, 12H), 7.31-7.46 (m, 3H), 7.68 (d, 1H) 499.75 5.00 (3, 2H), 5.05 (s, 2H), 6.76 (s, 1H), 6.82 (s, 1H), 7.23-7.40 (m, 12H), 7.63 (d, 2H), 7.72 (d, 1H), 7.90 (d, 1H) 493 76 5.02 (3, 2H), 5.08 (s, 2H ), 6.65 (s, 1H), 6.78 (s, 1H), 6.98 (t, 1H), 7.23-7.42 (m, 12H), 7.65-7.73 (m, 3H), 7.82 (d, 1H) 571 77 5.03 (s, 2H), 5.10 (s, 2H), 6.78 (s, 1H), 64S7 (s, 1H), 7,32-7.45 (m, 12H), 7.74 (4 3H), T81 (d, 1H) , 7.88 (d, 1H) 571 Example 78: 3- (4-Fluorobenzyl) -bu (1-methyl ~ 1Η) imidazole_4_plug> methyl-4 &quot; * (naphthalene-1-yl ) -1Η-Pirillo &lt; 78) The same procedure as in the synthesis of Ishten 44-3), but using 3- (4 ~ fluorobenzylpyridine 4- (sacrifice-butyl)>-1; -pyrrole and Preparation Example 31-2) The prepared compounds are prepared by first reading and reading. Pages printed by the Central Bureau of Standards of the Ministry of Economic Affairs are printed by the Consumer Cooperatives. The paper size is applicable to Chinese National Standards (CNS) Α4 Zhuge (210X297) 嫠 1 1 7 9 1506 Ministry of Economic Affairs Printed by the Consumers' Cooperative of the Central Government Bureau of Commerce / 1. .W. 2G: A7 _B7_ V. Description of the Invention (II3) The title compound, yield 75 产 率.! H NMR (CDC13) § 3.42 (3, 3H), 5.01 ( s, 2H), 6.73 (m, 3H), 7.11 (S) 1H), 7.24-7.57 (m, 8H), 7.67-7.75 (m, 2H) FAB MS (M + l): 410 Example 79: 1- (Bumethyl-1H-imidazol-4-yl) methyl-4- (naphthalene-buyl) -3- (4-phenoxybenzylidene) -1Η-pyrrole (79) was synthesized according to Example 44- 3) Same steps, but using 4- (cha-1-yl) -3- (4-phenoxybenzylidene) -1Η-pyrrole and the compound obtained in Preparation Example 31-2) to obtain the title Compound, yield was outside 70. ! H NMR (CDC13) $ 3.52 (s, 3H), 5.12 (s, 2H), 6.63 (d, 2H), 6.76 (d, 1H), 6.85 (d, 2H), 7.12 (t, 1H), 7.20 (s, 1H)} 7.28-7.40 (m, 7H), 7.51 (d, 2H), 7'68 (d, 2H), 7.74 (<1H), 7.83 (4 1H) FAB MS (M + 1): 484 Butternut 80: (S) -l- (lH-imidazol-4-yl) methyl-3- [N- (l-methoxycarbonyl-3 -methylformyl) propyl] aminoformyl-4 -Synthesis of (naphthalene-1-yl) -1Η-pyrrole U0) 80-1) Ethyl 3- (naphthalene-1-yl) acrylic acid_ Dissolve 22.4 g (0.10 mole) of triethylphosphine acetic acid in 500 Add tetrahydrofuran (1 ml) to potassium tetrabutoxide (12.4 g). To this solution was added 20 ml of tetrahydrofuran solution in which 15.6 g (0.10 萁) of naphthaldehyde was dissolved, and the mixture was stirred for 8 hours. The organic solvent was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed twice with water, dehydrated with anhydrous magnesium sulfate, concentrated, and subjected to column chromatography (eluent: hexane / ethyl acetate SS = 9 5/5, ν / ν) (Please read the back (Please fill in this page again)

， -IT This paper size applies the Chinese National Standard (CNS) A4 Zhuge (2 丨 0X297mm) 118 9 1506 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 119 91506 436487 at B7 V. Description of Invention (119), 20.3 g (0.090 moles, yield 90 ° F) of the title compound. lK NMR (CDC13) S l-42 (t, 3H), 4.30 (q, 2H), 6.50 (d, 1H), 7.40-7.60 (m, 3H), 7.73 (d, 1H), 7.82 (m, 2H ), 8.20 (d, 1H), 8.50 (d, 1H) 80-2) 3-Ethoxycarbonyl-4- (naphthalene-butyl) -1H-pyrrole 500 mg (1.89 mmol) ) The ethyl 3- (naphthalene-buthyl) acrylate and 368 mg (0.89 mmol) of p-methylbenzylsulfonylmethyl are gasified and dissolved in 10 ml of tetrahydrofuran. Tetrahydrofuran (10 ml) containing 255 mg (2.27 millitorles) of potassium tributoxide was added thereto, and the mixture was allowed to flow for 30 minutes. 10 l of water was added to the reaction solution, and the reaction was terminated by K, and the solvent was removed under reduced pressure. The residue was extracted with diethyl ether, washed with a sodium hydroxide aqueous solution, and dehydrated with anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was subjected to column chromatography (eluent: ethyl acetate / hexane = 1/3, ν / ν) to obtain 385 mg (1.45 mmol, yield 77) of the title compound. ! H NMR (CDC13) δ 0.86 (t, 3H), 4.02 (q, 2H), 6.8l (s, 1H), 7.48-7.61 (111, 5H), 7.90-7.97 (m, 3H), 8.92 (sf 1H) 80-3) 3-ethoxycarbonylimidazol-4-yl) methyl-4- (naphthalene-1-yl) -1 fluorene-pyrrole according to the procedures described in Examples 44-3) and 44-4), The title compound was prepared from the compound obtained in Example 80-2) and Preparation Example 28-2) in a yield of 39 places. (H NMR (CDC13) accounts for 1.1 l (t, 3H), 4.20 (q, 2H), 5.05 (s, 2H), 6.78 (s, 1H), 6.89 (s, 1H), 7.38-7.49 (Γη, 6H ), 7.85-7.97 (m, 3H) scales are applicable to China National Standard (CNS) A4 specifications (210X297 mm) (Please read the precautions on the back before filling this page)

'IT • X ,. Printed by the Central Bureau of Standards of the Ministry of Economic Affairs, a shellfish consumer cooperative, 4 3 64 87 ^ V. Description of the invention (1 2 0) 80-4) 3-Hydroxycarbonylimidazol-4-yl) methyl-4 -(Naphthalene-pyl)-1 hydrazone-pyrrole 220 mg (0.64 mmol) Example 80-3) The compound prepared in Example 80-3) was dissolved in 5 ml of 50% ethanol and 216 mg (3.8 mmol) of hydroxide Potassium was added dropwise thereto, and the mixture was refluxed for 7 hours. The reaction solution was cooled to room temperature, adjusted to pH 4-5, extracted with ethyl acetate, and dehydrated with anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain 162 mg (0.51 mmol, yield 80 F) of the title compound. This compound was used without further purification in the next reaction. : H NMR (CD3OD + CDCb) 3 5.01 (s, 2H), 6.82 (s, 1H), 6.87 (s, 1H)? 7.42- 7.70 (m, 7H), 7.82-7,89 (ιη, 3H) 80 -5) (S) -l- (lH-imidazol-4-yl) methyl-3-UU-methoxycarbonyl-3-methylthio) propyl] aminomethyl-4- (naphthalene-1- Base) -1Η-pyrrole 200 mg (0.60 milli-chills) The compound prepared in Example 80-4) was dissolved in 2 ml of dimethylformamide, followed by 150 ng (0.78 mmol) EDC and 105 mg 10. 78 millimoles) KOBT into it. The resulting mixture was stirred at 0¾ for 5 minutes. To the reaction solution was added 120 mg (0.60 mmol) of L-methionine methyl formaldehyde, followed by stirring at room temperature for 5 hours. The solvent was removed under reduced pressure, and 10 ml of a saturated NaHC03 solution was added to the residue. The resulting solution was extracted with acetic acid acetate, washed with an aqueous sodium hydroxide solution and water, and dried over anhydrous sodium sulfate and shrinkage. The residue was subjected to column chromatography (eluent: dichloromethane / methanol = 20/1, ν / ν) to obtain 104 mg (0.225 mmol, yield 37〆) of the title compound. I ----------- (Please read the precautions on the reverse side before filling out this page) The size of the paper used in this edition applies to the Chinese National Standard (CNS) Α4 specification (2ΙΟ × 297 mm) 120 91506 A7 B7 Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards Λ: ι; 5. Description of the invention (12 1) * H NMR (CDC13) ^ 1.21Cmt 1H), 1.55 (m, 3H), 1.80 (s, 3H), 3.42 (s , 3H), 4.43 ^, 1H), 5.05 (s, 2H), 5.60 (d, 1H), 6.71 (s, 1H); 6.95 (s, 1H), 7.21-7.45 (m, 7H), 7.75-7.87 (m, 3H) FAB MS: 463 (M + l) Example 81: (S) -3- [H- (l-hydroxycarbonyl-3-methylthio) propyl] aminomethyl-1--1- (1H- Synthesis of oxazol-4-yl) methyl-4 (naphthalene-1-yl) 1H-pyrrole U1) 70 mg (0.15 mmol) The compound obtained in Example 80-5) was dissolved in 2 ml of tetrahydrofuran / Formazan / water (3/2/1, v / v / v) solvent mixture, 10 mg (0.18 mmol) of lithium hydroxide was added thereto, and the mixture was stirred at room temperature for 4 hours. The solvent was removed under reduced pressure to obtain 68 mg (0.15 millimoles, yield 99.7 gt) of the lithium compound of the title compound. LH NMR (CD3OD + CDC13) § 1.25 (m, 1H), 1.49 (m, 3H), 1.85 ( s, 3H), 4,41 (m, 1H), 5.1 l (s, 2H), 5.58 (d, 1H), 6.70 (s, 1H), 6.89 (s, 1H), 7.15-7.38 (m, 7H ), 7.76-7.Sl (m, 3H) FAB MS: 449 (M + 1) Examples 82 to 9δ In the same manner as in Example 80, compounds 0 (Please refer to Tables 4-1 and 4-2 below were prepared. (Read the notes on the back before filling out this page)

This paper size applies the Chinese National Standard (CMS) A4 specification (2! 〇 X 297 mm) 12 1 91506 4 3 648? A7 B7 V. Description of the invention "22" Printed by the Consumer Cooperatives of the Central Sample Bureau of the Ministry of Economic Affairs 4 -1 Compound Special Weak NMR (CDCI3) S 1 I FAB MS (M + 1) 82 5.02 (s, 2H), 6.69 (d, 2H), 6.77 (s, 1H), 6.92-7.18 (m, 5H ), 7.40-7.58 (m, 6H), 7.75-7.87 (m, 4H) 393 83 4.06 (d, 2H), 5.01 (3, 2H), 5.57 (ΐ, 1H), 6.46 (d, 1H), 6.71 (s, 1H), 6.83 (3, 1H), 6.92-7.05 (m, 3H), 7.42-7.55 (m, 7H), 7.74-7.81 (m, 3H) 407 84 0.45 (brs, 2H), 1.22 ( brs, 4H), 2.95 (brs3 2H) S 3.37 (brs, 2H), 5.04 (s, 2H), 6.65 (3, 1H), 6.92 (s, 1H), 7.08 (s, 1H), 7.31-7.45 ( m, 6H), 7.72 (d, 1H), 7.82 (d, 1H), 8.12 (d, 1H) 385 85 2.32 (brs, 2H), 2.22 (brs, 2H), 3.23 (brs, 2H), 3.65 ( brs, 2H), 5.06 (s, 2H), 6.72 (s, 1H), 6.95 (s, 1H), 7.12 (s, 1H), 7.31-7.4δ (ιη, 6H), 7.81 (d, 1H), 7.85 (d, 1H), 8.1 l (d, 1H) 387 86 1.41 (brs, 2H), 2.86-3.25 (m, 6H), 4.97 (s, 2H), 6.68 (s, 1H), 6.85 (3, 1H), 7.06 (s, 1H), 7.21-7.35 (111, 6H), 7.72 (ά, 1H), 7.78 (d, 1H), 7.95 (d, 1H) 403 87 2 .04 (brs, 4H), 3.62 (brs, 4H), 5.03 (s, 2H), 6.91 (d, 2H), 7.22-7.48 (m, 7H), 7.81-7.88 ^, 2H), 8.02 (m, 1H) 435 88 1.46 (brs, 2H), 2.21 (brs, 2H), 3.14 (brs, 4H), 5.1 l (s, 2H), 6.88 (s, 1H), 7.02 (3, 1H), 7.11 (s , 1H), 7.32-7.51 (m, 5H), 1.62 (5, 1H), 7.72-7.80 (m, 2H), 8.05 (d, 1H) 386 89 i (CDC13 + CD3OD) 2.05 (s, 3H), 3.33 (brs, 8H), 5.13 (s, 2H), 5.90 (s3 1H), 7.06 (s, 1H), 7.21 (s, 1H), 7.30-7.55 (m, 4H), 7.64 (S) 1H), 7.8l (s, 1H), 7.88 (d, 1H), 8.06 (d, 1H) 400 90 2.62 (brs, 2H), 3.15 (brs, 2H), 3.S6 (brs, 1H), 4.35 (brs, 1H), 5.06 (s, 2H), 6.83 (s, 1H), 6.90 (s, 1H), 7.15-7.60 (111, 6H), 7.73 (d, tH), 7.82 (d, 1H), 8.06 (d , 1H) 389 (91 '). 22 (m, 1H), 0.63 (m, 1H), 0.83 (m, 1H), 1.24 (m, 1H), 2.6l (brs,: H), 3.24 (brs, 2H), 3.65 (brs, 1H), 4.94 (s, 2H), 6.71 (s, 1H), i.84 (s, 1H), 6.94 (s, 1H), 7.24-7.42 (m, 6H), 7.62 -7.70 (m, 2H), r.94 (d, 1H) 401 — clothing-; '(read the precautions on the back first, then ^! Write this page) The size of this paper is applicable to China National Standards (CNS) A4 size (210X297 mm) 122 9 1506 T 8 4 6 3 d V. Indicate "23" Table 4-2 Chemical compound # Compilation? (H NMRCCDCI3) 5 Ί FAB MS (M + 1) 92 1.37 (brSj 2H), 1.96 (brs, 2H), 3.52 (brs, 4H), 5.21 ( s, 2H), 7.08 (s, 1H), 7.20 (s, 1H), 7.37 (s, 1H), 7.54 (m, 5H), 7:70 (s, IH), 7.94 (m, 2H), 8.23 (d, 1H) 399 93 2.12 (brs, 2H), 3.02 (brs, 2H), 4.98 (Sj 2H), 5.24 (m, 1H); 6.82 (s, 1H), 7.03 (s, 1H), 7.20- 7.34 (m, 6H), 7.62-7.71 (m, 3H), 7.93 (d, | 1H) 361 94 2.24 (brs, 2H), 3.04 (brs, 4H), 3.11 (Sj 3H), 5.03 (s, 2H ), 6.77 (Sj 1H), 6.89 (s, 1H), 7.14-7.31 (01, 6H), 7.56-7.63 (m, 3H), 7.87 (d, 1H) 375 95 2.51 (m, 2H), 3.10 ( s, 3H), 3.21 (m, 2H), 3.47 (s, 3H), 5.05 (s, 2H), 6.68 (s, 1H), 7.05-7.48 (m, 7H), 7.74-7.85 (m, 2H) , 8.09 (d, 1H) 389 96 2.58-3.50 (brs, 8H), 5.16 (s, 2H), 6.98 (d, 1H), 7.08 (s, 1H), 7,20-7.27 (111, 2H), 7.47 (t, 1H), 7.67 (s, 1H), 7.71 (t, 1H), 8.08 (d, IH), 8.15 (d, 1H), 8.80 (d, 1H) 388 97 3.40 (m, 4H), 3.70-4.45 (brs, 8H), 3.11 (st 3H), 5.18 (s, 2H), 5.98 (d, 1H), 7.12 (s, 1H), 7.17-7.22 (m, 2H), 7.25 (d, 1H ), 7.30 (d, 1H), 7.3 5 (t, 1H), 7.62 (d, 1H), 7.90 (s, 1H) 413 98: CD3OD) 3.86 (s, 2H), 4.83 (s, 2H), 5.58 (t, 1H), 6.37 (d, 1H), 5.52 (s, 2H) S 6.81 (s, 1H), 7.05-7.35 (m, 9H) , 7.5l (d, 1H), 7.54 (d, tH), 7.58 (d, 1H) 432 (Please read the notes on the reverse side and fill in this page) Printed on paper The scale applies to China's national standard (CNS) A4 specification (210X297 mm) 123 91506 Μ 436487 B7 V. Description of the invention "4) Example 99: 1- (1-methyl-1H-imidazol-5-yl) methyl- 3- (morpholin-4-yl) {谙 Please read the notes on the back before writing this page) Synthesis of carbonyl-4- (naphthalene-1-yl) -1Η-pyrrole (99) According to Preparation Example 28-1 ), The same procedure as described in Example 85 was added to the compound prepared in Example 85, followed by the steps described in Preparation Examples 29-2) and 29-3) using methyl iodide to obtain the title compound, yield 55. . NMR (CDC13) &lt; 5 2.80-3.45 (111, 8H), 3.58 (s, 3H), 5.19 (s, 2H), 6.75 (d, 1H), 7.18 (d, 1H), 7.21 (s, 1H) , 7.35 (d, 1H), 7.40-7.50 (m, 3H), 7.72 (d, 1H), 8.03 (d, 1H) 'FAB MS: 401 (M + l) Example 100: (S) -l- [ (4-cyanobenzyl) -1H-oxazol-5-yl] methyl-3- [N- (l-methoxycarbonyl-3-methylthio) &gt; propyl] aminomethyl-4--4- Synthesis of naphthalene-1-yl) -1Η-pyrrole (100) 100-1) 1- [1- (4-cyanobenzyl) -1Η-imidazol-5-ylmethyl] -3-hydroxycarbonyl-4_ _1 ~ The basic compound K was prepared from the compound of Example 80-2) and Preparation Example 29-5), and the steps of Example 73 and Example 80-4) were sequentially performed to obtain the title compound with a yield of 75. Printed by Employee Consumer Cooperatives ^ 6. NMR (CDC13 + CD3OD) ^ 5.02 (s, 2H), 5.10 (s, 2H), 6.76 (s, 1H), 7.07 (m, 2H), 7.25-7.82 (m) 12H) 100-2) (S) -l- [l- (4-cyanobenzyl) -lH-oxazol-5-yl] methyl-3- [N- (1-methoxycarbonyl-3-methylthio) propyl] amine formamidine Base-4- (Cha-l-base) -1 Η-pyrrole The paper size applies to Chinese national standards (CNS &gt; A4 size (210X297 mm) 124 91506 4. 3 6 ^ B 7 A7 B7_ V. Description of the invention (25) Following the same procedures as those in Example 80-5), but using the compound prepared in Example 100-1), the title compound was obtained in a yield of 35. (Please read the notes on the back before Qin Wo Ben X) * H NMR (CDC13) ^ 1.85 (s, 3H), 2.04 (m, 1H), 2.13 (m, 1H), 2.42 (t, 2H), 3.6 l (s, 3H), 4.83 (m, 1H), 5.02 (5, 2H), 5.11 (s, 2H), 6.63 (s, 1H), 7.01 (d, 2H), 7.13 (d, 1H), 7.22 -7.43 (m, 7H), 7.65-7.92 (m, 4H) FAB MS: 578 (M + l) Example 101: (S) -l- [l-4-cyanobenzyl) -lH-imidazole-5- Of methyl] methyl-3- [N- (l-hydroxyl-I-yl-3-methylthio) propyl] aminomethyl-4- (pyridin-1-yl) -1Η-pyrrole (101) Following the same procedure as in Example 81, from the compound obtained in Example 100-2), the title compound, lithium rhenium, was obtained in a yield of 96%. lK NMR (CDC13 h- CD3OD) ^ 1.82 (s, 3H), 2.00 (m, 1H), 2.1 l (m, 1H), 2.36 (t, 2H), 4.82 (m, 1H), 4.89 (s, 2H ), 5.02 (s, 2H), 6.49 (s, 1H), 6.88 (d, 2H), 7.11 (d, 1H), 7.17-7.32 (ιη, 7H), 7.62-7.83 (ιη, 4H) FAB MS: 564 (M + 1) Printed Examples 102 and 103 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economy Follow the same steps as in Examples 100 and 101 to obtain the compounds shown in Table 5 below. 2] 0X297 mm) 125 91506 4 3 64 8 7 A7 __ · _B7 V. Description of the invention (126) Table 5 Compound No. Ή NMR $ FAB MS (M + l) 102 (CDC13) 0.67 (d, 3H), 0.78 (d, 3H), 0.82 (m, 1H), 0.90 (m, 1H), 1.10 (ιη, 1H), 3.52 (s, 3H), 4.32 (m, 1H), 5.02 (s, 2H), 5.17 ( s, 2H), 6.72 (s, 1H), 6.83 (s, 1H), 7.23-7.34 (m, 3H), 7.41-7.92 (m, 10H) 560 103 (CDCU + CD3〇D) 0.62 ((1, 3H), 0.71 (d, 3H), 0.79 (m, 1H), O.S8 (ra, 1H), 0.98 (m, 1H), 4.12 (m, 1H), '4.97 (s, 2H), 5.08 ( s, 2H), 6,77 (s, 1H), 6.82 (s, 1H), 7.14-7.30 (m, 4H), 7.38-7.84 (ra, 9H) 546 (Please read the note on the back before filling in (This page) Shellfish, Central Bureau of Standards, Ministry of Economic Affairs Printed by a Consumer Cooperative 126 Examples 104 and 105 Follow the same procedure as in Example 101 to obtain the compounds in Table 6 below. Table 6 NMR (CDCh) $ FAB MS (M + l) 104 1.95 (brs, 2H ), 2.33 (brs, 1H), 2.95 (brs, 5H), 4.93 (s, 2H), 5.05 (s, 2H), 6.62 (s, 1H), 7.05 (s, 1H), 7.1 l (d, 2H ), 7.28 (m, 2H), 7.5l (m, 3H), 7.63 (ra, 3H), 7.Sl-7.88 (m, 2H), 7.95 (d, 1H) 502 105 1.12 (brSj 2H), 1.88 (brs, 2H), 1.90 (s, 3H), 2.95 (brs, 2H), 3.34 (brs, 2H), 4.97 (s, 2H), 5.07 (s, 2H), 6.60 (s, 1H), 7.02 ( s, 1H), 7.10 (d, 2H), 7.29 (m, 2H), 7.46 (m, 3H), 7.60 (m, 3H), 7.80 (d, 1H), 7.85 (d, 1H), 7.97 (( 1, 1H) 515 Example 106: 1- [2- (1fluorene-oxazol-1-yl) ethyl] -3 -morpholin-4-yl) carbonyl-4- (cha-1-yl) -ih- Synthesis of pyrrole (106) 106-1 p-toluene nitrate-acid 2- (lH-fluorenyl ester) _ Standard of paper 拫 General national national standard (CNS) M specification (2IOX297 mm) 9 1506 4 v3 S 4 8 7 A7 B7__ V. Description of the invention (27) {Please read the notes on the back before filling this page) 0.24g (2.41 奄 mol) 2- (1Η-oxazole-1-yl) ethanol and 0.55 Grams (2.88 mTorr) Um dissolved in 20 liters of gas for methane • two to 0 &lt; C Zong fines 0.67 ml of triethylamine was added thereto, the mixture was stirred at room temperature for 4 hours broadcast. Remove the dried clams under reduced pressure. The residue was dissolved in 10 liters of ethyl acetate, and the cat 'M anhydrous magnesium sulfate was washed with M 1H acetic acid solution, a saturated solution of sodium bicarbonate, and an aqueous solution of sodium chloride in this order, and then concentrated. Residue. Column chromatography was performed (eluent: dichloromethane / methanol = 20/1 * V / V) to obtain 0.30 g (1.13 ’'yield 47¾) of the title compound. ! H NMR (CDCI3) δ 2.42 (s, 3H), 4.17-4.28 (m, 4H), 6.88 (s, 1H), 6.99 (s, 1H), 7.29 (d, 2H) t 7.45 (s, 1H) , 7.64 (4 2H) 106-2) 3-hydroxycarbonyl-4- (naphthalene-1-ylrole according to the same procedure as in Example 80-4) • Hydrolysis of the compound obtained in Example 80-2) to obtain the standard hydrazone Compound, yield 80%. * H NMR (CDC13 + CD3OD) s 7.12 (m, 3H), 7.20-7.31 (m, 3H), 7.50 (d, 1H), 7.68 (d, 1H), 7.76 (d, 1H) Central Bureau of Standards, Ministry of Economic Affairs Printed by Employee Consumer Cooperatives 10 6-3) 3-. (Manga-4-yl) Yiji-4- (naphthalene-1-kitayi Example 80-5), from Example 106-2) The prepared compound and morpholine gave the title compound. ^ NMR (CDCI3) d 2.68-3.62 (brs, 8H), 6.88 (s, 1H), 7.20 (s, 1H), 7.30-7.62 (m, 4H), 7.78 (d, 1H), 7.85 (d, 1H), 8.08 (d, 1H), 10.34 (s, 1H) 106-4) l- [2- (lH-oxazole-1- 棊) ethyl] -3- (morpholin-4-yl) carbonyl The basic paper size applies to the Chinese National Standard (CNS) A4 (210x297 mm) 127 9 1506 4 3 64 87 a? ^ _ B7 V. Description of the invention (1 28) -4- (naphthalene-1-yl) -1Η- The same procedure as in Example 44-3) was used for pyrrole. The compound obtained in Example 106-1) was reacted with the compound obtained in Example 106-3) to obtain the title compound. Yield 51%. NMR (CDC13) ^ 2.20 -3.72 (brsf 12H), 7.20 (s, 1H), 7.40-7.55 (m, 8H), 7.82 (d, 1H), 7.88 (4 1H), 8.05 (d, 1H) FAB MS: 401 (M + l ) Example 107: (S) -l- [3- (lH-Sialyl-4-yl) diyl] -3- [N- (l-methoxycarbonyl-3-methylthio) propyl] aminomethyl Synthesis of fluorenyl-4- (naphthalene-1-yl) -1Η-pyrrole (107)

107-1) 3-ethoxycarbonyl-4- (naphthalene-1-yl) -1- [3- (1-trityl-1H-imidazol-4-yl) allyl] -1H-pyrrole The compound prepared in Example 80-2) and the compound prepared in Preparation Example 30-4) were reacted according to the same steps as in Example 44-3) to obtain the title compound. (Please read the precautions on the back before filling this page) * H NMR (CDC13) δ 0.82 (t, 3H), 3.95 (q, 2H), 4.67 (s? 2H), 6.23 (d, 1H) , 6.47 (111, 1H), 6.63 (s, 1H), 7.02 (s, 1H), 7.25-7.81 (m) 24H)

