TW438782B - Novel 2,3-dioxo-1,2,3,4-tetrahydro-quinoxalinyl derivatives - Google Patents

Abstract

2,3-Dioxo-1,2,3,4-tetrahydro-quinoxalinyl derivatives of formula I, wherein one of the radicals R1 and R2 is a group R5 and the other is a group of formula -CH(R6)-alk-R7(Ia), -alk-CH(R6)-R7(Ib), -alk-N(R8)-X-R7(Ic), -alk-N<SP>+</SP>(R8)(R9)-X-R7A<SP>-</SP>(Id), -alk-O-X-R7(Ie) or -alk-S-X-R7(If), R3,R4 and R5 are each independently of the others hydrogen, lower alkyl, halogen, trifluoromethyl, cyano or nitro, R6 is unsubstituted or lower alkylated and/or lower alkanoylated amino, R7 is hydrogen; an aliphatic, cycloaliphatic or heterocycloaliphatic radical; acyl derived from carbonic acid or from a semiester or semiamide of carbonic acid, cyano, from sulfuric acid or from an aliphatic or aromatic sulfonic acid or from phosphoric acid or from a phosphonic acid ester; amino that is unsubstituted or aliphatically or araliphatically substituted and/or substituted by aliphatic, araliphatic or aromatic acyl; or an aromatic or heteroaromatic radical, R8 is hydrogen; an aliphatic or araliphatic radical; or acyl derived from an aliphatic or araliphatic carboxylic acid or from an aliphatic or araliphatic semiester of carbonic acid, or R7 and R8, together with X and the nitrogen atom bonding R8 and X, form an unsubstituted or substituted mono-or di-azacycloalkyl, azoxacycloalkyl, azathiacycloalkyl or optionally oxidised thiacycloalkyl radical bonded via a nitrogen atom, or an unsubstituted or substituted, optionally partially hydrogenated aryl or heteroaryl radical, R9 is an aliphatic or araliphatic radical, or R7, R8 and R9, together with X and the nitrogen atom bonding R8, R9 and X, form an unsubstituted or substituted quaternary heteroaryl radical bonded via the quaternary nitrogen atom, with A<SP>-</SP> being the anion of a protonic acid, alk is lower alkylene, and X (unless, together with R7 and R8 and the nitrogen atom bonding R8 and X or together with the nitrogen atom bonding R8, R9 and X, it forms part of one of the mentioned ring systems) is a divalent aliphatic, cycloaliphatic or araliphatic radical or a direct bond, and the pharmaceutically acceptable salts thereof can be used in the preparation of a medicament for the treatment of pathological conditions that are responsive to blocking of AMPA, kainate and/or glycine binding sites of the NMDA receptor.

Description

438782 A7 B7 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention

(One of the radicals R! &Amp; R2 in formula (I) is the R5 group, and the other is the formula-01 (1 ^) &quot; 311 {: -foot 7 (1 &amp;), -311 «:-CH ( Rg) -R7 (lb), -aik-N (Rg) -X-R7 (Ic), -alk-N ^ (Rg) (R9) -X-R7A * (Id) '-alk-OX-R7 ( Ie) or -alk-SX-R7 (If), R3, R4, and &amp; are each independently hydrogen, lower alkyl, halogen, trifluoromethyl, cyano or nitro, and are unsubstituted Or lower alkylated and / or lower alkylated amine groups, R7 is hydrogen, aliphatic-, cycloaliphatic or heterocyclic aliphatic radical, cyano, carbonic acid or half carbonate or hemiamine carbonate, Sulfuric acid or aliphatic or aromatic sulfonic acid or phosphoric acid or phosphonate-derived fluorenyl, unsubstituted or substituted with aliphatic or araliphatic and / or aliphatic-, araliphatic-, or aromatic fluorene -Substituted amino group, or aromatic · or heteroaromatic radical, R * is hydrogen, aliphatic- or araliphatic radical, or an aliphatic- or araliphatic carboxylic acid or a carbonate half-ester or Aromatic groups derived from araliphatic halides of carbonic acid, or 11 «together with X and bonded R * and the nitrogen atom of X to form an unsubstituted or substituted mono · or di-acyl ring bonded via a nitrogen atom Alkyl, acryl Fluorene cycloalkyl, azeticycloalkyl or selectively oxidized thiacycloalkyl radicals, or unsubstituted or substituted, optionally partially hydrogenated aryl or heteroaryl radicals, It is an aliphatic- or araliphatic radical, or ---—— ^ ___ This paper rule (CNS) A4 specification (21〇-297mm i (谙 Please read the precautions on the back before filling this page) Order- -4- i438782 A7 B7 Printed by Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention () 117 '&amp; and ^ together with the bond center, the nitrogen atom of ^ and \ forms a bond through the fourth nitrogen atom Unsubstituted or substituted fourth heteroaryl radical, and A · is an anion of a protonic acid, alk is a lower alkylene group, and X (unless it is together with &amp; and R «and the bond Rs and The nitrogen atom of X, or together with the nitrogen atoms of R *, R9 and X to form a part of the aforementioned ring system) is a divalent aliphatic-, cycloaliphatic- or araliphatic radical or a direct bond, provided that Is a group of the formula (Ic), R2 and Gen are each independently a fluorine, chlorine, bromine, methyl, ethyl or trifluoromethyl group and a compound of formula (I) where &amp; is hydrogen, when alk is Asia In the case of alkyl, ethylidene or propyl, the -1 ^ (118) 0 «17 group is not a benzene hydrazone that is selectively bonded via a nitrogen atom and / or is substituted with up to 6 (inclusive) carbon atoms. Alkyl substituted or substituted at the ω-position (wherein each group is independently hydrogen, alkyl, cycloalkyl, benzene-lower alkyl, or pico-lower alkyl, or together with the nitrogen that binds them Atoms form pyrrolidinyl, N-hexahydropyridyl, hexahydropyridyl, N'-lower hexahydropyridyl, morpholinyl, or azepinyl) substituted 5-membered monodi, tri- or Tetra-ΠΤheteroaryl radical), and its pharmaceutically acceptable salts, in the preparation of therapeutic pathological symptoms that respond to the blocking of the glycine-binding site of AMAP, kainic acid and / or NMDA receptors For pharmaceutical use, and related compounds of formula (I) and salts thereof, provided that in compounds of formula (1) of Zha, 113 and "4 is hydrogen and &amp; is a base of formula (115), when alk is sub When it is methyl, it is not an amine group or R7 is not a carboxyl group. The other condition is that in the compounds of Takeshi (I) where 113, R4 is hydrogen, and R2 is a group of formula (Ic), when alk is methylene % -N (R8) -X-R7 group is not 1-imidazole Or when alk is this paper scale applicable Chinese national standard Mi (CNS) eight 4 Specifications (2tOX297 mm) {Please read the back of the smell of the Notes then #i. This page)

A7 B7 1438782 V. Description of the invention (-N (R (i) -X-R7 group is not amine, dipropylamino, N_ (2-phenylethyl) _N_diamine and N'- (2-chlorobenzene) -hexahydropyridyl, the last condition is that Ri is a group of formula (Ic), and R2 and &amp; are each independently gas, chlorine, bromine, methyl, ethyl or trifluoromethyl In the compound of formula ① where &amp; is hydrogen, when alk is methylene, ethylene, or propylene, the 'group is not bonded via a nitrogen atom and is selectively fused with phenylhydrazone and / or is as many as 6 (including) carbon atoms are substituted by alkyl groups or groups of formula -NO ^ -Rb at the ω-position (where &amp; and 仏 are independently ΛΛ, and are hydrogen, fluorenyl, cyclohexyl, and benzene-lower-level Or Π lower than low-grade radicals, or together with the nitrogen atom that binds them to form pyrrolidinyl, N-hexahydropyridyl, hexahydropyridyl, NMS-level alkylhexahydropyridyl, morpholinyl or leaves Heptyl) substituted 5-membered mono-, di-, tri- or tetra-azaheteroaryl radical, its preparation method and unsubstituted or lower alkylated pharmaceutical composition containing the compound / Or lower alkylated amines are, for example, amine 'lower alkylamines , Lower alkylamine, N · lower amine-N-lower alkylamine or di · lower alkylamine. Aliphatic radicals are, for example, lower alkyl, amine-lower alkyl, lower alkylamine · lower Alkyl, di-superalkyl, lower alkyl, lower alkylamine-lower alkyl, lower alkyl, lower alkyloxy-lower alkyl, multidentate-lower alkyl, lower alkoxy-lower alkyl , Via a lower alkoxy-lower alkyl group, a lower alkoxy-lower alkoxy alkyl group, or a polyhalogen · grade alkoxy-lower alkyl group. Cycloaliphatic radicals are, for example, 3- to 8-membered , Especially 3- to 7-membered cycloalkyl radicals, which are unsubstituted or free or aliphatic esterified carboxyl groups and / or unsubstituted or lower alkylated and / or lower alkylated amines Substitute, such as equivalent cycloalkyl, carboxycycloalkyl, lower alkoxycarbonyl cycloalkyl, amine cycloalkyl or mono- or this paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 谙 Xinwen Read the memorandum again

Ordered by the Central Standards Bureau of the Ministry of Economic Affairs, printed by the Shellfish Consumer Cooperatives · 6 * Printed by the Central Standards Bureau of the Ministry of Economic Affairs, printed by the Consumers Cooperatives A7 B7 5. Description of the invention () Di-lower alkylamine cycloalkyl, namely cyclopropyl, cyclo Butyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 2-amine cyclohexyl, 4-cyclocyclohexyl, 3-cyclohexyl or 2-cyclohexyl. Heterocyclic aliphatic radicals are, for example, mono- or di-t-cycloalkyl, azacycloalkyl, or azithiacycloalkyl having 3 to 8 (inclusive), especially 3 to 6 ring atoms. Free radicals, which are unsubstituted or substituted with oxy, hydroxyl, and / or free or aliphatic esterified carboxyl groups, such as equivalent pyrrolidine-1-yl (pyrrolidinyl), pyrrolidine-2-yl, hexahydropyridine Steep-1-yl (N-hexapyridyl), hexahydropyridin-2-yl, morpholinyl, thiomorpholinyl, or unsubstituted or lower alkylated or lower alkylated hexahydropyridine Cultyl, such as pyrrolidinyl, oxopyrrolidyl, N-hexahydropyridyl, tris-N-hexahydropyridyl, lower alkoxy-N-hexahydropyridyl, morpholinyl, or thiomorpholinyl, Especially morpholinyl, 5-oxopyrrolidin-2-yl or 2-carboxypyrrolidinyl. Derivatives derived from carbonic acid or half carbonate or hemiamine carbonate are derived from, for example, aliphatic or araliphatic half esters or unsubstituted or substituted aliphatic, araliphatic, or aromatic ammonium carbonate And is, for example, a free or aliphatic or araliphatic esterified carboxyl group, such as lower alkoxycarbonyl or unsubstituted or substituted with lower alkyl, lower alkoxy, hydroxyl, halogen, and / or trifluoromethyl Benzene-lower alkoxycarbonyl, or unsubstituted or amine formamido, which is substituted by aliphatic, araliphatic or aromatic, like carbamate, lower alkylamine formamidine, di-lower alkylamine Formamidine, lower alkoxyamine, lower alkylamine formamyl, chrysene-lower alkylamine formamyl, amido-lower alkylamine formamyl, N-amine formamidine-lower alkane-N-lower alkane-amine Formamyl or aniline Formamyl or unsubstituted or lower alkyl, lower alkoxy, polyhalo-lower alkoxy, hydroxyl, halogen, nitro, carboxy, lower alkoxycarbonyl, phenyl, benzene Oxy and / or benzene-lower alkylamine formamyl substituted with trifluoromethyl. This paper size applies to China National Standard (CNS) A4 (2I0X297mm) (Please read the precautions on the back before this page) .. TΓ -7- Printed by the Central Standards Bureau of the Ministry of Economic Affairs and the Consumer Cooperatives A? B7 5. Description of the invention () The fluorenyl group derived from sulfuric acid or an aliphatic- or aromatic sulfonic acid is, for example, a sulfonic acid group, a lower alkylsulfonyl group, or an unsubstituted or lower alkyl group, A benzylsulfonyl group substituted with a lower alkoxy group, a halogen, a trifluoromethyl group, a carboxyl group, and / or a lower alkoxycarbonyl group, or a sulfonylsulfonyl group which is unsubstituted or substituted with a di-lower alkylamino group. The fluorenyl group derived from a phosphoric acid or a phosphonate is, for example, a phosphonate group or a tri-lower alkylphosphonic acid group. Amino groups which are unsubstituted or substituted with aliphatic or araliphatic and / or substituted with aliphatic, araliphatic or aromatic fluorenyl are, for example, amine, lower alkylamino, di-lower alkylamine Group, lower alkylamino, or benzene-lower alkylamino, benzamidine, or naphthyl unsubstituted or substituted with lower alkyl, lower alkoxy, halogen, and / or trifluoromethyl Amine group, or urea group or formamyl group. Unsubstituted or substituted aromatic radicals are, for example, unsubstituted or substituted with lower alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxyl, lower alkoxy Carbonyl, carboxyl, carbamoyl, sulfamoyl, lower-class. Oxocarbonylamino, lower alkylfluorenyl, halogen and / or trifluoromethyl substituted phenyl or naphthyl. Unsubstituted or substituted heteroaromatic radicals are 5- or 6-membered monocyclic heteroaryl radicals which are partially hydrogenated, or are bicyclic heteroaryl radicals consisting of 5- or 6-membered rings Like equivalent furanyl, lower alkylfuranyl (such as 4-methylfuran-2-yl), thienyl, imidazolyl (such as imidazol-4-yl), Ofazolyl, Sho-lower (oxy) 呷Oxazolyl (e.g. 2,5-dihydro-3-oxo-1,2-oxazolyl), thiazolyl, dihydrothiazolyl (e.g. 4,5-dihydrothiazolyl), qian-lower alkylthiazolyl (Such as 4-chanthiazolyl), lower alkoxy-lower alkylthiazolyl (such as 4-methoxycarbonylmethylthiazolyl or 4-ethoxycarbonylmethyl) This paper applies Chinese National Standard (CNS) A4 specifications (210 × 297 (Mm) (Please read the notes on the back first, and then this page) «^ 43878 2 Α7 Β7 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs $ 1 5. Description of the invention () Thiazolyl), tetrazolyl, pyridyl , Pyritoyl, indolyl (such as indoxy-3-.yl), quinolinyl (such as quinolinyl), phenylhydrazine, or carboxy-lower alkyl-2,3,4,5- Tetrahydro-1H-1-benzene Such as 1-methyl-2,3,4,5-Jun gas -111-1- benzene Bing azepinyl). The araliphatic radicals are, for example, unsubstituted or lower alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxy, lower alkoxycarbonyl, carboxyl, carbamidine Phenyl, lower alkyl, halogeno and / or trifluoromethyl substituted benzene · lower alkyl. The fluorenyl groups derived from aliphatic- or araliphatic carboxylic acids are, for example, lower alkylfluorenyl, lower alkenyl, or unsubstituted or lower alkyl, lower alkoxy, lower alkylene dioxy Phenyl, lower alkylene dioxy, hydroxyl, lower alkoxycarbonyl, carboxyl, carbamoyl, lower alkyl, halogen, and / or trifluoromethyl substituted benzene-lower alkyl. The fluorenyl groups derived from carbonate aliphatic or araliphatic half esters are, for example, 'lower fluorenyloxycarbonyl, or unsubstituted or substituted by lower alkyl, lower alkoxy, lower butanedioxy, lower Alkyloxy, hydroxy, lower alkoxycarbonyl, carboxyl, carbamoyl, lower alkanoyl, halogen and / or trifluoromethyl substituted benzene_lower alkoxycarbonyl. Unsubstituted or substituted mono- or di-cytidine, β-cyclohexyl, β-thiazyl, azetidine formed by R7 and R8 together with X and nitrogen atoms bonded to R * and X and bonded via the nitrogen atom A cycloalkyl or thiocycloalkyl radical which is selectively oxidized is' for example, 3- to 7-membered, especially 5- to 7-membered monocyclic mono- or di-'1 Cycloalkyl, azeticycloalkyl, or selectively oxidized thiacycloalkyl radicals or bicyclic azicycloalkyl radicals consisting of 5- and / or 6-membered rings, which are more preferred for the paper Applicable to China National Standard (CNS) A4 specification (210X297 mm) ---------- ^ II Λ1 /,-(谙 Please read the precautions on the back first and then # '-tthis page) -Order- 9- A7 B7 V. Description of the invention (phenyl, imidazolidinyl, tetrahydrothiazolyl, N-hexahydropyridyl, morpholinyl, thiomorpholinyl, hexahydropyridyl, high-N-hexahydropyridyl Or 1-azinebicyclononyl, which is unsubstituted or substituted by aliphatic, araliphatic- or aromatic radicals (like lower alkyl, lower alkyl, unsubstituted or substituted benzene-lower alkyl or Phenyl radical), free, esterified or aminated carboxyl (E.g. carboxyl, oxocyanine), unsubstituted or substituted anisolemethyl, unsubstituted or lower halogenated and / or lower alkylated amino (such as di · lower alkyl) Amine or lower alkylamido), 2-oximidazolidinyl, free or esterified phosphonic acid (such as tenanyl or tri-lower alkylphosphonic acid), tetrazolyl, aliphatic or aromatic Carboxylic acid-derived fluorenyl groups (such as lower alkyl fluorenyl or unsubstituted or substituted benzyl fluorenyl, such as azetidinyl), hydroxyl, oxy and / or lower alkoxy substituted, like pyrrolidinyl , Lower alkylpyrrolidinyl, carboxypyrrolidinyl (for example, 2% slightly steeper residue), lower alkoxycarboxypyrrolidinyl, hydroxypyrrolidinyl (for example, 3_trend [1 slightly steeper), and lower Alkyl pyrrolidinyl (eg 2-methylpyrrolidinyl), mono- or dioxopyrrolidinyl (eg 2-oxopyrrolidyl or 2,5-dioxopyrrolidyl), lower-grade (oxy) pyrrole Pyridyl (such as 2-methyl-5-oxo-pyrrolidinyl), lower _ (oxo) pyrrolidinyl (such as 2-methyl-5-oxo-H is slightly steeper), residual (oxy) Pyridyl steep base (for example, 5 Lu 2 Bei Bi is slightly steeper , 2-Pyridoxine-P than pyrrolidinyl or 2-hydroxyl-pyrrolidinol), lower alkoxide (oxy) pyrrolidinyl, 2-oximidazolyl (such as 2_oxy_3_benzene -Imidazolidinyl), tetrahydrothiazolyl (such as tetrahydrothiazolyl 4-yl), N-hexahydropyridyl, lower_N: hexahydropyridyl (such as 4 · methyl-N-hexahydropyridyl, 3-methyl-N-hexahydropyridyl or 4-but-N · hexahydropyridyl), second lower-N-hexahydropyridine (for example, 2,6_dimethylhexaphenyl B than pyridyl) Qian-N-hexahydro D ratio steep group (such as 4-residual hexahydro D ratio pyridyl, 2-chan-N-hexahydro B ratio pyridyl or 3-residual-N-hexahydropyridyl group), lower alkane Oxygen ore_N_hexahydropyridyl (such as ethoxylate _ ^ paper size applies to Chinese national standards (CNS &gt; A4 specifications (2) 0x297), please read the intent matters before t; page the Ministry of Economic Affairs Printed by the Central Government Bureau of Commerce, Industrial Workers Cooperatives -10 Α7 Β7 ^ = 43 87 8 2 V. Description of the invention () H · Hexahydropyridyl ^ 2-ethoxycarbonyl-N-hexahydropyridyl), Aniline醢 _; ^ -Hydropyridine. Pyridyl (such as 3-aniline methyl-N-hexahydropyridyl, 2-aniline methyl _N_hexahydro η than steep or 4-aniline methyl -N-hexahydropyridyl), oxyhexahydropyridyl (such as 4-oxo-N-hexahydropyridyl), dioxane (such as 3,6_oxy (benzene_lower house) _N_hexa Hydropyridyl, such as 2-section I-O-N, hexahydropyridyl), dioxo-hexahydropyridyl, oxo (benzene) -N-hexahydro B than pyridyl (eg 2-oxo-3-benzene -N-hexahydro (I-Hydroxyl or 2-oxo-5-benzene-N-hexahydropyridyl), N-hexahydropyridyl (such as 4-hydroxyhexahydro: steep or 3 avoid- N-hexahydropyridinyl), hydroxy (benzene-lower alkane) &gt; N · hexahydropyridyl (e.g. 2-benzylhydroxy-N-hexahydropyridyl), carboxyl (N-hexahydropyridyl) (Such as 2-Jun_4-jing_Ν_hexahydro 11 ratio steep group), di-lower amine-N-hexahydrofluorene specific steep group (such as 4-dimethylamine-N-hexahydro H than pyridyl) ), Lower alkylamine-N-hexahydropyridyl (such as 1 ethylamine-N-hexahydrolatino), lower alkylamine (benzene-lower institute &gt; N-hexahydro B than pyridyl (such as 4-Ethylamine_2-section_N-hexahydropyridyl), lower amidylamine (benzene) · N-hexahydropyridyl (such as 4-ethylamidamine_2_benzene-N-hexahydropyridyl) Benzene-N-hexahydropyridyl (such as 4-benzene-N-hexahydro this steep group), lower焼 O-N-hexahydroU ratio steep group (such as 4-methoxy-N-hexahydroU ratio steep group), lower alkoxy (lower alkyl) -N-hexahydropyridyl group (such as 4-methoxy-4 -Metahydrogen β ratio steep radical), di-lower fluorene oxygen-N-hexahydro! I than pyridyl (such as 4,4 · dimethoxy-N-hexahydrou than a steep group), di-lower alkoxy (lower disease> -N-hexahydropyridyl (such as 2_section * 4,4 -Dimethoxy-N-hexahydrolaridinyl), lower dioxin-N-hexahydroradical (such as 4_ethylenedioxy_N-hexahydropyridyl), hydroxy-lower alkane-N -Hexahydropyridyl (e.g. 2- (2-hydroxyethyl) · N-hexahydroH than a steep group, 2-trimethyl-N-hexahydro B than a steep group, 4- (1-hydroxyethyl) -N-hexa Hydrogen hydrazino, 4-hydroxymethyl-N-hexahydropyridyl), unsubstituted or halogenated benzate_N_hexahydropyridyl (e.g. 4- (4-fluorobenzylhydrazone) -N-hexahydro Pyridyl), lower alkyl-N-hexahydropyridyl (e.g. 4-acetamidine-N_hexahydropyridyl), or oximidazole_N_hexahydropyridyl (eg 4_ (2_ paper size Tongzhou T National Standard (CNS) Α4 Specification (210X297 mm) (Please read the precautions on the back before Xu ^ this page)-Order _ Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives-11-Ministry of Economic Standards 11438782 A7 B7 _ I- .. Printed by the Bureau Cooperative Consumer Cooperative Co., Ltd. I .. V. Description of the invention () Omidazoline) ~ N-Hexahydro B ratio steep base), Tube-N-Hydrogen B ratio steep base Oxy-N-Hydroxy Π ratio. Pyridyl (such as 2-oxo-N-hexahydropyridyl), U-Bicyclononyl (such as Y-bicyclononyl), hexahydropyridyl, lower alkane hexahydro Pyridyl (for example, 4-methylhexahydropyridyl), oxyhexahydro II (for example, 3-oxyhexahydro B specific well), dioxane (for example, 3,5-di) Hexahydropyridyl), unsubstituted or lower alkoxylated hexahydropyridyl (eg 4- (4-methoxy-benzene) hexahydropyridyl), morpholinyl, di_lower alkane Morpholinyl (eg 3,5-dimethylmorpholinyl) or thiomorpholinyl. Unsubstituted or substituted 'formed by R7 and Re together with X and a nitrogen atom bonded to R8 and X' Partially hydrogenated aryl radicals are, for example, phenyl, cyclohexadienyl, naphthyl, or tetrahydronaphthyl radicals, which are unsubstituted or lower alkyl, lower alkoxy, hydroxyl, halogen, Substituted by carboxyl, lower alkoxycarbonylamidine and / or trifluoromethyl, like phenyl, 4-hydroxyphenyl, 3-methoxyphenyl, 3-carboxyphenyl, 4-fluorophenyl, 2-fluorophenyl , 3-fluorophenyl, 3,5-bistrifluoromethylphenyl, cyclohexyl-], 3-dichloro-5-yl, or 1,2,3,4 -Tetrahydronaphthyl. Unsubstituted or substituted, optionally partially hydrogenated heteroaryl radicals formed by and R * together with a bonded 1 ^ and another nitrogen atom are, for example, selectively Partially hydrogenated pyrrolyl, which is unsubstituted or substituted with carboxyl, lower alkoxycarbonyl and / or lower alkylfluorenyl, like pyrrol-1-yl, 1,5-dihydropyrrole-1-yl, carboxypyrryl (E.g. 2-carboxypyrrol-1-yl or 3-tpyrazol-1-yl), lower alkoxycarbonylpyrrolyl (e.g. 3-methoxycarbonylpyrrol-1-yl, 3-ethoxycarbonylpyrrolyl) or 3-butoxycarbonylpyrrol-1-yl), lower pyrrolidyl (such as 3-ethylpyrrol-1-yl), furfuryl (such as furan-2-yl), thienyl (such as thienyl- 2-yl or thiophen-3-yl); is an imidazolyl group, which is unsubstituted or substituted by lower alkyl, via-lower alkyl, carboxyl, pentaalkyl, and / or lower oxocarbonylamine-lower alkyl Replacement, like imidazol-1-yl, low paper size applicable national national standard (CNS} Λ4 specification (210 ×: 297)} (Please read the precautions on the back before I page)

