TW379224B - Urea derivatives - Google Patents

Description

ίψ i I, the date of A7 supplemented from 1123 B7 V. Description of the invention (>) where R1 and R2 are each hydrogen or connected to form ethylene, R3 is hydrogen or low alkyl, and . ^ ^ Argon HS, for ic Ming 4 5 for R R X: the purpose of this compound

Under the preparation method, it may be \ — / I ~, '// (Please read the notes on the back ^, the form is filled out on this page) rr line. -I-THik Printed by paper Applicable to China National Standard (CNS) A4 specification (210X 297 mm) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (f) TECHNICAL FIELD The present invention relates to a novel urea derivative and its pharmaceutically acceptable salt . In particular, it relates to a novel urea derivative having a pharmacological activity such as serotonin (5-HT) antagonism and a pharmaceutically acceptable salt thereof. The urea derivative and its pharmacologically acceptable salt can be used as 5-HT antagonists to prevent CNS abnormalities such as anxiety, depression, obsessive-compulsive behavior, migraine, pressure eating disorder, A 1 zheime I * in humans and animals. Disorders, sleep disorders, bulimia, irritability, drug abuse such as coca test, alcohol, nicotine and benzodiazepine, schizophrenia, and abnormalities associated with spinal trauma and / or head injuries such as hydrocephalus . BACKGROUND ART An international patent application (International Publication No. WO 9 5/21844) W095 / 29177 is based on a patent cooperation treaty describing a urea derivative having a 5-HT2e receptor antagonistic effect. The invention shows that after intensive research, the inventors have obtained a urea derivative with extremely strong pharmacological activity. The urea derivative of the present invention is novel and can be represented by the following formula (I): R · '1

HC

00 \ This paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm) Printed by the Central Standards Bureau of the Ministry of Economy, Shellfish Consumer Cooperative Co., Ltd. to print and amend '4, year and month g supplement 87., P A7 — —', l, l:;: — B7_____; _V. Description of the Invention (a) is 〇 · 1 ni g, 〇 · 2 5 mg, 〇 ..5 mg, 1 mg, 20 mg, 50 mg, 1 mg Compound (I) is administered to a patient to treat a disease, and is generally administered at 0.1 mg / person and 100 mg / person daily. The following preparations and examples can be used to clarify the present invention. Example 1 Hydrogenated 0.2 g of 1-methyl-5-nitridinine in methanol (10 ® 1) with P d-C (10%, 0.1 g) for 3 hours. The catalyst was filtered off, and the solvent was dried under vacuum. The obtained amine was dissolved in tetrahydrofuran (1 Qml), and carbonyldiimidazole (0.184 g) was added. Stir at room temperature for 1 hour. N, N-dimethylformamide (5 ml) containing 3- (2-benzylpyrazol-3-yl) aniline (0.31 g) was added. Stir at room temperature for 66 hours and evaporate. The resulting solution was separated into ethyl acetate and water. The organic layer was washed with a disulfonic acid solution and dried over sodium sulfate. And purified by silica gel column chromatography (chloroform.-methanol: 0-10%?) To obtain 1 ^-[3- (2-benzylpyrazol-3-yl) phenyl] -N,-(1 -Methylindin-5-yl) ureamp: 108-112 ° C IR (Nujol, cm _1): 1640, 1605 NMR (DMSO-d6 > < 5): 3.75 (3H, s), 5.41 (2H , S), 6.34 (lH, d, J = 3Hz), 6.43 UH, d, J-2Hz), 6.90-7.05 (2H, s), 7.10-7.50 (7H, m), 7.58 (lH, d, J = 2Hz), 7.60-7.70 (2H, m), 8.47 (lH, s), 8.68 (lH, s) Mass: 422 (M + 1 +) Example 2 'The method of Example 1 can obtain the following compounds. N-[3-(1 -benzyloxycarbonylpyrazol-3 -yl) phenyl] -N '-(1 -methylindolin_ -24- (Please read the precautions on the back before filling this page) * ^ ^^^ 1 1 II _ i ^ ilt —m nnIJ '-* < 0 ^ ^^ — ^ 1 J,.:, ¾ — 丁 -¾ x— This paper size is in accordance with China National Standard (CNS) Λ4 specifications (2) 0X297 mm) ίψ i I ί, A7 supplemented from 1123 B7 V. Description of the invention (>) In the formula, R1 and R2 are each hydrogen or connected to form ethylene, and R 3 is hydrogen or low alkyl Base, and base base nitrate. ^ ^ ^ Argon HS, is ic Ming 4 5 is RRX: the purpose of this compound

Under the preparation method, it may be \ — / I ~, '// (Please read the notes on the back ^, the form is filled out on this page) rr line. -I-THik Printed by paper Applicable to China National Standard (CNS) A4 specification (210X 297 mm) 5. Description of invention (4 manufacturing method 1 ο2ν

/ R3 ΚΊ Β7 (u) or its salt reduction ir

N, (m) or its salt

Ra υ carbonyl dioxazole R5

νη2 (IV) or its salt

(la) or its salt -τΛ xCE Order Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) A7 B7 V. Description of the invention (4 Manufacturing method 2 R5 R4.

-COOH (V) or its salt 1) Diphenylphosphine barrier nitrogen 2) R1 ψ (VI) or its salt R! R · '-

-NHCON

N (Please read the notes on the back # (Fill in this page) • Install Ο

N (1) or its salt Customized law 3 Printed by Shellfish Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs p

(I b) or its salt (lc) or its salt: Cracking method 4 The paper size is applicable to the Chinese National Standard (CNS) A4 specification (2 丨 〇 X 297 mm) —S · ** 5. Description of the invention (Γ A7 B7

(νπ) or its salt (W) or its salt

Id) or its salt (#xiange read the notes on the back, and then 'fill in this page) \ Equipment · Method 5 Set by the central standard of the Ministry of Economy 印 Printed by employee consumer cooperatives

ch3 (K) or its salt (XVI) (I e) or its salt preparation method The paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 5. Description of the invention (k R5 R4 -NH2 A7 B7 (X) Or its salt ^ s, JITl

Ν ⑴ or its salt, please read the price back A Ϊ 事 硕 (XI) brick its salt • CAi / Ν -ΠΒ re / fill, 'Write this page for decoration, ϊ :! Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs The paper size of the paper is applicable to the Chinese national standard (CNS> Λ4 specification (210X 297 mm) A7 B7 V. Description of the invention (manufactured by R4

χ -NH2 (χΠ) or its salt

_Ν (Μ) or its salt Xu Min's note, \ Re (') Fill in -1 page f (If) or its salt 玎

R R4.

-NHCOO

NO, ⑽) or its salt

This paper size applies to China National Standards (CNS) A4 (2) 0X297 mm) 9 *** ΑΊ Β7 V. Description of the invention (^

(X) or its salt

(XVI) (VI) or its salt (Please read the notes on the back before filling this page)

He ml —HI—, 0¾ The definitions of R1, R 2, R 3, R 4, R 5, and X in the printing scheme of the staff consumer cooperative of the Central Standards Bureau of the Ministry of Economic Affairs are as described above, and Z is the base. In addition, the target compound obtained by the above production methods 1 to 9 can be converted into its branched chain within the scope of the compound of the present invention according to the following examples. Compound (I), (Ia), (Ib), (Ic), (Id) ', (Ie), (If),