107-2) 3-Ethoxycarbonyl-4- (naphthalene-phenyltrityl-1H-oxazol-4-yl) propyl] role 300 mg (0.49 mmol) Example 107-1) The obtained compound was dissolved in 2 ml of formazan • Pd / C with a catalyst amount was added thereto, and the mixture was stirred under a hydrogen atmosphere for 1 hour. The compound undergoes 滹 M removal catalyst_Scrape removal to remove the solvent in which the paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) 128 91506 4 3 6 8 7 a7 __'__ B7__ V. Description of the invention) . Residues were subjected to column analysis (eluent: dichloromethane / methanol = 98/2, V / V) »246 mg (0.40 millitorles, yield 82%) was titled (please read the note on the back first) (I write this page again)] compounds.-LH NMR (CDC13) s 0.92 (t, 3H), 222 (m, 2H), 2.73 (t, 2H), 4.01 (111, 4H), 6.70 (s, 1H), 6.82 (s, 1H), 7.32-7.73 (m, 21H), 7.91 (m, 3H) 107-3) (S) -l- [3- (lH-oxazol-4-yl) propyl ] Methoxycarbonyl-3-methylthio) propyl] aminomethyl-4- (naphthalene-1-yl) -1H-pyrrole according to the procedures of Examples 44-4) and 80-4) Example 107-2 ) Compounds obtained · Trityl removal and hydrolysis. The product thus prepared was then reacted simultaneously with the (L) -methionine methyl ester according to Example 80-5) to obtain a keto compound * with a yield of 29%. 4 NMR (CDC13) &lt; 5 ϋχιη, 2H), 1.90 (s, 3H), 2.12 (m, 2H), 2.31 (m, 2H), 2.73 (m, 2H), 3.54 (s) 3H), 4.02 ( m, 2H)} 4.56 (m, 1H), 5.77 (d, 1H), 6.72 (s, 1H), 6.90 (s, 1H), 7.42-7.67 (m, 7H), 7.82-8.01 (m, 5H) FAB MS: 491 (M + 1) Central Standard of the Ministry of Economic Affairs is printed for employee consumer cooperatives. Example 108: (S) -3- [N- (l-hydroxycarbonyl-3-methyltelluryl) propyl] aminomethylamino The synthesis of -1- [3- (1Η-pentaza-4-yl) propyl] -4- (cha-I-yl) pyrrole (1 0 8) was carried out in the same manner as in Example 81, but using Example 107-1 ) The compound obtained, the title compound was obtained, yield 95% »This paper size applies the Chinese National Standard (CNS) A4 (210X297 mm) 129 1506 Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 3 6487: 77 V. Description of the invention M0) 'h NMR (CDCh) s I.57 (m, 2H), 1.88 (s5 3H), 2.08 (111, 2H) 2.29 (m, 2H), 2.77 (m, 2H), 4.12 (m, 2H), 4.49 (m, 1H), 5.69 (d, 1H), 6.77 (s, 1H), 6.92 (s, 1H), 7.34-7.58 (m, 7H), 7.80-7.89 (m, 5H )-'FAB MS: 477 (M + 1) Example 109: oxazol-4-yl) propyl] 3- (morpholin-4-yl) carbonyl-4- (naphthalene-1-yl) _1pyrrole (1 Synthesis of 09) Following the same procedure as in Example 107-3), but using morpholine instead of methionine formic acid, the title compound was obtained in a yield of 42%. lK NMR (CDC13) $ 2.16 (m, 2H), 2.35 (brs5 2H), 2.63 (m, 2H), 2.80-3.50 (brs, 6H), 3.54 (s, 3H), 3.96 (m, 2H), 6.74 (d, 1H), 6.76 (s, 1H), 7.〇7 (s, 1H), 7.33 (t, 1H), 7.36-7.50 (m, 4H), 7.76 (d, 1H), 7.84 (d, 1H), 8.08 (4 1H) FAB MS: 415 (M + 1) Example 110: l- [l- (4-cyanobenzyl) -lH-oxazol-5-yl] methyl-3- [N- Synthesis of methoxyethyl) -H-methyl] aminomethyl-4-(naphthalene-1 -yl) -1 pyrene-pyrrole (11 0) 110-1) 3- [N- (2-methoxy Ethyl) methyl] aminomethyl-4- (cha-1-yl) -1 pyrene-pyrrole 100 mg (0.42 mmol) Example 106-2) The compound obtained with 38 mg (0.4 mmol) N- (2-methoxyethyl) -N-methylamine was reacted in the same manner as in Example 80-5) to obtain 110 mg (0.35 mol, yield 85) of the title compound. (Please read the precautions on the reverse side before filling out this page) Order-This paper size applies the national standard (CNS) A4 size (210X297 mm) 130 9 1506 A7 B7 / 136 ^ 37 V. Description of invention € 31) ( (Please read the notes on the back before filling in this page)! H NMR (CDC13) § 2.2 1 (s, 3H), 2.64 (brs, 1H), 2.75 (brs, 1H), 3.02 (s, 3H), 3.13 ( brs, 1H), 3.32 (brs, 1H), 6.72 (s, 1H), 7.05 (m, 2H), 7.21 (111, 2H), 7.54 (m, 1H), 7.78 (m, 2H), 8.04 (d , 1H), 8.78 (brs, 1H) 110-2) l- [l- (4-cyanobenzyl) -lH-oxazol-5-yl] methyl-3- [N- (2-methoxyethyl (N-methyl) -N-methyl] aminomethyl-4- (naphthalen-1-yl) -1Η-pyrrole 98 mg (0.32 mmol) Example U0-1) and 85 mg (0.32 mmol) Ear) The compound prepared in 9-5) in Preparation Example 2 was reacted in the same manner as in Example 44-3) * to obtain 115 mg (0.23 mmol, yield 72%) of the title compound. lH NMR (CDC13) § 2.41 (s, 3H), 2.75 (brSj 2H), 3.07 (s, 3H), 3.17 (brs, 1H) 3 3.32 (brs) 1H), 4.91 (s, 2H), 5.1 l ( s, 2H), 6.71 (s, 1H), 7.05 (s, 1H), 7.17 (d, 1H), 7.40-7.68 (m, 9H), 7.78 (d, 1H), 7.88 (d, 1H), 8.06 (d, 1H) FAB MS: 504 (M + l) Example printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 111: 1- [U-Bromobenzyl) -lH-imidazol-5-yl] methyl-3- Synthesis of [N- (2-methylchloroethyl) -H-formamidine] aminomethyl-4- (naphthalen-1-yl-1l-pyrrole (1 11)) 105 mg (0.29 millitorr) The compound obtained in Example 110-1) was reacted with 78 mg (0.29 mmol) of the compound prepared in Preparation Example 32-2) according to the same procedure as in Example 4 4 -3) to obtain 121 mg (0.21 mmol) Ear, 75% yield) of the title compound. This paper size applies Chinese National Standard (CNS) _ Α4 specification (210X29 &quot;? mm) 13 1 91506 ^ 3 64 8 7 A 7 B7 V. Description of the invention (132) lU NMR (CDCI3) δ 2.37 (s, 3Η) , 2.72 (brs, 2Η), 3.04 (s, 3H), 3.15 (brs, 1H), 3.31 (brs, 1H), 4.95 (s, 2H), 5.10 (s) 2H), 6.67 (s, 1H), 7.11 (s, (Please read the notes on the back before filling this page) 1H), 7.23-7.65 (m, 10H), 7.81 (d, 1H), 7.89 (d, 1H), 8.02 (d, 1H) ' FAB MS: 557 (M + l) Example 112: l- [l- (4-bromobenzyl) -lH-oxazol-5-yl] methyl-3- (morpholin-4-yl) carbonyl-4 -(Naphthalene-1-yl) -1） -pyrrole (112) Synthesis of 100 mg (0.33 mol) of the compound obtained in Example 106-3) and 105 mg (0.33 mmol) of Preparation 32-2) The obtained compound was reacted in a similar manner as in Example 44-3) * to obtain 130 mg (0.23 mmol). Yield 71¾) of the title compound. lH NMR (CDCb) ^ 2.04 (brs, 2H), 2.25 (brs, 1H), 3.03 (brs, 5H), 4.93 (s, 2H), 5.07 (s, 2H), 6.62 (s, 1H)) 7.10 ( m, 3H), 7.29 (π, 2H), 7.41 (m, 3H), 7.60 (m, 3H), 7.81 (d, 1H), 7.89 (d) 1H), 8.01 (d, 1H) FAB MS: 555 (M + l)

Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, Example I: 113-l- [l- (4-Cyanodinyl) -lH-imidazol-5-yl] methyl-3-morpholin-4-yl) thiocarbonyl-4 Synthesis of-(naphthalene-1-yl) -1Η-pykal (113) 20 mg (0.04 mmol) of the compound prepared in Example 104 and 13 mg of 2.4-bis (phenylthio) -1,3-- Diphthyl-2,4-diphosphate-2,4-disulfide was dissolved in 1 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 3 hours. Add 2 liters of saturated sodium bicarbonate solution to the reaction solution. The resulting mixture was extracted with ethyl acetate, and the anhydrous sodium sulfate was dehydrated. Distilled organic solvents are used to reduce the residue. The size of this paper is in accordance with Chinese national standards (CNS &gt; 8 4 specifications (210 × 297 mm) 132 91506 436487 A7 _______ B7 V. Description of the invention). Dicarbamidine / methanol = 9/1, v / v), 9 mg (0.017 mmol, 43% yield) of the title compound were obtained. ° H NMR (CDCh) $ 1.88 (brs, 2H), 2.64 (brs, 6H), 4.86 (s, 2H) 5.01 (s, 2H), 6.67 (s, 1H), 7.14 (m, 3H), 7.26-7.58 (m, 8H), 7.8l (m, 2H) 8.03 (d) 1H), 'FAB MS: 518 (M + l) Example 114: 3-N- (2-methoxyethyl) -N-methylaminomethylmethyl-K1-methyl-1H-hoof sleep Synthesis of 5--5-yl) methyl_4- (naphthalene-1-yl) _1H-titanium (1 1 4) 114-1) 4- (Cha-1-yl slightly 3--3-acid 2.64 mg ( 10 millimoles) The compound prepared in Example 80-2) was dissolved in 50 ml of 50% ethanol, and 2.24 g (40 millimoles) of potassium hydroxide was added thereto. The reaction mixture was refluxed for 7 hours, cooled to room temperature, adjusted to pH 4-5 ', and extracted with ethyl acetate, and the anhydrous sodium sulfate was dehydrated. The solvent was removed under reduced pressure to obtain .62 g (8.1 mmol, 81% yield) of the title compound. The product thus obtained was used in the next reaction without purification. ln NMR (CDC13) 8 6.60 (s, 1H), 7.32-7.49 (m, 5H), 7.54 (s, 1H), 7.84 (m, 2H), 9.92 (s) 1H) FAB (M + H): 236 114-2) 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4- (cha-1-yl) -lH-nth 234 mg (1 mmol) Example 114-1) The compound obtained was dissolved in 2 mmol 7 = ^^-(谙 Please read the precautions on the back before filling this page) __

.1T This paper is in accordance with Chinese National Standards (CNS) Λ4 size (210X297 mm) 133 91506 43 6487 A7 B7 V. Description of the invention (134) liters of dimethylformamide, followed by 230 mg (1.2 mmol) ) EDC, 101 mg milli 26, and amine ethylene tri XI

Mix 0 P ethyl ethoxylate in 2 I fix the product) N mixed in the solution, the solution should be dissolved in acid, the amino group should be amine, N-min)-5 grams, stir in the greenhouse Small when connected. Solution and dissolved in water and mixed with water and residual water until the sodium material is added and the solution is added with a mouthful of Λ = re-open the g standard, milligrams of agent &quot; V milli? 2 Μ 6 solvent 4 ^ &gt; The pressure was reduced to obtain the solution of the concentrated solution and potassium-saturated carbonic acid, carbonic acid, 1N, sulfuric acid, and water. There were no 10 passages. I took the water-washing esters and ears. (Please read the precautions on the back before filling this book. Page) &quot; Installation-'H NMR (CDC13) ί 2.46 (s, .2H), 2.80-3.40 (m, 7H), 3.40 (s, 1H), 6.80 (3, 1H), 7.00 (s, 1H) , 7.42 (m) 4H), 7.73 (d, 1H), 7.8 l (d, 1H), 8.17 (d, -5 1H), 10.66 (s, 1H) FAB (M + H): 309 114-3) 1- (1-methyl-1H-oxazol-5-yl) methyl-3- [N- (2-methoxyethyl) -H-methyl] amine formamidine.yl-4- (naphthalene- 1-yl) -1H-pyrrole 618 mg (2.0 mmol) Example 11 4-2 &gt; The compound prepared was dissolved in 10 ml of dimethylformamide, and at ot: 264 mg (6.6 mmol) Sodium hydride (60%) was added thereto, followed by stirring the stick compound for 5 minutes. 367 mg (2.2 mmol) of 5-gas methyl-1-methyloxazosinamidine was added to the mixture, and the whole mixture was placed in a chamber. Stir for 5 hours. Remove solvent & g under reduced pressure t; 10 ml of water was added to the residue. The resulting mixture was extracted twice with 20 ml of ethyl acetate, and the anhydrous sodium sulfate was dehydrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / formaldehyde = 90 / 10, V / V) to obtain 644 mg (yield 80%) of the title compound. This paper is sized to the national standard (CNS) A4 (210X297 mm) 134 9 15 0 6 4, 3 6 ^ δ 7 Α7 Β7 5. Description of the invention 35) (谙 Please read the notes on the back before filling in this page j Η NMR (CDC13) δ 2.42 (s, 2H), 2.71 (m, 1H), 3.10 (brs, 6H), 3.30 ( brs, 1H), 3.50 (s, 3H), 5.09 (s, 2H), 6.70 (s, 1H), 7.05 (s, 1¾ 7.15 (s, 1H), 7.30-7.49 (m, 4H), 7.72 (d , 1H), 7.84 (d, 2H), 8.08 (d, 1H) FAB (U + R): 403 Example 115: 1- (1-isobutyl-1H-imidazol-5-yl) methyl-3- Synthesis of [N- (2-methoxyethyl) -N-methyl] aminomethane- 4- (naphthalene-1-yl) -1Η-pyrrole (115) 618 mg (2.0 mmol) Example 114 -2) The obtained compound was dissolved in 10 ml of dimethylformamide, and at 0Ϊ: 264 mg (6.6 millitors) of sodium hydride (60%) was added thereto, and then the mixture was stirred for 5 minutes. 459 mg (2.2 mmol) of the compound prepared in Preparation Example 33-2) was added to the mixture, followed by stirring at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 20 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10, V / V) to obtain 667 mg (yield 75%) of the title compound. ! H NMR (CDCl3) s 0.90 (d, 6H), 1.75 (m, 1H), 2.41 (brs, 2H), 2.72 (brs, 1H), 3.01 (brs, 6H), 3.32 (brs, 1H ), 3.62 (d, 2H), 5.13 (s) 2H), 6.72 (s, 1H), 7.09 (s) 1H), 7.19 (s, 1H), 7.30-7.49 (m, 4H), 7.78 (d, 1H), 7.84 (d, 2H), 8.08 d, 1H) FAB (M + H): 445 Example 116: 1- (1-cyclohexylmethyl-1H-imidazol-5-yl) methyl-3- [ Synthesis of N- (2-methoxyethyl) -N-methyl] aminomethylamido- 4- (naphthalene-1-yl) -1 Η-laro (116) National Standard (CNS) Α4 Specification (210X297 mm) 135 91506 A7 A7: ¾ ¾ ash gray 榀 ifi.J. '; IJr-Consumer Bamboo Office Yinji B7 V. Invention Description 36) 618 mg (2.0 mmol) (Ear) Example 114-2) The compound obtained in Example 114-2) was dissolved in 10 ml of dimethylformamide, and 264 mg (6.6 mmol) of sodium hydride (60%) was added to 0 spoon, and then the mixture was stirred for 5 minutes. . To this mixture was added 647 g (2.2 mmol) of the compound prepared in Preparation Example 34-2), followed by stirring at room temperature for 5 hours. Remove the solvent by distillation under reduced pressure. Add 10 ml of water to the residue. The obtained stick compound was extracted twice with 20 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10, V / V). 726 mg ( Yield 75%) of the title compound. NMR (CDC13) δ 〇-87 (m? 2H), 1.12 (m, 3H), 1.30 (brs, 1H)? L40-1.80 (m, 5H), 2.41 (brs, 2H), 2.72 (brs, 1H) , 3.01 (brs, 6H), 3.32 (brs, 1H), 3.63 (d, 2H), 5.09 (s, 2H), 6.72 (s, 1H), 7.09 (s, 1H), 7.19 (s, 1H), 7.25 (s, 1H), 7.30-7.49 (m) 3H), 7.78 (d, IH), 7.83 (d, 2H), 8.08 (d, 1H) FAB (M + H): 485 Example 117: 3- [ N- (2-methoxyethyl) -N-methyl] aminomethyl-4- (naphthalene-1 -yl) -1- (pentyl-1H -oxazol-5-yl) methyl-1H -Synthesis of pyrrole (1 17) 618 mg (2.0 mmol) Example 114-2) The compound prepared in Example 114-2) was dissolved in 10 ml of dimethylformamide, and 264 mg (6.6 mmol) of sodium hydride was added to 0.00 (60%) to it, and the mixture was stirred for 5 minutes. 429 mg (2.2 mmol) of the compound prepared in Preparation Example 35-2) was added to the mixture, followed by stirring at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The obtained mixture was extracted twice with 20 ml of ethyl acetate M20, dehydrated with anhydrous sodium sulfate K, and concentrated | performed with a silica gel column chromatography (solvent: methane / methanol = 90/10-V / V) to obtain 714 mg (product Rate 78%) of the title compound. This paper is in the national standard (CNS_) Ad specification (210 &gt; &lt; 297mm) '136 91506 (Please read the precautions on the back before filling this page). Ding-5 436487 A7 B7 V. Description of the invention (137) W NMR (CDCI3) accounts for 0.90 (t, 3H), 1.08 (brs, 2H), 1.30 (ra, 2H), 1.45 (m, 2H), 2.41 (brs, 2H), 2.72 (brs, 1H), 3.01 (brs, 6H), 3.32 (brs, 1H), 3.63 (t, 2H), 5.09 (s, 2H)) 6.72 (s, 1H), 7.09 (s, 1H), 7.19 (s, lH ) /7.25Cs, 1H), 7.30-7.49 (m, 3H), 7.78 (d, 1H), 7.83 (d, 2H), 8.08 (d, 1H) FAB fM + H): 459 Example 118: 3- ( N- (2-methoxyethyl) -N-methyl] aminomethylmethyl-4- (naphthalene-butyl) -1- (1-octyl-1H -imidazol-5-yl) methyl-1H -Synthesis of pyrrole (118) 6 13 mg (2.0 mmol) of the compound prepared in Example 114-2) was dissolved in 10 ml of dimethylformamide, and Ot: 264 mg (6.6 mmol) was hydrogenated Soda (60%) to it * The mixture was then stirred for 5 minutes. To this mixture was added 508 mg (2.2 mmol) of the compound prepared in Preparation Example 36-2), followed by stirring at room temperature for 5 hours. Reduce the solvent by distilling and add 10 ml of water to the residue. The resulting mixture was extracted twice with 20 ml of acetic acid and acetic acid. The K sodium sulfate was dehydrated, and then subjected to shrinkage, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10-V / V) to obtain 760 mg (76% yield) of the title compound.

NivlRCCDCb) ^ 0.87 (t, 3H), 1.17 (brs, 2H), 1.30 (brs, 10H), 1.44 (111, 2H), 2.41 (brs, 2H), 2.72 (brSj 1H), 3.01 (brs, 6H) , 3.32 (brs, 1H), 3.62 (t, 2H), 5.09 (s, 2H), 6.72 (s, 1H), 7.09 (s, 1H), 7.19 (s, 1H), 7.25 (s, 1H), 7.30-7.49 (m, 3H), 7.78 (d, 1H), 7.83 ((3, 2H), 8.08 (d, 1H) FAB (M + H): 501 Example 119: 1- (1-decyl-1H -Oxazolyl-5-yl) methyl- [3- [N- (2-methoxyethyl) -N-methyl] aminomethylpyridyl-4- (naphthalene-1-yl) -1pyridine ) Synthesis (谙 Please read the notes on the back before filling this page)

The size of this paper is suitable for China and Fujian (CNS) A4 specification (210 × 297 mm) 137 91506 436487 A7 — B7 V. Description of the invention (138) 618 mg (2.0 millimolar) Example 114-2) The compound was dissolved in 10 ml of dimethylformamide, and 264 mg (6.6 mmol) of sodium hydride (60%) was added thereto, followed by stirring the mixture for 5 minutes. 567 mg (2.2 mmol) of the compound prepared in Preparation Example 37-2) was added to the mixture, followed by stirring at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 20 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: methylene chloride / methanol = 90/10 · V / V) to obtain 667 mg (product Rate 75%) of the title compound. 1E NMR (CDC13) § 0.87 (t, 3H), 1.17 (brs, 2H), 1.30 (brs? 14H), 1.44 (m, 2H), 2.41 (brs, 2H), 2.72 (brs, 1H), 3.01 (brs, 6H), 3.32 (brs, 1H), 3.62 (t, 2H), 5.09 (s, 2H), 6.72 (s, 1H)} 7.09 (s, 1H), 7.19 (s, 1H) 7 7.25 (s3 1H), 7.30-7.49 (m, 3H), 7.78 (d, 1H), 7.83 (d, 2H), 8.08 (d, 1H) FAB (M + H): 529 Example 120: 3- (N- (2-methoxyethyl) -H-methyl] aminomethyl-l- [l- (3-methylbutyl) -1H-imidazol-5-yl] methyl-4- (naphthalene-1 -Based) -1 Η -laro (1 2 0) synthesis 618 mg (2.0 mol) Example 114-2) The compound prepared in 10 ml of dimethylformamide | Add 0264 to 264 mg ( 6.6 millimoles) of sodium hydride (60%) into it • The mixture is then stirred for 5 minutes. 429 mg (2.2 mmol) of the compound prepared in Preparation Example 38-2) was added to the mixture, followed by stirring at room temperature for 5 hours. Reduce solvent to remove the solvent. Add 10 liters of water to the residue. The obtained mixture was extracted twice with 20 ml of ethyl acetate. Dehydrated with anhydrous sodium sulfate, concentrated, and subjected to silica gel column decantation (eluent: dichloromethane / methanol = 90/10 · V / V). 75%) of the title compound.

-(Please read the precautions on the back before filling in this page J

-1T The size of this paper is suitable for the National Standards of China (CNS) A4 specification (210 × 297 mm) 138 9 15 0 6 436487 A7 B7 V. Description of the invention (1 39)! H NMR (CDC13) ^ 0.91 (d, 6H ), 1.31 (q, 2H), 1.67 (m, 1H), 2.41 (brs, 2H), 2.72 (brs, 1H), 3.01 (brs, 6H), 3.32 (brs, 1H), 3.62 (t, 2H) , 5.09 (s, 2H), 6.72 (s, 1H), 7.09 (s, 1H), 7.19 (s, 1H), 7.25 (s? &Quot; 1H), 7.30-7.49 (m, 3H), 7.78 (d , 1H), 7.83 (d, 2H), 8.08 (d, 1H) FAB (M + H): 459 Example 121: l- [l- (2-methoxyethyl) -lH-oxazol-5-yl Synthesis of] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethylamidino- 4- (naphthalene-1-yl) -1 hydrazone-pyrrole (1 2 1) Mg (2.0 mmol) of the compound prepared in Example 114-2) in 10 ml of dimethyl formamide, in Ot: 264 mg (6.6 mmol) of sodium hydride (60%) was added to it, and then The mixture was allowed to stir for 5 minutes. 429 mg (2.2 millimoles) of the compound prepared in Preparation Example 39-2) was added to the mixture / then stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The obtained mixture was extracted twice with 20 ml of ethyl acetate and 20 ml of anhydrous sodium sulfate, and concentrated, and then subjected to silica gel column chromatography (solvent: dichloromethane / formaldehyde = 90/10-V / V). 667 mg ( Yield: 75%). Ή NMR (CDCb) $ 2.41 (brs, 2H), 2.72 (brs, 1H), 3.01 (brs, 6H), 3.32 (brs, 1H), 3.37 (s, 3H), 3.45 (t, 2H), 3.63 ( t, 2H), 5.09 (s, 2H), 6.72 (s) 1H), 7.09 (s, 1H), 7.19 (s, 1H), 7.25 (s, 1H), 7.30-7.49 (m, 3H), 7.78 (d, 1H), 7.83 (d, 2H), 8.08 (4 1H) FAB (M + H): 447 Examples-radical 1 -rL 1Λ-1 naphthyl T Ϊ 4 醯-methylamine methyl TJ group Gemini 5 1 1 -N Miles &gt; Mi i Η Ethyl Oxygen)-Shen Ji 2 Proton Oxygen ΓΝ 甲 甲 lltt Synthetic (Please read the precautions on the back before filling this page)

This paper size applies to the national standards of ten countries (CNS) A4 (210X297 mm) 139 91506 4 3 64 87 A7 Null middle section &quot;: quasi and m-T &quot; 'Zhe 卄 卄 卬 ______ B7 5 Description of the invention <40) 618 mg (2.0 millitorr) The compound prepared in Example 114-2) is dissolved in 10 ml of dimethylformamide | Add 264 mg (6.6 mmol) of sodium hydride to Ot (60% ) To this, the mixture was stirred for 5 minutes. To this mixture was added 459 mg to (2.2 mil) of the compound prepared in Preparation Example 40-2), followed by stirring at room temperature for 5 hours. The solvent was removed under reduced pressure * and 10 ml of water was added to the residue. The obtained mixture was extracted twice with 20 ml of ethyl acetate, and the anhydrous sodium sulfate was dehydrated, concentrated, and subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10 · V / V)-683 mg (yield). 70%) of the title compound. 'Η NMRfCDCls) δ 1.71 (m, 2H), 2.41 (brs, 2H), 2.72 (brs5 1H)? 3.01 (brs, 6H), 3.31 (s, 3H), 3.32 (brs, 1H), 3.48 (t, 2H), 3.63 (t, 2H), 5.09 (s, 2H), 6.72 (s, 1H), 7.09 (s, 1H), 7.19 (s, 1H), 725 (s, 1H), 7.30-7.49 (m , 3H)} 7.78 (d, 1H), 7.83 ((1, 2H), 8.08 (d, 1H) FAB (M + H): 461 Example 123: l- [l- (3-ethoxypropyl)- lH-imidazol-5-yl] methyl-3- [K- (2-methoxyethyl) -fluorenyl-methyl] aminomethyl-4- (Cai-buyl) -1 pyrene-pyrrole (1 2 3) Synthesis of 618 mg (2.0 mmol) Example 114-2) The compound obtained in Example 114-2) was dissolved in 10 ml of dimethylformamide, and 264 mg (6.6 mmol) of sodium hydride (60 mg) was added to Ot. %), And then the mixture was allowed to stir for 5 minutes. 459 mg (2.2 mmol) of the compound prepared in Preparation Example 41-2) was added to the mixture, followed by stirring at room temperature for 5 hours. The solvent was distilled off under reduced pressure * and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 20 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / formase = (Please read the precautions on the back before filling in "this (Page) Ding,-= I. This paper size is the national standard of Sichuan and Taiwan (〇 奶) 6 4 specifications (210/297 mm) 140 91506