-12- Printed wax by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 43 8782 A7 ___ B7 111 ___ V. Description of Invention () Class Academy miliji (such as 4- 甲 米 嗤 _ι_ 基, 2_ 甲 米 mile) Base or 2-ethylimidazol-1 · yl), di-lower pyrimidine (eg 2-ethyl-4 · methylimid-1-yl), hydroxy-lower pyrimidine (eg 4-light Carboximido-1-yl), Carboximido-imidazolyl (for example, Carboximidazole +), Carboxyl (lower alkoxycarbonyl and alkyl) imidazole (for example, 4- (3_third butoxycarbonyl) Prop-1-yl) -2- (2-fluorethylethyl and -yl); is a selectively partially hydrogenated thiazolyl 'which is unsubstituted or substituted with -lower alkyl and / or lower alkoxy _Lower alkyl substituted 'like thiazol-2-yl' 3,4 · dihydrothiazol_2-yl, such as 4: g Lizushiyl), lower alkoxy groups · lower alkylthiazolyl groups (such as 4 -Ethoxycarbonylethiazole-2-yl); is unsubstituted or substituted with 1¾¾ alkyl azol-1-yl or di-lower alkylpyrazolyl (such as 3,5_dimethyl Pyridyl); is a triazolyl (such as I, 2, melidyl), unsubstituted or optionally partially hydrogenated pyridine Radicals like pyridyl (e.g. pyrid-2-yl, 1,2,5,6-tetrahydropyridine-1-yl), oxydihydropyridyl (e.g. 2-solution- [beta], 2-di Hydrogen "than cyclo-1 -yl), oxytetrahydropyridyl (such as 2-oxo-f, 2,3,4-tetrahydro-pyridine small group); pyridyl (eg pyridyl_2_yl); Is an indioyl 'which is unsubstituted or substituted with a carboxyl, carboxy-lower alkyl, lower alkoxycarbonyl, lower alkoxy-lower alkyl, cyano-lower alkyl, and / or nitro group, like indium-2 · Carboxy, carboinyl (such as 2-carboindoxy small group or 3-carboin small group), tris-lower alkyl indioyl (eg 3-endoindol-1-yl), lower alkoxycarbonyl Indino (for example, 3, methoxycarbonyl-i-yl or 2-butoxycarbonyl indyl 1-yl), lower alkoxycurtain-lower alkoxymethyl (for example 3-ethoxycarbonyl indyl- 1-yl), cyano-lower alkylindenyl (for example, 3-cyanoindol-1-yl), nitrindolyl (for example, 5-nitroindolin-1), and phenylfuranyl (for example, benzene幷 furan-2-yl), unsubstituted or nitro-substituted benzimidazolyl (like benzimidazolyl, 5-nitrobenzimidazoline-1-yl, or 6-nitrobenzimidazo-1 -Base), four Quinolinyl (like 1,2,3,4-tetrahydroquinolin-1-yl), unsubstituted This paper size applies Chinese National Standard (CNS) A4 specification (210X297 public) (Please read the note on the back first Matters on this page) Order A7 B7 V. Description of the invention () or tetrahydroisoquinolinyl substituted by oxy (like 1,3,4-tetrahydroisoquinolin-1-yl or 2-oxy- 1,2,3,4-tetrahydroisoquinoline small group) or tetrahydrobenzoazepine (like 2,3,4,5-tetrahydro-1H-1-phenylazepine), 1 · base). The divalent aliphatic radical X is, for example, a lower alkylene, a lower alkylene and a lower alkylene radical, which are unsubstituted or substituted with an oxy group, a hydroxyl group and / or an amine group. Base, lower margin alkylene, lower alkenylene, oxygen-lower alkylene. (Including carbonyl), oxygen-lower alkylene, dioxy-lower alkylene, oxygen_lower alkylene, via-lower Alkylene, Oxy (Hydroxy) -lower alkylene, Amine · Lower alkylene, Amine-Lower alkylene, Warp · Lower alkylene, Residual-lower alkylene, Amines · Lower alkylene , Lower alkoxide • lower alkylene, lower alkoxy-lower alkylene or (0401-cardio-lower alkylene or ω-tfT-ot-oxy-lower alkylene. Divalent ring Aliphatic radicals X are, for example, 3- to 7-membered, especially 3- to 5-membered cycloalkylene radicals, such as cyclopropylidene, cyclobutylidene, or fluorenylcyclopentyl. Aromatic radicals X are, for example, unsubstituted or substituted with lower alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxy 'lower alkoxycarbonyl, carboxyl, carbamate 'Lower alkyl group, Halo and / or trifluoromethyl substituted benzene-lower alkylene or benzene-lower alkylene. Above and below, lower &quot; free radicals and compounds mean, for example, 'those containing up to 7 (Inclusive), especially radicals and compounds with up to 4 (inclusive) carbon atoms. Amine-lower alkyl is, for example, amine-Q-C4fluorenyl, like aminemethyl, 2.aminoethyl, 3 -Aminopropyl or 4-Aminobutyl. Amine-lower alkylene is, for example, 'Amine-CrC4Amidino, like amine methyl, 2-aminoethyl, 3-aminopropyl or 4-aminobutyl. Amine butyl. This paper size is applicable to Chinese National Standard (CMS) A4 specification (2 × 297297) -14- A7 B7 酲 43 8782 V. Description of the invention () Amine-lower alkylene is, for example, amine -crc7 alkylene, like amine methylene, 2-amine ethylene, 3-amine propylene or 4-amine butylene. Read the first note of the amine formamidine-lower alkylamine formamidine group as For example, carbamate-CrC4 is a carbamate group, such as carbamate carbamate, 2-carbamate carbamate #carbamate, propylcarbamate or 4-carbamate carbamate. Carbamate-lower fluorenyl is, for example, carbamate -CrC7 alkylene, like carbamate methylene, 2-carbamate ethylene, 3-carbamate propylene, 4-carbamate butylene, 5-carbamate pentylene or 6-Amine formamidine. N-Amine formamidine-lower alkane-N-Lower form-amine formamidine group is, for example, N-Amine formamidine-CVC4 house-N-CrC4 alkyl-Amine formamidine group, in particular It is like N-chima-N-methyl-amine formamidine. The carboxy-lower alkyl group is, for example, Jun-OC4 alkyl group, like carboxymethyl, 1- or 2-carboxyethyl, 3-copropane Or 4-Chlorobutyl "1 Jun-lower alkylamine formamidine is, for example, Jun-CrCU according to formamidine, like carboxyl ~~, ----- _ _,-· ~ Methyl, 2-ethylamine formamyl, 3-carboxypropylamine formamyl, or 4-carboamido group. -—.— *) Linear carboxy-lower alkylene is, for example, carboxylmethyl, 1- or @ extendingethyl, 1,3- (1-residual) propyl, 1,3- (3- Carboxy) propyl or 1,4- (4-carboxy) butyl. Da-lower alkylene is, for example, residual-CrC7 alkylene, like carboxymethylene, —I. —- ------2-Carboxyl printed by Shelley Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs Ethyl, 3-phenylene, 4-cyclopentyl, 5-carboxypentylene or 6-carboxyhexylene. The cyano-lower fluorenyl group is, for example, a cyano-CrC4 alkyl group, such as cyanomethyl, 1- or 2--— ___.-, cyanoethyl, 3rdyl or 4-cyanobutyl. Di-lower alkylamine cycloalkyl is, for example, di-CrC4 alkylamine cycloalkyl, like dimethylamine cycloalkyl, diethylamine cycloalkyl, N-ethyl-N-methyl-amine cycloalkyl, N -C-N-A · This paper size applies to China National Standards (CNS) A4 (210 X 297 mm) -15- Printed by A7 B7 of the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention () Amine Cycloalkyl, N-isopropyl-N-methyl-amine cycloalkyl or N-but-N-methyl-amine cycloalkyl, wherein the cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl Base or cyclohexyl. The di-lower alkylamino group is, for example, a di-CrC4 alkylamino group, such as dimethylamino, diethylamino, JN-ethyl ^ methyl-amino, lipidylbismethyl-amino, or N-butyl- N-methyl-amino-candi-lower alkylamine-lower alkyl is, for example, di-CVQ amine-CrC4 amine, like dimethyl ^ -electron-tris-Zr amine flat methyl, N- Prop-N-methyl-aminemethyl. 'Di-lower alkylamine formamyl is, for example, di-CVC4 amine formamyl, like dimethylamine formamyl, diethylamine formamyl, N-ethyl-N-methyl-aminoformamyl, N-propyl-N-methyl-amine formamyl, N-iso-N-methyl-aminoformamyl or N-butyl-N-methyl-amine formamyl. Dioxo-lower alkylene is, for example, * dioxo-C2-C4 alkylene, such as 1,2-dioxoethyl (acidoxy), 1,3- (1,2-dioxo) Propylene, 1,3- (2,3-dioxo) propane, or 1,4- (1,2-dioxo) propane. ^ Halogen is, for example, a halogen having a high atomic number of 5 (inclusive), such as chlorine, fluorine or bromine. Via-lower alkoxy-lower alkyl is, for example, via -CrC4 焼 oxy-CrC4 焼, like 2-Ethoxymethyl, 2-Methoxyethyl, 2- (2-Ethoxy) ethyl Or 3-methoxypropyl. The hydroxy-lower alkyl group is, for example, a hydroxy-CrC4 alkyl group, such as hydroxymethyl, 2-hydroxyethyl-I ·, 3-hydroxypropyl, or 4-transbutyl. 'Via-lower alkylene is, for example, via -CrC4 alkylene, like hydroxymethylene, 2-hydroxypropylene, 2-ethylene, 3-propylene or 4-butylene . N-lower grade courtyard-N-lower grade alkylamine-amine group is, for example, N-CrC7 courtyard brewing-N-CrC4 courtyard-This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm) (read first (Notes on the back of the Ge reading are on this page) Order 438782 at B7 V. Description of the invention () Amino groups, such as N-acetamidine-amino, N-propylamidine-N-methyl-amine, N-butylamine Methyl-amino, N-isobutylamidine-N-methyl-amine or N-trimethylacetamidine-N-methyl-amine. The lower alkylene dioxy is, for example, CrC4 alkylene dioxy 'like methylene dioxy, ethylene dioxy, or isopropylenedioxy; the lower alkylene dioxy is' for example, OC4 alkylene Dioxy, like ethylenedioxy or 1,3-propylenedioxy. The lower alkyl group is, for example, CrC7 alkyl, such as ethyl, propyl, butyl, isobutyl, or trimethylethyl. The lower alkylamino group is, for example, a CrC7 alkylamino group, such as an ethylamino group, a methylamino group, a butylamino group, an isobutylamino group, or a trimethylethylamino group. The lower alkylamine-lower alkyl is, for example, crc7amine-crc4, such as acetamidomethyl, propylamidomethyl, butylamidomethyl or isobutylamidomethyl, and trimethylamine. Ethylacetamidomethyl. Lower alkoxy-lower alkyl is, for example, crc7-oxo-crc4, such as acetase, oxomethyl, propionyloxymethyl, butyryloxymethyl, or isobutyryloxymethyl, and Trimethyacetamoxymethyl. The lower alkenyl group is, for example, a c3-c7 difluorenyl group, such as acrylyl, methyl Ff alkenyl, crotonyl, or ethyleneethenyl. '' Printed by the Central Standards Bureau, Ministry of Economic Affairs, Masonry Consumer Cooperatives (read the precautions on the reverse side of this page, and then this page). -Propen-2-enyl, 1,2-propen-2-enyl, 1,4-but-2-enyl, 1,2-but-3-enyl, 1,2-propenyl Pentyl, 1,2-hexenyl or 1,2-hex-5-enyl. Lower alkoxy is, for example, CrC7 alkoxy, prefered to be CrC4 alkoxy, like methoxy, ethoxy, propoxy, isopropoxy or butoxy, but it can also be isobutoxy Radical, second butoxy, third butoxy or monopentyloxy, hexyloxy or heptyloxy. This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X297 mm) -17- li 438782 V. Description of the invention () The lower alkoxycarbonyl group is, for example, 'Heart-0: 7 oxocarbonyl group, the preferred is CrG alkane Oxycarbonyl, like methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl or butoxycarbonyl, but it can also be isobutoxycarbonyl, second butoxycarbonyl, third butoxymine or monopentyloxy Alkyl, hexyloxycarbonyl or heptyloxycarbon. The lower alkoxycarbonylamino group is, for example, crc7 oxocarbonylamino group, prefered to crc4 oxocarbonylamino group, like methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropyloxycarbonyl Amine or butoxycarbonylamino. Lower alkoxycarbonyl-lower alkyl is, for example, C "C7J ^ oxycarbonylamine-crc4 alkyl, more preferred is Ct-c4 alkyloxycarbonyl amine_crc4 alkyl, like methoxycarbonylmethyl, ethoxy Carboxamide methyl, propoxy carboxamide methyl, isopropoxy carboxamide methyl, or butoxy carboxamide methyl. Lower alkoxycarbon · lower alkylamine formamidine is, for example, alkoxyten-Q-C4 alkane Carbamate, more preferred is CrC4 ortho-CrC4 carbamate, like carbamate, carbamate, acetoxycarbamate, carbamate, isopropyl Oxymethylamine formamidine or butylated irisamidine. 'Lower alkoxycarbonylcycloalkyl is, for example, ch: 7 oxocarbonylcycloalkyl, prefer 焉 Q-C4 oxocycloalkyl, Like methoxycarbonylcycloalkyl, ethoxycarbonylcycloalkyl, propoxycarbonylcycloalkyl, isopropoxycarbonylcycloalkyl or butoxycarbonylcycloalkyl, wherein the cycloalkyl group is, for example, cyclopropyl, Cyclobutyl, cyclopentyl or cyclohexyl. Lower alkoxy curtain-lower alkyl is, for example, crc7 alkyloxycarbonyl-crc4 alkyl, more preferred is crc4 alkoxycarbonyl-crc4 alkyl, like methoxycarbonylmethyl , Methoxycarbonylethyl, ethoxycarbonylmethyl, ethoxycarbonylethyl, methoxy Propyl, ethoxycarbonylpropyl, propoxycarbonylmethyl, propoxycarbonylethyl, isopropoxycarbonylmethyl, isopropoxycarbonylethyl or butoxycarbonylmethyl. The paper dimensions apply to Chinese national standards ( CNS} A4 size (210X297 mm)

T Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs-18- Printed by the Central Laboratories of the Ministry of Economic Affairs of the Bayer Consumer Cooperatives with 38782 at B7 V. Description of the Invention () Low-level alkoxy-lower alkylene is, for example, c " c7 oxenite &lt;: 2-(: 4 alkylene, more preferred is Crc4 oxygen ore-C2-C4 alkylene, like 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl) ; 1,3- (methoxycarbonyl) propanyl, 1,3- (ethoxycarbonyl) propanyl, 1,3- (propoxycarbonyl) propanyl, 1,3- (butyloxy) propene Propyl, 1,3- (second butoxycarbonyl) propane or 1,3- (third butoxycarbonyl) propane. Lower alkoxycarbonyl-lower alkyl is, for example, CrC4 -CVC7 alkylene, like methoxycarbonylmethylene, ethoxycarbonylmethylene, 2-methoxycarbonylethylene, 2-ethoxycarbonylethylene, 3-methoxycarbonylpropylene, 3- Ethoxycarbonylpropylene, Tunmethoxycarbonylbutylene, 4-ethoxycarbonylbutylene, 5-methoxycarbonylsylpentyl, 5-ethoxycarbonylpentylyl, 6-methoxycarbonylhexylene, or 6- Ethoxycarbonylhexylene. Lower alkoxy-lower alkoxy-lower alkyl is, for example, CrC4 oxo-CrC4 oxo-CrC4 oxo, like 2-methoxyethoxymethyl, 2-ethoxyethoxy Methyl, 2- (2-methoxyethoxy) ethyl or 2- (2-ethoxyethoxy) ethyl. Lower alkane-lower alkyl is, for example, a CrC4 alkoxy group, like 2-methyl Oxyethyl, ethoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, 3-methoxypropyl or 4-methoxybutyl. Lower alkylamine cycloalkyl is, for example, CrC4amidamine Cycloalkyl 'like methylamine cycloalkyl, ethylamine cycloalkyl, propylamine cycloalkyl, isopropylamine cycloalkyl or butylamine cycloalkyl, where the cycloalkyl is, for example, cyclopropyl, cyclobutyl , Cyclopentyl, or cyclohexyl. Lower alkyl is, for example, C "C7, is more preferred to CrC4, especially like methyl, or ethyl, propyl, isopropyl, or butyl, but May also be isobutyl, second butyl, third butyl or mono-^^^^ (such as pentyl 'hexyl or heptyl) (Please read the precautions on the back first and then the page) · This paper size is applicable to China National Standard (CNS) A4 specification (21〇 &lt; 297 mm) -19- A7 B7 1438782 V. Description of the invention () The lower alkylamine group is, for example, crc4 alkylamine group, Like methylamino, ethylamino, propylamino, isopropylamine or butyl Lower alkylamine-lower alkyl is, for example, CrC4 alkylamine-CVC4 alkyl, such as methylamine methyl, ethylamine methyl, 2-methylamine ethyl, 2-ethylamine ethyl, propylamine methyl, Isopropylamine methyl or butylamine methyl "lower alkylaminocarbamyl is, for example, CrC4 aminoaminocarbamyl, like methylaminocarbamyl, ethylaminocarbamyl, propylamino Carbaminyl, isopropylaminocarbamyl or butylaminocarbamyl. The lower alkylene may be straight or branched and bonded at any position, and is, for example, straight or branched CrC4 alkylene, especially like methylene, and 1,2-alkylene, 1,3- or 1,2-propylidene or 1,4- ~, 1,3- or 2,3-alkylene Butyl. Lower alkylene may be straight or branched and pairwise bonded at any position, and is, for example, straight or branched OQ extended alkyl, especially like methylene, U-ethylene, U- or 2,2-fluorenyl or 1,1-butylene. The N-lower compound-N-lower alkylsulfonium-amine group is, for example, NQ-C7 compound-N-CrC4 compound-amine group, such as N-ethyl-N-methyl-N-methyl-amine, NH-N-methyl -Amine, N-butylammonium-N-methyl-amine, N-isobutylammonium-amine or N-trimethylethenyl-N-methyl-amine. Lower alkylsulfonyl is, for example, C, C4, sulfonyl, like methanesulfonyl, ethylsulfonyl, or sulfonylsulfonyl. Oxy (hydroxy) -lower alkylene is, for example, oxygen (ca)- C2-C4 alkylene, like 1-oxy-2 · hydroxy · ethylethyl, 1,3- (1-oxy-2-hydroxy) {shenyl, ox-3-hydroxy) phenyl, 1,3- (2-oxo-3-hydroxy) propane or 1,4-(〗-oxo-2-hydroxy) oxetane ^ Oxy-lower alkylene (including carbonyl) is more preferred via a carbon atom with an oxy group Bonded to -N (R8)-group or oxy or thio group, and is, for example, equivalent oxygen-CrC4 This paper size applies to China National Standard (CNS) Λ4 specification (2 丨 0 &gt; &lt; 297 mm ) (Please read the notes on the back before copying this book) — Install — t book-Printed by the Consumers 'Cooperatives of the Central Standards Bureau of the Ministry of Economics -20 Printed by the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economics 438782 V. Inventions Description () Alkyl, like carbonyl or U- (l-oxy) ethanyl, and 1,3- (1-oxo) propyl or 1,4- (1-oxo) butyl. + Benzene -Lower alkoxycarbonyl is, for example, benzene-crc4 alkoxycarbonyl, like benzyl-oxycarbonyl or 1-phenylethoxycarbonyl, which is unsubstituted or substituted by crc4, Oxygen, hydroxy, halogen and / or trifluoromethyl substitution. Benzene-lower alkyl is, for example, benzene-CrC4 alkyl, like benzyl, 1- or 2-phenethyl, 3-phenylpropyl or 4 -Phenylbutyl, which is unsubstituted or lower alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxyl, lower alkoxycarbonyl, carboxyl, carbamoyl, lower alkyl Fluorenyl, halogen, and / or trifluoromethyl substitution. Phenyl-lower alkylamino is, for example, benzene-CrC4 alkylamino, like benzylamino, 1- or 2-phenylethylamino, 3-phenylpropylamino, or 4-Phenterminyl, which is unsubstituted or substituted by lower alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxy, lower alkoxycarbonyl, carboxyl, carbamoyl, Substituted with lower alkyl, halogen and / or trifluoromethyl. Benzene-lower alkylene is, for example, benzene-C2-C4 alkylene, like phenylethyl, l ** or 2-phenylpropyl Or 1- or 2-phenylene butyl, which is unsubstituted or lower alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxyl, lower alkoxycarbonyl, carboxyl, amine Formamyl, lower alkane Fluorenyl, halogen, and / or trifluoromethyl substituted. Benzene-lower alkylene is, for example, benzene-CrC7 alkylene, like benzyl, 2-phenylethylene, 3-phenylene, 4 -Benzylidene, 5-phenylpentylidene, or 6-phenylhexylene. This paper size applies to China's national standard (CNS &gt; M size (210 X 297 cm)) ---------- equipment -3 (Read the first note on the back, then this page) Order -21-Nu 438782 V. Description of the invention () Polydentate-lower alkoxy-lower alkyl is, for example, trifluoromethoxy-crc4 , Like trifluoromethoxymethyl, 2-trifluoromethoxyethyl, 3-trifluoromethoxypropyl or 4-trifluoromethoxybutyl. Polyhalo-lower alkyl is, for example, trifluoromethyl. Tri · lower alkylphosphonic acid groups, for example, tri-crc7 isophosphonic acid group, prefer tri-crc4 isophosphonic acid group, especially like trimethylphosphonic acid group, or its secondary like triethylphosphonic acid group, tripropylphosphine Acid, triisophosphonic acid or tributylphosphonic acid. The ω-B γ-oxy-lower alkenyl group is, for example, 1,3 · (3-Πγ-1-oxy) endoxy-2- storage group. The ω-ίΐ-α-oxy-lower alkylene group is, for example, 1,3- (3-methylol + oxy) alkylene. The compounds of the formula (I) having an acid group can form salts with bases. Compounds of formula (I) having bases can also form acid addition salts, and in the case where at least one additional acid group is present, internal salts can also be formed. ; Λ .- Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (read the notes on the back and read this page) and the salt formed by the compound of formula (I) with a base is, for example, a pharmaceutically acceptable base Formed salts, such as non-toxic metal salts derived from metals of groups Ia, Ib, IIa and lib, such as alkali metal salts (especially sodium or potassium salts), earth metal salts (especially calcium or magnesium salts), And ammonium salts with ammonia or organic amines or quaternary ammonium phosphonium, like selectively C-modified aliphatic amines, especially mono-, di- or tri-lower alkylamines (e.g. methylamine, ethylamine Or diethylamine), mono-, di-, or tri- (lower alkyl) amine (like ethanolamine, diethanolamine, or triethanolamine, ammonium (via methyl) methylamine or 2-tributylamine), or N- (Hydroxy-lower alkane &gt; N, N-di-lower home-amine or N- (Polyhydroxy-lower home &gt; N-lower amine (like 2- (dimethylamine) ethanol or D-glucosamine or bile Ii) or a fourth aliphatic ammonium hydroxide (such as tetrabutylammonium hydroxide). The acid addition salt of a compound of formula (I) is, for example, formed with a suitable mineral acid (such as a halogen acid, sulfuric acid, or phosphoric acid) Medically accessible Accepted salts, such as hydrochloride Paper size Applicable to Chinese National Standard (CNS) A4 (210X297 mm) -22-Printed by the Consumer Cooperatives of the Central Standardization Bureau of the Ministry of Economic Affairs 43 87 8 2 V. Description of the invention , Hydrobromide, sulfate, bisulfate, or phosphate; salts with the appropriate carboxylic acid, like lower alkanoic acids that are selectively hydroxylated (such as acetic acid, glycolic acid, propionic acid, lactic acid, or trimethylacetic acid) ), Lower alkanedicarboxylic acids that are selectively hydroxylated and / or substituted with oxy groups (such as oxalic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, pyruvate, apples Acid, ascorbic acid); and salts with aromatic-, heteroaromatic- or araliphatic carboxylic acids, such as those with benzoic acid, nicotinic acid or phenylglycolic acid, and with appropriate aliphatic- Or salts of aromatic sulfonic acids or N-substituted amine sulfonic acids, such as mesylate, benzenesulfonate, p-toluenesulfonate or N-cyclohexylamine sulfonate (cyclohexylamine sulfonate) Salt includes both whole and partial salts, that is, one, two, or three per mole of acid (I), which is more suitable Salts formed by 2 equivalents of base, or 1, 2 or 3 per mole of base of formula (I), more preferably 1 equivalent of salt formed by acid. For the purpose of isolation or purification, it can also be used not for medicine Accepted salts. Only pharmaceutically acceptable non-toxic salts can be used medically, so these salts are the preferred salts. The compounds of formula (I) have valuable pharmacological properties. They have effects on AMPA receptors, kainic acid The glycine-binding sites of the receptors and / or NMDA receptors exhibit a high degree of binding affinity. The affinity of the aforementioned receptors is comprehensive or selective, depending on the structure. The compounds of formula (I) are selected specifically for AMPA and / Or kainic acid binding site exhibits strong affinity and glycine binding site to NMDA receptor exhibits weaker affinity. The binding capacity of the compound prepared according to the present invention and its salt can be used to determine [3H] -AMPA in the meninges of rats (moles, rats) using radiography in vitro. This paper is in accordance with China National Standards (CNS) M specifications (210X297 mm) (Please read the notes on the back first, and then ^^-page) Order-23- Printed teeth 43S782 A7 B7 by the Central Bureau of Standards of the Ministry of Economic Affairs-Industrial and Consumer Cooperatives V. Description of the invention () [3H] -Red Translocation of alginic acid or [3H] -DCKA (5,7-dichloro-reninic acid) confirmed the determination of 50% translocation concentration (IC50) for several concentrations »To determine the binding affinity of AMPA receptors Radon uses, for example, the radiation receptor assay of Honore T., Lauridsen J. and Krogsgaard-Larsen in J. Neurochem. 38, 173-178, in which the compound of formula (I) exhibits from about 0.05 to about 5 μM ICWfi. For hydrobromide N- (2,3-diox-7-nitro-1 and 3,4-tetrahydroquinoline-5.ylmethyl> 2-amine-2-oxazoline, for example, measured The binding affinity of IC5a 値 0.3 μmol / l is kainic acid receptor, for example, using Simon J * R., Contrera JF and Kuhn MJ, J. Neurochem Inverse, 141-14 * 7 radioreceptors Experimental determinations in which the compound of formula (I) exhibits a 1C »値 of about 0.5 to 5 μM. The ability of a compound of formula (I) to bind to the kainic acid binding site of the NMDA receptor can be 'e.g.' in Baron M Β, Siegel BW et al., Eur. J. Pharmacol., Molec. Pharmacol. Section 206, 149-154 (1991) and Canton T., Doble A * et al., J. Pharm. Pharmacol. Surname 812- The radioreceptor assay of 816 (1992) was performed on murine cortex and murine hippocampus. In this experimental procedure, the ICs of the compound of formula (I) was in the range of about 0.005 to about 5 μM. For N- (7-bromo-2,3 · dioxo-1,2,3,4-tetrahydrofluorin-5-ylmethyl) -3-pan-ethanamine, for example, measured 0.007 micromole / Because of these properties, the compound of formula (I) has significant anticonvulsant properties. It can be measured in vivo, for example, in mice, for its significant protective effect against electric shock or metrazoe stimulant-induced convulsions, and can be used, for example, in Schmurz et al., Naimyn-Schmiedebergs Arch Pharmacol. 342, 61-66 (1990), the complete establishment of the electric rat model or metrazole-induced convulsions rat model measurement. This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X297 mm) (Please read the precautions on the back before f this page) Order- 槔. -24- Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs ^ 438782 V. Description of the invention () Therefore the compound of formula (I) and its pharmacologically acceptable Accepted salts are very suitable for the prevention and treatment of pathological symptoms that respond to the blocking of one or more of the aforementioned subtype excitatory amino acid receptors, such as neurodegenerative disorders, such as those caused by sudden onset, hypoglycemia, hypoxia, or brain Caused by symptoms of ischemic palsy; ischemic brain disorders (such as cerebral ischemia, cerebral ischemia with cardiac surgery or cardiac arrest, breath before and after birth, epilepsy, convulsions, Huntington's disease (H untingtotfschorea), Alzheimer's disease and Parkinsoii'siiisease, amyotrophic lateral sclerosis, spinal and brain trauma, and caused by neurotoxins or drug abuse Symptoms of poisoning and ocular ischemia, vascular and muscle spasms (like migraine or local or systemic spasms), convulsions (like epilepsy) and anxiety and pain (like trigeminal neuralgia). Compounds of formula (I) with a simpler structure (wherein the radicals other than R5 or 112 are, for example, amine-lower alkyl or hydroxy · lower alkyl) can also be used to formulate side chains with more complex structures (I) The intermediates of the compounds are substituted by conventional methods, such as the conventional nucleophilic substitution procedure, to replace the amino and hydroxyl groups of simpler compounds. The present invention particularly relates to a compound of formula (I) and a salt thereof, in which one of the radicals R and 2 is an R5 group and the other is a formula —CH (R 士 alk-R7 (la), -alk-CH ( &amp;)-R7 (lb), _aik-N (R8) -X-R7 (Ic), -alk "; Nr (R8) (R9) -X-R7A · (Id), -alk-OX-R7 ( Ie) or -aik-SX-R7 (If), R3, R +, and Rs are independent of each other, and are hydrogen, lower courtyard, halogen, trifluoromethyl, cyano or nitro, and R «is amine, lower Alkylamine, lower alkylamidine, N_lower amidine_N_lower alkylamidine-amine or di-lower alkylamine, this paper size is applicable to Chinese National Standard Plum (CNS) Λ4 specification (210x297 mm) ( Please read the precautions on the back of this page before ordering this page) Order -25- A7 B7 V. Description of the invention () R7 is printed by hydrogen, lower alkyl, amine-lower alkyl, lower Alkylamine-lower alkyl, dialkylamine-lower alkyl, lower alkylamine-lower alkyl, meridian-lower alkyl, lower alkyloxy-lower alkyl, polyhaloalkyl, lower alkyl Oxy-lower alkyl, hydroxy-alkoxy-lower alkyl, lower-alkoxy · ®-level alkoxy-lower alkyl or polyhalogen-lower Oxy-lower alkyl, 3- to 8-membered cycloalkyl, carboxycycloalkyl, lower alkoxycarbonylcycloalkyl, amine cycloalkyl, or mono- or double-ranked alkylamine cycloalkyl, pyrrolidinyl, oxygen Pyrrolidinyl, carboxypyrrolidinyl, N-hexahydropyridyl, chan-N-hexahydropyridyl, lower alkoxyquino-N-hexahydropyridyl, morpholinyl or thiomorpholinyl, carboxyl, lower alkyl Oxycarbonyl; Benzene · lower alkoxycarbonyl, unsubstituted or substituted with lower alkyl, lower alkoxy, hydroxyl, halogen, and / or trifluoromethyl; carbamoyl, cyano, lower alkylamine Formamyl, di-lower alkylamine formamyl, lower alkoxy group, lower alkylamine formamyl, qian · {distant alkylamine formamyl, amiformine-lower alkylamine formamyl, N-amine formamidine -Lower alkane-N-lower amine-carbamoyl; is aniline, which is unsubstituted or substituted by lower alkyl, lower alkoxy, polydentate-lower alkoxy, hydroxyl, halogen, nitro, Carboxyl, lower alkoxycarbonyl, phenyl, phenoxy, and / or trifluoromethyl substituted; sulfonate, lower alkylsulfonyl; benzylsulfonyl, which is unsubstituted or lower alkyl, lower Alkoxy , Halogen, trifluoromethyl, carboxyl and / or lower alkoxycarbonyl; sulfofluorenyl, phosphonic acid, tri-lower alkylphosphonic acid, amine, unsubstituted or substituted with secondary alkylamine , Lower alkylamino, di-lower alkylamino, lower alkylamino; benzene-lower alkylamino, benzamidine, or naphthyl, which are unsubstituted or substituted by lower alkyl, lower alkoxy , Halo and / or trifluoromethyl substitution; ureido, formamyl; phenyl or naphthyl, which is unsubstituted or lower alkyl, lower alkoxy, lower alkylene dioxy, lower Alkylenedioxy, hydroxy, lower alkoxycarbonyl, carboxyl, carbamoyl, and the size of this paper are applicable to the Chinese National Standard (CNS) Λ4 specification (210 X 297 mm) -26- A7 B7 1438782 V. Description of the invention () Aminosulfonyl, lower alkoxycarbonylamino, lower alkylfluorenyl, halogen and / or trifluoromethyl substitution; Furanyl, lower alkylfuranyl, thienyl, imidazolyl, oxazolyl, Ufazole Phenyl (dihydrooxazolyl), Residual_lower fluoren (oxo) oxazoline, thiazolyl, thiazolinyl (dihydro_azolyl), residual-lower Thiazolyl, lower alkoxide-lower alkane-thiazolyl, tetrazolyl, pyridyl, pyrenyl, glutamyl, quinolinyl, phenylhydrazine, or carboxy-lower alkane-2,3,4 , 5 gastric tetrahydro-1 private 1-phenyl acridine, printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs R8 is hydrogen, lower alkyl, amine-lower alkyl, lower alkylamine-lower alkyl, two -Lower alkylamine-lower alkyl, lower alkylamine-lower alkyl, via lower alkyl, lower alkyloxy-lower alkyl, polyhalogen-lower alkyl, lower alkoxy-lower alkyl, via 4S grade Alkoxy-lower alkyl, lower alkoxy-lower alkoxy-lower alkyl, polyhalogen-lower alkoxy-lower alkyl; benzene-lower alkyl, which is unsubstituted or substituted by lower alkyl, lower alkoxy Substituent, lower alkylene dioxy, lower alkylene dioxy, hydroxyl, lower alkoxycarbonyl, carboxyl, carbamoyl, lower alkyl, halogen, and / or trifluoromethyl; lower alkyl , Lower alkenyl; is benzene-lower alkylfluorenyl, which is unsubstituted or substituted by lower alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxy, Lower alkoxycarbonyl, carboxyl, carbamoyl, lower alkanoyl, halogen and / or trifluoromethyl substitution; lower alkoxycarbonyl; or benzene-lower alkoxycarbonyl, which is unsubstituted or lower alkoxy Substituent, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxy, lower alkoxycarbonyl, carboxyl, carbamoyl, lower alkyl, halogen, and / or trifluoromethyl, Or &amp; and together with X and the nitrogen atoms of bond IV and X to form pyrrolidinyl, imidazolidinyl, tetrahydrothiazolyl, N-hexahydropyridyl, morpholinyl, thiomorpholinyl, hexahydrogen paper Standards are applicable to China National Standards (CNS) Λ4 specifications (210X297g) -27- I43B782 f at B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () Pyrazine, high-N-hexahydropyridine Fluorenyl or 1-ΙΪ bicyclononyl, which is unsubstituted or substituted with lower fluorenyl, via-lower alkyl, unsubstituted or substituted benzene_lower alkyl or phenyl, carboxyl, lower alkoxycarbonyl , Unsubstituted or substituted aniline, di-lower amino, lower amino, 2-oxamido Hydrazino, ortho-acid, tri-lower sulfonyl, tetra-fluorenyl, lower fluorenyl, unsubstituted or substituted benzamidine, hydroxy, oxy, and / or lower alkoxy; Is a selectively partially hydrogenated pyrrolyl group, which is unsubstituted or substituted with a carboxyl group, a lower alkoxycarbonyl group and / or a lower alkylfluorenyl group; a furyl group, a thienyl group; an imidazolyl group, which is unsubstituted or lower Alkyl, substituted by -lower alkyl, carboxyl, jun-lower alkyl, and / or lower alkoxycarbonylamine-lower alkyl; is a selectively partially hydrogenated thiazolyl group, which is unsubstituted or substituted, lower Alkyl and / or lower alkoxycarbonyl-lower alkyl substitution; pyrazolyl, triazolyl, unsubstituted or substituted with oxy, unsubstituted or substituted with lower alkyl, optionally Parts of hydrogenated pyridyl, unsubstituted or substituted with oxy, optionally partially hydrogenated pyrimidinyl, pyrazolyl; is indolyl, which is unsubstituted or substituted by carboxyl, jun, lower alkyl, Lower alkoxycarbonyl, lower alkoxycarbonyl-lower alkyl, cyano-lower alkyl, and / or nitro substitution; benzamurofur Group, benzimidazolyl, unsubstituted or substituted with nitro, tetrahydroquinolinyl, tetrahydroisoquinolinyl, unsubstituted or substituted with oxo, tetrahydrophenylazepine; or Is phenyl, cyclohexadienyl, naphthyl or tetrahydrofluorenyl, which is unsubstituted or lower alkyl, lower alkoxy, hydroxyl, halogen, carboxyl, lower alkoxycarbonyl and / or trifluoromethyl Substituted; is lower alkyl, lower alkenyl, lower alkynyl; or benzene-lower alkyl, which is unsubstituted or substituted with lower alkyl, lower alkyloxy, halogen, and / or trifluoromethyl, or ( Read the first 4 $ items on the back

The paper size of the edition is applicable to the Chinese National Standard (CNS) Λ4 specification (21 × M7 mm) -28-Printed by the Ministry of Economic Affairs 4 * Central Standards Bureau A7 B7 V5. Description of the invention () ^, Gen and private, Together with X and the bond 118, ^ and another nitrogen atom form a pyridinium radical, which is unsubstituted or substituted with CVC4 alkyl, amine, crc4 or bis-crc4 alkylamino, and ^ is a hydrogen halide Acid, lower alkanesulfonic acid, or anion of benzenesulfonic acid that is unsubstituted or substituted with lower alkyl or halo, alk is lower alkylene, and X (unless it is accompanied by heart-to-heart and bonding to Nitrogen atom, or together with the bond R8, &amp; and the nitrogen atom of pyrene to form a part of the aforementioned ring system) are lower alkylene, lower alkylene, lower alkylene, oxygen-lower alkylene ( Including carbonyl), oxo-lower alkylene, dioxo-lower alkylene, oxy-lower alkylene, lower alkylene, oxygen (via Mδ-order alkylene, amine-lower alkylene, amine-lower Alkylene, Jun-lower alkylene, Residual-lower alkylene, Carbamate lower alkylene, Lower alkoxide-lower alkylene, Lower alkoxycarbonyl -Lower alkylene, ω-ΙίΤ-α-oxy-lower alkylene or ω4ΓΤ-α-oxy-lower alkylene, 3- to 7-membered cycloalkylene, or unsubstituted or lower Substituted by alkyl, lower alkoxy, lower alkylene dioxy, lower alkylene dioxy, hydroxyl, lower alkoxycarbonyl, carbamoyl, lower alkyl, halo and / or trifluoromethyl Benzene-lower alkylene or benzene-lower alkylene. In one aspect, the invention is particularly relevant, for example, compounds of formula (I) and salts thereof, in which one of the radicals &amp; Formula-industry ^^ team)-! ^! ^,-^-N (R8) -X-R7 (Ic), -alk-aX-R7 (Ie) or -alk-SX-R7 (If), R3, Gen and 115 are each independently hydrogen, lower alkyl, halogen, cyano or nitro,

Ri is amine, lower alkylamine, lower alkylamine, N-lower courtyard-N-lower alkylamine-amine or di-lower alkylamine, and this paper size applies Chinese National Standard (CNS) A4 specification ( 210X297 mm) (Please read the precautions on the back before this page) Order ^ 丨 -29- Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 1438 78 2 Α7 'Β7 V. Description of the invention () R7 is a carboxyl group, low grade Alkoxycarbonyl; is benzene-grade alkoxycarbonyl, which is unsubstituted or substituted with lower alkyl, lower alkoxy, hydroxyl, halogen, and / or trifluoromethyl; carbamoyl; anisole; It is unsubstituted or substituted with lower alkyl, lower alkoxy, hydroxyl, halogen, nitro, carboxyl, lower alkoxycarbonyl, phenyl, phenoxy, and / or trifluoromethyl; it is a phosphonate, mono _, Di_ or tri · # alkylphosphonic acid group or tetrazolyl group,

Re is hydrogen, lower alkyl 'or together with X and the nitrogen atom bonded to Re and X to form a pyrrolidyl, hexahydropyridyl or hexahydropyridyl radical, alk: is a lower alkylene, and X is low-grade basal radical, oxygen-low-grade basal radical (including cutting base), low-grade basal radical, amine-lower alkane radical, chin-lower alkane, lower alkoxy group lower alkane, amine methyl alcohol Also an alkylene group, or together with an n (r8) group, is ω_tTT-a-oxy-lower alkylene or ω-Πγ-α · oxy-lower alkylene which is bonded via an α_ carbon atom; Benzene_lower sub-radical, which is unsubstituted or substituted with lower alkyl, lower alkoxy, dentin, and / or trifluoromethyl; or in formula (Ic), together with R * and a bond; The nitrogen atom forms a pyrrolidinyl, hexahydropyridyl, or hexahydropyridyl radical. On the other hand, the present invention is particularly relevant, for example, compounds of formula (I) and salts thereof, preferably

one of fttr.