(II), (III), (IV), (V), (VI), (VII), (VIII), (IX, (X), (XI), (XII), (XIII), (XIV) And (XV) suitable salt is -10- This paper size is applicable to Chinese National Standard (CNS) Λ4 specification (210X 297 gong) Printed by A7 B7, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (9) Non-toxic conventional Pharmaceutically acceptable salts include salts with alkali or acid addition salts, such as salts of inorganic bases such as alkali gold salts (such as sodium, potassium, and planed salts) and alkaline earth metal salts (such as calcium salts, magnesium salts, etc.), Ammonium salts, etc .; organic phosphonium salts such as organic amine salts (such as triethylamine salt, pyridine salt, picolin salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, Ν, Ν'-dibenzyl ethylenediamine Salts, etc.); inorganic acid addition salts [such as hydrochloride, hydrobromide, hydroiodate, sulfate, phosphate, etc.]; organic carboxylic acid or sulfonic acid addition salts [such as formate, acetate , Trifluoroacetate, maleate, tartrate, mesylate, benzenesulfonate, p-toluenesulfonate, etc.]; alkali or acidic amino acid salts [eg, spermine, asparagus Glutamic acid Etc.]: etc., and is preferably an acid addition salt. In this text, suitable examples including the various definitions within the scope of the present invention are detailed below. The term " low " means C1-e unless otherwise specified , Especially C 1-4. Suitable "low alkyl" may be straight or branched Ci-6 alkyl, such as methyl, ethyl, n-propyl, isopropyl, butyl, iso Butyl, tertiary butyl, pentyl, hexyl, preferably -4 alkyl, and methyl, isopropyl or tertiary butyl is most preferably " heterocyclyl " may contain more than one selected from 0 , S and N heteroatoms are saturated or unsaturated, monocyclic or polycyclic heterocyclic groups, and especially the following heterocyclic groups containing 1 to 4 3 to 8 members of N (preferably 5 to 6 members) Miscellaneous monocyclic radicals, such as pyrrole-11- (read the first note and read the two notes on the back page to complete this page) The size of this paper is bound to the Chinese National Standard (CNS) A4 specification (210X 297 mm) Employees of the Central Standards Bureau of the Ministry of Economic Affairs Cooperative printing of A7 B7 V. Description of the invention (, ...), pyrrolinyl, oxazolyl, pyrazolyl, pyridyl and its N-oxides, dihydropyridyl, pyrimidinyl, pyrazolyl, da coax , Three miles [such as 4 4-1,2, 4-triazolyl, 1 Η-1,2, 4-triazolyl, 1 Η-1, 2, 3-triazolyl, 2 Η-1,2 , 3-triazolyl, etc.], tetrazolyl [such as 1Η-tetrazolyl, 2Η-tetrazolyl, etc.], oxazoline, 2-oxazolone, etc .; containing 1 to 4 N Saturated 3 to 8 (preferably 5 to 6) heteromonocyclic groups, such as pyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 2-oxazolone, etc .; containing 1 to 4 N Unsaturated fused heterocyclyl, such as indino, isoindoporyl, indoxolinyl, indolinyl, benzimidazolyl (such as 1 Η -benzimidazolyl, etc.), quinolinyl, iso Pyridinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl, (such as 1,2,3,4-tetrahydroisoquinolinyl, etc.), indazolyl, phenylhydrazone Triazolyl, oxazoline, 1¾azoline, hydrazone, etc .; unsaturated 3 to 8 members (preferably 5 to 6 members) containing 1 to 2 S and 1 to 3 N, heteromonocyclic groups, For example, oxazolyl, isoBfazolyl, fluorene | diazolyl [such as 1,2,4-dadiadilyl, 1,3,4-diazolyl, 1,2,5-11, etc. , Etc.] etc .; 1 ~ 2 0 and 1 ~ 3 N saturated 3 ~ 8 members ( 5 to 6 members are preferred) Heteromonocyclic groups, such as morpholinyl, syringyl, etc .; Unsaturated fused heterocyclic groups containing 1 to 2 値 0 and 1 to 3 N, such as benzoxazolyl, stupid Oxadiazolyl, etc. Unsaturated 3 to 8 members (preferably 5 to 6 members) containing 1 to 2 S and 1 to 3 N Heteromonocyclic groups such as carbazolyl, isocarbazolyl, and Oxadiazolyl [such as 1,2,3-carbadiazolyl, 1,2,4-carbadiazolyl, 1,3,4-carbadi'azolyl, 1,2,5-thiadiazolyl, etc. ], Dihydrocarbyl, etc .; 1 ~ 2 S and 1 ~ 3fliN saturated 3 ~ 8 members (preferably 5 ~ 6 members) miscellaneous -1 2-(Read the precautions on the back to read #rFill this page ) This paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm). Member of the Central Standards Bureau of the Ministry of Economic Affairs. Printed by A7, Industrial and Consumer Cooperative. V. Description of the invention (") Monocyclic groups such as thiomorpholinyl, carbazole Pyridyl, etc .; Unsaturated 3 to 8 members (preferably 5 to 6 members) heteromonocyclic groups containing 1 to 2 S, such as carbendyl, dihydrothienyl, dihydrodihexanone, etc .; Unsaturated fused heterocyclic groups containing 1 to 2 S and 1 to 3 N, such as benzoxazolyl, benzoxazolyl, etc .; unsaturated 1 to 3 8-membered (preferably 5-6 members) heteromonocyclic group, such as furyl, etc .; containing 1 0 and 1 ~ 2 3 unsaturated 3 to 8-membered (preferably 5-6 members) heteromonofluorenyl, such as Dihydrofluorenyl, etc .; Unsaturated fused heterocyclic groups containing 1 to 2 S, such as phenylhydrazine [such as phenylhydrazine [b] blind phenyl, etc.], phenylhydrazine, etc .; Unsaturated fused heterocyclic groups containing 1 0 and 1 ~ 2 S, such as phenyl hydrazone, P, P, and fluorinyl; etc .; The heterocyclic group may contain more than one suitable substituent such as hydroxyl, lower alkoxy, and lower alkyl Group, mono- or di- or trihalo-lower alkyl (such as trifluoromethyl, etc.), amine, protected amine, nitro, halogen [such as F, Cl, Br, I, etc.], fluorenyl, aryl, Aryl lower alkyl and the like. Appropriate " low alkoxy "may contain methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, isopentyloxy, hexyl and the like. Appropriate " mono- or di-substituted lower alkylamino group "may contain an amine group substituted with one or two lower alkyl groups [such as methyl, ethyl, isopropyl, third butyl, propyl, third pentyl, etc.], Preferred are methylamino, ethylamino, dimethylamino, diethylamino, di-n-propylamino, diisopropylamino, dibutylamino and the like. -1 3-(#Read the narrow notes on the back before filling in this page) Binding-order 8 paper sizes applicable to China National Standards (CNS.) Α4 specifications (210 × 297 mm) Μ 7 Employees of the Central Standards Bureau of the Ministry of Economic Affairs Printed by a consumer cooperative V. Description of the invention ((^) 1 1 " Protected Amine Group " "Amino Protective Group" Contains a fluorenyl group such as a low fluorenyl group [such as I 1 formamyl group> ethenyl group 1 Propionyl 9 valeryl > hexyl, etc.) > early (1 1 or two or three) haloalkanoyl (such as ethyl ethoxy) > bromoacetyl 9 dichloro please I ethoxy 9 — fluoroacetamidyl, etc.) Low-carbon carbonyl C such as methoxycarbonyl, read 1 1 ik 1 1} Ethyl carbonyl 9 propoxycarbonyl > third butoxycarbonyl third pentyloxycarbonyl back JI 1 > Hexyl carbonyl, etc.]) Aminomethyl 9 aryl fluorenyl C, such as benzyl fluorenyl 9 toluene Note 1 fluorenyl 9 naphthyl fluorenyl, etc.] 9 aryl alkane τ > * »axyl [such as phenethylfluorenyl, Styrene Matter 1 I f-group, etc.] Aromatic carbonyls [such as phenoxycarbonyl naphthyloxycarbonyl, etc.) Aromatic compounds such as phenylene C, such as benzyl ethyl m > phenyl propionyl, etc. 9 aryl acetaldehyde , ^ 1 | fluorenyl C, such as phenylacetaldehyde, fluorenyl, t, ethyl, etc.] »aryl lower alkoxycarbonyl groups with appropriate substituent I 1 [eg, benzyloxycarbonyl > phenethyloxycarbonyl > p-nitrobenzyl Oxy 1 1 carbonyl and other aromatic lower radicals such as aromatic lower radicals containing substituents [such as phenylene 1 bead 9 hydroxyphenylene, etc.] > DD early (or two or three) benzene lower radical C such as benzyl I > phenethyl 9 dityl 9 trityl, etc.] etc. 0 1 I The above amine protecting group contains amino acids and peptides commonly used in the field of peptide chemistry [1 group to temporarily protect the amino group 〇 1 Appropriate H-ring amino group " May be an aromatic ring containing more than one nitrogen atom as a hetero atom or! Λ I Of the composition together and may be saturated or non-saturated ring C3D early square or fused polycyclic cyclic amine group may further contain 1 I a to the N, 0 5 s and other hetero atoms. The Γ cyclic amino group can be a spiro or bridged ring compound. The composition of the cyclic amine group is unlimited. The number of members is not limited. 9 For example, the BD early ring group is 3--8 member ring and the bicyclic group is 7--1 1 member 1 1 ring 0 \ 1 1 This amido group may be a saturated or unsaturated αα containing 1 N heteroatom early ring 1 1 group 9 such as 1-azetidinyl > pyrrolidinyl > 2-pyrrolin-1- Base, 1-pyridine I 1 -1 4-1 1 1 1 This paper size applies to Chinese National Standard (CNS) A4 (210X 29 * 7 mm) A7 B7 V. Description of the invention (* —) Rotyl, piperidine Group, 1,4-dihydropyridin-1-yl, 1,2,5,6-tetrahydropyridine-1 -yl, homopiperidinyl; saturated or unsaturated monocyclic ring containing more than one 値 N as a heteroatom Groups, such as 1-pyridinyl, 1-oxazolyl, 1-pyrazolyl, 1-triazolyl, 1-tetrazolyl, 1-piperidyl, pegpiperidinyl, 1,2- Dihydropyridin-1-yl, 1,2-dihydropyrimidin-1-yl, perhydropyrimidin-1-yl, 1,4-diazacycloheptane-1-yl; containing 1 to 2 0 and 1 ~ 3®N is saturated with heteroatoms or Saturated monocyclic groups, such as Hiazolidine 3-yl, 2, 3-dihydroisotransazol-2-yl, and morpholinyl; containing 1 to 2 S and 1 to 3 値 N are saturated or Unsaturated monocyclic groups, such as oxazolidin-3-yl, isopyrimidin-2-yl, thiomorpholinyl; fused polycyclic groups such as indolinyl-1-yl, 1,2-dihydrophenylhydrazone Oxazol-1-yl, perhydropyrrole [1,2-a] pyridine-2 -yl; spiro ring groups such as 2-aziropyridine [4, 5] decane-2-yl; bridged heterocyclic groups such as 7-acylcyclo [2. 2.1] heptane-7-yl; etc. Appropriate " fluorenyl " may contain carbamoyl, aliphatic fluorenyl and aldehyde groups containing aromatic rings (known as arylfluorenyl), or fluorenyl groups containing heterofluorenyl (known as heterocyclic fluorenyl). The fluorenyl group can be derived from, for example, organic carboxylic acids, organic primary acids, organic sulfuric acids, organic sulfonic acids, and organic carbamic acids. Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (read «Read the notes on the mouth and then fill out this page) The appropriate examples of this base are as follows: Carbamate; Aliphatic base, such as low or high Alkyl groups [such as formamyl \, ethylamyl, propionyl, butylamyl, 2-methylpropanyl, pentamyl, 2,2-dimethylpropanyl, hexyl, heptyl , Octyl, nonanyl, decanal, ten-1 5-This paper size applies to China National Standard (CNS) A4 (210X 297 mm) A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs («4) 1 1 monomethyl J twelve methyl 9 thirteen methyl 9 thirteen methyl, 15 methyl pentyl > 1 1 ten_L methyl 9 17 methyl pentyl 9 18 methyl pentyl 9 Nine fluorenyl 9 icosyl 1 1) and so on; low or high fluorenyl carbonyl C such as cyclopropyl m yl cyclobutyl carbonyl j ring 谙 丨 first 1 pentyl carbonyl} cyclohexyl W 9 etc.]; low or local院 sulforyl group [such as Jia Chuanmin Min | Reading Foundation » Sulfofluorenyl group, etc.] »low or high sulfonylsulfonyl group C such as methoxy group 醯 1 I 1 group 9 ethoxysulfonyl group > etc.] 'etc. k 1 aromatic fluorenyl group such as Aromatic groups such as fluorenyl 9 Tolyl group S base matters 1 1 re \ etc] Aromatic low fluorenyl C such as phenyl low alkyl fluorenyl (such as phenethyl fluorenyl > phenyl propyl filled in this fluorenyl) phenyl butyl fluorenyl group 5 phenisobutylfluorenyl group 9 phenpentyl fluorenyl group 9 phenhexyl fluorenyl group 9 page 1 1 'etc.) > naphthalene low fluorenyl group (e.g. acetofluorenyl group 9 naphthopropyl fluorenyl group 9 fluorene group 1 1 ) Etc. 3 etc.) Aroylene fluorenyl C such as benzalkenyl fluorenyl (such as phenylpropenyl 1 I fluorenyl 9 phenbutenyl fluorenyl J benzylpropenyl fluorenyl 5 phenpentylyl benzene 1 hexadecene Fluorenyl? Etc.) naphthylene [such as tsapropenylnaphthylnaphthalene butenyl i naphthylpentene fluorenyl J, etc.] aryl lower alkoxycarbonyl groups [such as benzyloxycarbonyl 1 | groups (such as benzyloxy Groups) aryloxycarbonyl C such as phenoxycarbonyl 5 oxocarbonyl 1 I 9 and so on] aryloxy low alkyl C such as phenyl ethyl fluorenyl, phenoxypropyl fluorenyl 1 1 > C such as aniline and methyl 3 aryl thiamidine and methyl [such as aniline and methyl fluorenyl] 9 arylethyl m fluorenyl C such as phenethyl and methyl fluorenyl 1 1 I? Ethyl m fluorenyl 9 and others] aromatic Sulfofluorenyl [such as benzenesulfonyl > naphthalenesulfonyl 1 etc.] 9 etc. 9 i j. Heterocyclic fluorenyl such as heterocyclic carbonyl 9 heterocyclic oligoalkynyl [such as Kapan ethylsulfonyl 1 1) Panthenyl JI! Cephenyttenyl > Carpanthentyl > Carphenidinyl 1 1 B thiazolylethyl > Bloxadiazole ethylsuccinyl »Tetrazolyl ethylsyl > etc.)) Hetero 1 I Cycloalkenyl C such as heterocyclopropenyl t Heterocyclobutenyl »Heteropentyl 1 1 -1 6-1 1 1 1 This paper size applies to China National Standard (CNS) A4 (210X297 Mm) Central Standard of the Ministry of Economic Affairs Bureau ’s consumer cooperation Du printed A7 B7 V. Description of the invention () Alkenyl, heterocyclohexenyl, etc.]; Heterocyclic acetaldehyde fluorenyl [such as carbazole acetaldehyde fluorenyl, blind acetaldehyde fluorenyl , Etc.] " Heterocyclic carbonyl ", " Heterocyclic alkanoyl ", " Heterocyclic alkynyl ", and " Heterocyclic ethynyl " The " part may be a saturated or unsaturated monocyclic or polycyclic heterocyclic group containing one or more heteroatoms such as 0, S, N and the like. Appropriate " aryl " contains phenyl, naphthyl, tolyl, xylyl, cresyl, anisyl, etc., and is preferably phenyl or naphthyl. Appropriate " aryl lower alkyl 'contains benzyl, Phenethyl, phenylpropyl, diphenylmethyl, trityl, etc. The production methods 1 to 9 for preparing the object compound (I) of the present invention will be described in detail below. Production method 1 The target compound (I a) or a salt thereof can be prepared from compound (II) or a salt thereof. The reaction can reduce the nitro group, and then it can be prepared with carbonyldiimidazole and compound (IV). For suitable salts of the compounds (la), (II), (III) and (IV), refer to those exemplified for the compound (I). In the first step, the compound (II) is reduced to obtain the compound (III) or a salt thereof. The reduction reaction may include chemical and catalytic reduction. Suitable reducing agents for chemical reduction include metals [such as tin, zinc, iron, etc.] or combinations of metal compounds [such as chromium chloride, chromium acetate, etc.], and organic or inorganic acids [such as formic acid, acetic acid, propionic acid, trifluoroethyl 'Acid, p-toluenesulfonic acid, hydrogen acid, argon bromide, etc.]. The appropriate catalyst used for catalyst reduction is the user, such as platinum catalyst [such as platinum-1 7-(read the notes on the back and then fill in this page) • ϋ —. ^ 1 ^ 1 ^ 1. ^ 1 n ^ i ·-I — ^ ϋ · m —ϊ I- i ii · ni \ ** 1 ^