V. Explanation of the invention (41) _ B7 90/10-V / V) * 712 g (yield 71%) of the title compound were obtained. * H NMR (CDC13) ^ 1.20 (1, 3H), 1.70 (m, 2H), 2.41 (brs, 2H), 2.72 (brs, 1H), 3.01 (brs, 6H), 3.32 (brs, 1H), 3.50 (m, 4H), 3.63 (t, 2H), 5.09 (s, 2H), 6.72 (s, 1H), 7.09 (s, 1H), 7.19 (s, 1H), 7.25 (s, 1H), 7.30- 7.49 (m, 3H), 7.78 (d, 1H), 7.83 (d, 2H), 8.08 (d, 1H) FAB (M + H): 475 Example 124: l- [l- (3-isopropoxypropane) (Yl) -lH-imidazol-5-yl] methyl- 3- [N- (2-methoxyethyl &gt; -N-methyl] aminomethyl-4- (naphthalene-butyl) -1Η- Synthesis of pyrrole (124) 618 mg (2.0 mmol) Example 114-2) The compound obtained in Example 114-2) is dissolved in 10 liters of dimethylformamide • Add 0264 to 264 mg (6.6 ounces) of sodium hydride (60¾ ) To this, the mixture was stirred for 5 minutes after aging. 459 mg (2.2 millimoles) of the compound prepared in Preparation Example 42-2) was added to the mixture, followed by stirring at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 20 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate | concentrated, and subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10-V / V) &gt; to obtain 751 mg ( Yield 73%) of the title compound. lH NMR (CDCh) S 1.16 (d, 6H), 1.70 (m, 2H), 2.41 (brs, 2H), 2.72 (brs, 1H), 3.01 (brs, 6H), 3.32 (br5, 1H), 3.45- 3.55 (m, 3H), 3.63 (t, 2H), 5.09 (s, 2H), 6.72 (s, 1H), 7.09 (s, 1H), 7.19 (s, 1H), 7.25 (s, 1H), 7.30 -7.49 (m; 3H), 7.78 (d, 1H), 7.83 (d, 2H), 8.08 (d, 1H) FAB (M + H): 489 Example 125: l- [l- (4-bromobenzyl) ) -LH-oxazol-5-yl] methyl-3- [4 -A:.,) ¾-- (Please read the notes on the back before filling this page)-° This paper is suitable for China in China Standard (CNS) Λ4 specification (210X297 mm) 14 1 91506 ^ 436487 a? B7 V. Description of the invention 丨 42) Hexahydropyrine-1-yl] carbonyl- 4- (naphthalene-1-yl) -1 Synthesis of Lablaze (1 25) 12 5-1) of 3- [4-methylhexahydropyridine-1-yl] carbonyl_4- (cha-1-yl-1H-pyrrole according to Example 80-5) Same procedure · Compound prepared from Example 106-2) and 4-methylhexahydropyridine • Produced title compound 'Yield 90 ° ° H NMR (CDC13) ^ 1.15 (br, 2H), 1.87 ( br, 2H), 1.92 (s, 3H), 2.96 (br, 2H), 3.41 (br, 2H), 6.83 (s, 1H), 7.09 (s, 1H), 7.36-7.42 (m, 4H), 7.73 (d, 1H), 7.75 (d, 1H), 8.10 (d, 1H), 10.52 (s, 1H) FAB (M + H): 320 125-2) [1- (4-Bromobenzyl) -lH-oxazol-5-yl] methyl-3- [4-methylhexahydropyrazine-1-yl] carbonyl- 4- ( Naphthalene-1-yl) -1H-Tabyl 64 mg (0.2 mmol) The compound prepared in Example 125-1) was dissolved in 2 liters of dimethylformamide • In Ot: 26 mg (0.66 奄) Mol) sodium hydride was added thereto, and the mixture was stirred for 5 minutes. 66 mg (0.22 mmol) of the compound prepared in Preparation Example 32-2) was added to the stick and stirred at room temperature for 5 hours. The solvent was removed under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice from 10 liters of ethyl acetate, dehydrated with anhydrous sodium acetate, concentrated, and then subjected to silica gel column chromatography (eluent: digas methane / formaldehyde = 90/10, V / V) to obtain 91 mg of title compound (80% yield). lH NMR (CDC13) S 1.15 (br, 2H), 1.77 (br, 2H), 1.86 (s, 3H), 2.82 (br, -2H), 3.28 (br, 2H) f 4.87 (3, 2H), 3.88 (s, 2H), 6.55 (s, 1H), 6.79 (d, 2H), 6.97 (s, 1H), 7.16 (s, 1H), 7.36 (d, 1H), 7.36-7.39 (m, 5H), 7.50 (s, 1H), 7.7l (d, 1H), 7.79 ((1, 1H), 7.93 (d, 1H) FAB (M + H); 568 (诮 Please read the precautions on the back before filling this page)

The size of this paper is suitable / 彳 丨 '1, 闼 National Standard (CNS) A4 Specification (210X297mm) 142 9 15 06 A7 3 64 8? — ____: _ 一 _B7_ V. Description of Invention 1 (4 3) Example 126 : 1- [1- (4-Gabenzyl) -1Η-oxazol-5-yl] methyl-3- [4-methylhexahydropyridin-1-yl] carbonyl-4- (naphthalene-1 -Base) Synthesis of -0-Acrylic (126) 64 mg (0.2 mol) The compound obtained in Example 125-1) was dissolved in 2 ml of dimethylformamide, and 26 mg (0.66 mmol) was added to 0¾. Mol) Sodium hydride, and the mixture was stirred for 5 minutes. 55 mg (0.22 millitorr) of 1- (4-chlorobenzyl,)-5-chloromethyloxazolium sulfonate obtained in the same manner as in Preparation Example 32 was added to the mixture, and stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and milliliter of water was added to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate * dehydrated with anhydrous sodium sulfate, and then condensed, followed by silica gel column chromatography (eluent: diazenium methane / formase = 90/10, V / V) to obtain 77 mg The title compound (57% yield). lH NMR (CDC13) ^ -1.15 (br, 2H), 1.77 (br, 2H), 1.86 (s, 3H), 2.82 (br, 2H), 3.28 (br, 2H), 4.92 (s, 2H)} 4.95 (s, 2H), 6.60 (s, 1H), 6.9l (d, 2H), 6.0 l (s, 1H), 7.22 (s, 1H)} 7.26-7.36 (m, 3H), 7.36-7.48 (m , 2H), 7.56 (s, 1H), 7.77 (d, 1H), 7.82 (d, 1H), 7.93 (d, 1H) FAB (M + H): 524 Example 127: l- [l- (4- Fluorobenzyl) -lH-oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -H-methyl] aminomethylamidino-4- (naphthalene-1-yl) _ 1 Synthesis of hydrazone-pyrrole (1 2 7) 64 mg (0.2 mmol) The compound prepared in Example 114-2) was dissolved in 2 ml of dimethylformamide * Add 26 mg (0.66 mmol) to 0¾ Ear) Sodium hydrogen was added thereto, and the mixture was stirred for 5 minutes. Add 51 mg &lt; 0.22 mmol) of 1- (4-benzyl) -5-chloromethylimidazolium prepared in the same manner as in Preparation Example 32 (please read the precautions on the back and fill in " (This page) Binding paper size Shizhou Chinese National Standard (CNS) A4 size (210XZ97 mm) 143 91506

Five 'Explanation of the invention 1 (4 4) acid to the mixture • Stir at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate, K was dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (dissolved solution: dichloromethane / methanol = 90/10, V / V). 77 mg of the title was obtained. Compound (yield 80%). lH NMR (CDC13) ^ 2.12 (br5 3H), 2.72 (br, 1H), 3.00-3.20 (m, 5H), 3.32 (s, 1H), 4.97 (s, 2H), 3.98 (s, 2H), 6.64 (s, 1H), 6.95-7.10 (m, 5H), 7.21 (s, 1H)} 7.33 (m, 1H), 7.40-7.51 (m, 3H), 7.66 (s, 1H), 7.74 (d 1H) 7.81 (d, 1H), 8.08 (d, 1H) '' FAB (M + H): 497 Example 128: [1- (4-fluorobenzyl) -1H-imidazol-5-yl] methyl-3 -Synthesis of [4- (methylhexahydroBtfc hen-1-yl] carbonyl-4- (naphthalene-1-yl) -1Η-pyrrole (128) via the central part of the M part ^^ hH ^ fr ^ 竹 " Quot &quot; ^ J Pack-(Please read the precautions on the back before filling out this page) Order 64 mg (0.2 millirales) in Example 125-1) The compound prepared in 2 ml of dimethyl formamidine To this was added 26 mg (0.66 millitorr) of sodium hydride, and the mixture was stirred for 5 minutes. Add 51 mg (0.22 millitorr) of 1- (4-aminobenzyl) -5-aminomethyloxazolium acetic acid obtained in the same manner as in Preparation Example 32 to the mixture, and stir at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 liters of water was added to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate | K anhydrous sodium sulfate ^ water | concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10, V / V) * 79 mg of the title Compound (yield 80%). This paper size is in accordance with Chinese standards (CNS &gt; A4 size (210X297 mm) 144 9 1506 4 3 6 ^ 87 a? B7 V. Description of the invention 1 (4 5) lH NMR CCDCI3) δ U5 (br, 2Η) , 1.77 (br, 2H), 1.86 (s, 3H), 2.82 (br, 2H), 3.28 (br, 2H), 4.92 (s, 2H), 4.97 (s, 2H), 6.60 (s, 1H), 6.93 (d, 2H), 6.01 (3, 1H), 7.22 (s, 1H), 7.25-7.36 (m, 3H), 7.36-7.47 (ffl, 2H), 7.57 (s, 1H), 7.78 (d, 1H), 7.82 (d, 1H), 7.93 (d, lH) FAB (M + H) 508 Preparation Example 43: Synthesis of 5-Aminomethyl-1- (4-methoxybenzyl) -imidazolium hydrazone 4 3-1) The same procedure of 5-hydroxymethyl-1- (4-methoxybenzyl) imidazole according to Preparation Example 31) • Using dihydroxyacetone and 4-methoxybenzylamine sulfonium acid as starting materials, The title compound was obtained in a yield of 30%. O'H NMR (CDC13 + CD30D) § 3.75 (s, 3H), 4.50 (s, 2H), 5.15 (s, 2H), 6.86 (m, 3H), 7.08 (d, 2H), 7.42 (s, 1H) FAB (M + H): 219 43- 2) 5-Aminomethyl-1- (4-methoxybenzyl) oxazosinic acid, according to Preparation Example 28-2) Procedure, but using the compound prepared in Preparation Example 43-1) as the starting material, the title compound was obtained in a yield of 95%. Preparation Example 44: Synthesis of 5-chloromethyl-1- (3-chlorobenzyl) -imidazolium sulfonium sulfonate, ir ^ · ^ 卩 n eliminate co-operation · 4 卬 &quot; (Please read the back Note: Please fill in this page again. 44- 1) 5-Hydroxymethyl-: 1-(3-chlorobenzyl) oxazole according to the same procedure as in Preparation Example 31-1) • Use dihydroxyacetone and 3-chlorobenzylamine Osmium osmate as starting material • The title compound was obtained * in 60% yield. lR NMR (CDC13 + CD30D) § 3.81 (s, 3H), 4.47 (s, 2H), 5.25 (s, 2H), 6.99 (s, 1H), 7.05 (m, 1H), 7.14 (s, 1H), 7.30 (d, 2H), 7.61 (s, 1H) FAB (M + H): 239.5 This paper size is Shizhou 'Buhuo Country #Rate (〇 Post) 6 4 specifications (210 乂 297 mm) 145 91506 Good Ministry of Internal Medicine quasi-hybrid bamboo snoring system 4 3 64 87 A7 v A 7 B7 V. Description of the invention 1 (46) 44- 2) 5-chloromethyl-1- (3-chlorobenzyl) oxazosinic acid According to the same procedure as in Preparation Example 28-2), using the compound prepared in Preparation Example 44-1) as a starting material, the title compound was obtained (yield 92%). Preparation Example 45: Synthesis of 5-chloromethyl-1- (2-chlorobenzyl) oxazolium oxalate 45-1) 5-hydroxymethyl-1- (2-azabenzyl) oxazolyl Preparation Example 31 -1) The same procedure, but using dihydroxyacetone and 2-chlorobenzylamine osmium acid as starting materials • The title compound was obtained in 60% yield! NMR (CDC13) δ 3.24 (5, 2H), 4.44 (s, 2H), 5.26 (s, 2H), 6.78 (d, 1H), 6.90 (s, 1H), 7.15 (m, 1H)} 7.21 (m, 1H), 7.34 (d, 1H), 7.38 ( s, 1H) FAB (M + H): 239.5 45- 2) The same procedure as in Preparation Example 28-2) of 5-aminomethyl-1-(2-chlorobenzyl) oxazosinic acid, but using the preparation example 45-1) The obtained compound was used as a starting material to obtain the title compound * (yield 92%). Preparation Example 46: Synthesis of 5-chloromethyl-1- (2-fluorobenzyl) imidazolium sulfonate 46-1) 5-Hydroxymethyl-1- (2-fluorobenzyl) oxazole according to Preparation Example 3 1), but using dihydroxyacetone and 2-fluorobenzylamine sulfonium acid as starting materials * to obtain the title compound, 71% yield. OHH NMR (CDC13) 5 3.25 (s, 2H), 4.45 ( s, 2H), 5.27 (s, 2H), 6.79 (d, 1H), 7.17 (rn, 1H), 7.26 (m, 1H), 7.35 (d, 1H), 7.38 (s, 1H) FAB (M + H): 223 (翱 Please read the notes on the back before filling in this page) -a The paper size is suitable for China National Standard (CNS &gt; A4 size (210X297 mm &gt; 146 9 1506 A7 436487 B7) V. Description of the invention 1 (4 7) 46- 2) 5-Gasmethyl-1-(2-fluorobenzyl) imidazolium acid. According to the same procedure as in Preparation Example 28-2), the compound obtained in Preparation Example 46-1) was used as a starting material. Starting material to give the title compound (yield 93% ~). Preparation Example 47: Synthesis of 5-Aminomethyl-1- (4-methylbenzyl) oxazolium sulfonium sulfonium acid 47-1) Preparation of 5-hydroxymethyl-1-(4-methylbenzyl) imidazolium 3 bl 1) The same steps, but using dihydroxypropanthine and 4-methylbenzylamine osmium acid as starting materials, the title compound was obtained, yield 65% 〇! H NMR (CDC13) s 2.32 (s, 3H ), 4.50 (s, 2H), 5.19 (s, 2H), 6.95 (s, 1H), 7.05 (d, 2H), 7.15 (d, 2H), 7.59 (s, 1H) FAB (M + H): 219 '47- 2) 5-chloromethyl-1-(4-methylbenzyl) imidazolium acid, the same procedure as in Preparation Example 28-2) * The compound prepared in Preparation Example 47-1) was used as the starting Substance to give the title compound (yield 91%). Preparation Example 48: Synthesis of hydrazone methyl-1- (3-methylbenzyl) imidazolium sulfonate 48-1 31-1) The same steps * using dihydroxypropanidine and 3-methylbenzylamine sulfonium acid as starting materials to obtain the title compound, yield 60%! 4.45 (s, 2H), 4.52 (br, 1H), 5.13 (s, 2H), 6.80 (d, 1H), 6.90 (m, 2H), 7,08 (m, 1H), 7.17 (mt 1H), 7.34 (s, 1H) FAB (M + H): 219 (Please read the precautions on the back before filling this page)

、 1T Warp Department Clip &quot;-4,;: JB-T Elimination Cooperation: # 卬 EN This paper size is applicable to China National Standards (CNS) A4 specifications (210X297 mm) 147 91506 A7 436487 B7 V. Invention Note 1 (48) 48-2) 5-Aminomethyl-1-(3-methylbenzyl) oxazolium hydrazone -------- T, equipment ---- / .i. (Please read first Note on the back side, then fill in the tile) According to the same steps as in Preparation Example 28-2), using the compound prepared in Preparation Example 48-1) as the starting material, the title compound was obtained (yield 92%). Example 129: Methoxybenzyl) -1′-imidazol-5-yl] methyl (2-methoxyethyl) -N-methyl] aminomethylamidino-4- (ch-1-yl) -1H- Synthesis of pyrrole (129) 62 mg (0.2 mmol) The compound prepared in Example 114-2) was dissolved in 2 ml of dimethylformamide, and 26 mg (0.66 mmol) of sodium hydride was added to 0 * 〇. Into * the mixture was stirred for 5 minutes. 60 mg (0.22 毫克) of the compound obtained in Preparation Example 43-2) was added to the mixture, and the mixture was stirred at room temperature for 5 hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate * and dehydrated with anhydrous sodium sulfate and concentrated. Then, silica gel column chromatography (eluent: dichloromethane / methanol = 95/5 * V / V) was obtained to obtain 77 mg of the title. Compound (76% yield). lHNMR (CDCl3) $ 2.41 (m, 2H), 2.75 (m, 1H), 3.03 (m, 5H), 3.10 (m, 1H), 3.34 (m, 1H), 3.76 (m, 3H), 4.91 (3 , 2H), 4.93 (s, 2H), 6.62 (d, 1H), 6.82 (d, 2H), 6.90-7.07 (m, 3H), 7.21 (s, 1H), 7.32 (m, 1H), 7.43 ( m, 2H), 7.60 (s, 1H), 7.74 (d, 1H), 7.82 (d, 1H), 8.08 (d, 1H) FAB (M + H): 509, C31H32N403 Example 130: l- [l- (4-methoxybenzyl) -1H-oxazol-5-yl] methyl-3- (4-methylhexahydropyridin-1-yl) carbonyl- 4- (naphthalene-1-yl) -1 -att (1 30) Synthesis 64 g (0.2 mmol) The compound prepared in Example 125-1) was dissolved in 2 ml of dimethylformamide and added to Ot: 26 mg (0.66 mmol) ) Hydrogenated paper size: Tongzhou National Standard (CNS) Λ4 Appearance (2! 0X297 mm) 148 91506 £ 7 ___ £ 7 ___ 436487 A7 V. Description of Invention 1 (4 9) To this, stir the mixture for 5 minutes. 60 mg (0.22 mol) of the compound obtained in Preparation Example 43-2 was added to the mixture, and stirred at room temperature for 5 hours. The solvent was removed under reduced pressure, and ο 毫升 ml of water was added to the residue. The obtained glutamate was extracted twice with ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, and concentrated, followed by silica gel column chromatography (solvent: dichloromethane / methanol = 9〇 / 10, ν / ν). 79 g of the title compound were obtained (80% yield). ! H NMRCCDCls) δ 1.06 (br, 2H), 1.72 (111, 2H), 1.82 (s, 3H), 2.86 (br, 2H), 3.28 (br, 2H), 3.75 (s, 3H), 4.91 (s, 2H), 4.93 (s, 2H) S 6.63 (4 1H), 6.82 (4 2H), 6.90-7.07 (% 3H), 7.23 (s, 1H), 7_33 (m, 1H), 7.44 ( m, 2H), 7.61 (s, 1H), 7.75 (d, 1H), 7.82 (d, 1H), 8.08 (4 1H) FAB (M + H): 520, C32H33N502 Example 131: l- [l- ( 3-benzyl) -lH-oxazol-5-yl] methyl-3- [4-methylhexahydropyridin-1-yl) carbonyl- 4- (naphthalene-1-yl) -1） -pyrrole Synthesis of (1 3 1) 64 g (0.2 mmol) of the compound prepared in Example 125-1) was dissolved in 2 ml of dimethylformamide, and 26 mg (0.66 mmol) of sodium hydride was added at 0T. Thereto, the mixture was stirred for 5 minutes. 61 mg (0.22 mmol) of the compound prepared in Example 44-2) was added to the mixture * and stirred at room temperature for 5 hours. Remove the solvent by distilling and adding 10 ml of water to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: diazepine formazan / formase = 90/10, V / V). 75 mg of the title compound (71% yield). ---------- (Please read the notes on the back before filling this page) Central of the Booklet Service Department ^-^ MJr. Printed in Hezhu News Agency, the paper size is appropriate for the country of the country Standards (CNS) Λ4 specification (2 丨 0 × 297 mm) 149 9 1506 43 64 87 a? B7 V. Description of the invention (1 50) (H NMR (CDCI3) § 1.02 (br, 2H), 1.78 (br, 2H ), 1.87 (s, 3H), 2.84 (br, 2H), 3.30 (br, 2H), 6.64 (m, 2H), 7.01 (s, 1H), 7.10-7.30 (m, 4H), 7.31-7.47 ( m, 4H), 7.53 (s, 1H), 7.73 (d, 1H), 7.81 (d, 1H)} 7.96 (d, 1H) &quot; FAB (M + H): 524, C31H30N5OC1 Example 132: l- [l- (3-chlorobenzyl-fluorenyl-methyl] methyl- 3- [N- (2-methoxyethyl) -N-methyl] aminomethylmethyl-4- (naphthalen-1-yl) Synthesis of ΜΗ-pyrrole (1 3 2) 62 mg (0.2 mmol) of the compound prepared in Example 114-2) was dissolved in 2 ml of dimethylsulfonamide, and in Ot: 26 mg (0.66) was added奄 Mol) Sodium argon was added thereto, and the mixture was stirred for 5 minutes. 61 混合物 g (0.22 mmol) of the compound prepared in Preparation Example 44-2) was added to the mixture.皤 Removal of the solvent • Add 10 extra liters of water to the residue. The resulting mixture K10 奄 L of ethyl acetate Ester extraction twice. K anhydrous sodium sulfate dehydration * condensation, followed by silica gel column chromatography (eluent: dichloromethane / formase = 95/5, V / V) to obtain 80 mg of the title compound (yield 78 %). 'Η NMR (CDCl3) &lt; 5 * 2.39 (br, 2H), 2.71 (m, 1H), 3.02 (br, 4H), 3.09 (br, 1H), 3.32 (br, 1H)? 4.09 ( br, 1H), 4.97 (s, 2H), 5.04 (s, 2H), 6.64 (4 1H), 6.90 (m, 1H), 7.02 (d, 2H), 7.20-7.40 (m, 4H), 7.40- 7.60 (m, 3H), 7.74 (d, 1H), 7.76 (d, 1H)? 7.85 (s, 1H), 8.04 (d, 1H) FAB (M + H): 513, C30H29N4O2C1 Example 133: l- [ l- (2-airbenzyl) -lH_oxazol-5-yl] methyl-3- (4-methylhexahydrohexan-: i-yl) carbonyl-4-(naphthalene-1 -yl ) -1 Η-fltt slightly (133) containing 64 mg (0.2 mmol) of the compound prepared in Example 125-1) dissolved (please read the precautions on the back before filling this page)

11T

-I This paper is in accordance with China's national standard (CNS) A4 size (210X297mm) 150 91506 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 4 3 64 8? Η '5. Description of the invention (151) 2 ml Methylformamide, in Ot: Add 26 mg (0.66 millitorr) of sodium hydride to the mixture. Stir for 5 minutes. Add δ milligram (0.22 millier) to the compound prepared in Preparation Example 4 5-2). To the mixture, and stirred at room temperature for 5 hours. Remove the solvent under reduced pressure • Add 10 ml of water to the residue. The obtained mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium tellurate, and then subjected to shrinkage, followed by silica gel column chromatography (eluent: dichloromethane / formaldehyde = 90/10, V / \ f) to obtain 80 mg of the title compound (yield 76%) lH NMR (CD〇3) δ 1.06 (br, 2H), 1.80 (br, 2H), 1.86 (s, 3H), 2.84 (br, 2H), 3.30 (br, 2H), 4.98 (s, 2H), 5.11 (s, 2H), 6.63 (m, 2H), 7.01 (s) 1H), 7.12-7.30 (m, 4H), 7.32-7.46 (m, 4H), 7.53 (s, 1H), 7.73 (d, 1H), 7.8 l (d, 1H), 7.97 (d, 1H) FAB (M + H): 524, C31H30N5OC1 Example 134: l- [l- (2-chlorobenzyl) Yl) -lH-imidazol-5-yl] methyl-3- [N- (2methoxyethyl) -N-methyl] aminomethane- 4- (naphthalene-butyl) -1H-pyrrole ( Synthesis of 134) 62 mg (0.2 mmol) of the compound prepared in Example 114-2) was dissolved in 2 ml of dimethylformamide and added to Ot: 26 mg (0.66 mmol) of sodium hydride, The mixture was stirred for 5 minutes. 61 mg (0.22 mmol) of the compound prepared in Preparation Example 45-2) was added to the mixture * and stirred at room temperature for 5 hours. The solvent was removed by evaporation under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate, dehydrated and concentrated with anhydrous sodium sulfate, and then subjected to ridge column chromatography (eluent: dichloromethane / methanol = 95/5, V / V) to obtain 77 mg of the title. Compound (yield 75%) This paper size applies Chinese National Standard (CNS) Λ4 specification (2 丨 〇Χ Μ7 公公) 151 91506 Pack-(Please read the precautions on the back before filling this page} -1 ° Ministry of Economy Printed by the Consumer Standards Cooperative of the Central Bureau of Standards '彳 4 P.7, Λ,' ίΓ 5. Description of Invention G 52) * H NMR (CDC13) ^ 2.37 (br, 2H), 2.72 (111, 1H), 3.01 (br 4H), 3.10 (br, 1H), 3.32 (br, 1H), 4.18 (br, 1H), 5.04 (s, 2H), 5.17 (s, 2H), 6.65 (d, 1H), 6.76 (d, 2H), 7.04 (d) 1H), 7.13-7.35 (m, 4H), 7.36-7.50 (m, 4H), 7.71 (s, 1H), 7.75 (d, 1H), 7.82 (d, 1H), 8.01 (4 1H)

FAB (M + H): 513, C30H29N4O2CI Example 135: l- [l- (2-fluorobenzyl) -lH-imidazol-5-yl] methyl-3- (4-methylhexahydropyridine-1 -Yl) carbonyl-4- (naphthalene-1-yl) -lH-Dlt (135) Synthesis 64 mg (0.2 mmol) of the compound prepared in Example 12 5-1) was dissolved in 2 ml of dimethyl For formamidine, add 26 mg (0-66 mmol) of sodium hydride to 0TC, and stir the mixture for 5 minutes. 51 mg (0.22 millitorr) of the compound prepared in Preparation Example 46-2) was added to the mixture, and stirred at room temperature for 5. hours. The solvent was distilled off under reduced pressure, and 10 ml of water was added to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, concentrated * and then subjected to silica gel column chromatography (eluent: methylene chloride / methanol = 90/10, V / V) to obtain 79 mg of the title. Compound (yield 77%) lH NMR (CDC13) δ 1.06 (br, 2H), 1.8〇 (br, 2H), 1.86 (s, 3H) f 2.93 (br, 2H), 3.35 (br, 2H ), 5.03 (s, 2H), 5.06 (s, 2H), 6.66 (m, 2H), 6.87 (m, 1H), 7.12-7.30 (m, 4H)? 7.32-7.46 (m, 4H), 7.58 ( s, 1H), 7.77 (d, 1H), 7.82 (d, 1H), 7.97 (4 1H)