Ra, R4, and Rs are each independently hydrogen, lower-grade, halogen, cyano, or nitro; RT is phenyl, montyl, sulfanyl, thienyl, 0-threshold, or 3-membered ring radical , Which is unsubstituted or substituted with lower alkyl, lower alkoxy, endyl, lower _ oxygen base, unsubstituted or lower base, lower base oxygen, warp base, and transcript. The paper standards are applicable to the Chinese country. Standard (CNS) Α4 specification (210X297 mm) (谙 Read the precautions on the back first and then} this page}, 1T -adeno-30- A7 B7 438782 V. Description of the invention () Substitution with base and / or trifluoromethyl Benzene-lower alkoxycarbonyl, carbamoyl, unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxyl, halo, nitro, carboxy, lower alkoxycarbonyl, phenyl, phenoxy and / Or trifluoromethyl substituted aniline, cyano, nitro and / or trifluoromethyl, or lower alkyl, amine-lower alkyl, lower alkylamine-lower alkyl, di-lower Alkylamine-lower alkyl, lower alkylamine-lower alkyl, via-lower alkyl, lower alkyloxy-lower alkyl, polyhalogen-lower alkyl, lower Oxy-lower alkyl, hydroxy-lower alkoxy-lower alkyl, lower alkoxy · lower alkoxy-lower alkyl or polyhalogen-lower alkoxy · ^ alkyl, are hydrogen or lower alkyl, and alk is lower The alkylene group and X are oxygen-lower alkylene groups. The present invention is particularly related to compounds of formula (I) and salts thereof, in which one of the radicals and &amp; is a private group and the other is a formula -CI ^ R ^ -alk-MIa ^ -alk-CHCR ^ iR, (lb) '-aik-N (R8) -X-R7 (Ic) &gt; -3ΐ ^ ϊΤ (Κ8) (Κ9) -χ-Κ7Α' (Id) '-alk-OX-R7 (Ie) or -alk-SX-R7 (base of I0, R3, R4 and R5 are each independent, hydrogen, CrC4 alkyl (such as methyl or ethyl), atomic order up to 35 (including) halogen (such as chlorine, fluorine or bromine), trifluoromethyl, cyano or nitro, R6 is amine, CVC4 alkylamino, CVC4 amino, n-cvc4, N-CrC4 Alkyl-amine or di-CrC4 amine, R7 is argon, crc7 fluorenyl (such as methyl, ethyl, isopropyl, butyl, tertiary butyl, pentyl, 4-yl, hept-4 -Yl), hydroxy-CrC4 alkyl (such as 2-hydroxyethyl), polyhalogen-CrC4 fluorenyl (such as trifluoromethyl), CrC4 fluorenyl-CrC4 alkyl (such as methoxymethyl or 2-methoxy) Ethyl), 3- 6-membered cycloalkyl (such as cyclopropyl or cyclohexyl), 3- to 6-membered carboxycycloalkane This paper size applies to China National Standard (CNS) A4 specification (210 × 297 mm) (Please read the note on the back first Matters are again on this page) Order-Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Gland Economy-31-

U ^ S78S A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention () (such as 2- Qiancyclopentyl or 3- or 4-cyclocyclohexyl), 3- to 6-membered amine cycloalkane (Such as 2-aminocyclohexyl), pyrrolidinyl, carboxypyrrolidinyl (such as 2-carboxypyrrolidinyl), oxopyrrolidyl (such as 5-oxopyrrolidin-2-yl), N-hexahydropyridine Phenyl, hexachloropyridyl, morpholinyl or thiomorpholinyl, carboxyl, CrC4 oxocarbonyl (such as methoxycarbonyl, ethoxycarbonyl, or third butoxycarbonyl), benzene-CrCj ^ oxycarbonyl (such as benzyloxy Carbonyl group), carbamate group, cyano group, CrC4 carbamate group (such as carbamate group), CrC4 ^ oxocarboxamethane group (such as ethoxy carbamate group or 2-ethoxycarbonyl Methylamine formamidine group), Jun-CVC4 amine formamidine group (such as carboxymethylamine formamidine group), carbamylase ~ CrC4 amine formamidine group, N-carbamidine-CrC4 alkane-N-CVQ institute Carbamate, N · Cr-C4alkane-N-CrC4i Carbamate (such as N-carboxymethyl-carbamate), Carbamate-CrC4 Carbamate (such as carbamate) Formamyl), benzene-CrC4 alkylamine formamyl (such as benzylamine formamidine) Or 1-benz-3-phenyl-propylamine formamyl); is anilide formamyl, which is unsubstituted or substituted by CrC4 alkoxy, nitro, polyhalo-CrC4 ortho, phenoxy, or CrC4 ortho Carbonyl substitutions, such as anisole, 4-trifluoromethoxyanilide, 4-methoxyanilide, 2-methoxyanilide, 2-methoxyanilide, 3-ethoxycarbonylanilide, 3- Ethoxycarbonylanilide formamidine, 4-phenoxyanilide formamidine, or 4-nitroanilide formamidine; are sulfonate, (^-(^ alkanesulfonyl) (such as methylsulfonyl); benzylsulfonyl Fluorenyl, which is unsubstituted or substituted with CrC4 alkyl, CrC4 ^ oxy and / or carboxyl, such as benzenesulfonyl, tosylsulfonyl, 2-benzylsulfonyl, or 4-.methoxybenzenesulfonyl Is a naphthalenesulfonyl group which is unsubstituted or substituted with a di-CrC4 amine group (such as 5-dimethylamine naphthalenesulfonyl), a phosphonic acid group, an amine group, a CrC4 amine group, and a di-CrQ group Amine (such as dimethylamino), CrC4 amino (such as acetamido), benzene-CrC4 amino (such as benzylamino), benzamidine or naphthylamino, urea, methyl Fluorenyl; phenyl or naphthyl, which is unsubstituted or CrC4 or Q-C4 alkoxy事 # Customization This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -32- ^ 38 782 A7 B7 Central sample of the Ministry of Economic Affairs, printed by Bureau I-Industrial Cooperative Cooperatives , Crc4 fluorene dioxy, CrC4 alkylene dioxy, carboxyl, sulfamoyl,. CrC4 oxycarbonylamino, CVC4 oxy, hydroxyl, halogen, and / or trifluoromethyl substitution, such as benzene Methyl, naphthyl, 2-tolyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 3,4-methyldioxyphenyl, 2-xylylene , 3-naphthyl, 4-carboxyphenyl or 8-naphthyl, 4-aminosulfonyl phenyl, 4 »third butoxycarbonyl phenyl, 2-third butoxycarbonyl phenyl, 2-Ethyloxyphenyl, dihydroxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4 · dichlorophenyl or 3,5-bistrifluoromethylbenzene Is a furyl group (such as 2-furyl), a CrC4-furanyl group (such as dongmethylfuran-2-yl), a thienyl group, or an imidazolyl group (such as imidazol-1-yl or imidazol-4-yl), (Oxy) oxazoline (such as 2,5-dihydro-3-oxo-1,2-oxazolyl), thiazolyl, thiazolyl (dihydrothiazolyl) (such as 4,5-dihydro Oxazolyl), Jun-C "C4 alkylthiazolyl (4-carboxymethylthiazolyl), CrC4 orthothiazolyl · CrC4 orthothiazolyl (such as methoxycarbonylmethylthiazolyl or ethoxycarbonylmethylthiazolyl), tetrazolyl , Pyridyl, pyrimidinyl, indinoyl (such as indino-3-yl), quinolinyl (such as quinoline ▲ 4.yl), phenylhydrazine, or qian-CrC4yuan-2,3, 4,5-tetrahydro-1H-1-phenylhydrazine, such as 1-Jun-2-_2,3,4,5 · tetrahydro-1H-1-phenylhydrazine, R * is Hydrogen, Ct-C4 radical (such as methyl, ethyl or isopropyl), light-CrC4 radical (such as 2-ethyl), CrC4 oxo-CrC4 alkyl (such as 2-methoxyethyl), Hydroxyl &lt; VC4 oxo-CrC4 alkyl (such as 2- (2-hydroxyethoxy) ethyl), benzene-CrC4 alkyl (such as benzyl), pyridine-CrC4 alkyl (such as pyridylmethyl), CrC4 alkyl Fluorenyl (such as ethyl fluorenyl), benzyl alkyl fluorenyl (phenyl ethyl fluorenyl), CrC4 ^ oxycarbonyl (third butyloxycarbonyl) or benzene-CrC4 oxocarbonyl (such as benzyloxycarbonyl), or Together with X and bond, it forms nitrogen with pyrrolidinyl, carboxypyrrolidinyl (such as 2-carboxypyrrolidinyl), hydroxypyrrolidinyl (such as 3- via pyrrolidinyl), and hydroxy-CrC4 Pyrrolidinyl (eg 2 metmethyrrolidinyl), mono · or di-oxopyrrolidinyl (eg (please read the precautions on the back first ^^ write this page) Binding, ordering ~ thread Ί This paper size applies to China National Standard (CNS) A4 specification (2 丨 〇 X 297 mm) _ 33 _ 璧 4387 8 a A7 B7 V. Description of the invention () 2-oxopyrrolidyl or 2,5 · dioxopyrrolidyl), CrC ^ (Oxy) (1 than pyrrolidinyl (such as 2_methyl-5-oxo-pyrrolidinyl), hydroxy_crQ alk (oxy) _pyrrolidinyl (such as 2_methyl_5_oxo_larrolidine Radical), Jun (oxy) pyrrolidinyl (such as 5- Jun-2-oxo-II than pyrrolidinyl, 2-chan-4-hydroxy-pyrrolidinyl, or 2_ Jun-3 D-pyrrolidinyl) , R oximidazolidinyl (such as 2 to 3 benzene_amizonidinyl) 'tetrakithiazyl (such as tetrahydrothiazolyl stomach 1_yl), N_hexakidazimidin, alkane · N-hexa Hydropyridyl (such as 4-methyl-N-hexahydropyridyl, L-methylhexahydropyridyl, or 4-butane-N- /, hydrogen-pyridine), --- CrC4, -N-hexahydro If, steeper than (Such as 2,6-dimethyl-N-hexahydroU than fluorenyl), carboxy-N-hexahydropyridyl (such as 2 avoid_N_hexahydropyridyl, 3_ Jun_hexahydropyridyl or 4 ^ -Ν · hexahydropyridyl), CrC4 alkoxy curtain_N_hexahydropyridine Pyridyl (such as 2-ethoxycarbon-N-hexahydropyridyl or 4-ethoxy mine hexahydropyridyl), aniline_N_hexahydropyridyl (such as 2-aniline-N-hexahydro Pyridyl, 3 · aniline _N_hexahydropyridyl or 4-aniline methenyl hexahydropyridyl), oxyhexahydropyridyl (such as oxygen_N_ /, hydrogen this steep group), -oxy-N-hexa Hydrogen U than a steep radical, oxygen (benzene «institute) hexahydropyridine (such as 2 · section-4-oxo-N-hexahydropyridyl), oxygen (benzene) _ν-hexahydropyridyl (such as 2 3_benzene_ Ν-octahydroB than late group or 2-oxo-5-benzene-N-hexahydroB than a steep group), this steep group via hexahydro (such as 3 # N-hexahydropyridyl or 4- Hydroxy-N-hexahydropyridyl), hydroxy (benzene "4 courtyards) _N_hexahydro B ratio steep group (such as 2- 卞 4-jing-N-hexahydro II ratio steep group), several (via hexahydro B Specific steep group (such as 2_ Jun_4 meet -N-hexahydropyridyl), di_crCt alkylamine-N-hexahydro H than pyridyl (such as 4-dimethylamine-N-hexahydropyridyl), CrC »Indylamine-N-hexahydropyridyl (such as 4 ~ acetamidine · N-hexahydropyridyl), CrC Benzoamine (benzene-CrC4) -N-hexahydropyridyl (eg 4-acetamidine Amine-2-fN-hexahydropyridyl), crC4 Alkylamine (benzene) -N-hexahydropyridyl (e.g. 4-Ethylamine-2-benzene-N-hexahydro Specific steep radical), benzene_ &gt; 1-hexahydro late steep radical (such as 4-benzene-N-hexahydron specific steep radical), CVC4_oxy-N-hexahydropyridyl radical (such as 4 &gt; methoxy-N -Hexahydropyridyl), CrC4 Oxygen (CrQ Academy) Hexahydropyridyl (such as 4 · methoxybenzyl_N_hexahydropyridyl), Binxin must be in accordance with Chinese National Standard (CNS) 8-4 Specifications (210X: 297 mm) Please read the precautions on the back before printing on page P. Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs-34- A7 B7 _38782 V. Description of the invention () Alkoxy-N-hexahydropyridyl (Such as 4,4-dimethoxy-N-hexapyridyl), di-CrC4 (oxy-benzene-CrC4) -N-hexahydropyridyl (such as 2-benzyl-4,4-dimethoxy- N-hexahydropyridyl), CrC ^ alkanedioxy-N-hexahydropyridyl (such as 4-ethylenedioxy-N-hexahydropyridyl), hydroxy-CVC4 ^ N-hexahydropyridyl (such as 2N-methyl-N-hexahydropyridyl, methyl-N-hexahydropyridyl, 2- (2-Ethyl) -N-hexahydropyridyl or 4- (1-Ethyl) -N-hexahydropyridine Group), unsubstituted or halogenated benzamidine ~ N-hexahydropyridyl (such as 4- (4-fluorobenzylhydrazone) -N-hexahydropyridyl), C "C4 焼 醯 -N-hexahydropyridyl Base (such as 4-ethyl -N-hexahydropyridyl), oximidazolidine-N-hexahydropyridyl (such as 4- (2-oximidazolidine) -N-hexahydropyridyl), high-N-hexahydropyridyl, oxygen high -N-Hexahydropyridyl (such as 2-oxo-N-hexahydropyridyl), azinecyclononyl (such as 1-Παbicyclononyl), hexahydropyridyl, CrC4 alkane (Such as 4 · methylhexahydropyridyl), oxyhexahydropyridyl (such as 3-oxahydropyridine), dioxane (such as 3,5-dioxapyryl) ), Unsubstituted or lower alkoxylated phenylhexahydropyridyl (such as 4- (4-methoxypyridine) -hexahydropyridyl), morpholinyl, di-CrC4 morpholinyl (such as 3 , 5-dimethylmorpholinyl), thiomorpholinyl, phenyl, cyclohex-1,3-diazol-5-yl, hydroxyphenyl (such as 4-transphenyl), CrC4oxophenyl ( (Such as 3-methoxyphenyl), carboxyphenyl (such as 3-carboxyphenyl), halophenyl (such as 2-fluorophenyl, 3-fluorophenyl, or 4-fluorophenyl), trifluoromethylbenzene Base, bistrifluoromethylphenyl (such as 3,5-bistrifluoromethylphenyl), naphthyl or tetrahydronaphthyl (such as 1,2,3,4-tetrahydronaphthyl), nifedipine Imidazolyl (such as 5-nifebenzimidazol-1-yl or 6-nitrobenzimidazole -1-yl), tetrahydroquinolinyl (such as 1,2,3,4-tetrahydroquinolin-1-yl), tetrahydroisoquinolinyl (such as 1 , 2,3,4-tetrahydroisoquinolin-2-yl or oxo-1,2,3,4-tetrahydroisoquinolin B-lin-2-yl) or tetrahydrophenylhydrazine For example, 2,3,4,5-tetrahydro-1H-1-phenylhydrazine-1-yl), it is low-grade fluorenyl or this paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) ( Please read the notes on the back before t this page) Order- 槔 · Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs-35- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Together with X and the nitrogen atoms bonded to R8, R9 and X, a pyridinium radical is formed, which is unsubstituted or substituted with amine, crc4 alkylamino or di-crc4 alkylamino, and Y is the anion of the halogen acid , Allc is (^-(^ extended (alkylene) alkyl, such as methylene, ethylene or ethylene, and X (unless it is together with the heart and &amp; Bonding, &amp; forming a part of the ring system with the nitrogen atom of the fork) is a direct bond, CrC4 butane (Such as ethylene, propyl or butyl), CrC4 alkyl (such as methylene, ethylene, isopropylidene, isobutylene or dimethylpropylene), CVQ alkylene (Such as 1,2-pentadenylenyl), oxygen-CVQ alkylene (including carbonyl) (such as carbonyl, oxyethyl, 1,3- (1-oxo) propyl, 1,3- ( 1-Oxylenyl or 1,4- (1-Oxylenylbutyloxy) v Dioxo-CrC4 alkylene (such as acid oxalyl), oxy-CrC4 alkylene (such as 1-oxyethylene) Prop-2-enyl), hydroxy-CVC4 alkylene (such as 2-hydroxyethylene or 2-hydroxypropylene), oxy (c) -CrC4 alkylene (such as 1-oxy-2-hydroxy- Ethylene), amine-CrC4 alkylene (such as amine ethylene), amine-CVQ alkylene (such as 5-aminopentylene), end-CrC4 alkylene (such as 1-carboxyalkylene or 1,3- (1-Qian) propylene), Jun-CrC4 alkylene (such as 3-carboxypropylene), CrC4 alkoxy iron-CrC4 alkylene (such as ethoxycarbonylmethylene), ( ^-(: 4 alkoxy groups -C "C4 alkylene (such as 1,3- (1-tert-butoxide) propylene), ω-Ιΐγ-α-oxy-CVC4 alkylene (such as 1 , 3- (1-oxo-3-ΐίΤ) propyl) or ω-Πγ-α-oxy-CrC4 oxyalkylene (such as 1,3- (3-methyl-1--1-oxy) phenylene -2-Methenyl), 3- to 7-membered cycloalkylene (such as cyclopropylene), or benzene-CVQ55 alkyl or benzene which is unsubstituted or substituted with halo and / or trifluoromethyl -CrC4 alkylene (such as 2-phenylethylene, 1,2- (1-benzene) ethylene, 1,2- [1- (4-chlorobenzene)] ethylene or 1,3- ( 3-benzene) propane). In each case, the present invention also relates specifically to those compounds of the above formula (I) and their salts, in which the paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) (please read the note on the back first) Matters reprinted) -5

T -36- Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 438782 A7 B7 V. Description of Invention ()

Ri is formula_〇1 (1 ^)-311 £ -117 (1 &amp;), -alk-CH (Re) -R7 (Ib), -alk-N (R *)-X-R7 (Ic),- alk-NTiReXR ^ -XI ^ AJW), -alk-0-X-R7 (Ie) or -alk-SX-R7 (If), and ruler 2 is ruler 5 and ruler 3, 114, 115, 1 ^, 117, 118, 119, and industry are as defined above, provided that they are independently the base of formula (Ic), and 112 and 113 are each independently, and are fluorine, chlorine, bromine, methyl, ethyl, or trifluoromethyl And in the compound of formula (I) in which R4 is hydrogen, when aik is methylene, ethylene or propylene, the group is called (optional) 0 «17 group is not a phenylhydrazone fusion via a nitrogen atom bond And / or substituted with an alkyl group having up to 6 (including) carbon atoms or a group of the formula -Ntiy-Rb at the ω-position (wherein Gen and Rfc are each independently hydrogen, alkyl, cycloalkyl, benzene -Lower alkyl or pyrido-lower alkyl, or together with the nitrogen atom to which they are bonded, form pyrrolidinyl, N-hexahydropyridyl, hexahydropyridyl, N1-lower hexahydropyridyl, morpholine Or azepine) substituted 5-membered mono-, di-, tri-, or tetra-azaheteroaryl radicals. The present invention prefers the compound of formula (I) and its salt, wherein Gen is formula (la), -alk-CI ^ R ^ -R? (Ib), -alk-N (Rg) -X-R7 (Ic) or _allc-N &quot; (R *) (R9) -X-R7A_ (Id), and &amp; is 115, R3, R4, and &amp; are independent, and are hydrogen, CVC4, such as methyl or ethyl Group), halogens (such as chlorine, fluorine or bromine), trifluoromethyl, cyano or nitro groups with atomic numbers up to 35 (inclusive), amine groups, (^-(: 4 amine groups, C " C4 alkylamino, N-CrC4, N-CrC4 alkyl-amino or di-CrC4 alkylamino, R7 is hydrogen, alkyl (such as ethyl), -CVQ alkyl (such as 2- Radicals), polyhalo-C, -C4 alkyl radicals (such as trifluoromethyl), 3- to 6-membered cycloalkyl (such as cyclopropyl), 3- to 6-membered aziridine cycloalkyl (such as? Phenyl group), carboxyl group, CrC4 oxycarbonyl group (such as methoxycarbonyl group, this paper size applies Chinese National Standard (CNS) A4 specifications (210X297 mm) (谙 Please read the precautions on the back before t page)) Order-and, -37- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs &quot; 3 8 78 2 A7 A / B7 V. Description of the Invention () Ethoxycarbonyl or Third Butoxycarbonyl), Benzene-CrC4 Oxycarbonyl (such as benzyloxycarbonyl), carbamoyl, anilide, ^-(: 4 sulfofluorenyl (such as methanesulfonyl), amine, morpholinyl, benzamidine; Is phenyl, which is unsubstituted or substituted with carboxyl, sulfamoyl, crc4 oxo, crc4 oxo, halogen and / or trifluoromethyl, such as phenyl, 3-methoxyphenyl, 3 -Carboxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-bistrifluoromethylphenyl; furyl, thienyl, thiazolyl, thiazoline Hydrothiazolyl) (such as 4,5-diargythiazolyl), Qian-CrC4 thiazolyl (4-carboxymethylthiazolyl), CrC4 oxygen ore-(^-(^ alkylthiazolyl (such as 4-methoxy Carboxythiazolyl or 4-ethoxycarbonylmethiazolyl) or pyridyl, R * is hydrogen, CrC4 alkyl (such as methyl or ethyl), hydroxy-C "C4 alkyl (such as 2-hydroxyethyl) Benzene-CVQ radical (such as benzyl) or pyrido-CVQ alkyl (such as pyridyl), or the heart and heart together with X and the nitrogen atom that bonds with fluorene to form pyrrolidyl, carboxypyrrolidinyl ( Such as 2 predyl pyrrolidinyl), hydroxy pyrrolidinyl (eg 3-pyrrolidinyl), tetrahydrothiazolyl (eg tetrahydro 1-1-yl), N-hexahydropyridyl, C "C4J ^ -N-hexahydropyridyl (such as 4-methyl-N-hexahydropyridyl), di-CVQ-N-hexahydropyridyl (Such as 2,6-dimethyl-N-hexahydropyridyl), Qian-N-hexahydropyridyl (such as 2-jun-N-hexahydropyridyl, 3-carboxy-N-hexahydropyridyl, or 4 · Residual-N-hexahydropyridinyl), CrC4 alkoxy curtain · N-hexahydropyridyl (such as 2-ethoxy-N-hexahydropyridyl or 4-ethoxyl-N-hexahydropyridyl), Aniline-N-hexahydropyridyl (such as 2-aniline-N-hexahydropyridyl, 3-aniline-N-hexahydropyridyl, or 4-aniline-N-hexahydropyridyl ), Oxygen-N-hexahydropyridyl (such as 4-oxyhexahydropyridyl), di-C "C4 alkylamine-N-hexahydropyridyl (such as 4-dimethylamine-N-hexahydropyridyl) , Yuan-N-hexahydropyridyl (such as 2- (2-hydroxyethyl) -N-hexahydropyridyl), homohexahydropyridyl, azabicyclononyl (such as 1-azabicyclononyl), hexahydro Pycnyl, CrC4 hexahydropyridine (such as 4-methylhexahydropyridine), this paper size applies to Chinese national standards (CNS &gt; Λ4 specifications (210X 297 mm)) (Please read the note on the back first Matters on this page) Order -38-