、 1T ___ This paper size applies to Chinese National Standards (CNS) A4 specifications (210X297 mm) A7 B7 Printed by the consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs 5. Printed description of the invention () 1 1 Plate sponge platinum 9 Lead black 9 Columnar Platinum 9 platinum gaseous platinum wire etc.] 9 rake 1 1 catalyst [such as sponge rake i rake black > rake gasifier > m sulphur > columnar rake 9 Pd 1 -barium sulfate, P d-sulfonic acid m Etc.] 9 Nickel catalyst C such as reduced nickel nickel oxide N Read 1 thing 9 Ruan Lai nickel and other 3 Cobalt catalysts [such as reduction Ming 9 Ruan Lai cobalt and other 3 »Iron this Min 1 I read 1 Catalyst C such as reduction / Of iron > Ruan Laitie and other copper catalysts C such as reduced copper 9 Ruanbei 1 1 to copper ebony etc.] etc. Note 0 meaning anti m 厶 UA It is suitable to perform 9 matters in the presence of custom solvents for reaction • firr Μ bad shadow m 1 I then r 1 -Λ as water 5 methanol > ethanol »propanol 9 N, N -di Methylformamide, acetone f, or} or its mixed solution. In addition 5 When the acid used in the above chemical reduction is in a liquid 9 page 1 I It can also be used as a solvent 0 Furthermore, the appropriate solvent used for catalyst reduction can be the above 1!逑 Solvents ♦ Other conventional solvents such as ethyl m S, diII, oxane 3, tetrahydrofuran, etc. 1 I or a mixture thereof 0 I 1 Reaction temperature 4rrr The temperature is strictly determined and-»Generally, it is performed at room temperature or under heating. IT 1 is the second In the step>-The reduction product (m) or a salt thereof is reacted with carbonyldioxazole 1 1 and then with the compound (IV). 0 1! The reaction is preferably performed in the presence of a conventional solvent that does not adversely affect the reaction. 9 1 1 Such as water Methanol 5 Ethanol > Propanol 9 Ether) Eryuan 5 Tetrahydrofuran ί Λ N, N-dimethylm-fc · amine »Acetone t acetonitrile > Chloroform, Dichloromethane» Di 1! Ethyl Chloride, Ethyl Acetate Ester 9 Pyrex J Triethylamine 9 Benzene Or its mixed solution 0 1 The reaction temperature is not fixed and-»is usually carried out under cooling 9 at room temperature or under heating 0 1 Preparation method 2 1 The giant compound (worker) or its salt can be prepared from compound (V) or its salt 0 1 1 The compound (V) or its salt is reacted with diphenylphosphine azide) and then the compound 1 1 (VI) or its salt is reacted with 0 1 1 -1 8- 1 1 1 1 This paper size is applicable to China National Standard Vehicle (CNS) A4 specifications (210X 297 mm) 5. Description of the invention (M B7, shown below) Agent I ί Opinions on the habituation of the use of dissolved substances 鎏 Participants can be good salt should not be irresponsible} Counter- ≫ Responsiveness

V N Chlorofuran, chloromethane, chloromethane diS1, diform, gas ether, acetonitrile, ethanol * acetone, propanol, ethylamine, methyl alcohol methyl methyl, methyl hydrazine. Liquid heat mixed with or Benzylamine is cold and cold, like pyridine and pyridine, and fixed esters without acidity and ethyl temperature, should be synthesized by 3 alkanes. Salt may or may not be combined. The salt can be made by the reaction, or its reaction or d) the salt, its I substance, or ------- imitated I --- The compound is compounded. See 1 for the applicable method of salt. 1) C) Method and description b. The former example is combined with salt or (please read the precautions on the back first and fill in this page). The chemical compounds mentioned in the examples are shown in the reference table. The benzene is stored in the mech. The acetic acid should be antisulfafluoride. The central government bureau of the Ministry of Economic Affairs, the consumer cooperation, printed sulfonic acid and hydrogen bromate. B, trichloro chlorate, hydrogen acid such as propyl C, acid acid, organic acid, acetic acid, acetic acid and other organic acids. Following the good effects of non-hydrogenated bromine-free reaction, the anti-hydrogenation reaction is stored in chlorine), the acid should be sulfur, the acid should be reversed, and the upper house should be ΠM, the second one, this ether. . B liquid agent, miscible alcohol, which is propyl or acetic acid, alcohol amine and acetamidine, methyl alcohol, methyl alcohol, methyl alcohol, two-liquid water N-Yu N, acid paper size applies Chinese national standards (CNS ) A4 specification (210X 297 mm) A7 B7 5. Description of the invention (d) The reaction temperature is not fixed and is generally carried out under cooling, room temperature or heating. Production method 5 The target compound (Ie) or a salt thereof can be prepared from compound (IX) or a salt thereof. Compound (IX) or a salt thereof is reacted with compound (X V I) or a salt thereof. Suitable salts of the compounds (I e) and (IX) can be referred to those exemplified for the compound (I). The reaction should be carried out in the presence of customary solvents that do not adversely affect the reaction, such as water, methanol, ethanol, propanol, diethyl ether, di-bialkane, tetrahydrofuran, N, N-dimethylformamide, acetone, acetonitrile, chloroform, di Gas methane, dichloroethane, ethyl acetate, pyridine, triethylamine, benzene or a mixture thereof. In addition, when the acid used in the above reaction is in a liquid, it can also be used as a solvent. The reaction temperature is not critical and is generally carried out under cooling, room temperature or heating. Production method 6 The target compound (I) or a salt thereof can be prepared from compound (X) or a salt thereof. Compound (X) or a salt thereof is reacted with compound UI) or a salt thereof. Suitable salts of the compounds (X) and (X I) can be referred to those exemplified for the compound (I). (Read the precautions on the back before you fill out this page) :: Installation --- Order the printed products from the Central Consumers Bureau of the Ministry of Economic Affairs, Consumer Cooperatives. The reaction should be performed in the presence of customary solvents that do not adversely affect the reaction frrr, such as water 5 methanol } Ethanol > Propanol > Ether 9 DiPoxane J Tetrahydrofuran, N, N-Dimethylformamide 1 Acetone 9 Acetonitrile 9 Chloroform 5 Dichloromethane, Diethyl Ethane j Ethyl Pyridine 5 Triethyl Amine > Benzene or its warm liquid 〇 In addition > When the acid used in the above reaction is a liquid > It can also be used as a solvent. The reaction temperature is tse »and it is generally carried out under cooling 9 room temperature or under heating. Method 7 The giant compound (I f) or a salt thereof can be prepared from the compound (X II) or a salt thereof. -20- --- 1-1-- .. This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs ) Reacting compound (XII) or a salt thereof with carbonyldioxazole, and then reacting with compound (XIII) or a salt thereof. Suitable salts of the compounds (If), (XII) and (XIII) can be referred to those exemplified for the compound (I). This reaction can be carried out according to the method of the second step of the aforementioned production method 1. Production method 8 The object compound (I) or a salt thereof can be prepared from compound (XIV) or a salt thereof. Compound (XIV) or a salt thereof is reacted with compound (XV) or a salt thereof. Suitable salts of the compounds (XIV) and (XV) can be referred to those exemplified for the compound (I). This reaction can be performed according to the method of the aforementioned Production Method 6. Preparation method 9 The target compound (I) or a salt thereof can be prepared by reacting compound (X) or a salt thereof with compound (XVI) and then reacting with compound (VI)-or a salt thereof. Suitable salts of the compound (VI) can be referred to those exemplified for the compound (I). This reaction can be carried out according to the method of the second step of the aforementioned production method 1. The object compound (I) of the present invention can be isolated and purified according to conventional methods such as extraction, precipitation, layer separation, crystallization, recrystallization, and chromatography. The obtained target compound (I) can be converted into a salt thereof according to a conventional method. The target compound (I) and its pharmaceutically acceptable salt may contain a vehicle [such as an inclusion compound (such as a hydrate, etc.)]. The target compound (I) and its pharmaceutically acceptable salts of the present invention may have pharmacological activities such as 5-HT antagonistic action (especially 5HT antagonistic action), etc. Therefore, 2c can be used as a 5-Η T antagonist to prevent mesenteric nerve strips (CNS). If you are anomalous, -2 1-This paper size applies the Chinese National Standard (CNS) Α4 specification (210X297mm) (Read the notes on the back of the poem first ^ / and then fill out this page)

Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A 7 B7 V. Description of the Invention (%) Depression, abnormal obsessive-compulsive behavior, migraine, pressing disorder, Alzheimer's disease, abnormal sleep, dysphagia, irritability, prolapse Drug abuse such as cocaine, alcohol, nicotine and benzodiazepine, schizophrenia, and abnormalities associated with spinal trauma and / or head injuries such as hydrocephalus. The pharmacological data of the following representative compounds of the present invention may clarify the use of the compound of interest. (1) Test method: [3 Η]-mesu 1 ergine binding test drug with 5! ^ 20: The affinity of the binding site can be measured in the prefrontal cortex of white rats according to the method of Pazos et al., 1984 [3 H] -me.sulergine depends on the displacement force. . Membrane suspension (5fl0yu. 1) and [3 H] -mesiilergine (InM) in Tris-HCl buffer containing CaCl2 and ascorbic acid 0.1% (pH 7 · 4) at 37 ° C Cultivate 30 points. Non-specific binding was measured in the presence of m i a n s e r i η (1 # Μ). Use 30 / i M spiperone to prevent binding to the 5 Η T 2A binding site. 100 mg of test drug (1 (Γ5 Μ)) was added. The total amount of analysis was lQGQyu 1. Use the Brandel cell collector to quickly filter to stop the reaction and measure the radioactivity with a radiometer. (2) Test compound (a) N -(1 -Methylindolinol-5 -yl-N 1-[5-(5 -methylpyridin-3 -yl) pyridin-3 -yl) urea (b) N- [3- (imidazol-1-yl ) -Phenyl] -methylindole B- 5-yl) urea (〇1-[[3- (2-oxazolin-2-yl) -phenyl] -amino formaldehyde) Again! Ή Page 2 2-This paper size is in accordance with Chinese National Standard (CNS) Λ4 specification (2IO × 297 mm) V. Description of the invention (M)]-5 -methyl-2, 3-dihydropyrrole [2, 3-f] Indine hydrogen iodide (3) test results Compound inhibitory effect (%) (a) 8 1 (b) 88 (c) 9 7 The compound (I) of the present invention and its pharmacy when used for treatment or prevention The permissible salt can be used as the active ingredient of the compound, and it can be used in combination with organic or inorganic solids suitable for oral, parenteral or external use, or pharmaceutical excipients such as liquid excipients. This peony formulation can be a solid such as a lozenge ,powder, Capsules, or liquids such as solutions, suspensions, slurries, emulsions, lemon juice, and other oils. The printed preparations printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs may contain auxiliary substances, stabilizers, wetting agents, or other conventional additives, such as Lactose, citric acid, tartaric acid, stearic acid, magnesium stearate, clay, sucrose, corn flour, talc, gelatin, agar, animal gum, peanut oil, olive oil, cocoa butter, ethylene glycol, etc. Compound (I) of The dose may depend on the age and condition of the patient, the type or condition of the disease, the type of compound (I) to be administered, etc. Generally, the amount of 0.01 mg to 5 mg or more can be administered to the patient every day. A single dose-2 3- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 gong) Printed and amended by Shellfish Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs '4, year and month g supplement 87., P A7 —', l, l :; : —B7 _____; _V. Description of the invention (a) is 〇 · 1 ni g, 〇 · 2 5 mg, Ο .. 5 mg, 1 mg, 20 mg, 50 mg, 1 mg I) To the patient to treat the disease, usually Ol is administered daily mg / person and 100 mg / person. The following preparations and examples can be used to clarify the present invention. Example 1 0.2 g of 1-methyl-5 -nitroindin in methanol (100 〇 1) with P d -C (10%, 0.1 g) hydrogenated for 3 hours. The catalyst was filtered off, and the solvent was dried under vacuum. The obtained amine was dissolved in tetrahydrofuran (1 Qml), and carbonyldiimidazole (0.184 g) was added. Stir at room temperature for 1 hour. N, N-dimethylformamide (5 ml) containing 3- (2-benzylpyrazol-3-yl) aniline (0.31 g) was added. Stir at room temperature for 66 hours and evaporate. The resulting solution was separated into ethyl acetate and water. The organic layer was washed with a disulfonic acid solution and dried over sodium sulfate. And purified by silica gel column chromatography (chloroform.-methanol: 0-10%?) To obtain 1 ^-[3- (2-benzylpyrazol-3-yl) phenyl] -N,-(1 -Methylindin-5-yl) ureamp: 108-112 ° C IR (Nujol, cm _1): 1640, 1605 NMR (DMSO-d6 > < 5): 3.75 (3H, s), 5.41 (2H , S), 6.34 (lH, d, J = 3Hz), 6.43 UH, d, J-2Hz), 6.90-7.05 (2H, s), 7.10-7.50 (7H, m), 7.58 (lH, d, J = 2Hz), 7.60-7.70 (2H, m), 8.47 (lH, s), 8.68 (lH, s) Mass: 422 (M + 1 +) Example 2 'The method of Example 1 can obtain the following compounds. N-[3-(1 -benzyloxycarbonylpyrazol-3 -yl) phenyl] -N '-(1 -methylindolin_ -24- (Please read the precautions on the back before filling this page) * ^ ^^^ 1 1 II _ i ^ ilt —m nnIJ '-* < 0 ^ ^^ — ^ 1 J,.:, ¾ — 丁 -¾ x— This paper size is in accordance with China National Standard (CNS) Λ4 specifications (2) 0X297 mm) A7 B7 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the Invention (4) 5-Base) Urea NMR (DMSO-dg, < 5): 3.76 (3H, s), 5.50 (2H, s), 6.35 (lH, d, J = 3Hz), 7.03 (1H, d, J = 3Hz), 7.10-7.60 (13H, m), 7.69 (lH.br.s), 8.05 (2H, m), 8.30- 8.50 (2H, m), 8.75 (lH.br.s) Example 3 The following compound can be obtained according to the method of Example 1 "N-[3-(2-Aminino-4 -yl) phenyl ] -IT-(1-Methylindolin-5 -yl) urea mp: 200-205 ° C IR (Nujol, cm: 1640, 1610 NMR (DMSO-dg, (5): 3.76 (3H, s), 6.34 (lH, d, J = 3Hz), 6.91 (lH, s), 7.01 (2H, br.sj; 7.10-7.40 (6H, m), 7.69 (lH, d, J = 2Hz), 7.96 (lH.s ), 8.38 (lH.s), 8.58 UH, s) Mass: 364 (M + 1 +) Example 4 The following compound can be obtained by the method of Example 1. N-[3-(2 -oxazole-4 -yl) Phenyl 〕 -N '-U -forminol-5 -yl) urea mp: 200-203 ° C IR (Nujol, cm: 1620 NMR (DMS〇-d6,5): 3.76 (3H, s), 6.34 ( lH, d, J = 3Hz), 7.05-7.04 (6H, m), 7.50 (lH, s), 7.71 (2H, d, J = lHz), 7.85 (lH, s), 8.41 (lH.br .s), 8.57 UH.br.s), 12.21 (lH.br.s) Mass: 332 (M + 1 +) 'Example 5 _ 2 5-(Please read the notes on the back first # | Fill this page) '1 Pack. Order 13. This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of Invention (伫) The method of Example 1 can be obtained The following compounds. [3- (1-benzyl-3-azolyl) phenyl] -N '-(1-methyl 11- 11- (5-yl) urea) mp: 165-170 ° C IR (Nujol, cm: 1620 NMR (DMS〇-d6, < 5): 3.75 (3H, s), 5.38 (2H, s), 6.34 (lH.dJ = 2Hz), 6.67 (1H, d, J = 2Hz) (7.00-7.40 ( llH.m), 7.69 (lH, s), 7.80-7.95 (2H, m), 8.37 (lH, s), 8. 64 (lH, s)

Mass: 422 (M + 1 +) Example 6 To 5_ (3-methylpyrazol-5-yl) pyridine-3-carboxylic acid (70mg) was added triethylamine (0.048ml) and diphenyl disco nitrogen (0.073). m1). After refluxing for 3 hours, it was cooled. Add 5-amino-1-methyl-11-priming (61mS) to the reaction solution and benzene (5ml). Reflux for 1 day. After cooling, the reaction solution was dissolved in chloroform, washed with a sodium bisulfate solution, dried under sodium sulfate, and purified by silica gel column chromatography (chloroform: methanol = 9: 1, v / v) to obtain N- ( l-methyl-P-priming-5-yl) -Γ- [5- (5-methylpyrazol-3-yl) pyridin-3-yl) urea (61 «^). mp: 208-211 ° C IR (Nujol, cm: 1620 NMR (DMS0-dg, (5): 2.29 (3HTs), 3.75 (3H, s), 6.35 (lH, d, J = 3Hz), 6.49 (1H , s), 7.17 (lH, dd, J -9Hz, 2Hz), 7.27 (lH.dJ = 2Hz), 8.34 (lH.br.s), 8.40- 8.60 (3H, m ;, 8.78 (IH.br. s), 12.70 (lH, br.s)

Mass: 347 (M + 1 +) Example 7 -26- This paper size is applicable to China National Standard (CNS) A4 specification (ΉΟ × 297mm) --- J--i--i / installed-(read first read the back (Notes on the side / fill out this page)

---- L Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7__ V. Description of the Invention (〆) N-[3-(1 -benzyloxycarbonylpyrazol-3 -yl)] -N '-(1 -Methylindole-5 -yl) urea (02 1 g) in methanol (40 m 1) was hydrogenated with P d -C (103; 0.1 g) for 8 hours. Filter off the catalyst. The filtrate was distilled off and purified by silica gel column chromatography (gas-form: methanol = 0 ~ 3%, ν / ν) to obtain N- [3- (Β 比 azole-3-yl) phenyl] -N '-(1 -Methylindin-5 -yl) urea (86 mg) β mp: 173-178 ° C IR (Nujol, cm: 1630 NMR (DMSO-dg.5): 3.76 (3H, s), 6.35 (lH, d, J = 3Hz), 6.63 (lH.br.s), 7.16 (1H.dd, J = 9Hz, 2Hz), 7.20-7.40 C5H, m), 7.70 (lH.dJ = 2Hz), 7.77 (lH, br.s), 7.93 UH. br.s), 8.41 (lH.br.s), 8.62 (lH.br.s), 12.86 (lH.br.s)

Mass: 332 (M + 1 +) Example 8 The following compound can be obtained by the method of Example 1. N- (l-forminol-5-yl) -N '-[3- (5-methylpyrazol-3-yl) phenyl] urea.. Mp: 185 — 188 ° C IR (Nujol, cm _ b: 1630 NMR (DMSO-d6,5): 2.26 (3H, s), 3.76 (3H, s), 6.30-6.40 (2H, m), 7.15 (1H, dcU = 9Hz, 2Hz), 7.20-7.40 (5H, m), 7.71 (lH, d, J = 2Hz), 7.88 (lH.br.s), 8.43 (1H, br.s), 8.61 (lH.s), 12.54 (lH.br.s)

Mass: 346 (M + 1 +) Example 9 'The method of Example 1 gave the following compounds. N- [3- (3,5-Dimethylpyrazol-1-yl) phenyl] -N '-(Bujia B cited-27- This paper size applies to China National Standard (CNS) A4 specifications (210X297) (%) (Please read the notes on the reverse side before filling out this page) ¥ 1 Order printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives to print A7 B7 V. Description of the invention (4) P-do-5-yl) urea mp: 163 -171 ° C IR (Nujol, cm ~: 1620, 1600 NMR (DMS0-dg, 5): 2.18 (3H, s), 2.31 (3H, s), 3.76 (3H, s), 6.06 (lH.s) , 6.34 (lH, d, J = 3Hz), 7.05 (lH, d, J = 7Hz), 7.15 (lH, d, J = 9Hz), 7.20-7.40 (4H, m); 7.69 QH.s), 7.77 (lH, s), 8.47 (lH, s), 8.78 (lH, s)

Mass: 360 (M + 1 +) Example 10 The following compound was obtained by the method of Example 1. 1 «-(1-formin-8--5-yl) '^'-[3- (pyrimidin-4-yl) phenyl] urea mp: 206 — 209 ° C IR (Nujol, cm: 1620 NMR (DMSO -d6,5): 3.77 (3H, s), 6.36 (lH (d, J = 3Hz), 7.17 (lH, dd, J = 9Hz, 2Hz), 7.27 (lH, d, J = 3Hz), 7.35 ( lH (d, J = 8Hz), 7.43 (lH, d, J = 8Hz), 7.62 (lH.br. d, J = 9Hz), 7.70-7.80 (2H, m), 8.02 (lH.ddJ = 5Hz, lHz), 8.41 (lH.br.s), 8.48 (1H, br.s), 8.81 (lH.br.s), 8.89 (lH, d, J = 5Hz), 9.26 (lH.dJ = 1Hz)

Mass: 344 (M + 1 +) Example 11 The following compound was obtained by the method of Example 1. N-(1 -methyl P3I H-do-5 -yl) -N 1-[3-(2-Btt pyridyl) phenyl] urea

mp: 199 — 200 ° C IR (Nujol, cm-: 3250, 1610 -2 8-This paper size applies to Chinese National Standard (CNS) A4 specification (21 OX297 mm) I II _--1 — I— I I -II --- I- ^ n H (#Please read the notes on the back before filling in this page) Order printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives to print A7 B7 V. Description of the invention (β) NMR (DMS〇- d6,5): 3.76 (3H, s), 6.36 (lH, d, J = 2.9Hz), 7.15-7.91 (10H, m), 8.28 (lH, s), 8.46 (lH, s), 8.67 (lH .dJ = 4.7Hz), 8.76 (lH, s)