FAB (M + H): 508, C31H30N5OF Example 136: l- [l- (4-methylbenzyl) -lH-oxazol-5-yl] methyl-3- (4-methylhexahydroeye 1 -1_Base) Mine-based-4- (Synthesis of -1-Base slightly (136) ------------ (Please read the precautions on the back before filling this page) The scale is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 public viewing) 152 91506 436487 A7 B7 V. Description of the invention (153) (Please read the note on the back before filling this page) 64 mg (0.2 milli-ear) The compound obtained in Example 125-1) was dissolved in 2 liters of dimethylformamide, 26 mg (0.66 mmol) of sodium hydride was added thereto, and the mixture was stirred for 5 minutes. 57 gram (0.22 mol) of the compound obtained in Preparation Example 47-2) was added to the warm compound, and the mixture was stirred at room temperature for 5 hours. Reduce the solvent by distilling and add 10 ml of water to the residue. The resulting mixture, M10 ml, was extracted twice with ethyl acetate * K anhydrous sodium sulfate, dehydrated, concentrated, and then subjected to silica gel column chromatography (eluent: Dioxane / Methanol = 90/10 · V / V) to obtain 81 奄G of title compound (yield 80%)! H NMR (CDC13) § 1.09 (br, 2H), 1.83 (br, 2H), 1.86 (s, 3H), 2.24 (s, 3H), 2.93 (br, 2H) , 3.30 (br, 2H), 4.86 (s, 2H), 4.91 (s, 2H), 6.59 (d, 1H), 6.87 (m, 2H), 7.0 l (s, 1H), 7.07 (d, 2H) , 7.15 (s, 1H), 7.25 (ιη, 1H), 7.50 (m, 3H), 7.53 (s) 1H), 7.73 (d, 1H), 7.78 (d, 1H), 7.97 (d, 1H) FAB (M + H): 504, C32H33N50 Example 137: l- [l- (4-methylbenzyl) -lH-imidazol-5-yl] methyl-3 (morpholin-4-yl) carbonyl-4 -(Naphthalene-1-yl) -1Η-eyerole (137) synthesized by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, 62 mg (0.2 奄 mol) in Example 106-3) and dissolved in 2 奄1 liter of dimethylformamide, add 26 mg (0.66 mmol) of sodium hydride to 0¾ • stir the mixture for 5 minutes. 57 mg (0.22 millilitres) of the compound prepared in Preparation Example 47-2) was added to the warm compound. Stir at room temperature for 5 hours. Remove the solvent under reduced pressure • Add 10 ml of water to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate, dehydrated with anhydrous sodium sulfate, and concentrated. Then, silica gel column chromatography (brown solution: dichloromethane / methanol = 95/5, V / V) was obtained to obtain 80 mg of the title. Compound (yield: 81%) This paper size is applicable to the national standard (CNS) A4 specification (210 X 297 mm) 153 91506 A7 436487 __B7_ V. Description of the invention (l54) NMR (CDCh) 8 2.29 (s, 3H) , 2.30-3.60 (br, 8H), 4.94 (s, 1H), '4.99 (s, 2H), 6.61 (d, 1H), 6.91 (d, 1H), 7.07 (d, 1H), 7.12 (d, 2H), 7.21Cs, (Please read the notes on the back before filling this page) 1H), 7.32 ((1, 1H), 7.35-7.50 (ιη, 4H), 7.7l (s, 1H), 7.77 (d , 1H); 7.84 (d, 1H), 7.98 (d, 1H) FAB (M + H): 491, C31H30N4O2 Example 138: l- [l- (3-methylbenzyl) -lH-oxazole-5 -Methyl] methyl- (3- (4-methylhexahydropyridine-butyl) carbonyl-64- (naphthalen-1-ylcarbyl U38) Synthesis 64 mg (0.2 mmol) in Example 125-1) The obtained compound was dissolved in 2 ml of dimethylformamide, and 26 mg (0.66 mmol) of sodium hydride was added to the mixture. The mixture was stirred for 5 minutes. 57 mg (0.22 mmol) of the compound prepared in Preparation Example 48-2) was added to the mixture, and stirred at room temperature for 5 hours. Distill under reduced pressure. Remove the solvent * and add 10 ml of water to the residue. The resulting mixture was extracted twice with 10 ml of ethyl acetate, concentrated with anhydrous sodium sulfate, and then subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 90/10, V / V) to obtain 74 mg of the title. Compound (73% yield) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs! H NMR (CDC13) S 1.06 (br, 2H), 1.80 (br, 2H), 1.84 (5, 3H), 2.91 (br? 2H), 3.27 (br, 2H), 4.86 (s, 2H), 4.89 (s, 2H), 6.57 (d, 1H), 6.71 (d, 1H), 6.77 (s, 1H), 6.97 ( s, 1H), 7.01 (d, 1H), 7.15 (m, 2H), 7.25 (d, 1H), 7.37 (111, 3H), 7.51 (s, 1H), 7.70 (d, 1H), 7.72 (d , 1H), 7.98 (d, 1H) FAB (M + H): 504, C32H33N50, Preparation Example 49: Synthesis of 3- (naphthalene-1-yl) carbonyl-1H-thalol 49-1) N-methyl -1-Naphthalene hydroxy fatty acid methyl ester 3.44 g (20 millimoles) Benznaphthoic acid is dissolved in 20 ml of dimethylformamide. The paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 154 91506 Economy Department of Central Standards Bureau, Consumer Cooperation, Du printed 436487 V. Description of Invention (155), followed by 4.6 mg &lt; 24 Duramin "0 (:, 2.02 g (20 mmol) triethylamine and 3.24 D (24 milli Ear) HOBT into it. The resulting mixture was stirred at 0¾ for 5 minutes. To the reaction solution was added 1.35 g (20 mol ';) N, 0-dimethylhydroxylamine sulfonium acid, followed by stirring at room temperature for 5 hours. Remove the solvent under reduced haze, and add 100 liters of a saturated solution of potassium carbonate to the residue. The resulting solvent is extracted with ethyl acetate, and the hydrazone layer is sequentially washed with an aqueous solution of acetic acid; the aqueous sodium carbonate solution and water are washed, and anhydrous sulfuric acid Nat;! K without shrinking to obtain 3,04 g (1.50 mil) of the title compound. »H NMR (CDC13) ^ 2.42 (s, 3Η), 3.24 (s, 3H), 7.47 (m, 4H), 7.67 (d, 1H), 7.74 (m5 2H), FAB 216 (M + H) 49 '2) 1- (naphthalene-1-yl) -propan-2 -smell- _ 2.03 g (9.4 mole Ear) Preparation Example 49-1) The compound obtained in Preparation Example 49-1) was dissolved in 20 liters of anhydrous tetrahydrofuran, and 20 liters of a 1N solution of ethylene magnesium bromide-tetrahydrofuran was added at 0TC. The mixture was stirred at room temperature for 30 minutes, and then added. 20 ml of 1N acetic acid was added thereto, and the resulting solution was extracted with 50 ml of ethyl acetate. The organic layer was dehydrated with anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. 1.63 g (9 m ?, 96% yield) of the title compound was obtained. lH NMR (CDC13) d 6.92 (m, 1H), 7.51 (m) 4H), 7.74 (d, 1H), 7.85 (rat 2H), 7.98 (d, 1H), 8.3 l (d, 1H) 49-3 ) 3- (naphthalene-1-yl) carbonyl MH-pyrrole 901 mg (5 mol) Preparation Example 49-2) Compounds and 1.01 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) ) 155 91506 (Please read the precautions on the back before filling out this page) _ Order A7 436487 __B7_ V. Description of the invention (156) (Please read the precautions on the back before filling out this page) gram (5.5 奄 萁 ears) Tosylsulfonylmethyl isocyanide was dissolved in 10 ml of tetrahydrofuran. A solution containing 555 mg (5.5 mmol) of potassium third butoxide in 10 ml of tetraargine was added to the buffer, and the mixture was stirred for 30 minutes. 10 ml of water was added to the reaction solution M to terminate the reaction. . 20 ml of water was added to the residue, and the resulting mixture was extracted with ethyl acetate, washed with an aqueous solution of sodium chloride, and dehydrated with anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was subjected to silica gel column chromatography (eluent: ethyl acetate / hexane = 1/3 * V / V) to obtain 834 mg (4 millitorles, yield 80%) of the title compound. . NMR (CDC13) § 6.57 (s, 1H), 6.66 (s, 1H), 6.79 (s, 1H), 7.36 (m; 3H), 7.48 (d, 1H), 7.77 (d, 1H), 7.82 (d , 1H), 8.04 (d, 1H), 9.91 (s, 1H) Preparation Example 50: 4- (naphthalen-1-yl) carbonyl- 3- [N- (2-methoxyethyl) -N-methyl Synthesis of carbamate] -1H-pyrrole 50-1) 4- (naphthalene-1-yl) -4-oxo-2-butenoic acid 5.88 g (60 mmol) anhydrous maleic acid dissolved in 100 Anhydrous tetrahydrofuran * mixture was cooled to -781C. 4.14 grams (20 millitorr) of 1-bromonaphthalene dissolved in 100 ml of anhydrous tetrahydrofuran printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, and added 13.8 ml of a 1.6N n-butyllithium-hexane solution to -78¾ . This reaction solution was stirred for 5 minutes, and then it was added to a previously prepared anhydrous maleic acid solution using a cannula. The resulting mixture was stirred for 10 minutes, and water was added to M to stop the reaction. Solvent was removed by pressure. Acidification of the residual acetic acid aqueous solution. Extraction with ethyl acetate. The organic layer was washed with K water and an aqueous solution of sodium chloride, dehydrated with anhydrous magnesium sulfate, and condensed under reduced pressure, and subjected to column chromatography (solvent: ethyl acetate / hexane = 2/1 · V / V ) To give 1-35 g (6.0 millimoles; 30% yield) of the title compound. The scale of this paper applies the Chinese national standard (CNS &gt; A4 specification (2! 0 × 297 mm) 156 91506 43 64 8 7 A 7 B7 V. Description of the invention (157) lH NMR (CDC13) (5 6.8l (d, 1H) , 7.52-7.65 (m, 3H), 7.85 (d, 1H), 7.89 (d, 1H), 7.92 (d, 1H), 8.06 (d, 1H), 8.56 (d? 1H) (Please read the Note: Please fill in this page again) 50-2) N- (2-methoxyethyl) -N-methyl- 4- (naphthalene-1-yl) -4 -oxo-2-butenamidine 1.3 g (5.9 millimoles) The compound prepared in Preparation Example 50-1) was dissolved in 10 ml of dimethylformamide *, and then 17 grams (8.9 mill moles) were added at 0¾ (£ 1.2) and 1.2 grams (8.9 MM) 0811 to it. The resulting mixture was stirred for 5 minutes. To the reaction solution was added 530 mg (5.9 mmol) K- (2-methoxyethyl) -N-methylamine and 1.2 ml (8.9 Milli-ear) triethylamine, and then the mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure. An additional 50 ml of water was added to the residue. The resulting solution was extracted with ethyl acetate. The organic layer was washed with aqueous sodium chloride solution. • Anhydrous Dehydration and reduction of magnesium sulfate. Residue was subjected to column chromatography (eluent: ethyl acetate / hexane = 1/1 V / V) to obtain 1.4 g (yield of 4.7 millimoles) of the title compound. LH NMRCCDCb) ^ 3.05 (3, 3H), 3.32 (s, 3H), 3.54 (m, 2H), Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 3.65 (m, 2H), 740-7.58 (111, 4H), 7.71 (t, 1H), 7.89 (m, 2H), 8.03 (d, 1H), 8.54 (d, 1H ) 50-3) 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4- (naphthalen-1-yl) carbonyl-1 Η-larole 1.4 g (4.7 mmol Moore) Preparation Example 50-2) The compound prepared with 1.0 g (5.1 mmol) of p-toluenesulfonic acid methyl isocyanide was dissolved in 20 ml of tetrahydrofuran * plus 790 mg (7.0 mmol) of tert-butoxide Potassium to it • The paper size of the mixture applies the Chinese National Standard (CNS) A4 specification (2H3 X 297 mm) 157 91506 A7 436 at 87 ___B7_ Five 'Invention Note (ica) 1 b 〇 Stir at room temperature for 3 hours. Add 2 Lift the water to the reaction solution to stop the reaction. • Remove the solvent under reduced pressure. Extract the residue with ethyl acetate. • Wash with aqueous sodium hydroxide solution and dehydrate with anhydrous magnesium sulfate. Remove the solvent under reduced pressure and perform column chromatography (eluent). : Acetyl acetate / hexane = 2/3, V / V, 1.2 g (3.6 mol yield) 76%) of the title compound. NMR (CDC13) δ 3.04 (s, 3H), 3.35 (s, 3H), 3.47 (m? 2H), 3.64 (m, 2H), 6.55 (d, 1H), 6.63 (m, 1H), 7.21-7.40 (m, 4H), 7.74 (m, 2H), 8.00 (m, 1H), 11.4 (br, 1H) Example 139: [[(4-cyanobenzyl) -lH-oxazol-5-yl] a The synthesis of phenyl-3- (cha_ 1-yl) carbonyl-1H-pyrrole (139) was carried out in the same manner as in Example 1, but using the compound obtained in Preparation Example 29-5) and the preparation example 49-3) Compound obtained the title compound, yield 35%) 0 NMR (CDC13) § 4.86 (s, 2H), 4.95 (s, 2H), 6.52 (s, 1H), 6.61 (s, 1H), 6.89 (m, 3H) , 7.20 (s, 1H), 7.49 (m, 6H), 7.75 (s, 1H), 7.87 ((1, 1H), 7.95 (d, 1H), 8.11 (d, 1H) FAB: 417 (M + l ) Example 140: Synthesis of l- [l- (4-bromobenzyl) -lH-imidazol-5-yl] methyl-3- (naphthyl-phenyl) carbonyl-lH-Btt (140) is based on Example 1 The same steps, but using the compound prepared in Preparation Example 32-2) and the compound prepared in Preparation Example 49-3) to obtain the title compound "Yield 20% This paper size applies Chinese National Standard (CNS) A4 specification (210X297) 91506 I ---------- (Please read the notes on the back before filling out this page) Order the staff of the Central Standards Bureau of the Ministry of Economic Affairs Printed by the consumer cooperative 15 8 A7 B7 436 ^ ¾7 V. Description of the invention (159) (Please read the notes on the back before filling this page) lH NMR (CDC13) s 4.84 (s, 2H), 4.92 (s, 2H) , 6.54 (s, 1H), 6.67 (s, 1H), 6.78 (d, 2H), 6.93 (s, 1H), 7.22 (s, 1H), 7.38 (d, 2H), 7.50 (m, 3H), 7.58 (4 1H), 7.89 (d, 1H), 7.95 (d, 1H), 8.13 (d, 1H), 8.16 (s, 1H) &quot; FAB: 470 (M + l) Example 141: l- [l -(4-Bromobenzyl) -lH-oxazol-5-yl] methyl 2-methylaminoethyl) methyl] aminomethosyl-4- (ban-1-yl) yl-1H-pyrrole (141) was synthesized in the same manner as in Example 1, but using the compound prepared in Preparation Example 32-2) and the compound prepared in Preparation Example 50-3) to obtain the title compound 'Yield 0 LH NMR (CDC13) s 2.94 ( s, 3H), 3.25 (s, 3H), 3.42 (m, 2H), 3.48 (m, 2H), 4.72 (s, 2H), 4.78 (s, 2H), 6.64 (m, 4H), 7.28-7.48 (χη, 8H), 7.81 (111, 2H), 8.14 (m, 1H) FAB: 585 (M + 1) Printed by the Central Consumers Bureau of Ministry of Economic Affairs, Consumer Cooperatives Preparation Example 51: 1-naphthylglycine Synthesis of Ethyl Acetate 51-1) Ethyl N- (Dibenzylidene) Ethyl Glycine M · J. 0 'Donnell, R.L · Polt, J · Org. Chen · 47, 2663, 1982 Description of the reaction methods • • title compound in 90% yield. JH NMR (CDC13), 5 1.20 (t, 3H), 4.12 (m, 4H) 5 7.10-7 40fm 8H) 7.59 (d, 2H) This paper size is applicable to Chinese National Standard (CNS) A4 ^ grid (210 X 297) (Mm) 159 91506 A7 B7 436487 V. Description of the invention (ieo) 51- 2) Benzene methyl ethyl glycinate ethyl sulfonate hydrazine 1-naphthyl methanoate and the compound prepared in Preparation Example 51-1) According to the procedure described in "Singh et al., Tetrahedron Lett *, 34 (2) 211, 1993, the title compound was obtained in a yield of 48%. ^ NMR (DMSO-d6) '§ 1.78 (s, 3H), 3.65 (q, lH), 3.95-4.15 (m, 2H), 6.33 (s, 1H), 7.58-7.85 (m, 3H), 8.15 ( d, lH), 8.31 (d) lH), 8.38 (d, 2H), 8.42 (d, 2H) Preparation Example 52: 2- [l- (4-Aminobenzylimidazol-5-yl) thioethylamine The synthesis of 52- 1) U-benzyl) -5-hydroxymethyl-1H-oxazole uses dihydroxypropane dimer and 4-chlorobenzylamine sulfonium phosphonium as starting materials, according to JHDener, LH Zhang And H, Rapopor * t, in "1.0" 6 ·

Chen., 1993, 58, 1159 same steps as described * to obtain the title compound in 50% yield! NMR (CDC13 + CD30D) § 4.50 (s, 2H), 5.20 (s, 2H) 5 6.94 (s, lH )) 7.06 ((1,2¾ 7.32 (d, 2H), 7.46 (s, lH) 52-2) 1M4-ammonium benzyl 5, ammonium methyl, 1H-oxazolium sulfonium 3.00 g (13.5 mmol) ) The compound prepared in Preparation Example 52-1) was dissolved in 40 ml of chloroform, and 2.88 liters (40.5 millimoles) of thionyl chloride was added to the solution, and the mixture was stirred at room temperature with 2 hour. The organic solvent was removed under reduced pressure. 3.64 g (13.1 mol, 97% yield) of the title compound was obtained. This compound was used directly in the next reaction without purification. --------------, aT -----: 1 .. &gt; · (Please read the notes on the back before filling out this page) ____ \ Staff of the Central Bureau of Accreditation, Ministry of Economic Affairs The size of the paper printed by the consumer cooperative is applicable to the Chinese National Standard (CNS) A4 specification 210x297 mm 160 9 1506 436 heart 7_37_ V. Description of the invention (iei) 52-3) [1- (4 -Gabenzyl)- 1Η-oxazol-5-yl] acetonitrile (please read the precautions on the back before filling this page) 1.2 g (4.3 mmol) of the compound prepared in Preparation Example 52 = 2) is dissolved in 10 ml of dimethanine * Add 1.3 g (26 mmol) of sodium cyanide to it. The mixture was stirred in a chamber for 6 hours. Add 30 ml of water to it * mixture K extracted with ethyl acetate (20 ml X3) »organic layer K dehydrated with anhydrous sodium sulfate, concentrated • to give 0.96 g of 4.1 millijoules * yield 96%) of the title compound. This compound was used directly in the next reaction without purification. lH NMR (CDC13) d 3.70 (3,2Η), 5.12 (s, 2H), 6.88 (s, 1H), 7.34 (d, 2H), 7.62 (d, 2H), 7.71 (s, 1H) 52-4 ) 2- [1-(4-Anzylbenzyl) -1H-oxazol-5-yl] Thietamide. Printed 150 mg (0.64 mil) production of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 52- 3) The obtained compound was dissolved in a solvent mixture containing 1 ml of pyridine and 0.3 奄 of triethylamine, and then argon telluride was blown into the solution for 30 minutes to saturate the solution. The reaction solution was stirred at room temperature for 12 hours. The solvent was removed under reduced pressure, and 10 ml of water was added to the mixture and the mixture was extracted with 10 ml of ethyl acetate. The organic hydrazone was dehydrated with anhydrous sodium sulfate, concentrated, and then subjected to silica gel column chromatography (eluent: dichloromethane / formaldehyde = 20/1, V / V) * to obtain 110 mg (0.41 mmol). Yield 64% ) The title compound. JH NMR (CDCl3 + CD3OD) § 3.21 (s, 2H), 5.05 (s, 2H), 6.76 (s, lH), 7.24 (d, 2H), 7.61 (d, 2H), 7.67 (s31H) FAB: 266 (M + 1) Preparation Example 53: Benzyloxycarbonyl) Hexapyridyl] methyl_1H_ This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) 91506 16 1 436487, 〇 /. V. Invention Description (162) Synthesis of oxazol-5-yl} thioacetamide 53-1) 4-aminomethyl-1- (benzyloxycarbonyl) hexahydropyridine 22.2 g (0.2 mole) of 4-aminomethyl Hexahydropyridine is dissolved in 25Q ml of toluene. 21.2 g (0.2 mole) of benzaldehyde is added to it. The mixture Μ Dean-stack was refluxed for 3 hours and the water was removed, followed by cooling to 0¾. Slowly add 34.2 g (0.2 mol) of benzyl chloroformate to this while stirring. The mixture was stirred at room temperature for 3 hours, and 220 ml of IN KHS04 aqueous solution was added to it. The mixture was extracted three times with 200 ml of ether, and the aqueous layer was basified with M1N aqueous sodium hydroxide solution. The aqueous solution was saturated with sodium chloride. The aqueous layer was extracted with 100 ml of dichloromethane 3 times. The anhydrous magnesium sulfate was dehydrated and distilled under reduced pressure to obtain 38 g (yield 91% * molecular weight 248) of the title compound. lH NMR (CDCI3) § 1.11 (3,2¾ 1.49 (s, 3H)} 1.70 (d52H), 2.57 (d, 2H), 2_78 (s, 2H), 4'20 (s, 2H). 5.12 (s, 2H), 7.34-7.35 (m, 5H) 53-2) l- [1- (benzyloxycarbonyl) hexahydropyridin-4-yl] methyl-5-hydroxymethyl-2-mercapto-1H-oxazole Printed by the Central Standards Bureau, Ministry of Economic Affairs, Masonry Consumer Cooperatives (#Please read the notes on the back, and then fill out this page) The compound obtained in 24.8 g (0.1 mol) of Preparation Example 53-1 and 6.0 g (0.1 箅Ear) Acetic acid was dissolved in 50 ml of n-butanol, and 12.6 g (0.13 萁 ear) of potassium thiocyanate was added. A solution prepared by dissolving 15.2 grams (0.1 mole) of 1.3-dihydroxyacetone dimer and 10.0 grams (0.17 mole) of acetic acid in 50 ml of n-butyrate. The whole mixture was stirred at room temperature. After 48 hours, the solvent was removed by evaporation under reduced pressure, and the residue was redissolved in 200 ml of ethyl acetate | M 100 ml of water and washed 3 times. Pre-anhydrous magnesium sulfate dehydration &gt; and Maize shrinkage • 27 g (75 m? * Yield 75%) of the title compound were obtained. This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 16 2 9 1506 4 3 64 8.7 A7 _B7____ V. Description of the invention (I63): Η NMR (CDC13) § 1.22 (d, 2H), 2.30 ( s, 1H) 5 2.72 (s, 2H),

3.96 (s, 2H), 4.15 (d, 2H), 4.46 (s, 2H), 5.10 (s, 2H), 6.62 (s, lHX 7.26- 7.3 7 (m, 5H) 53-3) oxycarbonyl group> Hexahydropyridin-4-yl] methyl-5 -hydroxymethyl-1H-imidazole 18.05 g (50 mol) The compound prepared in Preparation Example 53-2) was added to 100 ml of 10% nitric acid and 10 奄A mixture of 1 liter of ethyl acetate was used, and the reaction mixture was cooled with ice water *, followed by stirring at room temperature for 3 hours. The mixture was extracted with 4N aqueous sodium hydroxide solution (extracted twice with 100 ml of ethyl acetate. The extracted organic solution was dehydrated with sulfuric acid and reduced in distillation. • 12.3 g (38 mmol, yield 75%) The title compound., LH NMR (CDC13) § l-16 (d, 2H), 1.56 (d, 2H), 1.98 (s) lH), 2.70 (s32H), 3.88 (d, 2H), 4.18 (s, 2H ), 4.49 (s, lH), 4.56 (s, 3H), 5.10 (s, 2H), 6.82 (s, 1H), 7.27- 7.40 (m, 6H) 53-4) benzyloxycarbonyl) hexahydropyridine- 4 -Methyl] methyl-5-gasmethyl-. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs

(谙 Read the cautions on the back first, then fill in this page. J 1H-oxazolidine 塩 9.9 g (30 mmol) Preparation Example 53-3) Dissolve the compound prepared in 50 liters of atmospheric imitation * in Ot: 7.1 g (60 mol) of sub-ambient was added to it »The reaction solution was stirred for 2 hours * the solvent was evaporated under reduced pressure to obtain 9.9 g (yield 95%, molecular weight 347.5) of the title compound. . This compound was used directly in the next reaction without purification. 53-5) benzyloxycarbonyl) hexahydropyridin-4-yl] methyl-1H-imidazole · This paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) 163 91506 43 ⑽ 7-V. Invention (164) 5-yl) acetonitrile was prepared according to the same procedure as in Preparation Example 52-3) using the compound prepared in Preparation Example 53 to obtain the title compound. Yield 39%. — * Η NMR (CDC13). Δ 1.19 (br, 2H), 1.60 (br, 2H), 1.90 (m5lH), 2.72 (br, 2H), 3.71 (s, 2H), 3.81 (d, 2H)} 4.22 (br, 2H), 5.11 (s, 2H)} 7.03 (s, lH), 7.29-7.36 (m, 5H), 7.51 (s, 1H) 53-6) 2- [l- [l- (benzyloxy Carbonyl) hexahydropyridyl] methyl-oxidazol-5-yl} thioacetamide was prepared in the same manner as in Preparation Example 52-4) using the compound prepared in Preparation Example 53-5) to obtain the title compound f in a yield 74%. * H NMR (CDCl3) § 1.21 (br, 2H), 1.63 (bra2H), L87 (m, lH), 2_71 (br, 2H), 3.31 (s, 2H), 3.84 (42¾ 4.25 (br, 2H), 5.12 (s, 2H), 7.10 (s, lH), 7.33-7.41 (m, 5fi〇, 7.62 (s, lH) FAB: 373 (M + l) (Please read the note on the back before filling in this page) Preparation Example 54: Synthesis of 3-O-3- (naphthalene-1-yl) -2-oxo-propionic acid methyl ester 7.80 g (49.9 mol) 1-Naphthaldehyde and 7.15 g (49.9 moles) of methyl dichloroacetate were dissolved in 100 ml of tert-butanol, and 6.15 g (54.8 moles) of tertiary butoxide were added to the mixture. Stir back at room temperature for 24 hours, then add 50 ¾ liters of water to stop the reaction. Remove the solvent and remove the residue with ethyl acetate. The layer is dehydrated with magnesium acetate and concentrated. N-hexane / ethyl acetate = 90/10, Gan Ba), get 2.5 grams (this paper size applies the Chinese National Standard (CNS) A4 size (210 X 297 mm) 164 91506 printed by the Offshore Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs System 4 3 64 8 7 A7 ___B7 _._ V. Description of the invention (l65) 9.52 奄 Morr 'yield 19%) The title compound: lH NMR (CDCl3) i 3.78 (s, 3H), 6.92 (s, 1H), 7.45-7.73 (m, 4H), 7.95 (ιη, 2Η), 8.12 (d, lH) &quot; Preparation Example 55 : 2 -Phenyl-3 '(N-P-b-yl) -3-Synthesis of 3-oxopropanoic acid methyl_ 55-1) 3- (naphthalene-1- 棊) -3 -oxopropionic acid methyl 10.2 g (59.9 奄 萁 ears) buprofen naphthalene and 4.8 g (60% in phosphorus oil * 120 mmol) NaH2H3 to 100 ml of dimethyl carbonate. • The mixture was refluxed for 24 hours. The solvent was removed under reduced pressure, 100 ml of HCI aqueous solution was added to the residue, and the resulting mixture was extracted with 100 ml of ethyl acetate. Washed with organic water (100 ml X3), K anhydrous magnesium sulfate was dehydrated, and the shrinkage was performed. The residue was subjected to a silica gel column. Chromatography (eluent: n-hexane / ethyl acetate = 9 0/10, V / V) to obtain 10.0 g (43.8 mmol, yield 73%) of the title compound. 'Η NMR (CDC13) d 3.75 (3 , 3H), 4.14 (s, 2H), 7.45-7.68 (m, 3H〇, 7.82-8.08 (m, 3H), 8.77 (d, lH) 5 5-2) 2 -Chloro-3- (Cai-1 -Yl) -3-methyl oxopropionate 4.56 g (20.0 mmol) Preparation Example 55-1), the compound obtained in the solution was dissolved in 50 ml of 1,2-dioxane, at 0 t: Add 2.70 grams (20.0奄 Mol) sulfur brewed into it. The mixture was stirred at room temperature for 3 hours. The solvent was distilled off under reduced pressure to obtain 4.70 g (17.9 mmol, 89% yield) of the title compound. [H NMR (CDCl3) § 3.75 (s, 3H), 5.82 (s, 2H), 7.50-7.72 (m, 3H) 5 7.85-8.15 (111, 3H), 8.65 (d, lH) (Please read first Note on the back, please fill in this again.) The size of the paper used for this edition is in accordance with Chinese National Standard (CNS) A4 (2 丨 0 X 297 mm) 165 9 1506 ^ 36487 V. Description of the invention (166) Example 142: 4-ethoxy Synthesis of carbonyl- 2- (1Η-oxazol-5-ylmethyl) -5 (naphthalene-1-yl) humidazole (142) 142-1) 2-Π1Η-oxazol-5-yl) acetamidin Ethyl] -3- (naphthalene-1-yl) -3-oxopropanoate The compound prepared in 293 mg (0.997 mol) of Preparation Example 5 2), 162 mg &lt; 0.996 millirr ) 4-oxazolium acetate acetic acid, 135 mmol (0.999 mmol) OBT and 191 mg (0.906 mmol) EDC to 10 ml of dimethylformamide * and then slowly add 202 mg (1.99 luxury) ) Triethylamine to it, while searching. The mixture was reacted at room temperature for 5 hours, and the solvent was removed therefrom under reduced pressure. Ethyl acetate was added to the residue by adding 30, followed by washing with a saturated sodium hydrogen sulfate solution and water. The organic layer was dehydrated with anhydrous magnesium sulfate, concentrated, and subjected to silica gel column chromatography (lysate: dichloromethane / formaldehyde = 95/5, V / V). 200 mg (0.547 mol, yield 55) %) The title compound. ! H KMR (CDCl3) δ 0.92 (t, 3H), 3.70 (Sj2H), 3.98-4.15 (m, 2H), 6.20 (d, lH), 6.92 (s, lH), 7.55 (m, 4H) , 7.65 (s, lH), 7.89 (d, lH), 8.06 (d, lH), 8.12 (br, lH), 8.2I (d, lH), 8.45 (&U; UH) Staff of the Central Accreditation Bureau, Ministry of Economic Affairs Printed by the Consumer Cooperative (please read the precautions on the back before filling out this purchase) 142-2) 4-ethoxycarbonyl-2_ (1H-imidazol-5-ylmethyl) -5- (naphthalene-butyl), etc. 100 g (0.27 mmol) of the compound prepared in Example 142-1) was dissolved in 5 ml of THF and refluxed for 6 hours. The solvent was removed by distillation under reduced pressure, and the residue was subjected to silica gel column chromatography (eluent: dichloromethane / methanol = 95/5 · V / V) * to obtain 40 mg (0.12 mmol, yield 44%) of the title compound. . This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X297 mm) 166 9 1506 436487 V. Description of the invention (1 6 7). Ή NMR (CDC13) S 〇-98 (t, 3H), 4.13 (q, 2H), 4.27 (s; 2H), 6.92 (s, 1H), 7.45- 7.58 (m, 4H), 7.65-7.75 (m72H), 7.89 (d, lH), 7.97 (d, lH) FAB: 348 ( M + l) Example 143: Synthesis of 2- (lH-oxazol-5-ylmethyl) -4- (morpholin-4-ylcarbonyl-5- (naphthalene-1-yl) azole (143) 31 mg (0.09 mmol) of the compound prepared in Example 142-2) was dissolved in a solvent mixture of tetrahydrofuran / methanol / water (0.6 ml / 0.3 ml / ml), and 6 mg (0.13 mmol) of beaver hydroxide was added. To it. The reaction solution was stirred at room temperature for 3 hours, and the solvent was removed at reduced pressure. The residual M.1N aqueous solution was adjusted to pH 6 and then extracted with ethyl acetate. Organic calendar κ anhydrous sodium sulfate dehydration, the concentrate is dissolved in 1 liter of dimethylformamide * at 01 plus 18 mg (0,13 mmoles) &gt; Η0ΒΤ and 26 mg (0.13 mmoles) EDC to Wherein, the mixture was stirred for 10 minutes. 9 microliters (0.09 mol) of morpholine and 18 microliters (0'13 millinemol) of triethylamine were added thereto, and the stick mixture was stirred at room temperature for 2 hours. The reaction solution was treated in the same manner as in Example 142-1) to obtain 14 mg (.04 mmol, 45% yield) of the title compound * H NMR (CDCI3) S 2.97 (br, 2H), 3.24 (br , 2H), 3.43 (br, 2H), 3.57 (br, 2H), 4.27 (s, 2H), 6.95 (s, 1H), 7.52-7.67 (111, 6¾ 7.81-7.95 (m, 3H) FAB; 389 (M + 1) Example 144: Synthesis of 4-ethoxycarbonyl-2- (1fluoren-oxazol-5-ylmethyl) -5- (case-1byl) pyrazole (1M) 105 mg (0.287 mmol) Ear) The compound prepared in Example 142-1) and the paper standard SI traceability standard (CNS &gt; A4 size (2IGX297 mm) 1 6 7 9 1 5 06 ----------- (Please read the note on the back before filling in this page)