II A7 B7 7, Η3 ^ 782 V. Description of the invention () Unsubstituted or lower alkoxylated hexahydropyridyl (such as 4- (4-methoxybenzene) -hydropyridyl), morpholinyl , Thiomorpholinyl, phenyl, cyclohexyl-U-dican_5_yl, hydroxyphenyl (such as 4-phenyl), (^-(: 4-dioxophenyl (such as 3-methoxyphenyl) ), Carboxyphenyl (such as &gt; residual phenyl), halophenyl (such as 2-fluorophenyl, 3 · fluorophenyl or 4-fluorophenyl), trifluoromethylphenyl, bistrifluoromethyl Phenyl (such as 3,5-bistrifluoromethylphenyl), nifedipine imidazolyl (such as 5-nifebenzimid-1-yl or 6-nitrobenzimidimi-1-yl), tetraphenyl Hydroquinolinyl (such as 1,2,3,4-tetrahydroquin-141 lin-1-yl), tetrahydroisoquinolinyl (such as 1,2,3, 4-tetrahydroiso_-14ίlin-1-yl) with a lower alkyl group or R7, R * and R? Together with X and the nitrogen atom bonded to R *, R9 and X to form an unsubstituted or amine Pyridinium radicals substituted with A, and A · is an anion of a hydrohalic acid, which is CVC ^ (alkylene) alkyl, such as methylene, and X (unless it is together with R7 and R * and bonded R * and X Nitrogen atom, or together with bond &amp; heart and X The atom forms a part of the aforementioned ring system) is a direct bond, CrQ alkylene (such as methylene, ethylene, propyl or butyl), ^ alkylene (such as methylene, methylene Ethyl, isopropylidene or 2,2 · dimethylene), oxygen_CK: 4-alkylene (including carbonyl) (such as carbonyl, oxyethyl, ^ (lyoxypropyl, 1, 4- (1-oxy) butylene), oxy_CrC4 alkenyl (such as 1-oxopropan-2-yl), amine · CrC4 alkylene (such as 5-aminepentylene), Jun- CrC4 ^ alkyl (such as 3-Jun-propylene), CrCt hospital oxygen, "suitable hospital base, ω-ηγ-ct-oxygen" 4 extension hospital base (such as ι, 3 · (ι ___ 3_Βγ | propane) Or ω-Hamma-α-oxy-CrC4 dilute group (such as 1,3- (3- [1 丫 -1-oxo) propane_2_canyl) or unsubstituted or by _ group and / Or trifluoromethyl-substituted benzene-crc4 subunits (such as 2-phenylphenylethyl) ° The present invention is particularly related to compounds of formula (I) and their salts, in which the paper size is applicable to China National Standard (CNS) A4 (210X297mm) (谙 Please read the notes on the back first, then this page) Ordered by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs-39 · The Central Standards Bureau of the Ministry of Economic Affairs Printed by Shelley Consumer Cooperative 3 8 7 8 2 a7 ___ _B7 V. Description of Invention ()

Ri is of the formula -CI ^ R ^ alk-I ^ (la), -alk-O ^ R ^ R? (Ib), -alk-N (R8) -X-R7 (Ic), or -alk-lSTiRiOCR + X -RW (Id) group, R2 is Rs group * Gen and Gen are independent, hydrogen, crc4 alkyl (such as methyl or ethyl), halogen (such as chlorine, fluorine or Bromine) or nitro, R5 is hydrogen, R7 is hydrogen, alkyl (such as ethyl), polyhalo-CrC4 alkyl (such as trifluoromethyl), 3- to 6-membered cycloalkyl (such as cyclopropyl ), 3- to 6-membered acridine cycloalkyl (such as morpholinyl), carboxyl, C "C4 alkyloxycarbonyl (such as methoxycarboxy or ethoxycarboxy); is phenyl, which is unsubstituted or carboxyl Sulfamoyl, CrC4oxy, halogen and / or trifluoromethyl substitution, such as phenyl or 3-methylphenyl; furyl (such as 2-fluoranyl), thiazoline (dihydrothiazole) (Such as 4,5-dihydrothiazolyl), Xiang-CrC4 thiazolyl (such as 4-carboxymethylthiazolyl) or CrC4 oxycarbonyl-CrC4 alkylthiazolyl (such as 4-methoxycarbonylmethylthiazolyl or 4-ethoxycarbonylmethylthiazolyl group), R8 is hydrogen, CrC4 group (such as methyl or ethyl) or pyrido-CrC4 group (such as pyridylmethyl), or heart and Re together with X and bonding The nitrogen atom of pyrene forms pyrrolidinyl, N-hexahydropyridyl, Jun-N-hexahydropyridyl (such as 3-carboxy-N-hexahydropyridyl or 4-carboxyhexahydropyridyl), CrC4 alkoxycarbonyl -N-hexahydropyridyl (such as 2-ethoxyl-N-hexahydropyridyl or 4-ethoxyl N-hexahydropyridyl), oxy-N-hexahydropyridyl (such as 4-oxo-N -Hexahydropyridyl), High-N-Hexahydropyridyl, Acrylbicyclononyl (such as 1′yahylcyclononyl), Hexahydropyridyl, CrC4Hexylpyridyl (eg 4-methylhexahydro) Pyridyl), unsubstituted or lower alkoxylated hexahydropyridyl (such as 4- (4-methoxyphenyl) -hexahydropyridyl), morpholinyl or thiomorpholinyl, this paper The scale is applicable to Chinese National Standard (CNS) A4 specification (2 丨 0X297 Gong) (read the precautions on the back before reading this page) -40- ο

8P A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () R9 is a lower alkyl group or a group of 118 and gen together and a bond 118, 1 ^ and an unsubstituted nitrogen atom or Pyridonium radicals substituted by amine groups, and A_ is an anion of a hydrohalic acid, alk is CrC4alkylene, such as methylene, and X (unless it is together with R? And R * and bonded Re With the nitrogen atom of X, or together with the nitrogen atom of Rg, R9 and X to form a part of the aforementioned ring system) is a direct bond, CrC7 alkylene (such as methylene, ethylene, propyl or Butylene), Ci_C4 # alkyl (such as methylene, ethylene, isopropylidene, or 2,2-dimethylene), oxy_CVQ alkyl (including carbonyl) (such as carbonyl, Oxyethyl (oxy) or propyl), amine-C1-C4 sub-radical (such as 5-aminopyridyl), Qian ": chemotyl (such as 3-triphenylene), or unsubstituted Or benzene_Ci_C.4 alkylene (such as 2-phenylalanyl) substituted by halo and / or trifluoromethyl. The present invention is particularly relevant. For example, the compound of formula (I) and its salt should preferably have the formula -alk-CHCR ^)-! ^ (Ib), -alk-N (R8) -X-R7 (Ic),- alk-On ^ ⑽ or _ 也 _ SX-R7 (If), R2 is hydrogen, &amp; and each are independent, are _ prime (such as bromine) or nitro with an atomic order up to 35 (inclusive), as Amine groups are privately-derived, benzyl, and Ben-CrQ oxonite (such as benzyl); anilide, which is unsubstituted or substituted by alkyl (such as methyl), and CrC4 methoxy (such as Methoxy), hydroxyl, halogen (such as fluorine, chlorine or bromine) with an atomic sequence of up to 35 (inclusive), nitrosuccinyl, hydroxyl (such as methoxy or ethoxy), phenyl, Phenoxy and / or trifluoromethyl substitution; or tetrazolyl, (CNS) A4 (21GX297) 41----------- ^ --- (Please read the Note on this page) _ Order 3 878 ^ _-_ ^ _ V. Description of the invention ()

Rs is hydrogen, or together with X and bond 118 with the nitrogen atom of pyrene to form a hexahydropyridyl radical; alic is methylene, X is CrC4 alkyl (such as methylene), or in formula (Ic ); X is carbonyl, amine-C, C4 alkylene (such as 5-aminopentylene), residual -CVC4 alkylene (such as 4-butylene), or together with N (R0 group via via α -Carbon atom bonded ω-αγ-a-C3-C5 alkylene (such as U- (3-nγ-1-oxy) phenylene), or together with Rs and bonded ^ and nitrogen atom Formation of a hexahydrone U ratio steep radical. The present invention favors compounds of formula (I) and their salts, where &amp; is the formula -CH (R6) -alk-R7 (la), -alk-CHiR ^ -RT ( lb), -alk-N (R8) -X-R7 (Ic) or -alk-N ^ ReXRiO-X-RWOd), and &amp; is 115, R3 and R4 are each independently, hydrogen, CrC4 alkyl Radicals (such as methyl or ethyl), halogens (such as chlorine, oxygen, or bromine) or nitro groups with atomic numbers up to 35 (inclusive),

Rs is nitrogen 5 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs R7 is hydrogen, alkyl (such as ethyl), polyhalo-C, C4 (such as trifluoromethyl), 3- to 6-membered ring Alkyl (such as cyclopropyl), 3- to 6-membered acryl Pf cycloalkyl (such as morpholinyl), carboxyl, &lt; ^ (: 4 oxocarbonyl (such as methoxycarbonyl or ethoxycarbonyl); is Phenyl, which is unsubstituted or substituted with a carboxyl, sulfamoyl, CrC4 alkoxy, halogen, and / or trifluoromethyl group, such as phenyl or 3-carboxyphenyl; furanyl (such as 241 sulfanyl ), Thiazolinyl (dihydrothiazolyl) (such as 4,5-dihydrothiazolyl), qian-CrC4 thiazolyl (such as 4-carboxymethylthiazolyl) or oxoalkoxy-CrC4 thiazolyl ( Such as 4-methoxycarbonylmethylthiazolyl or 4-ethoxycarbonylmethylthiazolyl),

Rs is hydrogen, CrC4 group (such as methyl or ethyl) or pico-CVC4 alkyl (such as pyridylmethyl), or this paper size applies Chinese national standards (CNS &gt; Λ4 specification (210X297 mm) -42 -______B7 V. Description of the invention () R7 forms a pyrrolidinyl, N_hexahydro with horse and X and bond 118 with another nitrogen atom. Pyridyl, carboxy-N-hexahydropyridyl (such as 3_carboxy_ Hexahydropyridyl or 4_qian_Hydroxypyridyl), CrC4 alkoxycarbonyl · N-hexahydropyridyl (such as 2-ethoxycarbonylhexahydropyridyl or 4-ethoxy iron_N · hexahydro Pyridyl), oxy · hexylhydropyridyl (such as 4_oxy · N_hexahydro: pyridyl), high-N-hexahydropyridyl, tfy bicyclononyl (such as gamma bicyclononyl), hexahydro Pyridyl, CrC4 hexahydropyridyl (such as 4-methylhexahydropyridyl), unsubstituted or lower alkoxylated hexahydropyridyl (such as 4- (4-methoxybenzene)- Hexahydropyridyl), morpholinyl or thiomorpholinyl, alk is CrC4 (alkylene) alkylene, such as methylene, and printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. Please read the note on the back $ Item on this page)-> f X (unless it is accompanied by R7 and R * and The R * and the nitrogen atom of X form part of the aforementioned ring system) are a direct bond, CrC7 # alkyl (such as methyl, ethylene, propyl or butyl), CrC4® alkyl ( (Such as methylene, ethylene, isopropylidene or 2,2-dimethylene), oxy_CrC4 alkylene (including carbonyl) (such as carbonyl, oxyethyl or 1,3- (1 -Oxyl) propyl, ^ Oxyl) butylene), oxy_Cl_c4alkenyl (such as 1-oxypropylene-2 · canyl), amine-CVC4 alkylene (such as 5-aminepentylene ), Jun-CrC4 alkylene (such as 3 pitch propyl), CrC4 alkoxy-CrC4 alkylene, ω-tiT-a-oxy-CrC4 alkylene (such as 1,3- (1-oxymT ) Propenyl) or oxy_CrC4alkenyl (such as 1,3- (3 · Πγ-1-oxy) propen-2-diyl), or unsubstituted or halogen and / or trifluoro Methyl-substituted benzene-Q-C455 alkyl (such as 2-phenylethylene). -Aspect 'The present invention is related, for example, to compounds of formula (I) and salts thereof, wherein

Ri is -alk-N (R8) -X-R7, and R2 is gas. This paper is suitable for Chinese New Years, Tao Xuzhun (CNS) A4 · (21GX297 mm) -43- A7 B7 &quot; 43S7q2 5. Description of the invention ( ) &Amp; and Gen are independent, halogen (such as bromine) or nitro with atomic number up to 35 (inclusive), (Please read the precautions on the back before $ page}

Re is an amine group, K · 7 is a carboxyl group, R8 is hydrogen, or together with X and a nitrogen atom bonded to R * and X to form a hexahydropyridyl radical, alk is a methylene group, and is a cardioxane (Such as methylene), carbonyl, or together with N (R «) is an alkyl group (a) -tfT-a-C3-C5 via (X-carbon atom bond) (such as 1,3- (3 -tfT-l-oxy) propane), or together with R8 and the bond R * and nitrogen atom of X to form a hexahydropyridyl radical. On the other hand, the present invention favors, for example, a compound of formula (I) and a salt thereof, in which the group is a group of the formula -alk-N (R8) -X-R7 (Ic), and R2, R3, Gen and P are independent It is hydrogen, CrC4 based (such as methyl or ethyl), halogen (such as chlorine, fluorine or bromine), cyano or nitro with atomic number up to 35 (inclusive). R7 is a phenyl, furyl, thienyl or pyridyl radical, which is unsubstituted or substituted by CrC4 alkyl (such as methyl), CrC4 alkoxy (such as methoxy), carboxyl, CrC4 alkoxycarbonyl ( (Such as methoxycarbonyl), carbamoyl, cyano, nitro, halogen and / or trifluoromethyl, or unsubstituted 3- to 8-membered cycloalkyl (such as cyclopropyl), QQ Alkyl (such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, second or third butyl), amine-C, C4 alkyl (such as amine methyl) or more Halogen-CrC4 radical (such as trifluoromethyl),

Re is ammonia, 1 alk is methylene, and this paper size is in accordance with Chinese national standards (CNS &gt; Λ4 size (2 丨 〇 X 297 mm) -44-

Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of Invention () X is carbonyl. The invention relates more particularly to compounds of formula (I) and salts thereof, wherein Rz is a R5 group, and K is a formula -alk-N (R8) -X-R7 (Ic) or -alk-N ^ RgXR + Xi ^ A- The radicals ⑽, 和, and R4 are each independently hydrogen, CrC4 radicals (such as methyl or ethyl), atomic stations (such as chlorine, fluorine, or bromine) or nitro, which are hydrogen I, R? Is 3- to 6-membered cycloalkyl (such as cyclopropyl), 3- to 6-membered acryl Df cycloalkyl (such as morpholinyl), carboxyl group, CrC4 oxocarbonyl (such as methoxycarbonyl) Or ethoxycarbonyl), thiazolinyl (dihydrothiazolyl) (such as 4,5-dihydrothiazolyl) or CrC4 oxygen curtain_CrC4 alkylthiazolyl (such as 4-methoxycarbonylmethylthiazolyl or 4-ethyl Oxycarbonylmethazolyl), &amp; is hydrogen or a QQ compound (such as methyl or ethyl), or R7 and R «together with X and the nitrogen atom bonded to Rs and X to form pyrrolidinyl, N-hexahydropyridine , Carboxy-N-hexahydropyridyl (such as 4-Jun-N-hexahydropyridyl), CrC4 alkoxycarbonyl-N-hexahydropyridyl (such as 4-ethoxycurtain-N-hexahydropyridyl) Oxo-N-hexahydropyridyl (such as 4-oxo-N-hexahydropyridyl) or homohexahydropyridyl, alk is methylene, and X (unless it is accompanied by Bonding the nitrogen atom form of fluorene and hydrazone to form a part of the aforementioned ring system) is a direct bond, Cr (M-alkylene (such as methylene, ethylene, propyl or butyl) or amine- CVQ alkylene (such as 5-aminepentylene) or residual -CrC4 alkylene (such as 3-residual propylene). The present invention is particularly related to the compounds of formula (I) and salts thereof mentioned in the examples, Especially its pharmaceutically acceptable salts. The preparation method of the compound of formula (I) of the present invention is as follows: The paper size is applicable to Chinese National Standard (CNS) A4 specification (21 × 297 mm) (Please read the note on the back first Matters on this page) Order ·-觫 · -45- 〇 Α7 Β7 V. Description of the invention () a) In the compound of formula (II)

N 0-R, N \ 〇—R ”(Please read the precautions on the back of this page and then ί this page) (Π) (in the formula (Π) the radicals K and R &quot; are the same or different hydroxyl protecting groups, radicals And one of K is the R5 group, and the other is the formula -CH (R'6) -alk-R7 (Ila), -alk-CH (R'6) -R'7 (Hb) '-alk-N ( R'8) -X-Rr7 (Πο) '-31 ^ (^ 8) (^) ^-^ 7 ^ (Od)' -alk-0-X-R'7 (lie) or -alk-SX- R'7 (IIf) group, in which ^ is a ^ group or a protected amine group,% is a ^ group, a protected carboxyl group or a protected amine methyl group, and a private group is a heart group or an amine protective group) , Removing the hydroxyl protecting group R 'and / or R &quot; and the amine protecting group that may be present, and if the protected carboxyl group or the protected aminomethyl group is present, remove the carboxyl group or the aminomethyl group from it Liberated, and / or b) in order to prepare a compound of formula (I) (wherein one of the radicals Gen and Gen is a base of formula (Ic), (le) or (If)) and its salt, formula (IΠ ) And (IV) compounds are condensed with each other, printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs

(m) and Y2-X-RV (IV) (wherein one of the radicals ^ and! ^ is an R5 group and the other is a formula -alk-Yjnia), and one of the radicals 1 and 1 is a hydroxyl group, Fluorenyl group or HN (RV) group, the other is a bond-removable group,% is 117 group, protected carboxyl group or protected amine formamidine This paper size applies Chinese National Standard (CNS) A4 specification (210 × 297) (%) A7 B7 5. Description of the invention () group and 疋 8 are &amp; or amine-protecting groups), remove the possible amine-protecting group 可能, and if protected carboxy RV or protected amine formamidine When RV is present, carboxyl or carbamate is released from it, or C) In order to prepare a compound of formula (I) (wherein one of the radicals &amp; 112 is R5 group, the other is formula -alk-CH ^ H ^ Ob), Re is an amine group and ^ is a carboxyl group), the compound of formula (Π) is treated with an acid,

, 0—R! 0—R &quot; (Π) (One of the radicals A and R &quot; 2 in formula (Π) is a private group, and the other is of the formula -alk ~ C (R'7) (R 士 R% 〇Ia '), and R &quot; are the same or different hydroxy protecting groups, 吣 is the protected amine group and RV is the same or different protected carboxyl group), and if necessary, convert the formed compound Into different compounds of formula (I), separating the mixture of isomers obtained according to this method into the individual components and isolating the preferred isomers and / or converting the free compounds obtained according to this method into salts, or The salt obtained in this way is converted into a comparable free compound. The Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs prints suitable hydroxyl protecting groups and R &quot; for example, the hydroxyl groups commonly used for temporary protection of the lactamyl group are protective groups, especially ether-forming groups (such as lower alkyl, more Methyl is preferred), and tri-lower alkylsilyl (like trimethylsilyl). Amino groups are, for example, fluorenyl groups other than &amp; such as fluorenyl groups derived from an aromatic carboxylic acid or an aromatic half carbonate, such as unsubstituted or substituted benzyl fluorenyl or Unsubstituted or substituted phenylcarbonyl (such as phenoxycarbonyl). This paper size applies to China National Standard (CNS) A4 (2 丨 0X297mm) -47-