Mass: 343 (M + 1) Example 1 2 containing N-(1 -formamidine-5 -yl) -N '-[3-[methylthioimidemethyl] phenyl] urea hydrogen iodide (0.22 g) of ethanol (20 ml) were added ethylenediamine (0.13 m 1) and acetic acid (0.22 m 1). After 7 hours at reflux, it was cooled, dried under vacuum and milled with water. The precipitate was collected by filtration, and dried with water and diethyl ether to obtain N- [3- (2-oxazoline-2-yl) phenyl] -N1- (1-methylindolinium-5-yl) urea. hydrogen. mp: 165 — 170 ° C (dec.) IR (Nujol, cm b: 1680, 1610 NMR (DMSO-d6, < 5): 3.76 (3H, s), 3.89 (4H, s), 6.35 (lH , d, J = 3Hz), 7.10-7. 80 (7H, m), 8.11 (lH, br.s), 8.69 (lH, br.s), 8.99 (IH.br.s)

Mass: 334 (M + 1 +) Example 13 in N, N-Di containing N-(1 -methylindolinol-5 -yl-(3-methylthioamine methylphenyl) urea (0.2g) Chloroacetone (0.05 nil) was added to methylformamide (3 ml). It was stirred at 100 ° C for 1.5 hours. After cooling, it was poured into water (30 m 1). Sodium bisulfate solution Adjust to P Η 9. The precipitate was collected by filtration, dissolved in aeroform-methanol (9: 1, ν / ν), dried over sodium sulfate, and subjected to silica gel column chromatography (chloroform: methanol = 0-3%, ν / ν) purification to obtain N-(1 -forminin '5 -yl) -N 1-[3- (4-methylblazol-2-yl) phenyl) urea (0.88g>. -2 9- 本Paper size applies Chinese National Standard (CMS) Α4 specification (2 丨 0 X 297 cm) (Please read the precautions on the back before filling this page)

、 1T Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs of the People's Republic of China A7 B7 V. Invention Description (W) mp: 228-230 ° C IR (Nujol, cm: 1625 NMR (DMS〇-d6, < 5): 2.44 (3H , s), 3.77 (4H, s), 6.35 (lH, d, J = 3Hz), 7.10-7. 55 (7H, m), 7.71 (lH, d, J = 2Hz), 8.23 (lH.br. s), 8.47 (lH.br.s), 8.83 (lH.br.s) Mass: 363 (M + 1 +) Example 14 The following compound can be obtained by the method of Example 13: ^)-(1-A11 11--5-yl) -N '-[3- (4-benzazol-2-yl) phenyl] urea mp: 220-223 ° C IR (Nujol, cm: 1620 NMR (DMS〇- d6 ≪ 5): 3.77 (3H, s), 6.37 (lH, d, J-3Hz), 7.17 (lH.dd.J = 9Hz, 2Hz), 7.25-7.65 (8H, m), 7.72 (lH, d, J = 2Hz), 8.06 (2H, d, J = 7Hz), 8.18 (lH, s), 8.29 (IH.br.s), 8.48 (lH, s), 8.89 (lH, s) Mass: 425 (M + 1 +) Example 15 The following compound can be obtained by following the method of Example 1. 1 [3- (111-1,2,4-triazol-3-yl) phenyl]-^-(1-formininH Do-5-based) urea mp: > 220 ° C IR (Nujol, cm 1): 1640 < (锖 Please read the precautions on the back before filling this page) -30- This paper size is applicable to Chinese National Standard (CNS ) Λ4 specification (210X 297 (Centre) A 7 B7 V. Description of the invention (μ) NMR (DMSO-d6, < 5): 3.76 (3H, s), 6.35 (lH, d, J-3Hz), 7.17 (lH, dd, J = 2 , 9Hz), 7.27 (lH, d, J = 3Hz), 7.33 (lH, s), 7.37 (lH, s), 7.48 (lH, m), 7.58 (lH, m), 7.70 (1H, d, J = 3Hz), 8.18 (lH.br.s), 8.44 (lH.br.s), 8.74 (lH.br.s)

Mass: 333 (M + 1 +) Example 16 The following compound was obtained by the method of Example 1. Caution for reading τέ: urea- [3- (carazol-4-yl) phenyl] methinin-5-yl) mp: 213 — 215 ° C IR (Nujol, cm ~ b: 1640 NMR (DMSO- d6, < 5): 3.76 (3H, s), 6.34 (lH, d, J = 3.0Hz), 7.16 (lH, dd.J = 8.7H ^, 2.0Hz), 7.27 (lH, d, J = 3.0Hz), 7.56 (lH.dJ = 7.4Hz), 7.28-7.50 (4H, m), 7.71 (III, d, J = 1.7Hz), 8.08 (lH, d, J = 1.9Hz), 8.15 (lH , s), 8.45 (lH, s), 8.71 (lH, s), 9.20 (1H, d, J = 1.9Hz) Mass: 349 (spare + 1 +) Example 17 The following compound can be obtained by the method of Example 1. Ν- [3- (2-methylcarbazol-4-yl) phenyl]-(1-methylindole-5-yl) urea is written on this page. Employees 'Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, Employees' Cooperatives Co., Ltd. 199 V1, mp: 198 IR (Nujol, cm A): 1630 NMR (DMSO-d6, (5): 2.73 (3H, s), 3.76 C3H, s), 6.35 (lH, d, J = 3.0Hz), 7.15 (1H , ddj = 8.7Hz, 1.9Hz), 7.26-7.52 (5H, m), 7.71 (lH.dJ = 1.8Hz), 7.85 (lH, s), 8.09 (1H, s ;, 8.41 (lH, s), 8.71 (lH, s) Mass: 363 (M + 1 +) -31 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) A7 B7 V. Description of the invention (M) Example 18 Method of Example 1 can The following compounds were obtained: (1- [3- (5-methylazol-4-yl) benzyl] -1 ^-(bumindin-5-yl) urea mp: 229-231 ° C IR (Nujol , cm _ 1): 1665 NMR (DMS〇-d6,5): 2.39 (3H, br.s), 3.76 (3H, s), 6.35 (lH.dJ = 3.0Hz), 7.14 (lH.dcU = 8.8 Hz, 1.7Hz), 7.17-7.40 (5H, m), 7.55 (lH (s), 7.69 UH.dJ-1.711ζλ 7. 77 nH.br.s), 8.41 (IH.br.s), 8.61 ( lH.br.s), 11.95 (lH.br.s)

Mass: 346 (M + 1 +) Example 19 The following compound was obtained by the method of Example 1. Coz- [3- (1-methoxazol-4-yl) phenyl]-(1 |-(1-formin11-5-yl) urea

mp: 90 — 110 ° C IR (Nujol, cm Γ b: 1660, 1610 NMR (DMSO-d6, < 5): 3.69 (3H, s), 3.76 (3H, s), 6.34 (lH.dJ = 2Hz ), 7.10-7. 40 (6H, m), 7.52 (lH, s), 7.62 (lH, s), 7.70 (lH, d, J = 2Hz), 7.87 (lH, s), 8.39 (1H, s ), 8.56 (lH, s) Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (锖 Read the precautions on the back before filling this page)

Mass: 346 (M + 1 +) Example 20 The following compound was obtained by the method of Example 1. v N- 〔3- (Iso-B, etc.-5-yl) phenyl] -ίΓ- (1-methylindole H-do-5- Basic paper size applicable to China National Standard (CNS) A4 (210x297 mm) Economy Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China A7 _ B7____ V. Invention Description (Λ （) mp: 199-202 X IR (Nujol, cm: 1630 NMR (DMSO-d6 > < 5): 3.77 (3H, s) , 6.35 (lH.dJ = 3Hz), 6.97 (lH.dJ = 2Hz), 7.17 (lH, dd, J = 9Hz, 2Hz), 7.20-7.50 (5H, m), 7.71 (lH (d, J = 2Hz ), 8.09 (lH, s), 8. 54 (lH, s), 8.66 (lH, dJ = 2Hz), 8.83 (lH, s) Mass: 333 (M + 1 +) 'Example 2 1 Example 1 According to the method, the following compounds can be obtained: N- [3- (imidazol-2-yl) phenyl] forminin-5-yl) urea mp: 230-235 (dec.) ° C IR (Nujol, cm: 1633 NMR ( DMS〇-d6, < 5): 3.76 (3il, s), G.35 (11U), 7.U) 7.55 1811, ⑴), J1 UH, s), 8.05 (lH, s), 8.47 ( lH, s), 8.67 (lH, s), 12.50 (lH.br.s) Mass: 332 (M + 1 +) Example 22 The following compound can be obtained by the method of Example 1. N- [3- (oxazole-butyl) phenyl] -N '-(butridinin-5-yl) urea mp: 180-185 ° C IR (Nujol, cm — 1): 1630 NMR (DMSO -d6> (5): 3.76 (3H (s), 6.35 (lH.dJ = 3Hz), 7.10-7.45 (7H, m), 7. 60-7.70 (2H, m), 7.78 (lH, s), 8.16 (lH, s), 8.56 (lH, s), 8.79 (lH.s) Mass: 332 (M + 1 +) -3 3-(Please read the precautions on the back before filling this page)

This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) A7 B7 V. Description of the invention (") Example 23 The following compounds can be obtained by the method of Example 1. N-[4-(oxazole-1 -yl) phenyl] -IT-(1 -methylindolin-5 -yl) urea mp: 234-239 ° C IR (Nujol, cm _ b: 1640 NMR (DMSO -dg.5): 3.76 (3H, s), 6.35 (lH, d, J = 3Hz), 7.08 (lH, s), 7.15 (1H, dcU = 9Hz, 2Hzj, 7.27 (lH, d, J = 3Hz ), 7.35 (lH, d, J = 9Hz), 7.50-7.65 (4H, m), 7. 66 (lH, s), 7.69 (lH, d, J = 2Hz), 8.16 (lH, s), 8.49 (lH, s), 8.76 (lH.s)

Mass: 332 (M + 1 +) Example 24 The following compound was obtained by the method of Example 1. N-[2-(imidazole-: 1-yl) pyridine-5 -yl] -1Γ-(bumidinB-do-5-yl) urea mp: 230 — 235 ° C IR (Nujol, cm — b: 1630 NMR (DMSO-d6,5): 3.77 (3H, s), 6.36 (lH, d, J = 3Hz), 7.11 (lH.s), 7.17 (1H, dd, J = 9Hzf2HzJ, 7.28 (lH, d, J = 3Hz ;, 7.36 (lll, d, J-91lz), 7.05-7.8U i21i, m), 7.89 (lH, s), 8.15 (lH, dd, J = 9Hz, 3Hz), 8.32 (lH , s), 8.54 (lH, d, J = 2Hzj, 8.64 (1H, 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) s), 8.91 (lH, s)

Mass: 333 (M + 1 +) Example 25 Add (N, N -dimethylformamidine containing 3- (2-imidazol-phenyl) aniline (0.17 g) to N- (1-forminidine 5--5-yl) carbamic acid 4-nitrobenzyl ester (0.30g) and triethylamine (0.14ml) e. Stir at room temperature for 6 hours. Ethyl acetate-34- This paper scale applies Chinese national standards ( CNS) A4 specification (210X 297 gong) A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs __V. Description of the invention (w) and delamination in sodium disulfonate solution. The organic layer was dried under sodium sulfate, Evaporation and milling with gas imitation can obtain N- [3- (2-oxazole-1-1-1yl) phenyl] _N '-(buminddo-5-yl) urea (0.21g) Mp: 199-201 ° C IR (Nujol, cm ~ 2): 1680, 1640 NMR CDMSO-d6,5): 3.76 (3H, s), 6.35 QH, d, J = 3Hz), 6.60 (lH.tJ = 3Hz), 6.88 (lH, U = 3Hz), 7.05-7.45 (6H, m), 7.70 (lH, d, J = 2Hz), 7.91 (lH, d, J = 2Hz). 8.44 (lH.s) , 8.77 (lH, s), 10.32 (lH, br.s)