I Order Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 4 3 6 4 8 7 A7 B7 V. Description of the Invention (168) (Please read the notes on the back before filling out this page} 116 mg (0.287 奄 萁 ear) Rosen Lawesson's Reagent was dissolved in 10 ml of tetrahydrofuran, and the mixture was refluxed for 6 hours. The solvent was reduced by removing the residue. • 10 ml of a saturated solution of sodium hydrogen carbonate was added as a residue. The resulting mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. , Concentrated, and subjected to silica gel column chromatography (eluent: methane / methanol = 95/5, V / V) to obtain 26 g (0.075 mmol, yield 26¾) of the compound of Example 142-2) and 24 mg (0.066 奄 萁, 23% yield) of the title compound. ! H NMR (CDC13) § 0.63 (ΐ, 3Η), 3.92 (q? 2H), 4.42 (sf2H), 6.97 (s51H), 7.405- 7.75 (m, 6H), 7.85-7.95 (m, 2H) FAB: 364 (M + l) Example 145: 2- [l- (4-Benzyl) -lH-imidazol-5-ylmethyl] -4-methoxycarbonyl-5- (naphthalene-1-ylazole Synthesis of (145) 130 mg (0.49 mmol) of the compound prepared in Preparation 52-4) and 129 mg (0.49 mmol) of the compound prepared in Preparation 54) were dissolved in 5 ml of acetic acid, and the mixture Reflux for 5 hours. The residue was removed by distillation under reduced pressure and subjected to silica gel column chromatography (eluent: dichloromethane / formaldehyde = 40/1, V / V). 45 grams were printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. (0.095 mol, yield 19%) Ke title compound. 'Η NMR (CDC13) s 3.50 (5,3 ^ / 4.26 (3,2 ^, 5.11 (s, 2H), 6.92 (d, 2H)) 7.07 (s, 1H), 7.21-7.43 (m, 7H) , 7.53 (^ 1¾ 7.83 (m, 2H) FAB: 474 (M + l) Example 146: 2- [l- (4-Gabenzyl) -lK-imidazol-5-ylmethyl] -4- (? Synthesis of Phenolin-4-yl) carbonyl-5- (naphthalene-buthyl) ¾azole (146) The paper size applies to the Chinese national standard (CNS M4 specification (2) 0X29? Mm) 168 91506 Printed by the Industrial and Commercial Cooperatives 436 ^ 87 a? B7__ 5. Description of the Invention (f69) Follow the same procedure as in Example 143, using the compound prepared in Example 145 · Obtained title compound * Yield 23%. 'H NMR (CDC13) § 2.63 (br, 2H), 3.02 (brs2H), 3.24 (br, 2H), 3.42 (br, 2H), 4.26 (s, 2H), 5.21 (s, 2H), 7.02 (m, 2H), 7.18 ( s, lH)} 7.31 (ιη, 2Η); 7.43-7.60 (m, 5H), 7.78-7.96 (m, 3H) FAB: 529 (M + l) Example 147: 2- [l- (4-chlorobenzyl) (Yl) -lH-oxazol-5-ylmethyl] -4- [N- (2-methoxy) 2-yl-K-methylaminomethylmethyl] -5- (naphthalene-1-ylazole (147 ) The synthesis was carried out in the same manner as in Example 143 using the compound prepared in Example 145, but KN- (2-methoxyethyl) methylamine was used instead of morpholine 'to obtain the title compound * yield 41%. LH NMR (CDC13) Θ 2.68 (br, 3H), 2.89-3.39 (1 ^ 711), 4_22 (s, 2H), 5.17 (s, 2H), 7.01 (m, 2H), 7.15 (s, lH), 7.33 (m, 2H), 7.40-7.6 l (m, 5H), 7.71-7.82 (m, 3H) FAB: 531 (M + l) Example 148: 2- [l- (4-chlorobenzyl) -lH- Synthesis of oxazol-5-ylmethyl] -5-methoxycarbonyl-4- (naphthalene-1-yl) triazole (148) (250 mg (0.95 mmol) in Preparation Example 52-4) Compound and 2 49 mg (0.95 pinch ears) of the compound prepared in Preparation Example 55-2) were dropped in 10 ml of acetic acid * mixture refluxed for 24 hours. The solvent should be removed during the steaming process and the residue was subjected to silica gel column chromatography ( Chlorolysate: Dimethane / formase = 40/1 * V / V) (谙 Please read the precautions on the back before filling this page) Order

Mi This paper is in accordance with Chinese National Standards (CNS &gt; A4 size (210X 297 mm) 169 9 1506 A7 B7 430487 V. Description of the invention 70) and 180 mg (0.38 millimolar • yield 40¾) of the title compound is obtained. lH NMRCCDCh) ^ 3.53 (s, 3H), 4.22 (s, 2H), 5.12〇, 2H), 6.91 (m, 2H), 7.11 (s, 1H), 7.21-7.54 (m, 7H), 7.83 (m , 3H) FAB: 474 (M + l) Example 149: 2- [l- (4-Anzylbenzyl) -1H-oxazol-5-ylmethyl] -5- (morpholin-4-yl) carbonyl -The synthesis of 4- (naphthalene-b'yl ') azole (149) was carried out in the same manner as in Example 143 using the compound prepared in Example 148 to obtain the title compound in a yield of 39%. lK NMR (CDC13) &lt; 5 2.38 (br72H), 2.82 (br, 2H), 3.21 (br, 2H), 3.42 (br, 2H), 4.27 (s, 2H), 5.21 (s, 2H), 6.98 ( m} 2H), 7.25 (m, 3H), 7.50-7.61 (m, 5H), 7.89-7.99 (ra, 3H) FAB: 529 (M + 1) Example 150: -Benzyloxycarbonyl) hexahydropyridine-4 -Methyl] -1H-imidazol-5-ylmethyl) -5 -methoxycarbonyl-4- (naphthalen-1-yl) tazole (150) Synthesis 124 mg (0.33 mil) Preparation Example 53 -6) and 87 mg (0.33 mil) of the compound prepared in Preparation Example 55-2) were dissolved in 10 ml of ethanol, and the mixture was refluxed for 20 hours. The solvent was removed under reduced haze, and the residue was subjected to silica gel column chromatography (solvent: dichloromethane / methanol = 95/5, V / V) to obtain 95 mg (0.16 mil, yield 48%) of the title compound. . (Please read the note $ on the back before filling this page) Ordering Economy I Deng Central Standards Bureau Shellfish Consumer Cooperative Co., Ltd. This paper is printed in accordance with Chinese National Standard (CNS) A4 (2 i 0 X 297 mm) 170 91506 43 6487 V. Description of the invention 丨 7 1) 'H NMR (CDC13) s U0 (br, 2H), 1.53 (br, 3H), 2.50 (br, 2H), 3.62 (s, 3H), 3.81 (d, 2H ), 4.19 (br, 2H), 4.41 (5,2¾ 5.I4 (d, 2H); 7.16 (s, 1H) 5 7.27-7.61 (ιη, 10H), 7.78 (s, lH), 7.91 (d, lH), 7.96 (d, lH) FAB: 595 (M + l) Example 151: 2- {l- [l- (benzyloxycarbonyl) hexahydroradicalmethyl] -1H_imidazol-5-ylmethyl Methoxy) ethylformamidinemethylammonyl] -4- (naphthalene-1-yl) · "azole (151) was synthesized in the same manner as in Example 143, using the compound prepared in Example 150 'but MN- (2 -Methoxyethyl) methylamine instead of morpholine to give the title compound '36% yield. lH NMR (CDC13) d 2.68 (br, 3H), 2.89-3.39 (m57H), 4.22 (s, 2H), 5.17 (s, 2H), 7.01 (m, 2H), 7.15 (s, lH), 7.33 ( m, 2H), 7.40-7.61 (ιη, 5Η), 7.71-7.82 (m, 3H) FAB: 638 (M + l) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling in (This page) Preparation Example 56: Synthesis of 4- (5-chloromethyl-1H-imidazol-1-ylmethyl) _hexaoxo-ntt salyl-1-carboxylic acid benzyl ester 56-1) 4-aminomethyl- 22.2 g (0.2 mole) of 4-aminomethyl-hexahydropyridine benzyl hexahydropyridine-1-carboxylate was dissolved in 250 ml of toluene, and 21.2 g (0.2 mil) of benzaldehyde was added thereto. The mixture K Dean-stack was refluxed for 3 hours, then cooled to 0 scoop, and 34.2 g (0.2 mole) of benzyl chloroformate was added thereto while stirring. The mixture is stirred at room temperature. 3 The paper size is applicable to China National Standard (CNS) A4 size (2i × 297mm) 171 91506 d36487 _ ^ __ 5. Description of the invention (172) hours, add 220ml of IN potassium hydrogen sulfate Aqueous solution into it. The mixture was extracted three times with 200 ml of diethyl ether. K sodium hydroxide dissociated the aqueous layer. Water-soluble: Saturated with sodium hydroxide and extracted 3 times with 100 ml of dichloromethane. # 机 溶液 Anhydrous magnesium tellurate was dehydrated, and radium was distilled under reduced pressure to obtain 38 g (yield 91% * molecular weight 248) of the title compound. NMR (CDCb) θ l_ll (s, 2H), L49 (s, 3H), l'70 (d, 2H), 2.57 (d, 2H), 2.78 (s' 2H), 4.20 (s, 2H), 3 · 12〇, 2Η), 7.34-7: 35 (m, 5H) FAB (M + H): 249 56-2) 4- (5-hydroxymethyl-2- 铕 -1H-oxazole-1- Methyl) _Hexahydropyridine-Benzyl Carboxylate Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Preparation Example of 24 · δg (0.1 Molar) 56-1) and the compound prepared in 6.0 g (0.1 moles) of 2 acid were dissolved in 50 ml of n-butanol, and 12.6 g (0.13 moles) of potassium thorate, 15.2 g ( 0.1 mol &gt; a solution prepared by dissolving 1,3-dihydroxypropane dimer and 10.0 g (0.17 mol) of acetic acid in 50 ml of n-butanol, and the whole mixture was stirred at room temperature for 48 hours Remove the solvent by distillation under reduced pressure. Add 200 ml of ethyl acetate to the mill and wash 3 times with Mioo ml of water. The organic layer M is dried over anhydrous magnesium acetate, and the solvent is removed by distillation under reduced pressure. * 27 g (75 millirales, yield 75% * molecular weight 361) title compound.! H NMR (CDC13) § 1.22 (d, 2H), 1.57 (d, 2H), 2.30 (s, lH), 2.72 (s, 2H), 3,96 (s, 2H), 4.15 (d, 2 H), 4.46 (s, 2H), 5.10 (s, 2H), 6.62 (s, lH), 7.26-7.37 (m, 5H) FAB (M + H): 362 This paper standard applies to Chinese National Standard (CNS) Λ4 specification (210X297 male sauce) 172 9 1506 436 ^ 87 V. Description of the invention (A7 B7 17 Printed by the Consumer Cooperatives of the Central Standards Bureau, Ministry of Economic Affairs, 56-3) 4- (5-hydroxymethyl-1H-oxazole-1 -Methyl) -Liuqilafan_1_Benzyl gallate 18.05 g (50 mol) The compound prepared in Preparation Example 56-2) was added to 100 liters of 10% nitric acid and 10 liters of acetic acid The entire mixture of ethyl acetate was immersed in ice water for 5 minutes, and then searched at room temperature for 3 hours. The mixture was desulfurized with 4N sodium hydroxide aqueous solution, and then extracted twice with K ml of ethyl acetate. The extracted solution, magnesium sulfate, was dehydrated, and the house was reduced to hunger to obtain 12.3 g (38 millimoles, yield 75% molecular 霣 329 ) Title Λ compound. lH NMR (CDC13) ^ 1.16 (d, 2H), 1.56 (d, 2H), 1.98 (s, lH), 2.70 (5,2Η), 3,88 (d, 2H), 4.18 (s, 2H), 4.49 (s, lH), 4.56 (^ 3¾ 5.10 (s, 2H), 6.82 (s, lH), 7.27-7.40 Cm, 5H) FAB (M + H): 330 56-4) 4- (5-gas Methyl-1H-imidazol-1-ylmethyl) -hexahydropyridine-benzoic acid benzyl ester 9.9 g (30 mol) Preparation compound 53-3) was dissolved in 50 ml of atmospheric imitation, listening Ot: Add 7.1 grams (60 milliliters) of thionyl chloride to it. The mixture was stirred for 2 hours * the solvent was distilled off under reduced pressure, and the residual osmic acid was removed in vacuo to obtain 9.9 g (yield 95%, molecular weight 347.5) of osmic acid of the standard compound. lH NMR (CDC13) d 1.12 (d, 2H), 1.53 (d, 2H), 2.65 (s, 2H), 3.82 (d, 2H), 4.22 (s, 2H), 4.42 (s, lH), 4.49 ( s, 3H), 5.12 (3,2¾ 6.60 (SilH)) 7.30-7.4 FAB (M + H): 349 H Straight Example 5 7:]-(4 -Benzyl benzyl) -5-methylmethyl-〇-担 _Danling but today 厶 this paper size applies Chinese National Standard (CNS) A4 specification (210X29? Mm) 173 91506 --------- 7 ^ 嚷-. .... {Please first (Read the note $ on the back and fill out this page), 1

1T 436487 V. Description of the invention A7 B7 17 to 57-1) 1-(4-chlorobenzyl) -5-hydroxymethyl-1H-oxazolyl JMDener, Zhang, H-iiapoport, J, Org, The procedure described in Chem 1993, 53, 1159, using dihydroxyacetone dimer and 4-chlorobenzylamine osmium phosphonium as starting materials | The title compound was obtained in 50% yield NMR (CDCl3 + CD3OD) 5 4.46 (s, 2H)? 5.26 (s, 2H), 7.0〇 (Sj1H) 3 7.07 (d, 2H), 7.50 (d, 2H), 7.65 (s31H) (谙 Please read the precautions on the back before filling this page) Department of Economics k Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 57- 2) 1- (4-Anzylbenzyl) ~ 5-chloromethyl-1H-oxazosacronic acid conversion according to Preparation Example 56-4) · But Preparation Example 57 is used -1) The obtained compound was used as a starting material to obtain the title compound in a yield of 96%. This compound was used without further purification in the next reaction. Preparation Example 58: Synthesis of 4- [N- (2-methoxyethyl) -N-methyl] aminomethane- 3- (naphthalene-1-ylazole 58-1) N-third butyl- H '-(naphthalene-: 1-ylmethylene) -hydrazine 5.0 g (32 millitorles) 1-naphthaldehyde and 3.99 g (32 millitorles) of tert-butylhydrazine hydrazone dissolved in 100 ml of methanol, The mixture was then reacted with 1 ml of acetic acid at room temperature for 24 hours. After removing the solvent under reduced pressure, add 20 ml of ethyl acetate to the residue. The mixture was washed with a saturated solution of sodium bicarbonate. The separated organic layer was further dehydrated with anhydrous magnesium sulfate, and distilled under reduced pressure to remove the solvent, to obtain 6.3 (28 millitorr, yield 86%) of the title compound. ΜΜ Zhang scale is applicable to Chinese National Standard (CNS) Λ4 specification (210X297 mm) 174 9 1506 436487 A7 __B7 V. Description of the invention (175) lH NMR (CDC13) 5 1.7〇 (s, 9H), 7.23 (s, lH ), 7.32 (m, lH), 7.42 (m, 2H), 7.80 (d, lH), 7.90 (d, 2H), 8.60 (d, lH), 9.91 (s, lH), 12.1 (br, lH) FAB (M + H): 227 58-2) 1- (Third-butyl) -3- (N-butyl) -lH-pyrazole-4-carboxylic acid acetamidine 6.3 (28 mmol) The compound prepared in Example 58-1) was dissolved in a solvent mixture of 2.44 (30.8 mmol) ethyl propionate in 27 ml of acetic acid and 32 ml of acetonitrile. The entire mixture was reacted in air for 3 days. The solvent was removed, and the residue was subjected to silica gel column decantation (brown solution: ethyl acetate / n-hexane = 9/1, v / v) to obtain 6.76 g (21 mmol, yield 75%) of the title compound Ο lR NMR (CDC13) δ 0.80 (t, 3H), 1.65 (s, 9H), 3.98 (q, 2H), 7.38 (m, 2H), 7.48 (m, lH), 7.55 (m, lH), 7.74 (m , LH), 7,85 (m, 2H), 8.21 (s, 1H), 11.31 (br, lH) FAB (M + H): 323 58-3) 3- (naphthalene-1-yl) _1 {1 The compound prepared in Preparation Example 58-2) of 3.65 g (11 * 3 millitorles) of pyrazole carboxylic acid was dissolved in 50 ml of formic acid, and the resulting solution was boiled under reflux for 2 hours. Demonize steam and remove the solvent, add acetic acid to it. The mixture was washed with a saturated aqueous solution of sodium carbonate and dehydrated with anhydrous telluric acid. The solvent was removed under reduced haze, and the residue was subjected to silica gel column chromatography (eluent: ethyl acetate / n-hexane = 6/4, v / v) to obtain 1.1 g (4.1 millitorr, yield 37¾) of the title compound. (See J. Hetero Chem., 31, 1447, 1994). f Paper scale suitable wealth Guan Jialin (CNS) A view (2 丨 Gx297) Chu 175 -----------. (Please read the notes on the back before filling this page) Printed by the Consumer Cooperative of the Bureau of Standards 9 1506 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 436487 B7 V. Description of the invention (176) * H NMR (CDC13) § 0.80 (t, 3H), 3.98 (q, 2H), 7.35 -7.60 (m, 5H), 7.90 (m, 2H), 7.94 (s, lH) — FAB (M + H): 267 53-4) 3- (naphthalene-1-yl) _1H -pyrazole acid 1 1 g (4.1 mmol) of the compound prepared in Preparation Examples 5.8-3) and 2-1 g (12.4 mmol) of potassium hydroxide were dissolved in 50 ml of methanol / water (1: 1 '). 1 ^ solvent mixture. The mixture was reacted under reflux for 12 hours. The solvent was distilled off under reduced pressure. The residue was washed with 1 H aqueous acetic acid solution, extracted with 50 ml of ethyl acetate, and dehydrated by anhydrous magnesium sulfate. The solvent gave 910 g (3.8 moles * yield 92 «) of the title compound. LH NMR (CD30D + CDC13) d 7.30 (111,311), 7.56 (d, lH), 7.80-7.95 (m, 3H), 8.07 (s, lH) FAB (M + H): 239 58-5) 4- [N- (2-methoxyethyl) -N-methyl] aminomethylnaphthalene-1-yl 238 mg (1 mmol) of the compound prepared in Preparation Example 5 8-4) was dissolved in 10 ml of dimethylformamide, and then 230 mg (1.2 mmol) of EDC was added. 101 g ( 1 millimolar) triethylamine and 162 g (1.2 millimolar) ΗOBT (buhydroxybenzotriazole). The resulting mixture was stirred at 0¾ for 5 minutes. To the reaction solution, add 124 g (1 michel-methoxyethyl) -N-limb (please read the precautions on the back before filling in this page)

Each paper size applies the Chinese national standard (CNS M4 specification (210X297 mm) 176 91506 Printed by the Central Government Bureau of the Ministry of Economic Affairs, Printed by Shellfish Consumer Cooperatives 4 3 6487 V. Description of the invention Π7?) 塩 酸 塩 | connect to room temperature 攒Mix for 5 hours. The solvent was removed under reduced pressure, and 10 ml of a saturated aqueous solution of potassium carbonate was added to the residue. The resulting mixture was extracted with 20 ml of ethyl acetate, washed with 10 ml of M: IN aqueous solution of acetic acid, washed with saturated sodium sulfate and washed with water, and dehydrated with anhydrous sodium sulfate, and condensed to obtain 247 grams of the title compound (0.8 Ears • Yield 80S;). JH NMR (CDC13) ^ 2.40 (s, 2H), 2.81Cs, 1H), 2.84 (3, ^), 2.96 (5,1¾ 3.02 (s, 4H), 3.15 (s, 1.5H), 3.34 (s, 1.5H) f 7.24-7.52 (111,4¾ 7.59 (s, lH), 7.77 (m, 2H), 7.93 (d, lH) FAB (M + H): 310 Preparation Example 59: 4- (? -Yl) carboxyl-3- (naphthalene-1-yl) -lH-pyrazole Synthesis 238¾ g (1 mol) of the compound prepared in Preparation Example 58-4) was dissolved in 10 ml of dimethylformamidine Amine, followed by 230 mg (1.2 mmol) of EDC. And 162 μg (1_2 mmol) of OBTT into it. The resulting mixture was at 0T; stirred for 5 minutes. To the entire mixture was added 87 μg (1 mmol). ) Morpholine * Then the mixture was stirred at room temperature for 5 hours. The solvent was removed by scraping, and 10 liters of a saturated aqueous solution of potassium carbonate was added to the residue. Then, the saturated sodium sulfate was dissolved and washed with water. The anhydrous sodium sulfate was dehydrated and concentrated to obtain 240 mg of the title compound (0.8 millijoules, yield 80S;). I 装 装-丨 (Please read the back first (Notes for filling in this page)