V. Description of the invention () The protected end group is protected in the form of an ester such as' except for esterification, and is, for example, an unsubstituted or substituted benzoate form or a tri-lower silane Ester form (like trimethylsilyl ester). The protected amine formamidine is, for example, the phthalimide form. Removal of the aforementioned protecting groups R · 'and / or R &quot; or release of the protected groups from the r'7 and / or r'8 groups according to Friendship is performed using conventional methods, such as treatment with acid, such as about 20% To about 40% hydrobromic acid (in acetic acid), or using moderate acid hydrolysis, such as about 1N to about 4N mixture of hydrochloric acid and acetic acid or tetrahydrofuran / ethanol. The starting material of formula (η) (where aik is u-lower alkylene) is, for example, prepared as follows: In equivalent compounds of formula (V), (please read the precautions on the back before ^-and (This page)

(V) Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (one of the free radicals R% and ir2 in formula (v) is a lower alkyl group, especially like a methyl group), and the nitro group is conventionally reduced to Amine groups, such as' reduction by catalytic hydrogenation in the presence of palladium or Raleigh nickel; the formed benzene-1,2-diamine is acidic (such as in the presence of hydrochloric acid) and is equivalent to the oxalic acid condensation formula Quinoline dione of (VI)

(VI) • Line: This paper size applies Chinese national standard (CNS &gt; A4 specification (21〇: &lt; 297 Gongao) -48- A7 B7 V. Description of the invention (). Halogenation of the compound with the introduction of halogen Hal Reagent (such as phosphorus oxychloride) is converted into equivalent 2,3 dihaloquinoline of formula (VI)

(ΥΠ); Please read this compound first, and replace the Hal group with a protected hydroxy group -OR 'or -OR "(like lower alkoxy group, especially methoxy group) by conventional methods, such as with a base Metal_ lower alkanolate (such as sodium methoxide) reaction is achieved; and the side chain of the compound of formula (Vni) will be formed,

I page

eOR 'VIII, OR &quot; (vm) Set the central standard of the Ministry of Economic Affairs, Employee Consumer Cooperatives, India, and dare to use halogenated reagents (such as N-bromosuccinimide in the presence of azo-isobutylamine) halogenated into equivalent A compound of formula (Vffl) (wherein one of the radicals R% and ir2 is a formula -alk-Yi group, the other is a 115 group (wherein \ is halogen, especially bromine), and R 'and R &quot; are hydroxyl groups Protect the base). This compound can then be further combined with the formula &lt; ^ 2 (11'6) -11'7 (\ ^ 11 &), 1 «^ 1 ^ &gt; X-RV (vmb), HO-X-RV (VIIIC) Or HS-XRWVnid) compounds (wherein R'6 is an amine group protected by a divalent araliphatic radical (such as benzylidene or especially benzyl), and is privately horse-based, protected carboxyl or The protected carbamoyl group and R'8 are a horse or amino protecting group). This paper size applies to Chinese national standards (CNS &gt; A4 size (2 丨 0X297) 嫠 -49-

R4 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs;.. A7 ".. One is the R5 group, the other is the group of the formula -alk-CHiR + RWITb) (where R «is an amine group), and the group of the formula -alk-N (R / 8) -X-R'7 (lie) (Where RV is a radical R7 other than chlorine), X is oxygen-free at the α-position, and is, for example, lower alkylene or lower alkylene, and R8 is hydrogen or aliphatic or araliphatic Or RV and 吣 together with X and bonded 趵 with the nitrogen atom of X to form an unsubstituted or substituted mono- or di-41-cycloalkyl, azinecycloalkyl, azinecycloalkyl or via nitrogen Atomically bonded thiocycloalkyl radicals, or radicals of the formula -alk_S-X_R'7 (IIf) (wherein% is the R7 group). In order to prepare compounds of formula (II) (wherein the radical R \ And one of R'2 is a group of the formula _allc-N (R's) -XR'7 ((IIc); Rs = hydrogen), the other is R5 group), can also be under reducing conditions (such as in two -A light metal hydride (such as an alkali metal borohydride), the compound of formula (IX)

Rio N 0-R- (IX) N, 0-R &quot; (The radicals R 'and R &quot; in formula (IX) are the same or different hydroxyl protecting groups, one of the radicals Rla and R2a is an R5 group, and the other One is a lower alkyl fluorenyl group, such as ethyl fluorenyl or especially methyl fluorenyl, reacts with an amine of formula HN (R8) -X-R'72 &lt; * a compound of formula (II) (wherein one of the radicals Rla and Ria Is a R5 group, and the other is a group of the formula -CH (R'6) -alk-R7 (Ha) (where R7 is a carboxyl group and alk is preferably a methylene group) may be, for example, boron trifluoride ether In the presence, the aldehyde of formula (IX) (wherein one of the radicals Rla and R2a is a private group and the other is a formamyl group) and carbamic acid The paper size applies the Chinese national standard (CNS &gt; Λ4 specification (210X297 (Mm) (Please read the precautions on the back first—page order-50- forging 43 8 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (> Lower alkyl esters and formula H-CH = CH-alk-Si (lower alkyl) 3's ω-tri-lower alkano-silicone · lower olefin reaction to convert formamyl to a group of formula -CH (R'6) -alk-CH = CH2 (ffa) , And will use the terminal vinyl group of the intermediate obtained as usual It can be obtained by oxidation (such as using sodium iodate / ruthenium oxide). The aldehyde of formula (IX) (wherein one of the radicals Ru and &amp; is a 5-base group and the other is a methyl group) can be represented by formula (Vffl) Halogen compounds (wherein one of the radicals 及 ^ and ^^ is halogen (such as bromine) and the other is 115 group) as the starting material, preferably in the bis (triphenylphosphine) chloride (Π) and In the presence of lithium chloride, it reacts with ethylene tri-lower alkanestanane (such as ethylene-tributyl-tin tin) to form a compound of formula (vm) (wherein one of the free radicals and 叱 &quot; 2 is vinyl , The other is the r5 group), and it is oxidized (for example, reacted with ozone / oxygen at -80 ° C to -40 ° C), and then reacted with triphenylphosphine. Another compound of formula (IX) is prepared (Wherein Ru is formamyl, R3 is hydrogen or nitro and 1 ^ and 11 »are hydrogen) The method includes, at 40 ° C to 100 ° C in the presence of an alkali metal-lower alkoxide (for example, in In boiling methanol / sodium methoxide), a compound of formula (vm) (where R% is a group of formula -alk-Yt (where \ is a halogen), and the rule &quot; 2, and 114 are hydrogen) are lower alkane 2 propane treatment in alcohol, and If necessary, the product formed is nitrated, and it is preferred to treat it with nitric acid, sulfuric acid, and trifluoroacetic anhydride in trifluoroacetic acid. A ketone of the formula (IX) (wherein one of the radicals and R2a is a Han group, the other is Lower alkylfluorenyl (such as ethenyl) can be a halogen compound of formula (VIII) (wherein one of the radicals RW1 and Rm2 is halogen (such as bromine) and the other is R5 group) as a starting material. Medium (such as bis (triphenylphosphine) t3oi) and lithium chloride), it is best to be in dimethylformamide, under heating, with 1-lower alkoxy · lower storage_tri_ Low-level reading

I Note

Page order: This paper size applies to China's national standard (CNS &gt; Λ4 specification (2 丨 0X297)) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 43Β? 82 λ7 ____ Β7 __ _ 5. Description of the invention () Institute-Tin Alkane reaction, followed by acidic treatment, to obtain a compound of the formula OX) (wherein Rh «and Rh is a lower alkyl group, the other is a private group). A compound of formula (\ ^ 0〇_ in which one of the radicals ^ and! ^ Is a group of the formula -alk-Yi, and the other is a &amp; group (wherein 1 is a halogen)) is also used as an advantageous preparation Compounds of formula (Π) (wherein one of the radicals R 彳 and see 2 is the R5 group 'and the other is a group of the formula -alk-N (R's) -XR'7 (nc) (wherein R7 is a radical According to this method, the halogen compound of formula (Vm) is converted to an equivalent formula by conventional methods, such as exhaustion with an alkali metal alkanolate (such as sodium methoxide). (νίΠ) compound (wherein one of the radicals is a methyl group), and under reducing conditions (for example, in the presence of sodium borohydride), the compound is further combined with the formula HN (R'8) -X-R The reaction of the compound of '7 (vnib). In order to prepare a compound of formula (Π) (wherein one of the radical and R is a R5 group, the other is a compound of the formula -alk-N (R'8> XR'7 (Dc) (Wherein R'7 is an R? Group other than hydrogen), X is (without oxygen at the X-position and is, for example, an oxyperalkylene or a carbonyl group, and one which is hydrogen), in the formula _ Compound (wherein one of the radicals 1 ^ and 1 ^ 2 is of formula -alk-l Base, the other is 115 bases (one of which is _ prime), the _ prime \ is converted into azide by conventional methods, for example, it is suitable to be mixed with alkali metal azide in dimethylformamide or Ammonium azide (such as sodium azide) reaction, the azide group is reduced to amine group by conventional methods, such as triphenylphosphine treatment in water, and the compound of formula (Vin) (wherein the free radical R% and One of R &quot; * 2 is a group of formula-industry ^^, the other is a group of R5 (one of which is an amine group) and an acid of the formula Hax-R7 (viile) or a reactive derivative thereof (like 醯Halogen (such as halides of the formula Hal-X-R7 (vmei)), anhydride (such as the anhydride of formula ινχ-0-χ-ιι7 (νπ &amp; 2)), sulfonic anhydride (such as methanesulfonic anhydride), and aromatic paper sizes apply China National Standard (CNS) A4 specification (2 丨 〇 X 297 mm) (Please read the notes on the back before t page)

-52- Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs' ^ 〇r ·) 7 q ^ A7 __ ^ __ B7 ____ V. Description of the Invention () * Family or araliphatic isocyanate (such as formula 0NC-R7 (vme3) Isocyanate) or aliphatic dicarboxylic anhydride (such as succinic anhydride). A compound of formula (vm) (wherein one of the radicals R 'and R &quot; 2 is a group of the formula -alk-V', the other is a private group, and \ is an amine group) as a starting material can also be prepared Compound of formula (Π) (wherein one of the radicals and! ^ Is a & group, and the other is a group of formula -alk-N (R, *)-XR.7 (Dc) (where R.7 is an esterification The phosphonic acid group R7, such as di-lower alkylphosphonic acid group), X is methylene, and ^ is hydrogen), first treated with formaldehyde (such as in ethanol containing formaldehyde solution), and in silane (such as In the presence of tri-lower-grade chlorosilane, the trimerized intermediate formed will react with a phosphite diester (such as a di-lower alkyl phosphite). In order to prepare a compound of formula (Π) (wherein one of radicals 1 and 2 is 碁 and the other is a base of formula -alk-OX-RV (ne)), in another preparation method, the same formula ( ΥΠΙ) compounds (wherein one of R, and r &quot; i2 is a group of the formula -alk-Yi, the other is a private group, and \ is a halogen) as a starting material, and the -alfc-Y! Group thereof is hydrolyzed Into the equivalent -alk-OH group, and the reaction product with a compound of the formula Hal-XR'7 (VIIIg) (where Hal is halogen, and rv is a heart group, a protected carboxyl group, or a protected carbamoyl group) )reaction. Compounds of formula (Π) (wherein one of the free radical% and 1 ^, especially R ',' is a group of formula -alk-N (R8) -X-R'7 (lie) (where aik is a lower subfluorene Rg is hydrogen and X and 疋 7 are as defined above), the other is R5 group) can also be equivalent to the compound of formula (VIII) (wherein one of the free radicals is halogen (such as bromine), the other is R5 group ) In the presence of a palladium catalyst, it is best to react with 1-lower alkoxy-lower-tri-lower alkanestanane in dimethylformamide under heating, preferably in a palladium catalyst (such as chlorine It is carried out in the presence of bis (triphenylene) fine (II)) and lithium chloride, followed by acidic subsequent processing to obtain the photo paper size. Common Chinese National Standard (CNS) Λ4 specification (21 × 297 mm) (read first read the back) (Notes for this issue)

B7 V. Description of the invention () When the compound of formula (VIII) (wherein the free radical and ^ and Chinese, one is a lower alkyl group, the other is an r5 group); the compound and 3h2n-x-rv The compounds are condensed, and the equivalent compound (vm) is formed (wherein one of the radicals Rmi and κ &quot; · 2 is a radical of the formula -alk '= NX-R'7, and the other is an &amp; radical (where Where alk 'is a lower alkenylene group), the outer ring double bond is reduced to a single bond by a conventional method, such as treatment with sodium borohydride. This method is particularly suitable for the preparation of a compound of formula (Π) (wherein one of the free radicals and shame, especially R \, is the formula -alk-NCR ^ X-RVOIc) (where alk is ethylene and X is lower Alkylene or lower alkylene or direct bond and R'8 is hydrogen), the other is R5 group), the above-mentioned compound of formula _ is reacted with 1-ethoxyethylene-tributane-tin Compound of formula (VHI) (wherein one of the radicals 疋 ^ and 疋 ^ is ethynyl and the other is R5 group) &gt; Printed by the Consumer Cooperative of the Central Government Bureau of the Ministry of Economic Affairs, using a similar method, or A compound of formula (Ιί) (wherein one of the free radical% and R'2 is obtained, in particular, is a group of formula -alk-N (R'8) -X_RV (nc) or -alk-OX-RV (Ie) , Alk is ethylene, and R, 8 is hydrogen and hydrogen, and X is as defined above, which is a halogen compound of the formula (Vin) defined above (wherein the radicals R &quot; \ and 11 '&quot; 2 One is halogen (such as bromine), and the other is R5 group), and should be in the presence of bis (triphenylphosphine) pin (Π) and lithium chloride, and ethylene-tri-lower-grade-stannane (such as Acetonitrile-stannane) reaction 'forms the equivalent formula (vm & g t; a compound (wherein one of the radicals 彳 and 疋 ^ is a vinyl group and the other is a private group); the compound is converted by a conventional hydroboration reaction, and then oxidized to an equivalent compound (νπΐ) (where One of the radicals 疋 ^ and 疋 &quot; is 2 for ethyl, and the other is for）). When needed, 2Cui ethyl is firstly mixed with methanesulfonyl chloride, then with an alkali metal azide, and finally with three Phenylphosphine is converted into 2-aminoethyl; if necessary, the reductive amination is used to replace the amine group with a group of the formula -n (& 8) _x-ri7. -54- The standard of this paper applies to Chinese national standards (CNS) Λ4 specification (210X297 mm) _38782 V. Description of the invention (.) Unless otherwise stated, the reaction of the compound of formula (vm) above is performed by conventional methods, preferably in an organic solvent such as tetrahydrofuran, Dihumane or dimethylformamide), or in a two-phase system (such as benzene / water or toluene / water), if necessary, in a basic condensation reagent (such as a third aliphatic amine (such as triethylamine) ) Or a third aromatic nitrogen base (such as pyridine), a fourth aliphatic- or aromatic ammonium salt (such as tetramethylammonium hydrogen sulfate ) Or a metal base (like an alkali metal hydroxide, an alkali metal carbonate or an alkali metal amine, such as sodium or potassium hydroxide, sodium or potassium carbonate, or sodium or potassium amine)), and Optionally in the presence of other adjuvants, N- (3-dimethylaminepropyl) -N · -ethyl-minediimide / 1- via benzotriazole, if necessary, under heat, For example, it is carried out in a temperature range of about 25 ° C to 120 ° C, preferably 50 ° C to 120 ° C. Printed by Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, which can be removed to form a bond Some is, for example, a reactive esterified hydroxyl group, such as a hydroxyl group that is esterified with a mineral acid or a sulfonic acid, especially a halogen atom (such as chlorine, bromine, or thallium); or is aliphatic or unsubstituted or substituted Aromatic sulfonated hydroxyl groups, such as lower alkanesulfonyloxy (like methanesulfonyloxy) or unsubstituted or substituted benzenesulfonyloxy (eg benzenesulfonyloxy, bromobenzenesulfonyl) Ethoxyl or tosylsulfonyloxy), in the compound of formula (II) (wherein the group or hydroxyl group) and the "_ curtain compound (where X is in the relative无 22α-position without oxygen) reaction, it can also be free or etherified hydroxyl, such as hydroxyl, lower alkoxy, benzyloxy, selectively nitrated phenoxy or formula -0-X-RV Group, such as a 1 group derived from a carboxylic anhydride or a sulfonic anhydride. The compound of formula (IV) containing this group is' for example, a carboxylic acid of formula HOOC-X-R7 (IVa) (wherein X is lower alkylene, lower alkylene, lower alkylene, carbonyl, amine-lower Alkylene, ammonium perfluoroalkylene or lower alkoxide-lower alkylene), formula Hal-C (= 0 &gt; X, R_7 This paper size applies to Chinese National Standard (CNS) A4 specifications (2丨 0 X 297 Gongkang) -55- Α7 Β7 V. Description of the invention () (IVb) carboxylic acid halide (where X is lower alkylene, lower alkylene, carbonyl or —bond), formula RVX-C (= 0) -0-C (= 0) -X-R7 (IVc) carboxylic anhydride (where X is lower alkylene, lower alkylene or one bond), formula Hal-S (02)- X-MIVd) sulfohalogen halide, sulfonic anhydride and dicarboxylic anhydride (such as succinic anhydride) of formula R7 &gt; S (02 &gt; 0-S (02) -R7 (IVe). In the method, formula (IΠ) and ( IV) The reaction of the compound is carried out by customary methods, preferably in an inert organic solvent (such as tetrahydrofuran, dioxane or dimethylformamide), or in a two-phase system (such as benzene / water or Toluene / water), if necessary, in a basic condensing agent (like a third aliphatic amine (such as triethylamine) ) Or a third aromatic nitrogen base (such as pyridine), a fourth aliphatic- or aromatic ammonium salt (such as tetramethylammonium sulfate) or a metal base (such as an alkali metal hydroxide, an alkali metal carbonate, or an alkali metal amine) Compounds such as sodium hydroxide or potassium hydroxide, sodium carbonate or potassium carbonate or sodium or potassium amination)), and optionally in the presence of other adjuvants, N- (3-dimethylamine propane hydrochloride Eredimine / 1-by benzotriazole, if necessary, under heating, such as about 25 ° C to 120 ° C, preferably 50eC to 120 ° C temperature range. Economic In the preferred embodiment of the present invention, for example, a consumer cooperative of the Ministry of Standards and Standards Bureau, for example, a compound of formula (m) (wherein 1 is a hydroxyl group) in a fourth aliphatic ammonium salt (such as tetraethylammonium hydrogen sulfate) ) In the presence of a two-phase system (such as benzene / water) with a compound of formula (IV) (where ¥ 2 is a halogen (like bromine)). In another preferred embodiment of the present invention, For example, a compound of formula (II) (wherein \ is an amine group) in a third aliphatic ammonium salt (such as triethylammonium, N- (3-dimethyl chloride) (C) Compounds of the formula HOOC-XR7 (IVa) (wherein the -C (0) -X- group is α-oxygen) in the presence of -N · -ethane-carbodiimide and 1-hydroxybenzotriazole. -The standard of low-level elongation paper is applicable to China National Standard (CNS) M standard (2 丨 0X297 mm) -56-ίν Α, Λ · .-h J · ^ 〇 / Η ρ 85 丨 1〇23〇 · Amendment page of the Chinese manual of the application (June 1989) A7 B7, amendment 1 qq year, month, private person R supplement

V. Description of the invention () group, ω-Πγ-α-oxy-low-level extension base or ω-x-γ-α-oxy-low-level extension storage base), or react with the formula RVX-C (= 〇)- 0-C (= 0) -X-R7 (IVc) carboxylic anhydride (where X is lower alkylene, lower alkylene or one bond) is reacted. The starting material of formula (m) can be prepared by a method known per se, such as the side chain of a compound of formula (Vffl), RM ,, R ', and R.R. N OR &quot; (VIII) (please first (Please read the notes on the back and fill in this page again.) The Ministry of Economic Affairs, Central Bureau of Standards, Consumer Consumption Cooperative, printed with halogen 1 (such as N-bromosuccinimide in the presence of azo-isobutyronitrile). Into a corresponding compound of formula (VIII) (wherein one of the radicals R and R 2 is a group of formula 4), the other is a R 5 group (wherein halogen, especially bromine), and ΪΤ Is a hydroxy protecting group) and removing the hydroxy protecting group redundantly and "or, if necessary, will form a compound of formula (VIII) (wherein one of the radical ^^ and rule, is a formula -alk-Y, , The other is the R5 group (wherein Yi is halogen) using conventional methods, such as the use of alkaline hydrolysis (such as in the presence of potassium carbonate), to convert into equivalent compounds (m &gt; where the brother is a hydroxyl group), Or react with an alkali metal azide (such as sodium azide) in dimethylformamide and then with triphenylphosphine in tetrahydrofuran And in each case removes the hydroxyl protecting groups R1 and R &quot; and converts them into equivalent compounds of formula (in) (wherein Y is an amine group). Method c) compounds of formula (Π) (wherein the free radicals R, And one of R &quot; 2 is an R5 group, and the other is a protected amine group R'6 in the formula -alk-C (RV) (R'6) -RV (a group based on na)), for example, An amine group protected by an amine protecting group mentioned in method a), such as a lower alkylamino group or a lower alkoxycarbonylamino group. Protected carboxyl R'7 This paper is in Chinese national standard (CNS &gt; A4 size (2! 〇 &gt; &lt; 297 mm) -57- 1438782 A7 B7 The description of the invention () is, for example, esterified carboxyl groups (such as lower alkoxycarbonyl or tri-lower alkoxysilane. Carbonyl), and unsubstituted or substituted benzene-lower alkoxycarbonyl or phenoxycarbonyl. In acid treatment, the protected carboxyl group 7 is hydrolyzed to a carboxyl group (one of which is decarboxylated), and the amine protecting group R'6 and (if present) the hydroxy protecting group R 'and / or R &quot; The starting material for method c) can be, for example, a compound of formula (m) (wherein one of the radicals 1 ^ and 1 ^ is a formula-industry-based group, and the group is a reactive esterified hydroxyl group, such as halogen or One of the aforementioned sulfonyloxy groups) is prepared by reacting with an aminomalonic acid derivative of the formula Hc (r'6) (rv) -rv by a conventional method. Compounds prepared according to this method can be converted into different compounds of formula (I) by conventional methods. , For example, aliphatic-, araliphatic-, or cycloaliphatic radicals (like lower alkyl), or by aliphatic-, araliphatic carboxylic acids, aliphatic- or araliphatic half-esters, or carbonic or aliphatic Or aliphatic-, araliphatic- or aromatic hemisulfonyl or aromatic sulfonic acid-derived fluorenyl groups (like lower alkyl sulfonyl, lower sulfonyl sulfonyl) or lower-grade- -Or a fluorenyl radical of a lower alkyne dicarboxylic acid (such as a lower alkyl transbutene difluorenyl group), which can be introduced by conventional methods, for example, derived from a lower alkylating agent (such as a halogenated lower alkyl group) or a reactive lower alkane acid Compounds (like lower alkyl chloride or lower alkyl), lower alkyl sulfonic anhydride or lower sulfonyl chloride or lower lower-or lower alkyne-dicarboxylic acid di-lower alkyl esters (like lower fumarate di-lower alkyl esters) ) The reaction, if necessary, is carried out in the presence of a conventional basic condensing agent. In particular, in the compound of formula (I) (wherein one of the radicals &amp; and &amp; is a radical of formula (Ic) and R * is hydrogen (1), you can introduce free radicals other than hydrogen