Mass: 348 (M + 1 + Example 26 The method of Example 25 can be obtained as follows: "N-[3- (2-tetrazolinone-1-yl) phenyl] -N ·-(buzoindox- 5-based) urea mp: 198-200 ° C IR (Nujol, cm — b: 1710, 1680, 1630 NMR (DMSO-d6,5): 3.40 (2H, t, J = 7Hz), 3.75 (3H, s ), 3.83 (2H, t), 6.34 (1H, d, J = 3Hz), 6.94 (lH, s), 7.00-7.40 (6H, m), 7.65-7.80 (2H, m), 8.42 (lH, s ), 8.69 flH.s) Mass: 350 (M + 1 +) Examples of urea examples of imitation compounds listed below I 5 ketozole ps phenylphenyl-5-p§l paper The scale is applicable to the Chinese National Standard (CNS) Λ4 specification (210 × 297 mm) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 _ ^ ___ B7______ V. Description of the invention (from) mp: 204-206 ° C IR CNujol, cm: 1630 NMR (DMSO-d6, < 5): 3.76 (3H, s), 6.35 (lH, d, J = 3.0Hz), 7.16 (lH.dd.J = 8.7Hz, 2.0Ηζλ 7.28 ClH, d, J = 3.0 Hz), 7.30-7.36 (4H, m), 7.6 ^ 1 (lH.s). 7.71 (lH.dJ -7.95 (lH.br.s), 8.45 (lH, s), 8.49 (lH.br.s ), 8.76 (lH.br.s)

Mass: 333 (M + 1 +) ‘Example 28 The following compound was obtained by the method of Example 25. N- [3- (carazol-5-yl) phenyl] -N '-(1-methylindhodo-5 -yl) urea mp: 190-191 ° C IR (Nujol, cm _3): 1630 NMR (DMSO-d6, (5): 3.76 (3H, s), 6.35 (lH, d, J-3.0Hz), 7.15 (lH.dd.J = 8.7Hz, 2.0Hz), 7.25-7.45 (5H, m ), 7.70 (lH.dJ = 1.8Hz), 7.86 (lH, s), 8.26 (lH, s), 8.51 (lH, s), 8.76 (lH, s), 9.09 (lH, s)

Mass: 349 (M + 1 +) Example 29 The following compound was obtained by the method of Example 25. {{-[3- (411-1,2,4-triazol-4-yl) phenyl]-{) '-(1-methyl 11 lead B--5-yl) urea mp: 197 — 198 ° C IR (Nujol, cm b: 1690 -36- This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) I --- J ------ \ installation-- (read first, read back) Note #; Complete this page) Order A7 B7 Printed by the Consumer Standards Cooperative Office of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of Invention (w) NMR (DMS〇-d6,5): 3.76 (3H, s), 6.35 (lH , d, J = 2.6Hz), 7.16 (lH.dd.J = 8.7Hz, l. 9Ηζλ 7.20-7.48 C2H, m), 7.35 (lH, d, J = 8.7Hz), 7.44-7.48 (2H, m ), 7.70 (1H, d, J = 1.9Hz), 7.80 (lH.br.s), 8.61 (lH.br.s), 8.86 (lH.br.s), 9.06 (2H, s) Mass: 333 (M + 1 +) Example 30 The following compound can be obtained by the method of Example 25. Ke- [3- (111-1,2,4-triazol-1-yl) phenyl]-^-(1-form Indolin-5-yl) urea mp: 218-219 ° C IR (Nujol, cm — 1).: 1640 NMR (DMSO-dg, (5): 3.76 (3H, s), 6.35 (lH.dJ = 3.2 Hz), 7.16 (lH, dd, J = 8.7Hz, 2.1Hz), 7.28 (lH, d, J = 3.2Hz), 7.33-7.43 (4H, m), 7.70 (1H, cU = 1.9Hz), 8.11 (1H. Br.s), 8.24 (lH, s), 8.53 (lH.br.s), 8.89 (lH.br.s), 9.25 (2H, br.s) Mass: 333 (M + 1 +) Example 31 The following compound can be obtained by the method of Example 25. Case-[3- (1-methoxazole- 5-yl) phenyl]-«|-(1-methylindio-5-yl) urea IR (Nujol, cm_h: 1660 NMR (DMSO-d6,5): 3.69 (3H, s), 3.76 ( 3H, s), 6.34 (lH, d, J = 2.9Hz), 7.04- 7.08 (2H.m), 7.14 (lH, dd, J = 8.7Hz, 1.9Hz), 7.26-7'44 (4H, m ), 7.63 (lH, s), 7.68 -7.71 (2H, m), 8.49 (lH, s), 8.69 (lH, s) Mass: 346 (M + 1 +) -37- This paper size applies to Chinese national standards (CNS) A4 specification (2 丨 〇X297mm). (Please read the precautions on the back before filling this page)

* 1T A 7 _ B7 V. Description of the invention (μ) Example 32 To a tetrahydrofuran (15 ml) containing 3- (oxazol-4-yl) aniline (0.17 g) was added Sodium diimidazole (0.17 3 g). Stir at room temperature for 5 hours. Tetrahydrofuran (5 m 1 U) containing 5 -methyl-2,3-dihydropyrrolo [2, 3-f] inH (0.18 g) was added and stirred at room temperature for 24 hours and evaporated. The resulting solution was separated into ethyl acetate and water. The organic layer was dried under sodium sulfate, and purified by silica gel column chromatography (aerobic-methanol: 0-10¾ v / v) to obtain 1- [[3- ( Oxazol-4-yl) carbamidine] -5 -methyl-2,3-dihydropyrrole [2,3-f] H Introduced P (0 · 1 4 g). Mp: 252-256 ° C IR (Nujol, cm-1): 1635, 1610 NMR (DMSO-d6, < 5): 3.26 (2H, t, J = 8Hz), 3.73 (3H, s), 4.18 (2H, t, J = 8Hz), 6. 30 (lH, d, J = 3Hz), 7.17 (lH.dJ = 3Hz), 7.20-7.50 (5H, m), 7.73 (lH, d, J-lHzX 7.97 (lH (s) , 8.05 (lH, s), 8.43 (lH, s), 12.00- 12.50 (lH.br.s)

Mass: 358 (M + 1 +) Example 33 Following the method of Example 32, the following compounds were obtained. 1- [[3- (1Η-1,2,4-triazol-3-yl) phenyl] carbamyl] -5 -methyl-2, 3-dihydropyrrole [2, 3-f ] 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) mp: > 220 X) IR (Nujol, cm: 1680 NMR (DMSO-d ^. ^): 3.27 (2H, t, J = 8Hz), 3.73 (3H, s), 4.19 (2H, t, J = 8Hz), 6. 31 (1H, cU = 3Hz), 7.18 (lH, d, J = 3Hz) (7.26 (lH, s), 7.38 (lli.ni), 7.67 (211, m), 8. 06 (lH.br.s), 8.30 (lH, br.s), 8.60 (lH.br.s) , 14.10 (lH.br.s)

Mass: 359 (M + 1 +) -38- This paper size is applicable to Chinese National Standard (CNS) Λ4 specification (2〗 〇297297 mm) Employees' Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs Cooperative Printing Association A7 B7 _ V. Description of the invention ( μ) Example 34 The following compound was obtained by following the method of Example 12. 1-[[3- (2-imidazolin-2-yl) phenyl] amine formyl] -5-methyl-2,3-dihydropyrrole [2,3 -f] indionium hydrogen iodide mp: 191-193 ° C IR (Nujol, cm: 1650 NMR CDMS 0-d6, < 5): 3.29 (2H, tJ = 8Hz), 3.74 (3H, s), 4.02 (4H, br.s), 4.18 (2H, t, J = 8Hz), 6.31 (lH, d, J = 3Hz), 7.20 (lH.dJ = 3Hz), 7.29 (lH, s), 7.66 (3H, m), 8. 05 (lH , s), 8.31 (lH, dJ = 3Hz) f 8.83 (lH.br.s), 10.45 (lH.br.s)

Mass: 360 (M + 1 +)-Example 35 In a 10 ml round-bottomed flask, N- [3- (carazol-5-yl) phenyl] carbamic acid 4-nitrophenyl ester (17111 ^), 5-formaldehyde was added. -2,3-dihydropyrrolidine [2,3-tocopherol (86 mg), dimethylformamide (1 m 1), and triethylamine (9 1 a 1), Stir at temperature for 6 5 hours. Add water (1 Q in 1) to dilute. After 30 minutes, the precipitate was collected by filtration and washed several times with water. Crystallization from 95% ethanol (8ml) fluorene can give 1-[[3- (blazol-5-yl) phenyl] aminomethylfluorenyl] -5-methyl-2,3-dihydropyrrole [2, 3-f] indrine (141mg) e mp ·: 175-1761 IR CNujol, cm _ J): 1645 φ NMR (DMSO-d6, < 5): 3.27 (2H, t, J = 8,2), 3.73 (3H, s), 4.18 (2H, tJ = 8.2), 6.32 (111.d, J = 3.0 into 7.19 (lH, d, J = 3.0), 7.26 (lH, s), 7.33 — 7.38 (2H, m), 7.58-7.70 UH.ni). 7.91 (lH.br.s), 8.05 (lH, s), 8.26 (lH, s), 8.56 (lH.br.s), 9.09 (lH, s). Example 36 The following compound was obtained by following the method of Example 25. N-[3-(2 -methylimidazol-5-yl) phenyl] -N,-(1 -methylindolin-5 -yl) P. -39- This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Read the precautions on the back before filling in this page) k. Order

V. Description of the invention (W 216 (dec.) ° C 1 A7 B7 mp: 214 FT-IR (KBr, cm 1420, 1300, 1230 NMR (DMSO-d6, (5): 2.31 (3H, s), 3.76 ( 3H, s), 6.35 (lH, dd, J = 3Hz), 7.1-7.4 (7H, m), 7.71 ClH.cU = 1.7Hz), 7.83 (1H,-bs), 8.40 (1H, bs), 8.56 (lH, s), 11.8 (lH.bs) APCI-Mass: 346 (M + HJ) Example 3 7 The following compounds can be obtained by the method of Example 25:): 3370, 3290, 1640, 1610, 1590, 1550, 1510, 1490, 1440,