-I-丁 _ This paper size is in accordance with Chinese National Standard (CNS) A4 specification ⑺0 &gt; &lt; 297 mm) 177 9 1506 Δ36487 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (178)! H NMR ( CDC13) δ 2.5 (br, 2H) 7 2.95 (br, 2H), 3.15 (br, 2H), 3.40 (br, 2H), 7.50 (m, 4H), 7.95 (m, 4H), 9.73 (br , lH) FAB (M + H): 308 Example 152: Benzyloxycarbonyl-hexahydropyridylmethyl) 1H-imidazol-5-ylmethyl] -4- [H- (2-methoxyethylmethyl) ] Synthesis of carbamoyl-3 -_ (naphthalene-1-yl) -1Η-pyrazole (152) 616 g (2.0 mol) Preparation Example 56_4) The compound prepared in 10 ml of dimethylformam Amine in Ot: Add 264 mg (6.6 mmol) of sodium carbonate (60¾) to it • Stir the entire mixture for 5 minutes. 765 mg (2.2 mils) of the compound prepared in Preparation Example 58-5) was added to the mixture ', and the resulting mixture was stirred at room temperature for 5 hours. The solvent was removed by skimming, and 10 liters of water was added to the residue. The resulting mixture was taken twice with 20 ml of ethyl acetate, 'dehydrated from anhydrous magnesium sulfate, concentrated * and then subjected to silica gel column chromatography (brown solution: dichloromethane / methanol = v / v)' to obtain the title compound (Yield 75¾) 〇'H NMR (CDC13) $ 1.1 (m, 2H), 1.37 (br, 1H), 1.50 (br, 2H), 2.35 (br, 1H) 5 2.55 (br, 2H), 2.71 (br, lH), 2.90-3.2 l (m, 7H), 3.35 (br, lH), 3.90 (br, 2H), 3.98 (d, lH), 4.50 (d, lH), 5.02 (s, 2H ), 5.10 (s, 2H), 7.21-7.40 (m, 6H), 7.41-7.60 (111,4¾ 7.70 (s.lH), 7.80 (s, lH), 7,95 (m, 2H), 8.13 ( d, lH) FAB (M + H): 621 (Please read the note on the back of the page before filling in this page) This paper size is applicable to the Chinese National Standard (CNS) A4 Sigma (210X297 public expense) 178 91506 436487 A7 B7 _ 5 Description of the invention (l79) Actual 钶 153: -Methoxycarbonylhexahydropyridin-4-ylmethyl) -1Η-眯 (谙 Please read the precautions on the back before filling this page] azole-5-ylmethyl] Synthesis of -4- [N- (2-methoxyethyl) methyl] aminomethane- 3- (naphthalene-phenyl) -1Η-pyrazole (153) 153-1) Hexahydropyridine-4- Methyl) -1′-oxazol-5-ylmethyl] -4- [N- (2-methoxyethyl) -N-methyl] aminomethyl- 3- (naphthalene-1-yl) -1H-pyridine 227 mg (0.36 mmol) The compound obtained in Example 15.2 was dissolved in methanol 2 hours. After the reaction was completed, the mixture was passed through 漶 and the solvent was removed. The filtrate was subjected to silica gel column chromatography (eluent: ammonia / methanol = 15/85, v / v) to obtain 128 g (0.26 mmol, yield 74 ») of the gadolinium compound. ! H NMR (CDC13) § 1.08 (s, 2H), 1.53 (m, 4H), 2.33 (s, 2H), 2.64 (br, 4H), 3.20 (m, 6H), 3.31 (s, 1H), 3.75 (d, 2H), 4.13 (m, 2H), 5, 10 (s, 2H), 6.71 (s, lH), 7.11 (s, lH), 7.30 (m, 9H), 7.74 (d, lH), 7.81 (d, lH), 7.90 (SjlH), 8.06 (d, lH) FAB (M + H): 486 Central Bureau of Standards, Ministry of Economic Affairs, Shellfish Consumption Cooperation, Du printed 153-2) 1- [1- (1- Methoxycarbonylhexahydropyridin-4-ylmethyl) -1H-oxazol-5-ylmethyl] -4- [H- (2-methoxyethyl) -fluorenyl-methyl] aminomethylfluorenyl- 3- (Naphthalene-pyl) -1Η-pyrazole 30 mg (62 micromolar) Example 153-1) The compound prepared in Example 153-1) was dissolved in 2 ml of digas methane, and 5.4 mg (6.9 micromolar) of a M syringe. &gt; Methyl chloroformate was added thereto, and the mixture was stirred for 2 hours. Removal of the solvent 'residue was reduced. The paper size applies the Chinese National Standard (CNS) Α4 size (210x297 mm) 1 7 9 9 1 5 06 Central Standard of the Ministry of Economic Affairs Printed by the Bureau ’s Consumer Cooperatives “A” B7 V. Description of the invention (189 silica gel column chromatography (solvent solution: dichloromethane / formaldehyde = 80/20, v / v), 27.8 g (5.3 micromoles * yield 85¾) ! H NMRCCDCb) δ lU (br, 2H), 1.33 (br, lH), 1.53 (br, 2H), 2.39 (s, 2H), 2.70 (br, 4H), 2.90-3,20 (br , 6H), 3.32 (s, lH), 3.62 (s, 3H), 3.78 (d, 2H), 4.16 (m, 2H), 5.16 (s, 2H), 6.74 (s, 1H), 7.10 (s, lH), 7.21-7.50 (m, 14H), 7.76 (d, lH), 7.84 (d, lH), 7.9i (s, lH), 8.07 (d, lH) FAB (M + H): 545 Example 154 : Bu [1- (4-bromobenzyl) -lH-imidazol-5-ylmethyl] -4- [H- (2-methoxyethyl) -N-methyl] aminomethyl-3- (Naphthalene-1-yl) -1 基 · pyrazole (1 5 4) was synthesized in the same manner as in Example 152, except that the compound obtained in Preparation Example 3 2-2) and the preparation example 58-5) were used. Compound • The title compound was obtained in a yield of 81X. ! H NMR (CDC13) $ 2.41 (s, 2H), 2.82 (s, lH), 2.85 (s, lH), 2.98 (s, 1H), 3.04 (s, 4H), 3.17 (s, 1.5H), 3.36 (s, 1.5H), 5.11 (s, 2H), 5.21 (s, 2H), 6.95 (d, 2H), 7.25 (d, 2H), 7.35-7.60 (ra, 5H), 7.64 (s, lH ), 7.72 (s, lH), 7.81 (ra, 2H), 8.11 (d, lH) FAB (M + H): 558 Example 155: Bu [1- (4-Azylbenzyl) -lH-imidazole-5 -Ylmethyl] -4- [N- (2-methoxyethyl) -N-methyl] aminomethylamido-3- (naphthalene-1-yl) -1Η-pyrazole (1 5 5) The synthesis follows the same steps as in Example 152, but uses the preparation made in Preparation Example 57-2) (谙 Please read the precautions on the back before filling this page) This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 180 91506 436487 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. V. Description of the invention (181) Compounds and compounds prepared in Example 58-5). The title compound was obtained with a yield of 81¾. lH NMR (CDC13) δ 2.41 (s, 2H), 2.82 (s, 1H), 2.85 (s, 1H), 2.98 (s, lH), 3.04 (s, 4H) t 3.17 (s, 1.5H), 3.36 (s51.5H)? 5.20 (ss2H), 5.25 (s, 2H), 6.97 (d, 2H), 7.26 (d, 2H), 7.35-7.46 (m, 5H), 7.47 (s, lH), 7.58 ( s, lH), 7.88 (m, 2H), 8.11 (d, lH) · FAB (M + H): 514 Examples of cyanobenzyloxazolylmethyl bu 4- [N- (2-methoxyethyl) The synthesis of -N-.methyl] aminomethylamino- (Ce-I-yl) -1H-ribazole (1 5 6) was carried out according to the same procedure as in Example 152, but using Preparation Example 29 · 5) Compound and Preparation Example 58-5 &gt; The compound 'obtained barrel title compound' yield 81¾. ! H NMR (CDC13) 8 2.41 (s, 2H), 2.82 (stlH), 2.85 (3,1 ^, 2.98 (s51H) 7 3.04 (s, 4H), 3.17 (s, 1-5H), 3.36 (s , 1.5H), 5.20 (s, 2H), 5.31 (s, 2H), 6.99 (d, 2H), 7.26 (d, 2H), 7.35-7.46 (m, 5H), 7.48 (s, lH), 7.57 (s, lH), 7.89 (m, 2H); 8.12 (d, lH) FAB (M + H): 505 Example 157: 1- [1-methyl-1H-imidazol-5-ylmethyl] -4 The synthesis of-[N- (2-methoxyethyl) -H-methyl] aminomethane- 3- (naphthalene-1-yl) -1Η-pyrazole (157) was carried out in the same manner as in Example 152, but Use 1-Methyl-5-Aminomethyl-1H- I -------- 7 ^ Attack-(Read the precautions on the back before filling this page)

I The paper size of the edition is applicable to the Chinese national standard (CNS &gt; A4 Zhuge (2 丨 0 X 297 mm) 181 91506 436487 A7 B7 Printed by the shellfish consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs塩 Acid acid and the compound prepared in Example 58-5) * The title compound was obtained with a yield of 81¾. LH NMR (CDC13) $ 2.42 (br, 2H), 2.71 (br, lH), 3.10 (br, 5H) , 3.30 (br, lH), 3.50 (s, 3H), 5.17 (s, 2H), 6.69 (s, 1H), 7.09 (s, lH), 7.41 (m, 9H), 7.74 (d, lH), 7.83 (d, lH), 7.89 (s, 1H), 8.05 (d, lH) FAB (M + H): 404 Example 158: 1- [1- (1-benzyloxycarbonyl) -hexamidinepyridine-4- Synthesis of propylmethyl) -lH-oxazol-5-ylmethyl] -4- (morpholin-4-yl) carbonyl-3- (Cai-1-yl> -1H-pyrazole (158) (2.0¾ mole) The compound obtained in Preparation Example 59 was dissolved in 10 ml of dimethylformamide, and 264 g (6.6 mole) of sodium hydride was added to the mixture. The whole mixture was stirred for 5 minutes. 765 mg (2.2 Shemol) of the compound prepared in Preparation Example 56-4) was added to the mixture, and then stirred at room temperature for 5 hours. The solvent was removed by distillation under reduced pressure, and water was added to the residue to obtain residue. 20 ml Ethyl acetate was extracted twice and concentrated with anhydrous magnesium amine gallate in water, followed by silica gel column chromatography (eluent: diazepine / methanol ^ 90/10, ν / ν) to obtain 930 mg of the title compound (Yield 75¾) ° NMR (CDC13) $ 1.11 (m, 2H), 1.37 (br, 1H), 1.50〇) γ, 2Η), 1.62 (br, 1H), 2.35 (br, 1H) , 2.55 (br, 2H), 2.71 (br, lH), 3.14 (br, 2H), 3.35 (br, 2H), 3.90 (br, 2H), 4.I5 (m, 4H), 5.02 (s, 2H ), 5.10 (s, 2H), 7.21-7.40 (m, 6H), 7.41-7.60 (m, 4H), 7'70 (s, lH), 7.80 (s, lH), 7.95 (m, 2H), 8.13 (d, lH) FAB (M + H): 619 --------- ^ Jin „I (Please read the notes on the back first # '· ^ · Writing to buy) * τ This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 182 91506 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 436487_b7_ V. Description of the invention (189 Example 159: Bu [1- (1-methoxycarbonylhexahydropyridine-4) -Ylmethyl) -1Η-amido-5-ylmethyl] -4-(_ 咐 -4-yl) kisyl) -3- (cha-1-yl) -1Η-pyrazole (159) Synthesis-159-1) 1- [1- (Hexahydropyridin-4-ylmethyl) -1H-oxazol-5-ylmethyl] -4- (morpholin-4-yl) dyne-3- (Ban -1- ) -1} 227 1- yl it suddenly g (Um 0.36 mole) of the compound prepared in Example 158 was dissolved in the methanol, add 20 mg of palladium hydroxide on carbon thereto, the mixture was reacted under 1 atm of hydrogen for 2 hours. After the reaction is completed, the mixture is passed through 滹 and the solvent is removed. The residue was subjected to silica gel column chromatography (eluent: ammonia / formaldehyde = 15/85, v / v) to obtain 120 g (0.26 mol • yield of 74JO of the title compound. ^ NMR (CDCb) δ l .〇6 (m, 2H), 1.43 (m, 3H), 2.36 (br, 5H), 2.41-3.79 (br, 13H), 3.78 (d, 2H) f 5.22 (s, 2H), 6.88 (s, 1H) 5 7.12 (d, 2H), 7.26 (m, lH) 3 7.35 (m, 3H), 7.63 (s, lH), 7.75 (d, lH), 7.80 (d, lH), 7.93 (d, lH ) FAB (M + H): 484 159-2) Methoxycarbonyl hexahydropyridin-4-ylmethyl) -1H-oxazol-5-ylmethyl] -4- (morpholin-4-yl) carbonyl -3- (naphthalene-pyl) -1H-pyrazole 30 mg (62 μmol) Example 151-1) The compound prepared in Example 159-1) was dissolved in a 2 ml digas methane · K syringe and 5.4 mg (6.9 μmol) Ear) Methyl formate was added thereto, and the mixture was stirred for 2 hours. The solvent was removed under reduced pressure, and the residue was subjected to silica gel column chromatography (eluent: dichloromethane / formaldehyde = 80/20, this paper size applies to Chinese national standards (CNS &gt; A4 size &lt; 210X297 mm) 183 91506 ( Please read the precautions on the back before writing this page) [Package_ ('-4 Order 4 3 6487 A7 _ B7 V. Description of the invention (1δ4) ^ / 0, 27.8 mg (5.3 microcalibers, product The title compound with a yield of 85.0. * H NMR (CDC13) δ 1.05 (br, 2H), 1.32 (br, 1Pi), 1.53 (br, 2H), 2.31-2.72 (m, 5H), 3. · 03 to 3'33 (m, 7H), 3.62 (s, 3H), 3.66 (m, 2H), 4.13 (br, 2H), 5.12 (s, 2H), 6.71 (s, lH), 7.03 (s, lH), 7.14 (s, lH), 7.24 ~ 7.43 (m, 5H), 7.74 (d, lH), 7.82 (d, lH), 8.10 (d, lH) FAB (M + H): 543 Example 160: [1- (4-Bromobenzyl) -lH-oxazol-5-ylmethyl] -4- (morpholin-4-yl) carbonyl-3- (naphthalene-1-yl) -1Η-pyrazole The synthesis of (160) was carried out in the same manner as in Example 152, but using the compound prepared in Preparation Example 32-2) and the compound prepared in Preparation Example 59) to obtain the title compound in a yield of 8Π ° lH NMR (CDCb) § 2.35 ( br, 2H), 2.80 (br, 2H), 3.15 (br, 2H), 3.35 (br, 2H), 5.29 (s, 2H), 5.31 (s, 2HX 7.00 (d, 2H), 7.20-7.35 (m, 3H), 7.40-7.60 (m, 4H), 7.72 (s, lH), 7.80 (s, lH), 7.90 (m, 2H) , 8.01 (d, lH) FAB (M + H): 556 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) Example 161: l- [l- (4- Benzyl) -lH-oxazol-5-ylmethyl] -4- (morpholin-4-yl) carbonyl-3- (naphthalene-1-yl) -1pyrazine (161) The same steps as 152, but using the compound prepared in Preparation Example 57-2) and the compound prepared in Preparation Example 59, the title compound was obtained with a yield of 8U ° This paper size is applicable to the Chinese National Standard (CNS) A4 specification (2 丨 0X297 Mm) 18 4 91506 436487 ^ B7 _ 5. Description of the invention (l85) 'η NMR (CDCb) 3 2.35 (br, 2H), 2.80 (br, 2H), 3.15 (br, 2H) 5 3.35 (br, 2H ), 5.29 (s, 2H), 5.31 (s, 2H), 7.00 (d, 2H), 7.20-7.35 (m, 3H), 7.40-7.60 (m, 4H), 7.72 (s, lH), 7.80 ( s, lH), 7.90 (m, 2H), 8.01 (d, lHr FAB (M + H): 512 cyanobenzyl) -lH-oxazol-5-ylmethyl] -4- (what? _ 4-yl) furyl-3- (naphthyl-phenyl) -1H-pyrazole (162) was synthesized by the same procedures as in Example 152, but using Preparation Example 29-5) and the compound obtained in Preparation Example 59) to obtain the naked title compound, yield 8 1¾ ° JH NMR (CDC13) § 2.35 (br, 2H), 2.80 (br, 2H), 3.15 (br, 2H), 3.35 (br, 2H), 5.28 (s, 2H), 5.34 (s, 2H). 7.03 (d, 2H), 7.20-7.35 (m, 3H), 7.40-7.60 (m, 4H), 7.72 (s, lH), 7.80 (s, lH), 7.90 (m, 2H), 8.01 (d, lH) FAB (M + H): 503 Example of printing by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 163: 1- [1-methyl-1H-oxazol-5-ylmethyl] -4- (morpholin-4-yl) carbonyl- 3- (naphthalene-1-yl) -1fluorene-pyrazole (163 ) Was synthesized according to the same procedure as in Example 152, but using the compound prepared in 1-methyl-5-chloromethyl-1H-oxazolium sulfonate and Preparation Example 59 to obtain the title compound 'Yield ° NMR (CDC13) $ 2.35 (br, 2H), 2.80 (br, 2H), 3.15 (br, 2H), 3.35 (br, 2H), 3.62 (s, 3H), 5.29 (s, 2H), 7.20-7.35 (m, 3H) , 7.40-7.60 (ιη, 2Η), 7'72 (s, lH), 7.80 (s, lH), 7.90 (m, 2H), 8.01 (d, lH) FAB (M + H): 402 paper size Applicable to Chinese National Standard (CNS) A4 (2 丨 0〆297mm) 185 9 1506 A7 B7 436487 V. Description of the invention (1S6) Tube inspection example 1 (Please read the notes on the back first Xiang Zaiqi wrote this page)

The Ras method was used to analyze the inhibitory activity of a certain galactam ester. ^ Analyzed in this experiment * The Ras method was prepared using a modified Pomp method and the recombinant method of Popianoo et al. (Biolian, 1992, 31, 3800). Description of the purification of the glycosyltransferase and its use according to known methods (see. Chuns et al., Biochemica et Biophysica Acta * 1 9 92, 278t 1129) is described in Korean Patent Application No. 97-14409

Ras receptor (Ras-CVLS) protein. The enzyme reaction was performed in 50 microliters of 50 ία Μ Η E P E S nano buffer solution (containing 25aiM potassium potassium, 25mM magnesium chloride, 10mM DTT, and 50 / Μ zinc chloride). 1.5 W M Ras receptor protein, 0.15 «Η 氚 -farnesyl phosphate and 4.5 nM farnesyl transfer were used. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. In more detail, in the initial step, farnesyl transfer was added to the above solution, and the reaction was maintained at 3710 for 30 minutes, and then 1 ml of ethanol solution containing 1M HCi To stop the reaction. Tongcheng's precipitate was adsorbed to a GF / B filter by using a Hopper collector (Hopper # FH225V) that was bound to a container, cleaned by ethanol, and the LKB / 3 counter was used to detect the radioactivity of the drier. Calculate the titer of the enzymes that are subject to the unsaturated state (here, the unsaturated and the Ras receptor proteins have a parameter relationship with farnesyl transferase). An amount of the compound M of the present invention dissolved in DMS0 was less than 5¾ of the total reaction solution, and the enzyme inhibitory activity was measured. Enzyme inhibitory activity M In the presence of the test compound, the amount of farnesyl incorporated into the Ras receptor protein * is expressed as a percentage of the amount of farnesyl incorporated into the Ras receptor protein without the test compound. The IC50 of the test compound is defined as the enzyme. This paper is a common Chinese national standard (CNS> A4 specification (2) 0X297 mm). 1 8 6 9 1 5 06 5. Description of the invention (i87) The concentration at which the activity is inhibited by 50¾. The inhibitory activity of ergoyl uranyl uranyl Ue "anyl" sequestration, M to evaluate the selective enzyme inhibitory activity of the compounds of the present invention. According to Schaber's method (Schaber et al., J 'Biol. Chem. 1990, 265, 14701 ) Improved method to purify geranyl geranyl geranyl transferase from bovine brain | for geranyl geranyl pyrophosphate and Ras-CVIL receptor protein, perform the same as farnesyl transfer The experimental procedure is shown in Table 7 below.

The Ras method was used to analyze the activity of a certain ester body in this experiment. In this experiment, a Rat2 cell line * showing C-Harvey-Ras protein with transformation activity was used, and the C-terminus of K-Ras was replaced by MH-Ras. Rat2 cell line transformed with a fusion protein derived from the polybasic lysine segment (Korean Patent Application No. 97-14409. This experiment uses the KDeclue method (Declue «ΚΕ. Et al., Cancer Research, 1991, 51 , 712). The experimental method will be described in more detail later. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page). 3x 10s transformed Rat2 The cells of the dystrophin cell line were spread on a 60mm cell culture dish and cultured in a 37t cell culturer for 48 hours to a density of 50 ¾ or higher, and then treated with the M test compound. The solution was dissolved in DMS0 The compound of the invention. The concentration of dimethylamine used in the control group and the test group is IS:. After 4 hours of treatment of the M compound *, each milliliter of the medium contains 150WC 丨 radioisotope [3SS] -labeled methionine, and culture 2 After 0 hours, Wash the food with water, and use 1 ml of ice-cold cell lysing solution (50mM HEPES nano buffer solution. It contains the paper size applicable to China National Standard (CNS) A4 specifications (210 X 297 mm) 18? 91506 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs: 6 4. 8 7 V. Invention Description (5 π Mg -fb Μ, 1 mH DTT, 1S; NP40, 1 m M EDTA, 1 m M PMSF &gt; 2k M Leupeptn, 2w M pepsin A and 2wM antipain] were lysed, and M12,000gX &amp; minute centrifugation was performed to obtain a clear solution above the lysed cells. The radioactivity of the supernatant was measured. Isotope amount | and normalization * to obtain quantitative results of immunoprecipitation reaction, and then add the monoclonal antibody Y13-259 (Furth, M, E. et al., J. Virol * 1982, 43, 294) f that specifically binds to Ras protein And at 4t: reaction for 15 hours, add protein A (bound with goat-anti-mouse immunoglobulin antibody) -agar suspension to the solution and react at 4C for 1 hour. Then remove the non-specifically bound products, and immunoprecipitate M Buffer solution (50mM Tris-Cl buffer containing 5 0mM sodium chloride, 0.5¾ sodium dioxycholate, 0.5040, and 0.USDS). The forged material was added to the buffer solution for electrophoresis and boiled, followed by electrophoresis using a 13.5 JKSDS polypropylene ammonium gel. After electrophoresis, draw the gel and dry. The gel is then * exposed to the X-ray film * to develop and print. From the experimental results, the strength of the protein band bound with or without the Ras protein farnesyl group was measured. The concentration of the test compound that inhibited 50¾ farnesyl binding was defined as CIC50 * is the inhibitory activity of Ras farnesyl transfer in vivo. The test results are shown in Table 7 below. (Please read the precautions on the back before filling this page) ·-= * hi This paper size is applicable to the Chinese National Standard (CNS) A4 specification (21 × 297 mm) 188 9 1506 436487 V. Description of invention (iw) Ministry of Economic Affairs Printed in Table 7-1 by the Consumer Standards Cooperative of the Central Bureau of Standards Compound No. H-Ras ic5〇 (&quot; m) H-Ras CIC50〇 (^ M) K-Ras ic50 (&quot; m) K-Ras CIC5〇 (μ M) 1 0.0011 0.025 0.0035 10 2 0.00085 0.025 0.002 10-50 3 0.001 0.025 0.0024 15 4 0.047 0.1-1 0.75 10-100 5 0.0037 0.025 0.0085 10-50 6 0.001 0.025 0.002 10-50 7 0.0006 0.025 0.0022 10-50 8 0.004 0.025 0.008 10-50 9 0.005 0.025. 0.0066 10-50 10 0.00085 0.0125 0.005 10-50 11 0.004 0.025 0.008 10-50 12 0.005 0.025 0.0066 10-50 13 0.00085 0.0125 0.005 10-50 14 0.002 0.0125 0.005 10-50 15 0.005 0.025 0.01 10-50 16 0.0012 0.0125 0.005 10-50 17 0.002 0.025 0.003 10-50 18 0.001 0.025 0.002 10-50 (Please read the precautions on the back before filling this page)

This paper size applies to China National Standard (CNS) A4 (2I0X297 mm) 189 9 1506 8 4 6 3 4

7 B V. Description of the invention (ig〇). Table 7-2 The central bag of the Ministry of Economic Affairs v Beigong Cooperative Co., Ltd. Printing bag compound number H-Ras IC5〇 (^ M) H-Ras CICi〇 (^ M) K-Ras IC5〇 (aM) K-Ras CIC々M) 19 0.001 0.020 0.003 10-50 20 0.001 0.020 0.002 10-50 21 0.001 0.021 0.001 10-50 22 0.001 0.020 0.002 10-50 '23 0.002 0.023 0.002 10-50 24 0.002 0.025 0.003 10-50 25 0.002 0.015 0.005 10-50 26 0.002 0.015 0.003 10-50 27 0.006 '0.025 0.005 10-30 28 0.001 0.020 0.002 10-30 29 0.002 0.010 0.004 10-20 30 0.002 0.010 0.004 10-20 31 0.002 0.012 0.005 10-20 32 0.002 0.015 0.003 10-50 33 0.002 0.018 0.003 10-50 34 0.002 0.020 0.003 10-50 35 0.001 0.025 0.002 10-50 36 0.001 0.025 0.002 10-50 37 0.002 0.025 0.003 10-50 38 0.002 0.025 0.004 10-50 39 0.002 0.020 0.003 10-50 40 0.002 0.025 0.003 10-50 41 0.003 0.015 0.004 10-50 This paper size is applicable to China National Standard (CNS) A4 size (210X297 mm) 190 9 1506 ------ ------- ^ Install-(Please read the precautions on the back before writing this page) Order 436487 A7 B 7 V. Description of the invention (1Q1) Table 7-3 Compound number H-Ras Ι ^ 〇 (μΜ) printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs H-Ras CICj〇 (μΜ) K-Ras IC5〇 (^ M ) K-Ras CICs'oC ^ M) 42 0.004 0.015 0.003 10-50 43 0.001 0.015 0.002 5-10 44 0.25 1-50 0.1-10 10-100 45 0.13 1-50 0.1-10 10-100 46 0.12. 1 -50 0.1-10 10-100 47 0.09 1-50 0.1-10 10-100 48 0.15 1-50 10 10-100 49 0.03 0.7 0.485 &lt; 20 50 0.15 1-500.1-10 10-100 51 0.27 1 -50 0.1-10 10-100 52 0.07 1-50 0.1-10 10-100 53 0.3 1-50 0.1-10 10-100 54 0.39 1-50 0.1-10 10-100 55 0.06 1-50 0.1-10 10 -100 56 0.04 1-50 0.1-10 10-100 57 0.038 1-50 0.1-10 10-100 58 0.025 1-50 0.1-10 10-100 59 0.57 1-50 0.1-10. 10-1 ⑻ 60 0.2 1-50 0.1-10 10-100 61 0.74 1-50 0.1-10 10-100 62 0.068 1-50 0.1-10 10-100 63 0.23 1-50 0.1-10 10-100 This paper's scale is applicable to Chinese national standards ( CNS) A4 specifications (21 ο X 297 mm) 7 ^ Pack 1.1 {Please read the precautions on the back before writing this page), Word 436487 V. Description of the invention (192) Central standard of the Ministry of Economic Affairs Printed by the Consumer Cooperatives of the Prospective Bureau 7-4 Chemical Co., Ltd. No. H-Ras ic5〇 (^ m) H-Ras 〇Ι〇5〇 (μ Μ) K-Ras IC3〇 (^ M) K-Ras CICio (^ M) 64 0.16 1-50 0.1-10 10-100 65 0.42 1-50 0.1-10 10-100 66 0.12 1-50 0.1-10 10-100 67 0.02 3 0.1-10 &gt; 50 68 0.12 1- 50 0.1-10 10-100 69 0.55 1-50 0.1-10 10-100 70 0.21 1-50 0.1-10 10-100 71 0.12 1-50 0.1-10 10-100 72 0.05 1-50 0.1-10 10- 100 73 0.002 0.2 0.02 &gt; 10 74 0.01 0.1-1 0.01-0.1 10-100 75 0.005 0.2 0.16 20 76 0,004 0.1-1 0.1-10 10-100 77 0.004 0.1 0.12 20 78 0.0045 0.1 0.2 10-100 79 0.005 0.1 0.1 &gt; 50 80 8.21 1-50 0.1-10 10-100 81 0.68 1-50 0.1-10 10-100 82 0.4 1-50 0.1-10 10-100 83 0.26 1-50 18.5 10-100 84 0.72 1- 50 1.83 10-100 85 0.03 4 0., 1-10 &gt; 50 This paper size applies to China National Standard (CNS) A4 specifications (2! Ο X 297 mm) --------- y-pack- -(Please read the notes on the back before filling out this page) 192 9 1506 43 64 8 A7 B7 V. Description of the invention Printed by the Central Standards Department of the Ministry of Economic Affairs 扃 Shellfish Consumer Cooperatives 7-5 Compound No. H- Ras IC ^ oi μM) H-Ras CIC5〇 (^ M) K-Ras IC5 (M) 1 K-Ras CICio (^ M) '86 0.03 2 0.1-10 &gt; 50 87 0.06 1-50 0.1-10 10-100 88 0.6 1-50 0.1-10 10-100 89 0.014 1 0.1-10 10-100 90 0.0425 1-50 0.1-10 10-100 91 2.15 1-50 0.1-10 10-100 92 0.07 1-50 0.1-10 10-100 93 0.32 1-50 0.1-10 10-100 94 0.2 1-50 .0.1-10 10-100 95 0.0007 0.01-0.1 0 · 1 &quot; 1 10-50 96 0,23 1-50 1 -10 10-100 97 12 10-100 10-100 10-100 98 0.90-0.9 1-50 0.1-10 10 &quot; 100 99 0.0030 0.1 0.1 &gt; 50 100 1.8 &gt; 1 0.1-10 &gt; 20 101 0.01 &gt; 5 0.8 &gt; 50 102 0.45 1-50 22 &gt; 50 103 0.064 0.1-10 1.7 10-100 104 0.0005 &lt; 0.05 0.006 &lt; 10 105 0.0004 0.05 0.09 &gt; 50 106 0.9 1-50 10-100 10- WO 107 10 1-50 0.1-10 10-100 (Please read the precautions on the back before filling this page)