I mean

The dimensions of the paper are applicable to the Chinese National Standards of Operation (CNS) A4 specification (210X297 mm) -58-Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs «243 878 2 A7 87 V. Description of the invention () (I) Compounds (wherein one of the radicals is a group of formula (Ic), (Id) or (If) where X is a bond) and 117 and / or R * is hydrogen The atom R7 and / or R2 can be replaced by conventional radicals R7 and / or Re which are not hydrogen. Furthermore, compounds of formula (I) containing an esterified- or amido-carboxylated carboxyl group can be hydrolyzed to equivalent carboxylic acids by conventional methods, and compounds of formula (I) containing a free carboxyl-group can be esterified or amido-modified using a compensation method . Furthermore, in the formed compound of formula (I), the cyano group can be converted into a tetrazolyl group by a conventional method, for example, by reacting with a hydroazide acid. The formed salt can be converted into a free compound by methods known per se, for example by treatment with a base (such as an alkali metal hydroxide, metal carbonate or metal bicarbonate), or with another salt-forming base mentioned at the outset, or Treatment with acids (such as mineral acids), for example with hydrochloric acid, or with another hydrochloric acid mentioned at the outset. The formed salt can be converted into different salts by methods known per se; acid addition salts, for example, using an appropriate different acid in an appropriate solvent (those formed in which the inorganic salt is insoluble and thus eliminated from the reaction equilibrium) Metal salts (such as sodium, barium, or silver salts) are processed and converted, and basic salts are converted into salts by releasing free acids. Compounds of formula (I) (including their salts) may also be obtained in the form of hydrates' or may contain solvents for crystallization. In view of the close relationship between the free form of a novel compound and its salt form 'The above-mentioned and below-mentioned free compounds and their salts, when appropriate and convenient, of course also include equivalent salts and free compounds, respectively. This paper size applies to China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before ^^ this page)

-59- Printed by Shelley Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs ^ 43 8 7 82 at _______B7_ V. Description of the invention () The non-mirromeric isomeric mixture and racemate mixture formed by () can be based on the physical and chemical The difference is separated into pure non-mirromeric isomers or racemates by known methods, such as by chromatography and / or fractional crystallization. The formed racemate can also be decomposed into optical enantiomers according to known methods, such as recrystallization from an optically active solvent, by means of microorganisms, or by reacting the formed non-image isomeric mixture or racemate with an optically active auxiliary compound, such as Depending on the acid group, base or functionally modifiable group present in the compound of formula (I), it reacts with an optically active acid, base or optically active alcohol to form a non-image isomeric salt or functional derivative (such as an ester ), And after separating it into non-mirromeric isomers, the desired specular isomers can be released therefrom by appropriate conventional methods. Suitable bases, acids, and alcohols for this purpose are, for example, optically active green bases, such as Papaya, Cinconine or Beloxin, or D- or 1 ^ 1-phenyl) ethylamine, 3-methylhexa Gas · pyridine, ephedra, and amphetamine can be synthesized similarly to bases, optically active carboxylic acids or sulfonic acids, such as cinchoni sodium 0- or L-tartaric acid, D- or L-di-o- Toluene tartaric acid, 0- or 1 ^ malic acid, 1 &gt; or 1 ^ phenylglycolic acid or D- or L-camphorsulfonic acid, and optically active alcohols, such as methyl alcohol or D- or M1-benzene) ethanol. The present invention also relates to those forms of the process in which the compound obtained as an intermediate at any stage in these processes is used as a starting material and the remaining steps are carried out, or the starting material is used in the form of a salt, or, in particular, under reaction conditions form. The present invention also relates to novel starting materials, which have been developed especially for the preparation of the compounds of the present invention, and in particular can be used to form the starting materials described at the beginning as the more preferred compounds of formula (I), and to their preparation methods and their use. Uses of intermediates. This is especially applicable to the compound of formula (IX) and its salts, ---------- pack-- (please read the precautions on the back before f this page) Standard (CNS) Λ4 specification (210X297 male dustpan) -60- r- ~ \

N ^ o—R, Ό—R &quot; Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives-A7 B7 V. Description of the invention ((IX) In formula (IX), the radicals R and R &quot; are the same or different One of the free radicals Rla and R2a is a methyl group, and the other is a lower alkyl group, especially a methyl or ethyl group, or the formula -CH (R'6) -alk-R7 (Ha), -alk-CH (R \)-RV (nb), -alk-N (R'8) -X_RT7 (lie) '-alk-N ^ fR' ^^^ XR ^ A '(Ud) '-alk-OX-RV (De)' -alk-SX-R'7 (Hf) ^ -alk-YKIIIa), wherein \ is a hydroxyl group, a reactive esterified hydroxyl group, a fluorenyl group, or a formula -N ( R'8) -H group, RV is a R7 group which is not argon, or a protected carboxyl group or a protected amine formamyl group, and 吣 is a phenyl group or an amine protecting group, of which 113, 1 to 4 , Gen, 116, 117, 118, 311 {: and: ^ are the definitions of compounds of formula (1), especially the preferred groups of compounds of formula (I), provided that the compounds of formula (I) (where Rla is In a lower alkyl group or a group of the formula (lie), (lie), or (Hla)), when R 2a and R 3 are independent, they are fluorine, chlorine, bromine, methyl, ethyl, or trifluoromethyl and K When hydrogen, low The fluorenyl group Rla is not a methyl fluorenyl group, or the group of formula (nc) is not a phenylfluorene fusion via a nitrogen atom bond and / or is substituted or substituted by an f group having up to 6 (inclusive) carbon atoms. On the ω-position, the bases of S_N (Re &gt; Rfc (where &amp; and &amp; each are independently hydrogen, courtyard, ring courtyard, benzene-lower grade or lower grade courtyard or together with the face that bonds them) Formation of __, hydrogen-proofing relay group, .6 gas-ribbed well group, N '· lower hexahydrolysyl group, or _ or yahyl surface group) substituted 5_-, di- or tetra-azaheteroaryl group free Base, or benzine or… base is not a hydroxyl paper size applicable to China National Standards (CNS) A4 specifications (210X297 mm (please read the precautions on the back before t this page)

-61-Printed by A7 B7, Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the Invention () Methyl, 1-Ethyl and propyl, or (Ilia) group is not halomethyl, 1-haloethyl · And 1-halopropyl. The present invention favors the compounds of formula (00) and their salts, in which the radicals 拗 and R &quot; are the same or different hydroxy protecting groups, one of the radicals Ru and R2a is a R5 group, and the other is a lower alkyl group, particularly Is like formamyl or ethylamyl, or has the formula -311 ^ (^ 8)-^ '7 (11 &lt; :), -solitary-] ^ (^ 8) (119) -X-RVA' (nd) , -Alk-OX-RV (lie), -a] kSX-R'7 (Πί), or -alk-Y! (Ma), where Yi is hydroxyl, halogen, lower alkylsulfonyloxy, sulfo An alkoxy group or a group of the formula -N (R'8) -H, RV is a 117 group, a protected carboxyl group or a protected carbamoyl group, and a privately-known horse-based or amine-protecting group. R3, R4, and R5 are each independently hydrogen, CrC4 radical, halogen, cyano, or nitro group with atomic number up to 35 (inclusive), privately amine, R7 is carboxyl, CVC4 oxocarbonyl; benzene -CrC ^ oxycarbonyl, which is unsubstituted or substituted with CrC4 alkyl (such as methyl), CrC4 oxygen, hydroxyl, halogen and / or trifluoromethyl with an atomic order up to 35 (inclusive); Fluorenyl; Aniline, which is unsubstituted or substituted by CrC4 alkyl, CrC4 oxygen, hydroxyl, and atomic number up to 35 ( ) Of halogen, nitro, carboxyl, CrC4, oxocarbonyl, phenyl, phenoxy, and / or trifluoromethyl; tetrazolyl or phosphonic acid, R * is hydrogen, or together with X and bond ^ Forms a pyrrolidyl, hexahydropyridyl, or hexahydropyridyl radical with the nitrogen atom of pyrene, X is a carbonyl group, CrC4 alkylene, CrC4 alkylene, amine-CrC4 alkylene, and Jun-Cr C4 alkylene, or together with N (R8) group, are ω-πγ-α- each bonded through an α-carbon atom. This paper size applies the Chinese National Standard (CNS) Λ4 specification (2 丨 0 × 297 mm) (please Read the notes on the back of the book before choosing this page)-Binding-Binding-62- Do 43δ? 82 Α7 __ Β7 V. Description of the invention () Oxy_C3-〇 # alkyl or ω-fl 丫-(X- Oxygen- &lt;: 3-(: 5alkenyl); is benzene-CrC4 alkylene (such as 2: phenylethylene), or in formula (Ic), together with X and nitrogen atoms bonding Rs and X Forms a pyrrolidyl, hexahydropyridyl, or hexahydropyridyl radical. The present invention prefers compounds of formula (IX) and their salts, in which the radicals R 'and R &quot; are the same or different lower alkyl groups Rla is a radical of formula (nia), where \ is a hydroxyl group, Halogen or -N (R) &gt; H (where R'8 is Rs group), R * 2a is R5 group, R3, R4 and private are independent, they are hydrogen, CrC4 group, atomic number up to 35 (including) halogen, cyano or nitro, and alk is CrC4 alkylene. The present invention also relates to a pharmaceutical composition containing the compound of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient and a preparation method thereof . The medicinal ingredient of the present invention (including the compound of the present invention or a pharmaceutically acceptable salt thereof) is used as a enteral (such as oral and rectal) and parenteral drug for warm-blooded animals. This composition alone contains effective pharmacological ingredients Or together with a pharmaceutically acceptable carrier. The daily dosage of the active ingredient depends on the age and individual circumstances and the manner of administration. Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. Novel pharmaceutical ingredients contain, for example, about 10% to 80%, and those preferred are about 20% to 60% effective ingredients. The pharmaceutical compositions for parenteral or parenteral administration of the present invention are, for example, those in the form of single doses, such as dragees, dragees, capsules or suppositories, and ampoules. These preparations are prepared by methods known per se, such as by conventional mixing, granulating, sugar-making, dissolving or freeze-drying methods. For example, an oral pharmaceutical composition can be mixed with an active ingredient and a solid carrier. The paper size is applicable to China National Standard (CNS) Λ4 specification (210X: 297 mm) -63-

A7 B7 V. Description of the invention () Combined to selectively granulate the resulting mixture, and if necessary or necessary, ‘after adding the appropriate adjuvant, process the mixture or granules to form tablets or dragee cores. Suitable carriers are in particular tinctures, such as sugars (such as lactose, sucrose, mannitol or glucositol), cellulose products and / or calcium phosphates (such as tricalcium phosphate or calcium hydrogen phosphate), and binding agents, such as Starch paste made from corn, wheat, rice or potato starch, gelatin, tragacanth, methyl cellulose and / or polyvinylpyrrolidone, if necessary, containing a decomposing agent, such as the aforementioned starch, and carboxymethyl starch, Cross-linked polyvinyl pyrrolidone, agar, alginic acid or its salt (such as sodium alginate adjuvant, especially flow agent, flow regulator and lubricant, such as silicic acid, talc, stearic acid or its salt (such as stearic acid) Magnesium or calcium stearate), and / or polyethylene glycol. Sugar-coated tablets have suitable, selectively enteric coatings, especially using concentrated sugar solutions, which may contain gum arabic, talc, polyvinylpyrrolidone , Polyethylene glycol and / or titanium dioxide, or use a coating solution dissolved in a suitable organic solvent or solvent mixture, or to prepare an enteric coating, use a suitable cellulose product solution, such as ethyl phthalate cellulose or phthalate Hydroxypropylmethyl Cellulose. Dyes or pigments can be added to tablets or sugar-coated tablets coatings, for example, to identify or label different active ingredient doses. Other oral pharmaceutical compositions printed by the Ministry of Economic Affairs, China Standards Bureau, Zhengong Consumer Cooperative, are hard gelatin capsules and Soft sealed capsules composed of gelatin and plasticizers (such as glycerol or sorbitol). Hard gelatin capsules can contain active ingredients in the form of granules, such as blended fillers (like lactose), binders (like starch) and / or lubricating Agents (like talc or magnesium stearate), and stabilizing agents if needed ^ In soft capsules, the active ingredient should be dissolved or suspended in a suitable liquid (such as fatty oil, paraffin oil or liquid polyethylene glycol), also Stabilizers can be added. ”This paper size applies Chinese National Standards (CNS). Λ4 specifications (210X297). -64- A7 B7. Printed by the Consumers' Cooperative of the Central Standardization Bureau of the Ministry of Economic Affairs. 5. Description of invention () Appropriate composition for rectal medicine Substances are, for example, suppositories consisting of an active ingredient and a suppository. • Substrate combination. Suitable suppository substrates are, for example, natural or synthetic triglycerides, paraffin, poly Diol or higher alkanol. Gelatin rectal capsules can also be used, which contain active ingredient and substrate combination> Suitable substrate is, for example, liquid triglyceride, polyethylene glycol or paraffin. Suitable for non-menstrual Enteric donors are especially water-soluble active ingredient aqueous solutions, such as water-soluble active ingredient aqueous solutions, and active ingredient suspensions, such as using a suitable lipophilic solvent or carrier, such as fatty oils (such as sesame oil) or synthetic fatty acid esters ( (E.g. ethyl oleate or triglyceride), equivalent oily injection suspensions, or aqueous solutions containing viscosifying substances (such as sodium carboxymethylcellulose, sorbitol and / or polydextrose) and optionally stabilizers Suspension for injection. The dosage of the active ingredient depends on the species of warm-blooded animal, age and individual circumstances, and the way of taking it. Under normal circumstances, the oral dose for patients weighing about 75 kg is estimated to be about 10 mg to about 500 mg per day. Below Examples are provided to illustrate the invention; temperature units are pressure units are mbar. Example 1: Hydrogen bromide N- (7-bromo-2,3-digas-U, 3,4 &gt; Tetrahydroquinoline-5-ylmethylglycine. 380 mg (0.921 mmol) N -(7-bromo-2,3-dimethoxypyridin-5-ylmethyl) &gt; tert-butyl glycine is dissolved in 6 ml of a solution of about 25% hydrogen bromide in acetic acid, and 70. (:, the solution was stirred for 2 hours. • The mixture was cooled to 20 ° C and diluted with ether. The solid was filtered off and washed with ether. Drying under high vacuum to give the title compound as a white powder. Read first After reading and reading the matter, the re-bound book size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) -65- Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () W-NMR (250 MHz, DMSO-Ds + 5% D2〇) δ = 7.42, 7,37 (2 doublet, 2H), 4.32 (single peak, 2H), 3.91 (single peak, 2H); MS: 328.2 ( M + H) +; melting point = 28leC (decomposition). The starting materials can be 'for example, prepared as follows: also) 5-mo-2,3-diamine-toluene in the presence of about 27 ° C and 1.5 grams of nickel 15 grams (64.9 millimoles) of 4-bromo-2-methyl-6-nitro-aniline was dissolved in 300 millimoles The ethanol solution was hydrogenated for 4 hours. The reaction mixture was filtered and concentrated by evaporation to give the title compound as a brown oil. IH-NMR (250 MHz, CDC13) 6 = 6.76, 6.73 (2 doublet, 2H), 3.22 (single Peak, 21 ^ 2), 2.14 (single peak,) \ ^) »b) 2 ^ -5-formamidine 4-diargyridine-2,3-dione will be 13.05 g (6 tun 9 mmol) ) 5-Bromo-2,3-diamine-toluene and 6.42 g (U equivalent) of oxalic acid were stirred under reflux in 2N hydrochloric acid for 16 hours. The mixture was cooled and the solid was filtered off and washed with water to give the title as a brown solid. Compound. IH-NMR (250 MHz ^ DMSO) δ = 11.98, 11.32 (2 unimodal, 2NH), 7.13 (unimodal, 2H), 2.33 (unimodal, Me). 〇7-Bromo-2,3-di Ammo-5_Applying chrysophylline Reflux 17 g (66.6 mmol) of 7-bromo-5-methyl-fluorene, 4-dihydroquinoline-2,3-dione in 80 ml of phosphorus oxychloride Stir for 5 hours and 40 hours at 20 eC. The mixture is concentrated by evaporation and dried under high vacuum. The saturated solution of potassium carbonate is carefully added to the residue, the solid is filtered off and washed with water to give a brown solid. Title compound * [H-NMR (250 MHz, DMSO) δ = 8.16, 7.99 (2 double peaks, 2H), 2.63 (single peak, Me) »d) 7-bromo-5, methyl-2-3-dioxo-sialoline This paper applies Chinese National Standard (CMS) Μ specifications (210X297 cm) (Please read and read the notes on the back page)-Φ -66-Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Ⅴ. Description of the invention () will be 2.97 grams (129.5 millimoles) ) Sodium is dissolved in 100 ml of methanol. The solution was added to a solution of 18.9 g (64.7 mmol) of 7-bromo-5-methyl-2,3-dichlorosialoline in 60 ml of methanol, and the mixture was heated at reflux for 20 hours. The mixture was cooled and 15 ml of water was added. The solid was filtered off and washed with methanol and water to give the title compound as a beige solid. W-NMR (250 MHz, DMSO) 6 = 7.73, 7.58 (2 doublet, 2H), 4.05, 4.03 (2 singlet, 2Me), 2.58 (single peak, Me). e) 7-bromo-5-bromomethyl-2,3-dimethoxy-dichloroline 15 g (53 mmol) of 7-bromo-5-methyl-2,3-dimethoxy-quinoline 9.9 g (1.05 equivalent) of N-bromosuccinimide and 0.87 g (0.1 equivalent) of azoisobutyronitrile were dissolved in 100 ml of carbon tetrachloride, and the solution was stirred under reflux for 24 hours. The solid was filtered off, and the filtrate was diluted with dichloromethane and washed once with water and brine. The organic phase was dried over sodium sulfate and concentrated by evaporation. The residue was recrystallized from ethyl acetate and hexane to give the title compound as pale orange crystals. iH-NMR (250 MHz, CDC13) δ = 7.90, 7.68 (2 doublet, 2H), 4.95 (single peak, 2H), 4.20, 4.13 (2 singlet, 2Me)-f) N- (7 -Bromo-2,3-dimethoxy-quinolinline-5-ylmethylglycine tert-butyl ester 850 g (2J5 mmol) Methoxyquinoline, 0.982 ml of triethylamine and 719 mg of tributyl glycinyl hydrochloride were dissolved in 15 ml of acetonitrile, and the solution was stirred at reflux for 18 hours. The mixture was concentrated by evaporation and the residue was dissolved Rinse in ether with 5% aqueous sodium carbonate and brine. Collect the organic phase, dry over sodium sulfate, and concentrate by evaporation. Chromatograph the residue on silica gel with ethyl acetate and petroleum ether (1: 2). The title compound was obtained in the form of a yellow oil. The size of this paper applies to China. National Standard (CNS) A4 (210X29 &quot;? mm) (Please read the precautions on the back before filling out this page) Order -67- 8 2 A7 B7