N- [3- (2-Isopropazol-5-yl) phenyl] 5-yl) urea m. P.: 1 4 0-2 0 5 (amorphous) ° CN-(1 -formin Please read the notes before reading B. Min. 1¾ and fill in%. Page 1, 33.70, 3270, 2970, 1660, 1610, 1590, 1550, 1490, 1440, printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives. FT-IR (KBr, cm 1230 NMR (DMSO-d6,5): 1.28 (6Hfd, J = 7Hz), 2.9-3.1 (lH, m), 3.76 (3H, s), 6.35 (1H, d, J = 3Hz), 7.1-7.4 (7H, m), 7.70 (lH, d, J = 1.6Hz), 7.80 (lH, s), 8.37 (lH, s), 8.60 QH, s ;, 11.83 (lH.bs) APCI-Mass : 374 (M + H +) Example 3 8 Following the method of Example 25, the following compounds can be obtained: "N- (1-methylindole-5-yl)-(Γ-[3- (2 -Third-butoxazole- 5-yl) phenyl] dolphinmp: 129 — 150 (dec.) ° C IR (Nujol, cm A): 3300-3100, 1650, 1580, 1530, 1450, 1320, 1280, 1220 NMR (DMSO-d6 ， (5): 1.34 (9H, s), 3.76 (3H, s), 6.35 (lH, dd, J = 3Hz), -4 0-This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) ) A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention (Pair) 7.1-7.4 (7H, m), 7.71 (1H, cU = 2Hz), 7.76 (IH.m). 8.36 (lH, s), 8.63 (1IU). 11. 77 (lH.bs) 'APCI-Mass: 388 (M + H4) Example 39 The following compound can be obtained by following the method of Example 25. N- (1-methylindobor-5-yl) -N '-[3- (2-trifluorometimidazol-5-yl) benzene Base) urea mp: 208-210 ° C FT-IR (KBr, cm _ X): 3288, 3126, 3074, 2922, 1660, 1616, 1583, 1556, 1514, 1485, 1444, 1422, 1398, 1302, 1230 cm-1 NMR ① MSO-d6, (5): 3.76 (3H, s), 6.35 (lH, d, J = 3Hz), 7.12-7.19 7.26 -7.37 (5H, m), 7.71 (lH.dJ = l- 7Hz), 7.89 (lH.bs), 7.97 (lH, bs), 8.40 (lH, bs), 8.67 ClH.s), 13.71 (lH.bs) APCI-Mass: 400 (M + H +) Example 40 Example The method of 25 can obtain the following compounds. N- [3- (1,2-dimethylimidazol-5-yl) phenyl] -N '-(1-methylHindol-5-yl) urea mp: 209-210 ° C FT-IR (KBr , cm ~ Χ): 3325, 3099, 1703, 1583, 1543, 1493, 1429, 1296, 1250, 1211 cm " 1 NMR (DMSO-d6,6): 2:35 (3H, s), 3.53 (3H, s), 3.76 (3H, s), 6.34 (lH, d, J = 3Hz), 6.84 (lH, s), 6.9-7.0 (lH, m), 7.1-7.2 (lH, m), 7.2-7.5 ( 4H, m), 7.56 (lH.bs), 7.69 (lH, d, J = 2Hz), 8.47 (lH, s), 8.68 (lH, s) s APCI-Mass: 360 (M + H +) -4 1 -(Read the precautions on the back before you fill in this page) This paper size applies to Chinese National Standards (CNS) A4 specifications (210X297 mm) Α7 Β7 Printed by the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention (ο) Example 4 1 The following compound was obtained by following the method of Example 25. [3- (4-methylazol-1-yl) phenyl] -N '-(1-formylindol-5-yl) urea mp: 194-197 ° C IR (Nujol, cm ~ 1): 1640, 1605 NMR (DMSO ~ d6,5): 2.17 (3H, s), 3.76 (3H, s), 6.35 (lH.dJ = 3Hz), 7.1 -7.4 (7H, m), 7.70 (lH, s) , 7.76 (lH, s), 8.03 (lH, s), 8.56 (lH, s), 8.78 (lH, s) APCI- Mass: 346 (M + Γ) Example 42 The following compound can be obtained by the method of Example 25 . (|]-(1-methyl | 1 lead | 1-dol-5-yl) -N1- [3- (2-methylbrazol-5-yl) phenyl] urea mp: 209-212 ° C FT-IR (KBr, cm _ b: 3286, 1624, 1589, 1558, 1487, 1431, 1333, 1300, 1242 cm'1 NMR (DMS0-dg, 5): 2.68 (3H, s), 3.76 (3H, s), 6.35 (IH.dJ = 3Hz), 7.1-7.4 (6H, m), 7.70 7.78 7.96 (UJ, s), SAH (lJl.s), 8.72 (lH, s) APCI-Mass: 363 (M + H +) Example 43 The following compound can be obtained by the method of Example 6. 1 N-(1 -methyl H3I B-do-5 -yl) -N '-[3-(pyridine-3 -yl) phenyl] urea-42- (# First read the weep on the back and then fill out this page). T'-1. Packing — • IIIII, 1TK. 11. This paper size applies the Chinese National Standard (CNS) Α4 specification (210 × 297 mm) Central Standard of the Ministry of Economic Affairs A 7 B7 ___ printed by the Bureau's Consumer Cooperatives V. Description of Invention (Drama)

mp: 172-174 ° C IR (Nujol, cm _ b: 3260, 1630 NMR (DMSO-dg.5): 3.76 (3H, s), 6.35 (lH, d, J = 2.9Hz), 7.16 (lH, dd, J = 8.7Hz, 2.0Hz), 7.27-7.54 (lH, s), 8.59 (lH.dd.J = 4.7Hz, 1.5Hz), 8.75 (lH, s), 8.85 (lH, d, J = 1.8Hz)

Mass: 343 (M + 1) + Example 4 4 Following the method of Example 6, the following compounds were obtained. 1- [[3- (pyridin-3-yl) phenyl] aminocarbamyl] -5 -methyl_2,3-dihydropyrrolidine [2, 3-f] B mp: 181 (dec.) ° C IR (Nujol, cm — b: 1640, 1600 NMR (DMSO-d6, < 5): 3.28 (2H, t, J = 8.3Hz), 3.73 (3H, s) (4.19 (2H , tJ = Θ.ΘΗζ '). 6.31 (lH, d, J = 2.8Hz), 7.18 (lH, d, J = 3.0Hz), 7.27 (lH, s), 7.33-7.54 (3H, m), 7.67 aH, d, J = 7.8Hz), 7.95 (lH, s), 8.02-8.06 (2H, m), 8.56-8.60 (2H (m), 8.87 (lH, d, J = 1.8Hz)

Mass: 369 (M + 1) + Example 45 To 1-methylindole-5-carboxylic acid (100mg) in benzene (5ml) was added triethylamine (159 # 1) and diphenylphosphonium nitrogen (121 //1). After refluxing for 4 hours, it was cooled to room temperature. Add 3- (imidazole-butyl) -6-nitroaniline (140 mg). Reflux for 4 hours. After cooling, it will be dissolved in ethyl acetate, washed with water (, dried under sulfuric acid pin, and purified by silica gel column chromatography (chloroform: methanol = 10: 1) to obtain [^-[3- (味 mile_1-yl) -6-Nitrophenyl]-() |-(1-A11 lead 1 | Duo_5- -43- This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) (郐 先 阖Read the note on the back and write this page) Order the A7 B7 of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the Invention (Knowledge) Urea (long). Mp: 220 ° C (dec.) IR (Nujol , Cm — 丄): 3300, 1710, 1615 NMR (DMSO-d6,5): 3.77 (3H, s), 6.38 (lH.dJ-2.5Hz), 7.17-7.22 (3H, m), 7. 30 ( lH, d, J = 3.0), 7.39 (1H, cU = 8.7Hz), 7.49 (lH, dd, J = 9.2Hz, 2.3Hz), 7.77 (1H, d, J = 2.0Hz), 7.81 (lH, t, J = 1.5Hz), 8.26 (lH, s), 8.31 (lH, d, J = 3.0Hz), 8.37 (lH, s \ 8.68 (lH, d, J = 2.4Hz) ♦

Mass: 377 (M + l) + Example 46 To 4-m-nitrobenzene gas carbonyl gas (0.61 g) was added to methane (50ml) containing 3- (imidazol-1-yl) aniline (0.48 g). 〇 Stir for 1 Q minutes at room temperature. Add 5-methyl-2,3-dihydropyrrole [2,3-Π indole (0.52 g) and triethylamine (D.84inlU, stir at room temperature for 7 hours, and then sequentially with sulfonic acid Wash with sodium hydrogen solution and water, dry under sodium sulfate, and dry under vacuum. Purify by silica gel column chromatography (chloroform-methanol: 0-3¾ v / v) to obtain 1- [[3- (味 azole_ 1-yl) Phenyl] aminocarbinyl] -5 -methyl-2,3-dihydropyrrolid [2,3-f] indine (0.61 g).

mp: 211-214 ° C IR (Nujol, cm ~ 2): 1665, 1645 NMR (DMSO-d6 > (5): 3.27 (2H, t, J = 8Hz), 3.73 (3H, s), 4.18 (2H , t, J = 8Hz), 6.31 (lH, d, J = 3Hz), 7.12 (lH, s), 7.15-7.30 (3H, m), 7.43 (lH, t, J = 8Hz), 7.50-7.70 ( 2H, m), 7.87 (lH, t, J = 2Hz), 8.05 (lH, s), 8.16 (lH, s), 8.64 (lH, s) APCI-Mass: 358 (M + Γ) Example 47 3- (1-methyloxazol-5-yl) aniline (87ffig), dimethylformamidine-44- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) (Notes again ^ write this page)

A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (β) Amine (lml) and triethylamine (40 # 1). Add 4-nitrophenyl chloroformate (UOmg) at 5 ° C. . After stirring for 30 minutes, 5-methyl-2,3-dihydropyrrole 骈 [2,3-f] P indole (86 mg) was added, and then triethylamine (0.14 m1) was added. Stir at room temperature overnight (16 hours). Pour in water (3Qml). After 30 minutes, filter the precipitate and wash with water. It was dissolved in a silica gel column and washed with brine, dried (thormium sulfate), filtered, and evaporated. Purified by silica gel column chromatography. Stirring in isopropyl ether (IQml) can obtain 1-[[3-(trimethylindino-5 -yl) phenyl] aminomethylamidino] -5 -methyl-2, 3-dihydropyrrole [ 2,3-f] indole. mp: 224-226 V Mass: 372 (M. + 1) IR (Nujol, cm: 1655 NMR (DMSO, δ): 3.27 (2H, t, J = 8.2Hz), 3.71 (3H, s), 3.73 ( 3H, s), 4.17 (2H, t, J = 8.2Hz), 6.31 (lH, d, J = 2.5Hz), 7.03 (lH, bs), 7.11 (lH.dJ = 8.0Hz), 7.18 (lH. dJ = 3.0Hz), 7.26 (lH, s), 7.37 (lH, dd, J = 7.8Hz, 7.8Hz), 7.60 (lH.dJ = 8.1Hz), 7.70 (1H, sj, 7.71 (lH, s) , 8.03 (lH, s), 8.52 (lH, s). Example 48 The following compound can be obtained by the method of Example 47. 1- [[3- (1,2-dimethylazol-5-yl) phenyl ] Aminomethyl]-5 -methyl-2,3-dihydropyrrolo [2,3-f] indole mp: 224-227 0C FT-IR (KBr, cm- '): 3263, 2941 , 1662, 1610, 1564, 1529, 1473, 1425, 1331, 1279, 1246cm'1 NMR (DMSO-06,5): 2.36 (3H, s), 3.26 (2H, U = 8Hz), 3.56 (3H, s ) t 3.73 (3H, s). 4.17 (2H, t = 8Hz), 6.31 (lH, d, J = 3Hz), 6.85 (lH, s), 7.0 —7.10 7.17 (1H, -45- (Please Read the notes on the back before filling this page), binding ΗΛ This paper size applies Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) A7 B7 V. Description of the invention (from, d, J = 3Hz), 7.26 (lH, bs), 7.36 (1H, U = 8Hz), 7.5-7.6 (lH, m), 7.66 (lH.bs), 8.03 8.51 (lH.bs)