-ΰτ h〗 4 This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) 193 9 1506 436487 V. Description of the invention (194) A7 B7 Table 7-6 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs H-Ras ic5〇 (&quot; m) I H-Ras CICsoC ^ M) K-Ras ICso (μM) K-Ras CICio (^ M) 108 0.26 1-50 0.1-10 10-100 109 8.6 1- 50 1-50 10-100 110 0.0006 ο.οοδ 0.0015 10 111 0.002 0.03 0.002 4 112 0.004 0.015 0,006 10 113 0.004 &lt; 0.1 &lt; 0.1 10-100 114 0.001 0.015 .0.100 &lt; 100 115 0.002 0.025 0.035 &lt; 50 116 0.004 0.030. 0.062 &lt; 50 117---&lt; 50 118 —--&lt; 40 119---&lt; 30 120--one &lt; 20 121 one--&lt; 40 122 _--&lt; 30 123---&lt; 40 124-&lt; 20 125 0.002 0.006 0.004 4 126 0.001 0.012 0.004 5 127 0.002 0.015 0.005 5 128 0.002 0.010 0.010 5 129 0.003 0.025 0.004 10-50 This paper size applies to the Chinese National Standard (CNS) A4 Specifications (210X297 mm) (Please read the notes on the back before writing this page)

.TJ Order 194 9 1506 4364 87 V. Description of the invention (19 Jan. Table 7_7 Printed by the Consumers 'Cooperative of the Ministry of Economic Affairs and the Central Bureau of Standards and Printing Co., Ltd. $ Compound m:' No. H-Ras IC50 (^ M) H-Ras CICjoi ^ M) K-Ras ICjo (^ M) K-Ras CICj〇 (^ M) 130 0.002 0.025 0.003 10-50 131 0,001 0.0125 0.0023 10-50 132 0.0035 0.025. 0.011 10-50 133 0.00065 0.025 0.002 10-50 134 0.0027 0.025 0.002 10-50 135 0.0024 0.03 0.004 10-50 136 '0.0016 0.025 0.0024 10-50 137 0.0017 0.020 0.0021 10-20 138 0.0014 0.025 0.0035 10-50 139 0.005 0.07 37 7 140 0.09 1-10 10-50 10-50 141 0.23 1-10 10-100 10-50 142 12 &gt; 50 &gt; 50 &gt; 50 143 1.2 20 &gt; 50 &gt; 50 144 0.38 5 50 &gt; 50 145 0.007 0.1 0.07 25 146 0.09 1 10 50 147 0.002 0.05 0.03 10 148 1.7 30 &gt; 50 &gt; 50 149 5 50 &gt; 50 &gt; 50 150 8 &gt; 50 &gt; 50 &gt; 50 151 4.6 50 &gt; 50 &gt; 50 CNS) A4 specification (210 X 297 mm) 195 91506 (Please read the notes on the back before filling this page) 4 3 64 87 A7 __B7 V. Description of invention (l W) Ministry of Economic Affairs Table 7-8 Compound 'No., H-Ras 1050 (μM) H-Ras CICjot ^ M) K-Ras ICi0 (^ M) K-Ras 152 0.023 0.1 0.07 10 153 0.03 0.15 0.1 20 154 0.03 0.15 0.2 10 155 0.02 0.1 0.2 15 156 0.02 0.1 0.2 40 157 0.01 0.1 5 &gt; 50 158 0.25 1 2 30 159 0.3 1.2 4 50 160 0.3 1.5. 3 40 161 0.2 1 2 50 162 0.25 1 2 50 163 0.15 1 10 &gt; 50 (Please read the precautions on the back first and then write% of this page)

• 1T This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 196 91506

Claims (1)