APC1-MS: 386 (M + HO Example 4 9 The method shown in Example 25 can be used to obtain the following compounds. N- [3- (l-Isopromazol-5-yl) phenyl] formin B-Do 5- Base) urea

mp: 213-215 ° C FT-IR (KBr, cm- '): 3313, 3099, 2973, 1697, 1662, 1581, 1544, 1487, 1423, 1290, 1230cm-1 NMR (DMSO-de, (5) : 1.42 (6ad, J-7Hz), 3.76 (3H, s), 4.35 -4.49 (lH, m), 6.35 (lH, d, J = 3Hz), 6.92 (lH, d, J = 0.8Hz), 6.94 -6.98 (1H, m), 7.12-7.18 (1H, m), 7.26 -7.47 (4H, m), 7.56 (lH, m), 7.68 (lH.dJ = 1.7Hz), 7.93 (lH.m), 8.48 UH.s), 8.71 (lH, s) APCI-MS: 374 (M + H +) Example 50 The following compound was obtained by the method of Example 25. Printed by N- [3- (2- (oxazolyl-I) -phenyl) phenyl] -N '-(1-methylindole B- (5-yl)) Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs (Read the notes on the back and fill out this page)

mp: 222-227 V FT-IR (KBr, cm- '): 3276, 3215, 3099, 1728, 1684, 1616, 1591, 1554, 1491, 1442, 1439, 1335, 1302, 1232 NMR (DMSO-d6, (5): 3.76 (3H, s), 6.34 (lH.dJ = 2.6Hz), 6.76 (1H, m), 7.06-7.36 C6H, m), 7.46 (lH, m), 7.69 (lH; d, J = 1.7Hz), 8.48 (lH, s), 8.52 (lH, s), 10.0 (lH.bs), 10.5 (lH, bs) 丨 APCI-MS: 348 (M + H +) -46- Applicable to this paper size Chinese National Standard (CNS) Λ4 Specification (2) 0X297 mm) Printed by the Sheller Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ^ A7 _B7____ V. Description of the Invention (shirt) Example 51 The following compound can be obtained by the method of Example 47. N _ (buprofen-5 -yl) -N, · [3-(pyrimidin-5 -yl) phenyl] urea mp: 228 — 230 ° C (dec.) 1R (KBr, cm-1) : 3300, 3140, 3101, 3041, 1649, 1608cm · 1 NMR (DMSO-de, ^): 3.76 (3H, s), 6.35 (lH.dJ = 3.0), 7.13-7.18 (lH.m), 7.27 ( lH, t, J-3.0), 7.33 ^ 7.49 (3H, m), 7.54-7.59 ClH, m), 7.70 (lH, s), 7.85 (lH, s), 8.55 (lH, s ;, 8.74 (lH , s), 9.09 (2H, s ;, 9.21 (lH.s; MS: 344 (M + 1+)) Example 52 The following compound can be obtained by the method of Example 4 6. 1- [[3-oxazole-butyl ) Phenyl] aminomethylamido] _2,3_dihydropyrrolidine [2,3-f] IndB mp: 133-140 ° C IR (Nujol, cm- '): 1620, 1600 NMR (DMSO -de, < 5) 3.24 (2H, t, J = 8Hz), 4.16 (2H, U = 8Hz), 6.32 (lH, s), 7.10 -7.40 (4H, m), 7.43 (lH, U = 8Hz ), 7.50- 7.70 (2H, m), 7.88 (lH, s), 8.04 (lH, s), 8.17 (lH, s), 8.63 (lH, s), 10.84 (lH, s) MS, 344 (M + r) Example 53 The following compound can be obtained by following the method of Example 46. '1- [[3- (1-methylazol-5-yl) phenyl] aminomethylfluorenyl] _2,3-dihydropyrrole [ 2, 3-f] InB Duo-4 7-(Read the notes on the back first, then fill out this ) This paper size applies to China National Standards (CNS) A4 specification (210X297 mm) A7 B7 ____ V. Description of the invention (price; mp: 235 ~ 243 ° C (dec.) IR (Nujol, cm * " 1) : 1665 NMR (DMSO-de, (5): 3.24 (2H, t, J = 8Hz), 3.71 (3H, s), 4.16 (2H, t, J = 8Hz), 6.32 (lH, s), 7.04 (lH, s), 7.11 (lH, d, J = 8Hz), 7.20 (2H, s), 7.37 (lH, tJ = 8Hz), 7.60 (1H, d, J = 9Hz), 7.70- 7.72 (2H , m), 8.03 (lH, s), 8.50 (lH, s), 10.83 (1H, br, s). MS: 358 CM + Γ) ί., V pack (zinc read the precautions on the back before filling out (This page) Order-/ ^ Printed by the Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs

—47—A The size of this paper is applicable to China National Standard (CNS) A4 (210X 297mm)

Claims (1)

r # 'Positive A8 B8 C8 D8, patent application scope No. 8 6 1 1 8 0 8 6 "Urea derivative" patent case (Amended on December 23, 1987) The scope of patent application: 1. A formula ( I) Compound and its pharmaceutically acceptable salt: R5 I) (Please read the note on the back,-', then fill out this page) where R1 and R2 are each hydrogen or connected to form ethylene, R3 is hydrogen or low radical, R4 is oxazolyl, pyrazolyl, adjacent Pyridyl, pyrimidinyl, triazolyl, imidazolinyl, 2-oxazolyl, 2-oxazolyl-, oxazolyl, iso-oxazolyl, thiazolyl, each of which may have one or more substituents selected from Phenyl, amine, lower alkyl, benzyl, benzyloxycarbonyl or tridentate lower alkyl, R 5 is hydrogen. Nitro, and X is CH or N. A method for preparing a compound of the following formula and a pharmaceutically acceptable salt thereof: W Meng Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs / R3 This paper applies the Chinese National Standard (CNS) A4 specification (210X297 mm) r # 'positive A8 B8 C8 D8, patent application scope No. 8 6 1 1 8 0 8 6 "Urea derivative" patent case (87 (Amended on December 23, 2010) The scope of patent application: 1. A compound of formula (I) below and its pharmaceutically acceptable salt: R5 I) (Please read the note on the back,-', then fill out this page) where R1 and R2 are each hydrogen or connected to form ethylene, R3 is hydrogen or low radical, R4 is oxazolyl, pyrazolyl, adjacent Pyridyl, pyrimidinyl, triazolyl, imidazolinyl, 2-oxazolyl, 2-oxazolyl-, oxazolyl, iso-oxazolyl, thiazolyl, each of which may have one or more substituents selected from Phenyl, amine, lower alkyl, benzyl, benzyloxycarbonyl or tridentate lower alkyl, R 5 is hydrogen. Nitro, and X is CH or N. A method for preparing a compound of the following formula and a pharmaceutically acceptable salt thereof: W Meng Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs / R3 This paper applies the Chinese National Standard (CNS) A4 specification (210X297 mm). Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. A8 B8 C8 D8. 6. In the patent application formula, R 1 and R 2 are each hydrogen or connected. Forms ethylene, R3 is hydrogen or lower alkane, R4 is midazolam, pyrazolyl, pyridyl, pyrimidinyl, triazolyl, imidino, 2-imidazolidinyl, 2-imidazolinone , Oxazolyl, isoxazolyl, thiazolyl, each of which may have one or more substitutions 碁 one selected from phenyl, amine, lower alkyl, thyryl, flat-cheek or tridentate lower alkyl, R5 Is hydrogen or nitrate, and X is CH or N, which contains (1) the compound of the following formula or a salt thereof: 'o2n where R3 is as defined above, and reduction can obtain the compound of the following formula or a salt thereof: (read Xiange Read the notes on the back, then fill out this page) • Install. H2N The definition of R3 in the formula is as above, and then reacted with carbonyldiimidazole, and then with the compound of the following formula or its salt: -2-This paper size applies to China National Standard (CNS) A4 specification (210X297 mm), δτ A8 B8 C8 D8 Scope of patent application In the formula, R4, R5, and X are defined as above to obtain a compound of the following formula or a salt thereof: (Please read the precautions on the back before filling out this page)-Equipment · In the formula, R3, R4, R5, and X are as defined above, or (2) The compound of the following formula or its salt: Order Printed by the Staff Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs. In the formula, R4, R5, and X are as defined above, and react with diphenyl basic dinitrogen, and then react with the compound of the following formula or its salt: r R2 ~ 3-This paper size applies Chinese National Standard (CNS) A4 specification (210X297 (Mm) A8 B8 C8 D8 6. The scope of patent application: R1, R2, and R3 are as defined above, and the compound or salt thereof can be obtained as follows: 3 2 R or the X and 5 R salts as defined above 3 ^^ 1 nfn ϋιΛ ^ I nn —Η / i nn I. (Please read the precautions on the back before filling out this page) Order Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economy Printed in Chinese R Returned in Chinese The base is Z or the X and 5 R 4 R 3 R 2 R salts as defined above or its combination formula L This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) N N Printed by BS C8 D8 of the Central Standards Bureau of the Ministry of Economic Affairs, F. Cooperative, Patent application scope / R3 where R1 ·, R2, R3 and x are defined as above, and react with the compound of the formula: m2 h2n can obtain the compound of the following formula or Salt / R3 wherein 1 ^, R 2, R 3, R 5 and X are as defined above, or (5) the compound of the following formula or its salt: The definitions of 1 ^, 1? 2, 1 ^ 3, 1 ^ and the fork in the N formula are as follows to react with the compound of the following formula: -5-This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) (please first (Read the notes on the back and fill out this summer) ^^ 224 BS C8 D8 Patent application scope The compound of the following formula or its salt can be obtained: In formula N, R1, R2, R3, R5 and X are as defined above, or (6) the compound of the following formula or a salt thereof: R5 · R4 -NH, (please read the precautions on the back before filling this page) If. I In, 1T The R4, R5, and X definitions in the formula printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs are as above. Its salt reaction: The definitions of R1, R2 and R3 in N formula are as above, and the compound of the following formula or its salt can be obtained: -6 This paper size is applicable to China National Standard (CNS) Λ4 specification (210X 297 mm) Ψ '" ^ 4 < bcd 6. Scope of Patent Application In the formula, R1, R2, R3, R4 (7) is defined as the compound of the following formula or its salt / R3 5, and X is as above: V: or R5, R4- -NH2 wherein R4, R5 and X are as defined above, react with carbonyldioxazole, and then react with a compound of the following formula or a salt thereof: The definition of R3 in the formula printed by the Central Standards Bureau of the Ministry of Economics & Men's Consumer Cooperatives is as above, and the compound of the following formula or its salt can be obtained N (Please read the notes on the back before filling this page) This paper size applies to Chinese National Standard (CNS) Λ4 specification (210X297 mm) ABCD patent application scope where R3, R4, R5, and X are as defined above, or (8) the compound of the following formula or its salt: R \ _R4-H- 4 + -NHC00 -N02 wherein R4, R5 and X are as defined above, and react with a compound of the following formula or a salt thereof: (Please read the precautions on the back before filling out this page) 1 Pack-Order Printed by the Central Laboratories of the Ministry of Economic Affairs and Consumer Cooperatives The compound of the following formula or its salt can be obtained: R5 (9) Add the compound of the following formula or its salt R5 RL -NH2 -8-This paper size applies to Chinese National Standard (CNS) Λ4 specification (21 〇 × 297 mm) ⑴ ......---.---. Bimu A8 B8 C8 D8 R4, R5 and X are as defined above and react with a compound of the formula: 02N And react with a compound of the following formula or a salt thereof N / R3 where R1, R2 and R3 are defined as above, the compound of the following formula or its salt can be obtained: (Please read the precautions on the back before filling this page) Printed by the Consumer Cooperative of the Central Bureau of Standards, Ministry of Economic Affairs 'N where R1, R2, R3, R4, R5 and X are as defined above. A serotonin antagonist peony composition comprising, as the active ingredient, the compound of the first patent range or a pharmaceutically acceptable salt thereof, and mixed with a pharmaceutically acceptable carrier. -9-This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) --- r Pack -------- Order ----- ^. ': Like ---- A8 B8 C8 D8 Scope of patent application 4. If the composition in the scope of patent application item 3 is used to prevent and control central nervous system (CNS) abnormalities such as anxiety, depression, obsessive-compulsive behavior abnormalities, migraine, alkali Coguel such as A1 abuse, physical disorders Drug and food pressure relief 脱 e syndrome irritability, dysphagia, dysphoria, dysentery, hemiazepine, diquinone, and dunguni are affected by the head or \ and often different wounds and wounds. 0 and ' 〇 Shennao Jingshui, if due to injury, (please read the precautions on the back 赓 /, and fill out this page) • Binding · Binding · J 「丨 Line Ministry of Economic Affairs Central Standardization Bureau Staff Consumer Cooperative Co., Ltd. This paper is applicable to paper standards China National Standard (CNS) A4 specification (210X297 mm)