43 64 8 Rev. Zheng No. 87119691 Patent Application Amendment to the Appendix (August 18, 89) Kind of oxazole derivative represented by the following formula (1): (1) where: * "ηι An integer of 1 to 4 * A represents hydrogen; any straight or branched ^^^ alkyl group which may be substituted by C3-C? Cycloalkyl or Ci-C6 alkoxy group; or a group selected from the group consisting of: Ri 'neutral formula -R1 prime ~. SC1, or hydrogen, as the base oxybenzyl, self-based oxygen, t alkylcarbonylhydroxy, cyanocyanine or hydrogen or E, formula P and Ministry of Economy Printed by the Staff Welfare Committee of the Central Bureau of Standards to substitute for phenyl or oxy-C benzene C1. It is intended to substitute for keto or ·, phenyl hydrogen argon shows the R3 oxy. Group of groups 91506 This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 male; * t) 1 436487 H3 where I Π2 and n3 are each independently shown as 0, 1, 2, 3, or 4; fi5 and R9 are each independent R6 and R8 are independently hydrogen, C1-C6 alkyl, C1-C6 alkoxy, cyano, hydroxy, or halogen. R7 shows Hydrogen; C1-C6 alkyl; C1-C6 alkoxy; hydroxy; or dentin, Rio represents hydrogen, Ci-Ce alkyl or C1-C6 alkoxy, and Y represents a group selected from the group: s In the formula, when X is in the ring, it is represented by 0 or S * When X is outside the ring, it is represented by 0, B represents hydrogen or Ci-C6 alkyl which may be optionally substituted with phenyl * C represents hydrogen or may Any Ci-Ce alkyl substituted with a phenyl group; or a base selected from the group consisting of: Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Ril and 12 each independently show hydrogen or Ci-C6 alkyl, (113 and 1-14 each show independently hydrogen, Ci-C6 alkyl, phenyl, or + t (: HlJarX_Rli) This paper size is applicable to Chinese National Standard (CNS) A4 Specification (210 X 297 gold) 2 91506 H3 436487 (where X is defined as before), Π4 is an integer from 2 to 4, and Ris is a C1-C6 alkyl group, and D represents an amino acid residue or an amino acid residue Sci-Cs alkyl ester; benzyl; or a group selected from the group consisting of: ft0. 00 ΓΛ Η I ^ &quot; 5 RS; The definition of IR 1 0 is as shown in the previous IQ. 0 or S * Z shows 0 'S' S = 0, S〇2, C = 0 or C = S * or CH-R20 or N-R2〇 (where R20氲, lower alkyl or hydroxyl) · ns represents an integer of 1 to 3, R16 and R17 each independently show hydrogen; phenyl; hydroxycarbonyl; alkoxycarbonyl; optionally substituted with phenyl or cyanophenyl (^- (: 6 alkyl; or + (eH2) ar * ^ Rli) Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs and δ 1 R, each 4 9 Ω 1 and QR cyanocyanine, such as halogen Standalone ο Alkyl 6 C Alkylthioalkyl Alkylthioalkylsulfanyl Alkyloxyalkyloxane 6 C-1 C Alkylbenzyl or benzylbenzyloxy This paper size applies to China Standard A (CNS) A4 specification (210X 297 male #) 3 9 1506 H3 436487 In the formula, Rll and Rl2 have the same definitions as before, I represents Ci-Cs alkoxy, or it is selected from the following Group base 1 tK16 f R-I7 'where * Ris, R17, and Z have the same definitions as before, L shows the base selected from the following groups: Ή / · If not, and (2) when A is In the illustration, the definitions of Z and Q are as before. However, (1) When R3 is hydrogen &gt; Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Or its hydrazone or its isomers. 2. An oxazole derivative according to item 1 of the scope of the patent application, wherein η 1 represents an integer of 1 to 3, and A represents hydrogen; any straight or fluorene substituted with Cs-C7 cycloalkyl or Ci-Cs alkoxy, or Branched Ci-Cia alkyl; or a group selected from the group consisting of: In the formula, Ri and R'i each independently show hydrogen, halogen, cyano, hydroxycarbonyl, and Ci-C. The paper size is applicable to China National Standard (CNS) A4 (210 X 297) 4 91506 43 64 8 7 H3 Alkoxy, benzyloxy, or Ci-Cs alkyl · R2 represents hydrogen or Ci-Cs alkyl, or -EF- · where E is -C (0)-, and F is hydrogen; any Ci-C6 alkyl substituted with oxy or phenyl; Ci-C6 alkoxy optionally substituted with phenyl; or phenyl, R3 represents hydrogen or Ci-Csfluorenyl, R4 represents a group selected from the following group : In the formula, Π2 and Π3 each independently show 0, 1, 2, 3, or 4; R5, lie, Rs, and (ίθ each independently show hydrogen, Ci-Ce alkyl, Ci-Ce alkoxy, hydroxyl, or halogen, R7 represents hydrogen; Ci-Ce alkyl; Ci-Ce alkoxy; hydroxyl; or halogen, Rio represents hydrogen, methyl or methoxy, and Y represents a base selected from the following groups: Staff Benefits, Central Bureau of Standards, Ministry of Economic Affairs Printed by the committee X. G Ή O ’ In the formula, when X is in the ring • it is expressed as 0 or s, when X is outside the ring | it is expressed as 0, B is hydrogen or Ct-Cs alkyl which can be optionally substituted with phenyl. Standard (CNS) A4 specification (210 X 297 cm) 5 91506 43 64 8 7 H3 Cs alkyl; or a base selected from the group C of the group C shown below with argon or optionally substituted with phenyl: J R u R! 3 where Rii and Ri2 each independently show hydrogen, or Ci-Cs alkylR13 and Rl4 each independently show hydrogen, Cl-C6 alkyl, phenyl, or ten (Ctyn * -X_Rl5 (where X The definition is as above), Π4 is 2 and! ^ 5 is a C1-C6 alkyl group, D is an amino acid residue or a lower alkyl ester of an amino acid residue; benzyl; or it is selected from the following groups Base: Rto Wei 10 ί ^ ιτ R | 9 ^ 19 Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs. The definition of R i 〇 is as shown in the previous IQ, 0 or S * Z is 0, S 'S = 0' S〇2, or C = 0, or CH-R is shown. R20 is hydrogen, lower alkyl or hydroxyl), ns is an integer from 1 to 3, • Paper size applies Chinese National Standard (CNS) A4 specification (210X 297 public copy) β 91506? 36 heart 7 _ ^ _ H3, Ri6 and R17 each Independently shown hydrogen i phenyl; hydroxycarbonyl; alkoxycarbonyl; id-Cs alkyl can be substituted by phenyl or cyanophenyl; or + (™ ώτ ^-heart, where R4, Q and R10 are as defined above R18 and R19 each independently show hydrogen; halogen; cyano; C1-C6 alkyl; Ci-Cs alkoxy; alkoxyalkyl; alkylthio; alkylthioalkyl; alkylthioalkoxy; benzyl Phenyl; or benzyloxy, G represents a group selected from the group: / ' In the formula, Rii and R12 are as defined above, and I represents Ci-Ce fluorenyloxy, or a group selected from the following groups: Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs Among them, the definitions of Rie, Ri7, and Z are the same as above, and L is the base selected from the following sister groups: 91506 This paper size is applicable to China A standard (CNS) A4 specification (210 X 297 at public expense) 7 4 3 6 4 8 H3 3. If you apply for the imidazole derivative in item 1 of the scope of profit, where γ indicates And c shows-test. 4. If the imidazole derivative of item 1 of the scope of patent application is selected from the following group: 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-methyl [1- (3,4-methyldioxybenzyl) -1Η-oxazol-5-ylmethyl] -4- (naphthalenepyrrole (1), [1- (3,4-methyldioxybenzyl) -1Η -Imidazol-5-ylmethyl] -3- (morpholin-4-yl) carbonyl-4- (cha-1-yl) -1Η-pyrrole (2), 1- [1- (3,4-methyl) Dioxybenzyl) -1′-imidazol-5-ylmethyl] -3- (4-methylhexahydropyridine-butyl) carbonyl- 4- (naphthalene-1-yl) -1′-pyrrole (3-yl Carbamidinyl naphthyl, oxo 4 / IV dirole 9A] oxazolyl acetofluorene Xanthylamine XJ methylmethyl methyl imprinted ethyl ethoxymethyl- 1X I Naphthalene. Methylmethylamine F-_methylmethylmethyl I 5 t oxazolonenaphthalene D 3- (morpholin-4-yl) carbonyl- (4-naphthalene-1-ylnaphthalene-1-ylmethyl) Yl) -1Η-imidazol-5-ylmethyl] -1H-pyrrole (6), 3- (4-methylhexahydropyrimidin-1-yl) carbonyl-U-naphthalene-phenyl) -1- [ 1-Chazyl-methyl) -1H-oxazol-5-ylmethyl] -1H-pyrrole (7), The size of this paper is applicable to China Standards (CNS) A4 (210 X 297 cm) 91506 438487 3-[(ί- (2-methoxyethyl) -N-methyl] aminomethylamino-l- [i ((R) -〇t) -methylbenzyl) -1Η-imidazol-5-ylmethyl] -4- (naphthalene-1-yl) -1Η-pyrrole (8), l- [l- (U) -〇t-methylbenzyl) -1Η-imidazol-5-ylmethyl] -3- (many-4-yl) carbonyl- 4- (naphthalene-butyl) -1Η-pyrrole (9 ), [[L-((R) -a-methylbenzyl) -1'-oxazol-5-ylmethyl] -3- (4-methylhexahydropyridin-1-yl) carbonyl-4 -(Naphthalene-1-yl) -1Η-pyrrole (10), 3- [N- (2-methoxyethyl) -N-methyl] aminomethylamidino-l- [l ((S) -α -Methylbenzyl) -1'-imidazol-5-ylmethyl] -4- (naphthalene-1-yl) -1 [1-pyrrole (1 1), l- [l ((S) -ct -formyl Benzyl) -1′-oxazol-5-ylmethyl] -3-morpholin-4-yl) carbonyl-4- (ban-1-yl) -1′-laro (12), lU ((S ) -ct-methylbenzyl) -1Η-imidazol-5-ylmethyl] -3- (4-methylhexahydropyridin-1-yl) carbonyl-4- (naphthalene-1-yl) -1Η -Pyrrole (13), v 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4- (naphthalene-1-yl) -1-11- (phenethyl) -1bimidazol-5-ylmethyl] -1H-pyrrole (14) Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs 3- (Manga-4-ji) -Curtain- 4- (Prohibited-Buji) -1- [1- (phenethyl) -1Η-imidazole-5- Methyl] -1H-BH; (15), 3- (4-methylhexahydropyridin-1-yl) carbonyl-4- (Cai-1-yl) -1- [1- (phenylethyl Yl) -1H-pyrazol-5-ylmethyl] -1H-pyrrole (16), 3- [N- (2-methoxyethyl) -N-methyl] aminoformyl-bu [; 1 -(2-methoxy) phenethyl-1H-oxazol-5-yl] methyl-4- (naphthalene-1-yl) -1Η- 91506 This paper size applies to China® Home Standard (CNS) A4 (2I0 X 297 g) H3 Pyrrole (17), [1- (2-methoxy) phenethyl-1H-imidazol-5-yl] methyl-3- [4-methylhexahydropyracine -1-yl] carbonyl-4- (naphthalene-1-yl) -ih-pyrrole (18- [3- [N- (2-methoxyethyl) -N-methyl] aminomethylamido-l- [ l- (4-methoxy) phenethyl-1H -mi-5--5-yl] methyl-4- (cha-1-yl) -1 [{-pykal (1 9), 1- [1 -(4-methoxy) phenethyl-1H-oxazol-5-yl] methyl-3- [methylhexahydropyrazine-1-yl] simian.yl- 4- (naphthalene-1-yl ((20 g) phenethyl-1H-imidazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethane- 4- (naphthalene- 1- Yl) -1Η-pyrrole (21), 1- [Bu (2-fluoro) phenethyl-1H-oxazol-5-yl] methyl-3- [4-methylhexahydropyrimidin-1-yl ] Carbonyl-4- (naphthalene-1-yl) -1 propyrrole (22), 1- [1- (2-chloro) phenethyl-1H-imidazol-5-yl] methyl-3- [N- (2-Methoxyethyl) -N-methyl] aminomethylamidino-4- (cha-1-yl) -1H-pyrrole (23), printed by UL-BEI [1- (2-chloro) phenethyl-1H-imidazol-5-yl] methyl-3- [4-methylhexahydropyridine-1-yl] carbonyl-4- (naphthalene-1-yl) -1Η-pyrrole (24), 1- [1- (3-ambiene) phenethyl-1H-oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N- Methyl] aminomethyl-4- (naphthalen-1-yl) -1Η-pyrrole (25), 1- [1- (3-chloro) benzylethyl-1H-hepta-5-yl] methyl -3- [4 -Methylhexahydropyridin-1-yl] carbonyl- 4- (naphthalene-1-yl) -1Η-pyrrole (26), This paper size applies to China National Standard (CNS) A4 Specification (210 X 297 male director) 9 1506 10 H3 &quot; 436487 3- [fl- (2-methoxyS group) -N-methyl] aminomethylmethyl-4- (naphthalene-butyl) -1- [1- (3 ~ phenyl) propyl-1H-imidazol-5-yl] methyl-1H-pyrrole (27), 3- [4-methylhexahydropyridine-1- Yl] carbonyl- 4- (ban-1-yl) -1- [1- (3-phenyl) propyl-1H-imidazol-5-yl] methyl-1H-pyrrole (28), '3- [ N- (2-methoxyethyl) -N-methyl] aminomethyl- 4- (naphthalene-1-ylnaphthalene-2-yl) methyl-1H-oxazol-5-yl] methyl- I-la-role (29), 3-U-methylhexahydropyridine-carbonyl] carbonyl-4- (naphthalene-1-yl) -1- [1- (naphthalene-2-yl) methyl-1H -Imidazol-5-yl] methyl-1H-% role (30), 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4- (naphthalene-1-yl Naphthalene-b-yl) ethyl-1H-imidazol-5-yl] methyl-lH-pyrrole (31), 3-U-methylhexahydropyridin-1-yl] carbonyl-4- (naphthalene-; ! -Yl) -1- (1- [2- (naphthalene-1-yl) ethyl-1H-imidazol-5-yl] methyl-1H-pyrrole (32 bu [1-U-bromo) phenylethyl -1H-imidazol-5-yl] methyl-3_ [N- (Printed by 2-Wethylethyl) -K-methyl] aminomethyl-4- (Cha-buki) -1H-pyrrole (33), 1- [1- (4-bromo) phenethyl-1H-imidazol-5-yl] methyl-3- [4-methylhexahydropyridine -1-yl] carbonyl- 4- (Cha-buyl) -1Η-laro (34), fluoro) phenethyl-1H-imidazol-5-yl] methyl-3- [N- (2-methyl Oxyethyl) -N-methyl] amine Fluorenyl-4- (ban-1-yl) -1Η-pyrrole (35), 1- [1- (4-fluoro) phenethyl-1H-oxazol-5-yl] methyl-3- [4 -The paper size of this paper applies the Chinese National Standards (CNS) A4 specification (210X 297 meters) 9 15 0 6 11 Λ86Α87 _ ^ _ H3 Hexahydropyridine-1-yl] carbonyl-4- (naphthalene-1-yl) -1Η -pyrrole (3S), 3- [N- (2-methoxyethyl) -N-methyl] amine methyl pickle-l [l- (4-methyl) phenethyl-1H -oxazole -5-yl] methyl-4- (naphthalen-1-yl) -1Η-pyrrole (37), 1- [1- (4-methyl) phenethyl-1H-imidazol-5-yl] methyl -3- [4-methylhexahydropyridine-butyl] carbonyl- 4- (naphthalene-1-yl) -1Η-pyrrole (38) 1- [1- (4-chloro) phenethyl-1H- Oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethylsulfanyl-4- (naphthalen-1-yl) -1pyridine (39) , 1- [1- (4-chloro) phenethyl-1H-imidazol-5-yl] methyl-3- [4-methylhexahydropyridine-butyl] carbonyl-4- (ban-1- Yl) -1Η-pyrrole (40), 3- [H- (2-methoxyethyl) -N "methyl] aminomethylamido-4- (naphthalene-1-ylnaphthalene-2-yl) ethyl ] -1H-oxazol-5-yl) methyl-1 hydrazone-pyrrole (4 1), 3 &quot; [4-methylhexahydropyridin-1-yl] carbonyl- 4- (naphthalene-1-yl) -1- {BU [2- (naphthalene-2- ) Ethyl] -1H -oxazol-5-yl) methyl-1H-pyrrole (42) 'Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 1- [1_ (4 * · diabase) ¾: ethyl- 1H-brand salyl-5-yl] methyl_3_ [4_methylhexahydropyridin-1-yl] carbonyl- 4- (naphthalene-1-yl) -1Η-pyrrole (43) 1- (1 Azole-4-yl) methyl-4- (cha-; 1-yl) -3- (1 «phen-2-yl) carbonyl-lH-ntt (44), (1H-imidazol-4-yl) ) Methyl-4- (naphthalene-butyl) -3-(«phen-3-yl) carbonyl-1H-pyrrole (45), 9 1506 This paper is applicable to China National Standard (CNS) A4 (210X 297) decline),. 12 4 3 64 87 H3 Printed by 3-benzylpyrazol-4-yl) methyl-4- (naphthalene-1-yl) -1 Η -laro (4 S ), 3- (2-bromobenzylidene) -1- (1Η-oxazol-4-yl) methyl-4- (naphthalene-1-yl) -1Η-pyrrole (47) 3- (3- Mobenzylpyrazole-4-yl) methyl-4- (naphthalene-1-yl) -1Η-pyrrole (48) 3- (4-bromobenzyl) -1- (1Η-oxazole 4-yl) methyl-4- (naphthalene-1-ylrole (49) and (1H-oxazol-4-yl) methyl-3- (2-methylbenzyl) -4- ( Prohibit-1-yl) -1 啦 -lacrole (50), (1H-oxazol-4-yl) methyl-3- (3-methylbenzylidene) -4- (naphthalene-1-yl ) -1Η-pyrrole (51), 1- (1H-oxazol-4-yl) methyl-3- (4-methylbenzyl) -4- (naphthalene-1-ylrole (52), 1- (1H-oxazol-4-yl) methyl-3- (3-methoxybenzylidene) -4- (prohibited-:!-Yl) -1 Η-laro (5 3), 1 -(1Η-oxazol-4-yl) methyl- 3- (4-methoxybenzyl) -4- (ban_1-ylbenzo (54), 3- (2-chlorobenzyl) ) -1- (1Η-oxazol-4-yl) methyl-4- (naphthalene-1-yl) -1Η-pyrrole (55), 3- (4-chlorobenzyl) -1- (1Η -Oxazol-4-yl) methyl 4- ( Naphthalene-Bulkika (56), 3- (2,4-Dibenzobenzyl) -1- (1Η-imidazol-4-yl) methyl-4-(naphthalene-1 -yl) -1Η -Pyrrole (5 7), 3- (4-fluorobenzylidene) -1- (1Η-oxazol-4-yl) methyl- (4- (This paper uses China National Standards (CNS) A4 specification (210X297), Γ777Ί 13 91506 H3 436487 naphthalene-1 -yl) -1 Η -pyrrole (5 8), 3- (2,4-difluorobenzyl) -1- (1 [ 1-oxazol-4-yl) methyl-4- (naphthalene-1-yl) -1Η-pyrrole (59), 3- (4-cyanobenzyl) -1- (1Η-imidazol-4- (Methyl) methyl-4- (naphthalene-1-yl) -1Η-pyrrole (60), (1H-oxazol-4-yl) methyl-3- (4-methyl 碇 methyl-benzidine Yl) -4-(naphthalene-1 -yl) -1 fluorene-pyrrole (6 1), 1-UH-imidazol-4-yl) methyl-3- [4- (2-methylthioethyl) benzene Fluorenyl) -4- (naphthalene-1-yl) -1Η-pyrrole (62), 1-UH-oxazol-4-yl) methyl-3- [4- (2-methylthioethoxy) benzene Mesyl) -4- (ban-1-yl group (63), 1- (1H-oxazol-4-yl) methyl-3- (3-methylthiomethyl-benzyl) -4 -(Naphthalene-phenyl) -1Η-pyrazole (64), imidazol-4-yl) methyl-4- (Cai-1-yl) -3- (3-phenylbenzyl) (65), 1- (1H -Mizil-4-yl) methyl- (4- (cha-1-yl) -3- (4-phenylbenzyl) -1) -pyrrole (66) Printed by (1H-imidazol-4-yl) methyl-4- (naphthalene-1-yl) -3- (4-phenoxybenzyl) -1H- Pyrrole (67), 3- (4-benzylbenzylideneimidazol-4-yl) methyl-4- (naphthalene-1-yl) -1pyridine (68), 1-UH-oxazole-4 -Yl) methyl-4- (cha-1-yl) -3- (naphthalen-1-yl) carbonyl- 1Η-Btt (69), oxazol-4-yl) methyl-3- (4- Methyl benzamidine) -4- (N-methylindenamidine-3-yl) -1Η-η ratio (70), 915 0 6 This paper is sized to comply with China National Standard (CNS) A4 (210X297) Public love) i 4 H3 436487 5-n-butyl-3- (2,4-dibenzobenzyl) -1- (111-oxazol-4-yl) methyl-4- (Cai-1- Eg (71), 5-benzyl-3- (2,4-dichlorobenzyl) -1- (1 (1-oxazol-4-yl) methyl-4- (naphthalene-1- (72), 1- [1- (4-Cyanodinyl) -111-imidazol-5-yl) methyl-4- (ch-1-yl) -3- (phenphen-2-yl) Carbonyl-I-I-laro (73), [[(1- (4-Gabenzyl) -1, -oxazol-5-yl) methyl, 4- (naphthalen-1-ylphen- 3-yl) carbonyl-1H-pyrrole (74), 3-benzyl-cyanoyl) -1Η-heptyl-5-yl] methyl-4- (prohibited-1.-jita (75), 3- (3-bromobenzylidene-bu [1- (4-fluorobenzyl) -1Η-imidazol-5-yl] methyl-4- (fluoren-1-yl slightly (76), 3- ( 4-bromobenzyl-l- [l- (4-airbenzyl) -1'-oxazole- 5-yl] methyl-4- (naphthalene-1-yl) -1'-pyrrole (77), 3- (4-fluorobenzylidene) -1- (1-methyl-1H-oxazol-4-yl) methyl-4- (ban-1-yl) -111-lata (78), 1- (1-methyl-1Η-imidazol-4-yl) methyl-4- (naphthalene-1-yl) -3- (4-phenoxybenzyl) -1Η-pyrrole (79), economical Ministry of Standards and Technology Administration of the People's Welfare Commission of the PRC Printing Base-4 Zolimidinylmethylamine r—J-propylpropylthiomethyl Kr he- C-based 3 1 -ylnaphthalene / 1-methyl T-carbonyl hydroxymethyl (1-yl-r N 4 _ — '_ 3 miles)-hoofylmethylamine t-_yl propionate VI / thiomethanyl nitropyrazolyl \ J / quizyl Phenyl phenylmethylamine ntf; This paper size applies to China Standards for Household Standards (CNS) A4 (210 X 297 cm) 5 1 9 1506 4 3 6 4. 8 7 _._ ^ _ H3_ 3- (N-benzylamine formamidoxazol-4-yl) methyl-4- (cha-: L-yl) -1 pyrene-pyrrole (8 3), 1-UH- Oxazol-4-yl) methyl-4- (naphthalene-butyl) -3- (hexahydropyridin-1-yl) carbonyl-1H-pyrrole (84), 1- (1H-imidazol-4-yl) Methyl-3-(morpholin-4-yl) carbonyl- 4- (naphthalene-butyl) -1 Η-larrole (8 5), 1- (1Η-oxazol-4-yl) methyl-4 -(Naphthalene-1-yl) -3- (thiomorpholin-4 -yl) carbonyl-lH-afc (86), imidazol-4-yl) methyl-4- (Cai-1-yl) -3 -(S, S-dioxothiomorpholin-4-yl) carbonyl- 1H-diazole (87), 1 (1H-imidazol-4-yl) methyl- 4- (naphthalene-1-yl)- 3- (hexahydropyridin-1-yl) carbonyl-1H-l (l) (88), 1- (1H-oxazol-4-yl) methyl-3- (4-methylhexahydropyridine-1 -Yl) carbonyl- 4- (Proto-1-ylrole (89), imidazol-4-yl) methyl-4- (cha-1-yl) -3- (¾azolidine-3 -yl) carbonyl- 1H-pyrrole (90), 3- (4-hydroxyhexahydropyridin-1-yl) carbonyl M- (1Η-oxazol-4-yl) methyl-4 (naphthalene M-yl) -1Η-pyrrole ( 91) Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs 1- (1ί-imidazol-4-yl) methyl-4- (naphthalene-1-yl) -3 -(4-oxohexahydropyridin-1-yl) carbonyl-1H -laro (92), 3-N- (2-hydroxyethyl) aminomethylamidin-1-UH-oxazol-4-yl ) Methyl-4- (naphthalene-1-yl) -1Η-pyrrole (93), 3- [N- (2-hydroxyethyl) -methyl] -carbamoyl-1- (1H-imidazole-4 -Yl) methyl- (4- (1-1-yl) -1) -pyrrole (94), (1H-imidazol-4-yl) methyl- 3- [N- (2-methoxyethyl) -N-A paper size is applicable to China National Standards for Standards (CNS) A4 (210 X 297 public directors) 91506 16 H3 436487 based] Aminomethylamidino-4- (naphthalene-butyl)-1Η-account slightly (95 ), Bu (1H-oxazol-4-yl) methyl-3- (morpholin-4-yl) carbonyl-4- (of phosphon-4-yl) -1Η-pyrrole (96), 4- (1 , 2-Dihydropyridin-5-yl) -1- (1Η-imidazol-4-yl) methyl-3- (mangan-4-yl) carbonyl-1H -pyrrole (97), 3-N- (4-cyanobenzyl) carbamoyl-oxazolyl-4-yl) methyl-4- (naphthalene-1-yl) -1hydrazone-pyrrole (98), 1M1-methyl-1H-oxazole-5 -Yl) methyl-3- (methyl-4-yl) carbonyl_4- (ban-1-yl) -1Η -la slightly (99), (S) -l- [l- (4-benzylbenzyl) ) -1Η-oxazol-5-yl) methyl-3-U- (1-methoxycarbonyl-3-methylthio) propyl] aminomethyl- 4- (CAI-BUKI) -1H-pyrrole (100), (S) -l- [l- (4-fluorobenzyl) -1H-oxazol-5-yl) methyl-3- [N- (1-Hydroxycarbonyl-3-methylthio) propyl] aminomethyl-4- (naphthalen-1-yl) -1 fluorene-larol (1 0 1), (S) -l- [l- (4-cyanobenzyl) -1Η-oxazol-5-yl) methyl-3- [N- (1-methoxycarbonyl-3-methyl) butyl] aminomethylfluorenyl 4- (naphthalene- (Bulk) -1H-pyrrole (102), printed by (S) -l- [l- (4-cyanobenzyl) -1 咪 -imidazol-5-yl) methyl- 3- [N- (1-hydroxycarbonyl-3-methyl) butyl] aminomethylamido-4- (naphthalene-1-yl) -1 Η-laro (1 0 3), 1- [1- (4-cyanobenzyl) -1′-imidazol-5-yl) methyl-3- (morpholin-4-yl) carbonyl- 4- (naphthalene-1-yl) -1′-pyrrole (104), [ 1- (4-cyanobenzyl) -1'-imidazol-5-yl) methyl-3- (4-methylhexahydropyrine-1-yl) carbonyl-4- (naphthalene-1-yl) -1 ' -Pyrrole (105), this paper size is applicable to China Standard S (CNS) A4 (210 X 297 public love) 17 9 15 0 6 436487 ___H3_ 1- [2- (1Η-oxazole-1-yl) ethyl 3- (morpholin-4-yl) carbonyl-4- (naphthalene-1-yl) -lH-pyrazole (106), (S) -1- [3- (lH-imidazol-4-yl) propane ] -3- [N- (1-methoxycarbonyl-3 -methylthio) propyl] aminomethylamido-4- (naphthalene-1-ylrole (107), (S) -3- [N- (l-hydroxycarbonyl-3-methylthio) propyl] aminomethyl-1- [3- (1Η-imidazol-4-yl) propyl] -4- (naphthalene-1-yl) -1Η- Pyrrole (108) '1- [3- (1Η-oxazol-4-yl) propyl] -3- (morpholin-4-yl) carbonyl-4- (Cai-1-yl) -1Η -laro (109), [1- (4-Azylbenzyl) -1'-imidazol-5-yl) methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethylamidino -4- (naphthalene-1-yl) MΗ-pyrrole (110), [1-U-bromobenzyl) -1Η-oxazol-5-yl) methyl, 3- [N- (2-methoxy Ethyl) -N-methyl] carbamoyl-4- (naphthalen-1-yl) -1Η-pyrrolylcarbonylbenzylbromochyl 11 I (-5 Printed by the Staff Welfare Committee of the Central Bureau of Standards of the Ministry of Economic Affairs [1- (4-cyanobenzyl) -1Η-oxazol-5-yl) methyl-3- (morpholin-4-yl) thiocarbonyl-4- ( Naphthalene-1-yl) -1'-pyrrole (113), 3-N- (2-methoxyethyl) -N-methyl] aminomethyl-1-U-methyl-1H-oxazole-5 -Yl) methyl- 4- (naphthalene-1-yl) -1Η- € (114), 1- (1-isobutyl-1H-oxazol-5-yl) methyl-3- [ N- (2-Methoxyethyl) -N-methyl] aminomethylamidino- 4- (naphthalene-phenyl) -1Η-pyrrole (115) This paper size is applicable to China National Standard (CNS) A4 (210X297) Public love) \ g 9 1506 H3 436487 1- (1-cyclohexylmethyl-1H-oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -methyl] amine methyl Fluorenyl- 4- (naphthalene-butyl) -1 fluorene-pyrrole (116), 3- [N- (2-methoxyethyl) methyl] aminomethyl-4- (naphthalene-butyl) -1 -(1-pentyl-1H-oxazol-5-yl) methyl-1H-laq (117), 3- [N- (2-methoxyethyl) methyl] aminomethyl-4- (Naphthalene-1-yl) -1- (1-octyl-1H-imidazol-5-yl) methyl-1H-pyrrole (118), 1- (1-decyl-1H-imidazol-5-yl] Methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethane- 4- (Cai-1-yl) -1Η-pyrrole (119), 3- [N- ( 2-methoxyethyl) -M-methyl] aminomethyl (3-methylbutyl) -1） -imidazol-5-yl] methyl-4- (Cha-Bulkika (120), 1 -[1- (2-methoxyethyl) -1Η-imidazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminoformyl-4- (Naphthalene-1-yl) -1Η-pyrrole (121), 3- [H- (2-methoxyethyl) -N-methyl] aminomethyl-methyl-methoxypropyl) -1Η -Imidazol-5-yl] methyl-4- (naphthalene-1-yl) -1Η -laroline (122), printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs, 1- [1- (3-ethoxy Propyl) -1） -imidazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethylamidino-4- (naphthalene-butyl) -1Η- Pyrrole (123), 1-. [1- (3-isopropoxypropyl) -1 [1-imidazol-5-yl] methyl-3- [1 (2-methoxyethyl) -H-methyl Yl] aminomethyl-4- (cha-buyl) -1Η-pyramine (124), 1- [1- (4-bromobenzyl) -1Η-oxazol-5-yl] methyl-3 -[4 -Methyl paper size is applicable to Chinese National Standards (CNS) A4 specifications (210X 297 male cages) 91506 19 3 6487 H3 Hexahydropyridine-1-based printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs] 4- (naphthalene-1-yl) -1Η-pyrrole (125), λA- [1- (4-chlorobenzyl) -1Η-oxazol-5-yl] methyl-3- [4-methylhexadecane Hydropyridine-butyl] carbonyl- 4- (naphthalene-butyl) -1Η-laro (Γ26), 1- [1- (4-fluorobenzyl) -1Η-oxazol-5-yl] methyl -3- [N- (2-methoxyethyl) -N-methyl] aminomethylamido-4-(naphthalene-TL-yl) -1H -pyrrole (127), 1- [1-U-fluoro Benzyl) -1Η-imidazol-5-yl] methyl-3- [4-methylhexahydro Pyridin-1-yl] carbonyl- 4- (naphthalene-1-yl) -1Η, pyrrole (128), methoxybenzyl) -1Η-oxazol-5-yl] methyl-3- [N- ( 2-methoxyethyl) -N-methyl] aminomethylamidino- 4- (naphthalene-phenyl) -1Η-pyrrole (129) '1- [1- (4-methoxybenzyl) -1Η- Imidazol-5-yl] methyl-3-U-methylhexahydropyrimidin-1-yl] carbonyl-4- (naphthalene-1-yl) -1Η-pyrrole (130), 1- [1- (3 -Gas benzyl) -1H-imidazol-5-yl] methyl-3- [4-methylhexahydropyridin-1-yl] carbonyl-4- (ch-1-yl) -1H-pyrrole (131 ), 1- [1- (3-chlorobenzyl) -1'-panazol-5-yl] methyl- 3- [N- (2-methoxyethyl) -N-methyl] aminomethyl -4- (Proto-1-yl) -1Η-pyrrole (132), [1- (2-chlorobenzyl) -1Η-oxazol-5-yl] methyl-3- [4-methylhexa Pyridin-1-yl] carbonyl- 4- (naphthalene-1-yl) -1Η-pyrrole (133), 1- [1- (2-azabenzyl) -1Η-oxazol-5-yl] formyl -3- [K- (2-methoxyethyl.yl) -N-methyl] aminomethyl-4- (naphthalene-1-yl) -1Η-pyrrole (134), [1- (2 -Fluorobenzyl) -1Η-oxazol-5-yl] methyl-3- (4-methylhexahydropyridin-1-yl) carbonyl- 4- (naphthalene-1-yl) -1Η-pyrrole ( 135), 20 This paper size applies to China National Standard (CNS) A4 Lattice (210 X 297 degrees) 915 0 6 436487 l- [l- (4-methylbenzyl) -1H-oxazol-5-yl] methyl- 3- [4-methylhexahydropyridine- 1-yl] carbonyl-4- (naphthyl-butyl) -1H-pyrrole (136), [1- (4-methylbenzyl) -1H-oxazol-5-yl] methyl-3- ( Morpholin-4-yl) carbonyl-4- (naphthyl-phenyl) -1Η-pyrrole (137), lU- (3-methylbenzyl) -1Η-oxazol-5-yl] methyl-3- (4-methylhexazyl-1-yl) -Ci- (4- (Cai-1-yl) -111-Lahu (138), [1- (4-fluorobenzyl) -1Η- 眯Azol-5-yl] methyl-3- (naphthalen-1-yl) carbonyl-1H-pyrrole (139), 1- [1- (4-bromobenzyl) -1Η-oxazol-5-yl] methyl -3- (naphthalene-TL-yl) carbonyl-1Η- € (140), [1- (4-bromobenzyl) -1Η ~ oxazol-5-yl] methyl-3- [N- (2-methoxyethyl) -N-methyl] aminomethyl-4- (naphthalene-1-yl) carbonyl-1H-pyro (141), 4-ethoxycarbonyl-2- (1Η-Η Azol-5-ylmethyl) -5-(naphthalene-1-yl) wow (142), 2- (1 fluorenazol-5-ylmethyl) -4- (morpholin-4-yl) carbonyl -5- (Naphthalene-1-yl) Mingli (143), 4-ethoxycarbonyl-2- (1 (-oxazol-5-ylmethyl) printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs- 5- (naphthalene-1-yl) -thiazole (144), 2- [1- (4-chlorobenzyl) -1'-imidazol-5-ylmethyl] -4-methoxycarbonyl_5_ (ban-1 ~ Yl) _Sleep (145), 2- [1- (4-chlorobenzyl) -1Η-oxazol-5-ylmethyl-4- (morpholin-4-yl) carbonyl-5- (naphthalene -1-yl) -ι «azole (146), 2- [1- (4-chlorobenzyl) -1Η-oxazol-5-ylmethyl-4- [N- (2-methoxy) ethyl -H-methylaminomethylmethyl] -5- (naphthalene-1-yl) -pyrazole (147) 91506 The paper is suitable for China National Broadcasting Standard (CNS) A4 (210 X 297 public love) 2 J H3 436487 2- [l- (4-chlorobenzylimidazol-5-ylmethyl-5-methoxycarbonyl_4 ~ (ban-1-yl) -i®mile (148), 2- [1- (4-chlorobenzyl) -1'-imidazol-5-ylmethyl-5- (morpholin-4-yl) carbonyl-4- (naphthalene-1-yl) -pyrazole (149), benzyloxymethylene ) Hexahydropyridin-4-ylmethyl] -1H-Tizol-5-ylmethyl) -5-methoxycarbonyl-4- (naphthalene-1-yl) -pyrazole (150), benzyloxycarbonyl) Hexahydropyridin-4-ylmethyl] -1H-oxazol-5-ylmethyl} -5- [H- (2-methoxy) ethyl-N-methylaminomethylmethyl] -4- (Cha-1-yl) -1-l (151), benzyloxycarbonylhexahydropyridin-4-ylmethyl] -1H-oxazol-5-ylmethyl] -4- [N- (2-methyl Oxyethyl ) -N-methyl] aminomethyl-3- (naphthalene-1-yl) -1Η-pyrazole (152), methoxycarbonylhexahydropyridin-4-ylmethyl] -1H -imidazole-5- N-methyl] -4- [N- (2-methoxyethyl) methyl] aminomethyl-3--3-methyl- (1-_1-sulfanyl (153), [1- (4-benzyl) -1Η-imid-5-ylmethyl] -4- [N- (2-methoxyethyl) methyl] aminomethylamidino- 3- (naphthalene-phenyl) -1Η-pyrazole Central Printed by the Staff Welfare Committee of the Standards Bureau (154), [1- (4-chlorobenzyl) -1Η-imid-5-ylmethyl] -4- [N- (2-methoxyethyl) -Η -Methyl] aminomethylamido- 3- (naphthalene-1-yl) -lH-pyrazole (155), 1- [1- (4-cyanobenzyl) -1'-imidazol-5-ylmethyl] -4- [N- (2-methoxyethylmethyl] aminomethylamino- 3- (ban-1-yl mile. (156)) This paper size applies to China National Standard (CNS) A4 (210X 297 gold) 22 915 06 H3 436 487 1- [1-methyl-Iff-oxazol-5-ylmethyl] -4- [N- (2-methoxyethyl) methyl] aminomethyl-3 -(Naphthalene-phenyl) -1Η-oxazole (1 5 7), benzyloxycarbonyl-hexahydropyridin-4-ylmethyl] -1H -imidazol-5-ylmethyl] -4- (morpholine- 4-yl) carbonyl- 3- (naphthalene-butyl) -1 {1-pyrazole (158), methoxycarbonyl -Hexahydropyridin-4-ylmethyl] -1H -oxazol-5-ylmethyl] -4- (mangan-4-yl) carbonyl-3- (naphthalene-1-yl) -1Η-pyridine Oxazole (1 5 9), [1-U-bromobenzyl) -1'-imidazol-5-ylmethyl] -4- (mandan-4-yl) carbonyl-3 · '(naphthalene-1-yl ) -1Η-pyrazole (160), [1-U-chlorobenzyl) -1Η-oxazol-5-ylmethyl] -4- (morpholin-4-yl) carbonyl- 3- (naphthalene- 1-yl) -1′-pyrazole (161), cyanobenzyl) -1′-amidazol-5-ylmethyl] -4- (morpholin-4-yl) carbonyl-3- (naphthalene-1-yl Azole (162) and 1- (1-methyl-1H-oxazol-5-ylmethyl) -4- (morpholin-4 -yl) carbonyl-3-(naphthalene-1 -yl) -1 Η- Pyrazole (16 3). 5. — A method for manufacturing an imidazole derivative such as the one in the scope of patent application, which is characterized by: printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs / TΓ 物 合 化合ηH.J (2) Yiding Institute item 1X Fan Weili specifically requested to apply IX η Chinese formula A stupid three indication Γ Τ and the formula below and below are stored in alkali, and the traditional Chinese medicine is dissolved in the]] / radical reaction compound This paper size is applicable to China National Standard (CNS) A4 specification (2IOX 297 male) 23 91506 436487 H3 should be used (where B, C, D and X are as defined in item 1 of the scope of patent application), The trityl group in the product thus obtained was removed in the presence of fluoroacetic acid, and K was obtained as a compound represented by the following formula (la): HK OaJ (wherein ni, B, C, D, and X (as defined in the first patent application scope); or (b) the compound represented by the following formula (4): N--(CHiin-Cl · HCI (4) Printed by the Staff Welfare Commission of the Central Bureau of Standards, Ministry of Economic Affairs (where Π1 and A are as defined in the scope of patent application No. 1), in a solvent, in the presence of a base, with a compound of formula (3) Reaction to obtain a compound represented by the following formula (1b): C X (lb) (where η 1, C, and D are the Chinese papers (CNS) A4 specifications (210X297 public capital) 2 4 9 1506 H3) as specified in the scope of the patent application; 1); or (c) using the compound represented by the following formula (5): (5) The reaction with the compound of formula (3) in a solvent in the presence of a base, and the trityl group of the product thus obtained are removed in the presence of trifluoroacetic acid to obtain a compound represented by the following formula (6): Printed by the Shell Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs (wherein | B, C, D, and X are as defined in item 1 of the scope of patent application) Compound: (Ic) (where IB, C, D and X are as defined in item 1 of the scope of patent application); or (d) hydrolysis of the compound represented by the following formula (7): B 炚 乂, 0 £ t 〇 (7) C This paper size applies to China National Standards (CNS) A4 specifications (210X 297 male D 25 9 15 0 6 (where ni, A, B and C are as defined in item 1 of the scope of patent application), and the following formula is obtained (3) Compounds shown: 0 (in the formula, m, A, B and C are as defined in the first patent application scope); then in the presence of a coupling agent, react with a compound represented by the following formula (9): HNR 1 eR 1 7 (9 ) (Where R16 and Ri7 are as defined in item 1 of the scope of patent application), a compound represented by the following formula (Id) is obtained: Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs (where Ni, A, B, C, JU6 and R17 are as defined in item 1 of the scope of patent application); or (e) in the presence of a vulcanizing agent, Conversion of a carbonyl group in a compound represented by the following formula (le) to an oxocarbonyl group * 0 This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 public directors) 26 9 1506 H3 (where ni, A, B, C, and D are as defined in item 1 of the scope of patent application). The compound represented by the following formula (If) is obtained: Of) (wherein “ni, A, B, C and D are as defined in the first patent application scope); or (f) the compound represented by the following formula (Is): Η / N Ν DX GS) R2-T Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs (where B, C, D, and X are as defined in item 1 of the scope of patent application), in a solvent with the following formula (10) (10) (In the formula, R2 is as defined in item 1 of the scope of patent application, and T indicates that the hydroxy group of Chinese formula or denature should be reversed or The following is the definition of the item of the chemical compound in the formula 1 No. Fan Li specially requested to apply for X and D 91506 This paper size applies to China National Standard (CNS) A4 specifications (210X297 public love) 2 7 4 3 6 4 8 7 (g) A compound represented by the following formula (11): (In the formula, A, G and I are as defined in item 1 of the scope of patent application), cyclization in an inert solvent to obtain a compound represented by the following formula (li): (In the formula, A, G and I are as defined in item 1 of the scope of patent application). Or (h) convert the amido group in the compound of the formula (11) into a thiamine group to produce the following formula ( 12) Compound shown: ο Hf'Nο Μ5 G 2 P / PIS Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs (where A, G, and I are as defined in item 1 of the scope of patent application), and then cyclized in an inert solvent to obtain the following formula (1J The compound shown The size of this paper uses the Chinese National Standard (CNS) A4 (210 X 297 public directors) 28 91506 8 7 __ ^ _ H3_ (where A, G and I are as defined in item 丨 of the application scope) Or (i) a compound represented by the following formula (13): NH: (U) (wherein A is as defined in item 1 of the scope of patent application), in a solvent with a compound represented by the following formula (14a): C1 0 (Ua) (where G and I are As defined in item 1 of the Shen He patent scope), a compound of formula aj) is obtained; or (J) a compound of formula (13) is reacted with a compound represented by the following formula (14b) in a solvent, 0 0 Ministry of Economic Affairs Printed by the Staff Welfare Committee of the Central Bureau of Standards (Ub) (where G and I are as defined in item 1 of the scope of patent application), and the following formula (lk) is obtained: Standard (CNS) A4 size (210 X 297 male directors) 2 g 91506 436487 H3 (Ik) (wherein A, G and I are as defined in item 丨 of the patent application scope); or (k) the compound represented by the following formula (U): It is G and A oxygen, alkane I 6 in C formula 1- (C-based di Fan Li specially asked to explain the existence of the base under water is shown in> -f, the meaning of the producer can be obtained by the formula The combination of the lower and the lower deposits is shown in the Chinese medicine solution reaction counter. 5 Printed by the Staff Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs of China VJ-based oxyalkane 6 C is defined by the definition of 1X. Fan Li specially requested to apply for the formula of G and A as shown in the definition of Yiding or compound b / 1 VI / 6 1 / Γ \ W W Α / J \ of 9 15 0 6 This paper size applies to a national standard (CNS) A4 specification (210 X 297 male dragon) 3 〇H3 厶 (IS) (where A is as defined in the scope of the patent application ()), In a solvent, in the presence of a base, and react with a compound represented by the following formula (17),, α Η-N (Π) (where G and L are as defined in the scope of the patent application) To obtain a compound represented by the following formula (In): A L (In) 〇 Printed by the Staff Welfare Committee of the Central Bureau of Standards, Ministry of Economic Affairs , N Μ (Wherein A, G and L are as defined in item No. of the scope of patent application); or (m) the compound represented by the following formula (13): Cbz OS) Chinese paper standard (CNS) applies to this paper size A4 specification (210X 297 gm) 31 91506 H3 (where Cbz represents benzyloxycarbonyl group), in a solvent in the presence of a base, react with a compound of the following formula (17), followed by deprotection to obtain the following formula ( 1〇) The compound shown: [{/ (In the formula, G and L are as defined in item 1 of the patent application scope), and then coupled with the compound represented by the following formula (19): TEF (19) (In the formula, E and F are as in patent application scope 1 As defined in the item) to obtain a compound represented by the following formula (1 p): / E ~ F ' 4 3 648 H3 (where B, C, D and X are as defined in item 1 of the scope of patent application) A compound represented by the following formula (8): OH ¢ 8) (In the formula, ni, A, B and C are as defined in item 1 of the scope of the patent application. Group II medicine is transferred to the Fankili patent method. Please apply for the same amount. The effect t has 8 treatments, including the treatment of the inclusion of zozobium and the prevention of the use of the system. The group of medicine and medicine of the 8th paragraph Fanli. Specialists apply for cancer treatment 9 and prevention of use The items of the group medicine are 8. The range of the fan is narrow, please apply for treatment and prevent the 3J series of medicine. 8 --JJ- τνπ Special request for congee treatment, such as treatment, printed by the Employee Welfare Committee of the Central Standards Bureau of the Ministry of Economic Affairs, and printed on item 8 of the disease area and Fan Yanli's liver type, please apply for treatment and prevention The group of drugs of the group 0 causes the symptoms of infection. The paper size is applicable to the Chinese Standard for Household Standards (CNS) A4 (210 × 297 male thin) 33 91506 Annex IV A. £ 土 ·· 士 application date // ^ 7 〇 · Dou, case number P7 &quot; &quot; &quot; Category 〇〇ΐΰ ^ 0 / ° έ. ΑΗΚ ί // (, ^ The above blocks are to be filled out by this Bureau) WJE \ Supplement I A4 C4 436487 -、 = Name Chinese oxazole derivative with inhibitory activity on farnesyl transferase and its manufacturing method English IMIDAZOLE DERIVATIVES HAVING AN INHIBITORY ACTIVITY FOR FARNESYL TEiANSFERASE AND PROCESS FOR PREPARATION THEREOF name nationality s Xuan Ai Zhong Zhong Ren Gao Jin. ¾ CnJ 7.12. Yi Huanquan Quan Xianxian Tai Cheng Li Zheng Guo 郑 $ *-, _ 1 6 § 1 6 1 1 IBt 3. Li Chenhao 4. Zheng Yuanxi 8. Chu Chengqiu 9. Cui Taisheng 13. Jin Xuancheng 14. Li Xuan He Chengyu and You Xingui Shen Zhengjin * 05 5 11 —Invention I. People create residences and residences 1 -ί --f sc ........ &quot; 『I-TMgTWTMrmtTHWT Big Big Big Big Big Big Big Big * ••• ♦ •• I ♦ * -k * * * * * 0123456 1234567891111111 Makuba City $ rgm City City rlrrff City West isisilllii Tian Tian Tian Tian Tian Tian Tian Tian Tian Tian Tian Tian Tian Tian Greatly Greatly Greatly Greatly 1-ilsiaaiisis 1 4Λ1λκ141 Modal 41 Modal 15PS1 I Modal t IIGIIGIGX-^^ &amp; &amp; ^ J0bc0 &amp; L &amp; 00L6'LE4 · π_ 8LLA888 88 8 6η 3 —333 33 3 Tunu ΓΤ \ Ι frf rsfsrws§rBFBF2rapgr &gt; TBP »gr & g t; F »&gt; r &gt; ytT) 7 house 125S: 5 live -3o Rong 66-1-&gt; J53 1¾ ο 500 9HOS 32 1 〇Φ1 10 even 2; 58-20 Shelves 90-80- * ο 3 Binding name (name) LG Chem Co., Ltd. Ministry of Economic Affairs !!.? 2 * 4:!? IKx ^ it Cooperative Co. Printed Line III. Applicant's Nationality Residence, Residence (Office) Representative Name South Korea Seoul, Korea 20% of Yeouido-dong, Yeongdeungpo-gu is applicable to China in a standard paper. National Standard (CNS) A4 specification (210X297 mm) (revised page) 9T5W 436487 'Γ89Γ5ΓΤΒ ~ ^ 7γ year AJ5 Β5 Λ, / 4 2. Abstract of Chinese invention (Name of the invention 1_Inhibitory activity of imidazole is biological and its production method. The present invention is a novel imidazole derivative having inhibitory activity on farnesyl transfer s as shown by the following formula (I): , Or an acceptable hydrazone or its isomer, [Formula I] wherein A, η and Y are defined as shown in the description; there are also methods for preparing compounds of formula (I); K is an intermediate in the preparation of a compound of formula (I); and B contains a compound of formula (I) as an active ingredient Weigh composition. (Please read the notes on the back before filling in the columns on this page) English Abstract of Invention (ACTIVITY FOR FARNESYL TRANS: FOR PREPARATION THEREOF iG AN; FERAS :; E AND PROCESS Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs present. .invention relates to a novel imidazole derivative represented by ttie following formula (1) which shows an inhibitory activity against famesyl transferase: [Formula I] Ηώ-ϊ · or pharmaceuticaily acceptable salts or isomers thereof in which A, ni and Y are defined in tfie specificadon; E〇ra process for preparation of the compound of fonmiia (1); to intermediates which are used in the preparation of the compound of formula (1); and to a pharmaceutical composinoa comprising Che compound of formula (1) as an active ingredient The size of this paper is applicable to China National Standard (CNS) A4 (210X297mm) 2 (Repair IHM) 9 1506 43 64 8 Revision. 丨 No. 87119691 Patent Application Amendment to the scope of this patent (89 August 18th Kinds of the oxazole derivative represented by the following formula (1): (1) In the formula, * ″ represents an integer of 1 to 4 * A represents hydrogen; can be optionally passed through C3-C? Cycloalkyl or Ci-C6 alkoxy Substituted straight or branched ^^^ alkyl; or a group selected from the group consisting of: Ri 'neutral formula -R1 prime ~. SC1, or hydrogen, as the base oxybenzyl, self-based oxygen, t alkylcarbonylhydroxy, cyanocyanine or hydrogen or E, formula P and Ministry of Economy Printed by the Staff Welfare Committee of the Central Bureau of Standards to substitute for phenyl or oxy-C benzene C1. It is intended to substitute for keto or ·, phenyl hydrogen argon shows the R3 oxy. Group of groups 91506 This paper size applies to China National Standard (CNS) A4 (210 X 297 male; * t) 1