Printed by the Consumer Cooperative of the Central Government Bureau of the Ministry of Economic Affairs. 5. Description of the invention () lH-NMR (250 MHz, CDCb) δ = 7.88, 7_57 (2 doublet, 2H), 4.20 (single peak, 2Η), 4.15, 4.12 (2 singlet, 2Me), 3.32 (single peak, 2Η), 1.42 (single peak, 9Η). Example 2: The following compounds were also prepared using a method similar to that described in Example 1: Hydrogen bromide N- (7-bromod, 3-dioxo-1,2,3,4-tetrahydroquinoxaline- 5-ylmethyl) -β-alanine, melting point = 271 ° C (decomposition); N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrobromide -5-ylmethyl)-(L &gt; glutamic acid, melting point = 220 ° C (decomposition); hydrobromide 1 ^ (7-bromo_2,3-dioxo-1,2,3,4-tetrahydro Quinoxaline-5-ylmethyl)-(L) -phenylalanine, melting point = 249 ° C (decomposition); dihydrobromide &lt; xN- (7-bromo-2,3-dioxo-1,2, 3,4 ~ tetrahydroquinoline-5-ylmethyl)-(L) -lysine, melting point = 256 ° C (decomposition): N- (7-bromo-2,3-dioxo-hydrobromide- 1,2,3,4-Tetrahydroquinoxaline-5-ylmethyl) -hexahydropyridine-2-carboxylic acid ethyl ester, melting point = 240 ° C (decomposition); N- (7-bromohydrobromide) -2 &gt; dioxo-1,2,3,4-tetrahydroquinoline-5 · methylformate &gt; · hexahydropyridine glacial ethyl carboxylate, melting point &gt; 250 ° C; hydrobrominated N- (7 -Bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -hexahydropyridine-3-epiate, melting point &gt; 260 eC; hydrobromination 7-bromo-M5-nitro-benzimidazole-1.ylmethyl) -1,4-dihydro-quinolinol D-2-2,3-dione, melting point = 2 46t: (decomposition); 7-bromo-5- (6 · nitro-benzimidazine) hydrobromide_1, wood dihydro-quinoxaline-2,3-dione, melting point = 278 ° C (Decomposed); Chinese National Standard (〇 阳) 8 4 specifications (2 丨 0 \ 297 male dragon) (Please read the precautions on the back before filling this page)-* 68-A7! ----- B7 iT Year, month, and day W. Description of the invention () Supplementary Example 3 of the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. Example 3: The following compounds were prepared by a method similar to that described in Example 1, but using 7-bromo, 5- Bromomethyl-2,3-dimethoxy-8-nitro-quinoline is substituted for 7-bromo-5-bromomethyl-2,3-dimethoxy · • xoline as the starting material: N-hydrobromide N -(7-bromo-2,3-dioxo-8 · nitro-i, 2,3,4-tetrahydroquinoline-5-ylmethyl) dimethylamine-hexahydropyridine, melting point = 209 t ( Decomposition); N- (7-bromo-2,3-dioxy · 8-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -1,2,3, hydrobromide 4 · Tetrahydroquinoline, melting point = 213 ° C (decomposition); N- (7-bromo · 2,3 · dioxy_8-nitro-1,2,3,4-tetrahydroquinoline hydrobromide Porphyrin-5-ylmethyl) -β-alanine, melting point = 254 ° C (decomposition); dihydrobromide occ- (7-bromo-2,3-dioxo-8-nitro-1,2,3 , 4- Hydroquinazoline methyl lysine, melting point = 180 ° C (decomposition); N_ (7- Mo-2,3 · diox-8-nitro-1,2,3,4-tetrahydrobromide) Quinoline-5 · yltoluidine, melting point = 218 ° C (decomposition); N- (7-bromo-2,3-dioxo-8-nitro-1,2,3 + tetrahydroquine hydrobromide Pyridin_5_ylmethyl) · glycine, melting point = 238 ° C (decomposition); N- (7-bromo-2,3-dioxo-8-nitro-1,2,3,4 hydrobromide -Tetrahydroquinoline-5-ylmethyl) -hexahydropyridine-4-junconate, melting point = 260 (decomposed). The starting materials can, for example, be prepared as follows: a) 7-bromo · 5-momethyl liao 3-dimethylargon-8 · nitrazine 20 ml of sulfuric acid is cooled to 0 ° C, and then 5 g (13-8 ml) Moore) 7-bromo-5-bromomethyl-2,3-dimethoxy-quinoxaline. After another 15 minutes, 1.46 g (1.05 equivalent) of potassium nitrate was added, and the mixture was stirred at 20 ° C for 15 hours. The mixture was poured onto ice, and the solid was filtered off and washed with water to give the title compound as a beige solid. This paper size is applicable to China National Ladder (CNS) A4 specification (210 X 邛 7 mm) (Please read the precautions on the back before filling this page) Order -69- Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, Yinli A7 B7 V. Description of the invention () W-NMR (250 MHz, DMS (MD6) δ = 8.14 (single peak, H), 5.09 (single peak, 2H), 4.12, 3,99 (2 single peak, 21 ^). Implementation Example 4: The following compounds were prepared by a method similar to that described in Example 1, except that 7-bromo-5-bromomethyl was substituted with 5-bromomethyl-2,3-dimethoxy-7-nitro-phosphonium -2,3-Dimethoxy-pyridoline as starting material: Hydrogen bromide N> 0,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoxaline-5-yl A &gt; Ethyl hexahydropyridine carboxylate, melting point = 287 ° C (decomposition); N- (2,3-dioxo-7-bromo-1,2,3,4-tetrahydroquinoline hydrobromide Porphyrin-5-ylformate &gt; β-alanine, melting point = 241 ° C (decomposition); α-N- (2,3-dioxo-7-nitro · 1,2,3,4-dihydrobromide) Tetrahydroquinoline-5-ylmethyl MD) ~ Amino acid, melting point = 185eC (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydrobromide) Hydroquinoline-5-ylmethyl) -glycine, melting point = 271 ° C (decomposition); hydrobromide 1 ^-(2,3-dioxo -7-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl)-(1 &gt; bond amino acid, melting point = 143 ° C (decomposition); hydrobromide N- (2,3 -Dioxo-7-nitro-1,2,3,4-tetrahydropyridin-5-ylmethyl)-(L) -phenylalanine, melting point = 204 ° C (decomposition); dihydrobromide &lt; xN- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl)-(L &gt; lysine, melting point = 150 ° C (decomposition). The starting material, 5-bromomethyl-2,3-dimethoxy-7-quinoxaline, can, for example, be prepared as follows: A,) 5-bromomethyl-2.3-dimethylgas-quinoline CNS &gt; Λ4 specification (210X297mm) (please read and read the notes on the back before t page) --70- Consumption Cooperation with Employees of the Central Standards Bureau of the Ministry of Economic Affairs Du printed A7 __B7__. 5. Description of the invention () The title compound is available Similar to the method described in Example 1C, Id and le, using 5-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoline (CAS accession number 61875-33-0) as Preparation of starting materials: ΒΛ 5-Momethyl-2,3-dimethoxy-7. Analgesine 25 ml of sulfuric acid was cooled to 0 ° C, and then 9.5 g (33.55 mmol) of 5-bromomethyl-2 was added. , 3-Dimethoxy-quinoxaline. After another 10 minutes, 3.39 g (1 equivalent) of nitrate was added. Isopropyl, and the square ° C, and the mixture was stirred for 1 hour. The mixture was poured on ice, and the solid was filtered off and washed with water to give the title compound as a gray-brown solid. W-NMR (250 MHz, DMSO-D6) δ = 8.62, 8.40 (2 doublet, 2H), 5.02 (single peak, 2Η), 4.27, 4.19 (2 singlet, 2Me) »5-bromomethyl -2,3-Dimethoxy-7-nitro-quinoxaline can also be prepared as follows: 5-methyl-7 Gongshen · _2,3-dione will be 9.3 g (55.63 mmol) 2,3- A mixture of diamine-51 toluene and 14 g of oxalic acid in 93 ml of 6NHC1 was heated at reflux for 30 minutes, and then stirred at room temperature overnight to complete the reaction. The suspension was filtered, washed with water 'and dissolved in 250 ml of 2NNaOH, and heated under reflux until a homogeneous solution was formed. After cooling, the mixture was acidified to pH 3, and the 5-methyl-7 · # -quinoxaline-2,3-dione formed was filtered off. h2) 2.3-Digas-5-methyl-7man-quinoxaline 62 ml of POCI3 was added to 5-methyl-7-nitro-quinoxaline-2,3-dione obtained in a2), and the mixture was Heat at reflux for 18 hours. Excess POCU was removed under reduced pressure. The residue was neutralized with a 10% aqueous sodium carbonate solution, filtered and dried. 2.3-dimethylargin-5-shen-7-nitrate-sleeping phospholine Please read the notice first, and the bound paper size is applicable to Chinese National Standard (CNS) Α4 specification (2 丨 〇297297) -71-A7 ⑹38782 B7_____ 5. Description of the invention () The crude 2,3-dichloro-5-methyl-7-nitro-quinoxaline obtained in A0 was dissolved in 1.24 g (27 mmol) of sodium dissolved in 140 ml of methanol. The solution was boiled and heated for 4 hours. After cooling, the mixture was concentrated using a rotary evaporator, neutralized with 2NHC1, extracted with ethyl acetate, dried over sodium sulfate, filtered, and concentrated using a rotary evaporator. Using dichloromethane as the eluent and filtering through silica gel, the title compound was obtained as yellowish crystals. Melting point: 167-168 ° C, TLC: hexane / ethyl acetate 9/1: R. 0.40 〇 Yang 5-bromomethyl-2,3-dimethyl gas-7 becomes difficult. 0.249 g. 0 mmol 1) 2,3-Dimethoxy-5.methyl-7 gluconate. Pyroline, 0.178 g (1 mmol) of N-bromosuccinimide and 0.016 g (0.1 mmol) of azoisobutyronitrile are dissolved in 3 The CC14 * suspension was heated at reflux for 20 hours. The reaction mixture was rinsed with water and brine, and concentrated using a rotary evaporator. Crystallized from ethyl acetate to give the title compound-ILC: hexane / ethyl acetate 6/1: Rp0.63, W-NMR (CDC13) : δ 8.64 (doublet, J = 3, 1H), 8.41 (doublet, J = 3, 1H), S.02 (single peak, 2H), 4.27 (single peak, 3H), 4.20 ( (Single peak, 2H) »Example 5: The following compounds were prepared using a method similar to that described in Example 1, but with 6-methyl-7 ^^-l, 4-chlorosalaline-2,3 -Di-copper replaces 7- Mo_5-methyl-1,4-dihydroquinoline-2,3 · dione as the starting material: Hydrogen bromide N- (2 printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs , 3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-6-ylmethyl) _β-alanine, pour point = 305 ° C (decomposition); ct-dihydrobromide N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoxaline · 6-ylmethyl)-(L) -lysine, melting point = 230 ° C (decomposition) ; Hydrogen bromide N- (2,3 · dioxin-7 rhyme-1,2,3,4-tetrahydroquinolinolinyltoluidine acid, melting point = 228 ° C (decomposition); this paper size is applicable to China National Standard (CNS) Λ4 Specification (210x297 cm) -72-

Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention () N- (2,3-dioxo-7-nitrate-1,2,3,4-tetrahydroquinoline-6-bromo-6- Dimethyl)-(L) -glutamic acid, melting point = 235 ° C (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquine hydrobromide) Pyridin-5-ylmethyl) -glycine, melting point = 27 (TC (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquine hydrochloride) Pyridin-6-ylmethyl) -hexahydropyridine-4-carboxylic acid, melting point = 255 ° C (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4-tetra Hydroquinoline-6-ylmethyl) hexahydropyridine-4-carboxylic acid ethyl ester, melting point = 288-289 ^: (decomposition). Example 6: N_ (74t-2.3-dioxo-7H, 2,3 , 4-Tetrahydroquinoxaline-5 · methylformate) -hexahydropyridine glacial acid at 1.20 g (3.12 mmol) hydrobromide N- (7-bromo-2,3 · Dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -hexahydropyridine 4-carboxylic acid ethyl ester (Example 2) in 12 ml of 2N sodium hydroxide The solution was stirred for 16 hours. The mixture was acidified with 2N hydrochloric acid, and the resulting solid was filtered off, washed with water and ether to give the title compound as a white solid. W-NMR (250 MHz, DMSO-D6 + 10% D20) δ 7.45, 7.38 (2 doublet, 2Η), 4.46 (single peak, 2Η), 3.4 (multiplet, M), 3.0 (multiple, 2Η), 2.05 (multiple, 2Η), I.9 (multiple peak, ytterbium), 1.7 (multiple peak, ytterbium) »MS: 381 (M1). Melting point &gt; 30 (TC. Example 7: N- (7- Mo-2,3-dioxo- 1,2,3,4-Tetrahydroquinoline-5-ylmethyl V hexahydropyridine-4-benzylcarboxamide at -20 ° C, 382 mg (1 mmol) N- (7 -Bromo-2,3-dioxo-1,2, M-tetrahydroquinoxaline-5-ylmethyl) -hexahydropyridine · 4-endanoic acid (Example 6), 186 mg (2 equivalents) aniline '480 mg (2-5 equivalents) of hydrochloride N- (3-dimethylamine propane) -N · -ethyl-echimine and 384 mg (2.5 equivalents) of 1-trans-benzopyrtriazole in dry dimethyl Methamidine is stirred in 48 papers in accordance with Chinese national standards (CNS &gt; Λ4 specification (210 × 297)) I --------- 11 (闻 Please read the precautions on the back before reading this page) Order -Similar 1_ -73-Right 43 878 of A7 B7 V. Description of Invention () iu »·

I Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. The mixture was poured onto water and extracted three times with 100 ml of dichloromethane. The organic phase was collected and concentrated by evaporation. The residue was dissolved in 30 ml of dichloromethane and the solution was stirred for 30 minutes. The white solid was filtered off, washed with dichloromethane and dried. W-NMR (250 MHz, DMSO-D6) 12.0, 11.8 (2 singlet, 2ΝΗ), 9.9 (single peak, ΝΗ), 7.6 (doublet, 2H), 7.30-7.15 (multiplet, 4H), 7.01 (Triple Bee, H), 3.77 (single peak, 2H), 2.95 (multiple peak, ZH), 238 (multiple peak, 1H), 2.05 (multiple peak, 2H), 1.85-1.60 (multiple Peak, 4H). MS: 456 (M1). Melting point> 250 ° C β Example 8: The following compounds were also prepared using methods similar to those described in Examples 6 and 7: N- (7-bromo-2,3 · dioxol-8 hydrochloride 1, 2,3,4-Tetrahydroquinoxaline-5-ylformate &gt; Hexahydropyridine-4 acetic acid, melting point = 278 ° C (decomposition); hydrochlorinated N &lt; 2,3-dioxo-7- Nit-1,2,3,4-tetrahydroquinoxaline-5-ylformate &gt; hexahydropyridine &gt; 4-carboxylic acid, melting point = 294 ° C (decomposition); N- (7-bromohydrochloride) -2,3-dioxo-1,2,3,4-tetrahydroquinoline_5 · ylmethyl) · hexahydropyridine-2-residue, melting point = 225-2401 (decomposition); N- ( 7-bromo-2,3-dioxotetrahydroquinoline-5-m-hexahydropyridine-3 ceramic acid, melting point> 250 ° C; N- (7- Mo-2,3-dioxohydrochloride) -1,2,3,4 · Tetrahydroquinoline-5-ylformate &gt; Hexapyrazine-3-phenylendrazamine, melting point &gt; 260 ° C; N- (7-bromo-2,3 -Dioxo1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -hexahydropyridine-2, benzamidine. Example 9: Amine-7-gang-2,3 -Dioxol · 1,2,3,4 · Tetrahydroquinol (please read the precautions on the back before filling this page)

This paper size is applicable to China National Standards (CNS) A4 (210X297 mm) -74- Printed by A7 B7, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () Will be 15 mg (0.5 millimolar) 5-Aminomethyl-7-bromo-2,3-dimethoxy-1,2,3,4-tetrahydroquinoline in 3 ml of acetic acid and 3 ml of 48% hydrogen bromide in acetic acid . After 18 hours at 20 ° C, the mixture was diluted with ether, and the solid was filtered off and washed with ether. iH-NMR (250 MHz, DMSO-D6) δ 12 · 15 (2 singlet, 2NH), 8.10 (broad, NH2), 7.42, 7.35 (2 doublet, 2H), 4.28, 4.20 (multiple peak, 2H ). Melting point> 250 ° C. The starting materials can, for example, be prepared as follows: a) Azide-7-mo-2,3-dimethoxy-1,2,3,4-tetrahydroquinoline at 20 ° C, 743 mg (2 equivalents) Sodium azide was added to 2.07 g (5.72 mmol) of 7-bromo-5-bromomethyl-2,3-dimethoxy-tetrahydroquinoline in 25 ml of dimethylformamide. In solution. After 3 hours, the mixture was poured into water, extracted with ether, washed with water and brine, and dried over magnesium sulfate. The solvent was concentrated by evaporation. iH-NMR (250 MHz, CDC13) δ 7'92, 7_58 (2 doublet, 2H), 4.80 (single peak, 2H), 4_18, 4.13 (2 singlet, 2_. b) 5-Amine-7 -Bromo-2,3-dimethoxy-1,2,3,4-tetrahydroepidinoline 4.47 g (13.8 mmol) 5-azide-7-bromo-2,3-dimethoxy -1,2,3,4-Tetrahydroquinoline was dissolved in 35 ml of tetrahydrofuran and 3.98 g (1.1 equivalents) of triphenylphosphine was added. The mixture was stirred at 20 ° C for 4 hours. 746 mg of water was added, and the mixture was stirred for another 3 hours. The solid was filtered off and extracted with ethyl acetate and sodium carbonate solution. The organic phase was collected, washed with brine, dried over magnesium sulfate and concentrated by evaporation. The residue was layered on silica gel with ethyl acetate and petroleum ether (1: 1). iH-NMR (250 MHz, CDCI3) δ 7.85, 7.53 (2 doublet, 2Η), 4.22 (single peak, 2Η), 4J2 (single peak, 2Me). This paper size applies to Chinese National Standard (CNS) Λ4 size (2 m X 297 cm) (Please read the precautions on the back before t this page)

-75- I :) I :) Printed by the Central Standard of the Ministry of Economic Affairs and Consumer Cooperatives A7 B7 V. Description of the Invention () 眚 Example 10: 3- 丨 (7-Bromo-2,3-dioxo-U and 4-tetrahydrodark lame-5 side a-)-ammonamidine-propionate ethyl ester 3S1 mg (1 mmol) hydrochloride 5-amine methyl-7-bromo- 2,3-dioxo-1,2,3,4_tetrahydroquinoline, 217 mg (1.5 equivalents) of fumarate monoethyl ester, 0.210 ml of triethylamine, 383 mg (2 equivalents) of hydrogen chloride N- (3-dimethylamine-propyl) -ethyl-carbonyldiimide and 270 mg (2 equivalents) of 1 M-benzopyrtriazole were stirred in dry dimethylformamide for 18 hours. The mixture was poured into 700 ml of water and 3 ml of 1N hydrochloric acid and stirred for 15 minutes. The solid was filtered off, washed with water and dried. W-NMR (250 MHz ^ DMSO-D6) δ 12.0, 11.4 (2 singlet, 2_, 9.18 (triple peak, ΝΗ), 7.23, 7.18 (2 doublet peak, 2Η), 7.05, 6.64 (2 doublet peak , 2Η), 4.50 (doublet, 2Η), 4. [8 (quartet, 2Η), 1.24 (triple peak, 3Η). MS: 395 (M &quot;). Melting point = 288-293 Example 11: 3- 丨 (7-bromo-2,3-dioxo-1,2,3,4-tetramidine_ 喏 carved-5-ylmethyl) -aminomethyl- • acrylic acid will be 144 mg (0.36 mmol) Moore) 3-[(7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline_5-ylmethyl) -carbamate ethyl acrylate and 76 mg lithium hydroxide The hydrate was dissolved in 18 ml of tetrahydrofuran / water (2: 1), and the solution was stirred for 1 s. 50 ml of water was added, the tetrahydrofuran was evaporated and concentrated, and the solution was acidified with 1N hydrochloric acid. The solid was filtered off and washed with water. Washed and dried. JH-NMR (250 MHz, DMSO-De) δ 12.9 (COOH), 12.05, 11.38 (2M 2NH), 9.17 (triple peak, NH), 7.24, 7.18 (2 double peak, 2H) , 6.98, 6.60 (2 doublet, 2H), 4.50 (doublet, 2Η). MS: 367 (IVf) 〇 Melting point> 250 ° C. Example 12: 3- 丨 (7- 漠 -2, 3-dioxo-U, 3,4 · tetrahydrodarkamine-5-ylmethyl) · Fine for amines _Acrylamide standard of this paper is applicable to Chinese storehouse standard (CNS) Λ4 specification (2 丨 0X297mm) (#Read the precautions on the back before t this page) Order -76- Consumption by Male Workers, Central Bureau of Standards, Ministry of Economic Affairs Cooperatives printed as 82 (A7 ____B7 V. Description of the invention (). The title compound was prepared by a method similar to that described in Example 7, but with 3-[(7-bromo-2,3-dioxo-1 ， 2,3,4 &gt; Tetrahydroquinoxaline-5-ylmethyl) amine formamidine] -propionic acid substituted for hydrogenation 1 ^-(7- Mo-2,3-monooxy-1 »2,3 , 4 ~ tetrahydrosialin-5-ylmethyl) -hexahydro {1 than steep_3 ceramic acid as a starting material. Melting point> 250 ° C. Example 13: The following compounds are also used similar to the examples Prepared by the method described in 9 to 12: N- (7- Mo-2,3-_oxy-1,2,3,4-tetraaminopyrimidin-5-ylmethyl) -2- (3-benzene- Methyl ethyl amine, melting point &gt; 300 ° C; {[(?-Mo-2,3-_ • oxy-I, 2,3,4-tetraazapyrimidin_5 · ylmethyl) -aminomethyl Enzyme] -methyl} -carbamic acid third butyl ester, melting point = 238-242 ° C (decomposition); {[(7_bromo-2,3-dioxo-I, 2,3,4-tetrahydroquinol Porphyrin-S-ylmethylamine formamidine] methyl} -carbamic acid f-ester, melting point = 225-230 ° C (decomposition). Example 14: 7-bromo-2,3-dioxo-U? 4-tetrahydro-amidine-5-ylmethoxyacetamidine 1.14 g (3.81 mmol) 7-bromo-5-hydroxymethyl- 2,3-Dimethoxy-tetrahydroquinoline, 840 ml (1.5 equivalents) of tert-butyl bromoacetate and 65 mg (0.05 equivalents) of tetrabutyl hydrogen sulfate, intercepted in 40 ml of benzene and 4 ml of 50% hydroxide Stir in the pin solution for π hours. 100 ml of water and 100 ml of ether were added to the mixture, the organic phase was separated, and the aqueous phase was extracted once more with ether. The organic phase was collected, washed with brine, dried over magnesium sulfate and concentrated by evaporation. The residue was dissolved in 30 ml of acetic acid and 10 ml of 2N hydrochloric acid, heated at reflux for 2 hours, and cooled to 20 eC. 20 ml of water was added, the solid was filtered off, washed with water and dried. W-NMR (250 MHz, DMSO-D6) δ 12.0, 11.45 (2 singlet, 2NH), 7.30, 7.28 (2 doublet, 2Η), 4.62 (single, 2Η), 4.19 (single, 2Η) »MS: 328 ° V. Melting point &gt; 250 ---------- ^ ------ π ------ ^ (谙 Please read the notes on the back first, then t this page) This paper size applies to Chinese national standards (CNS) Λ4 specification (210X297gt) -77- Printed by Shellfish Consumer Cooperative, Central Standards Bureau of the Ministry of Economic Affairs ㈣38782 V. Description of invention () The starting materials can be, for example, prepared as follows: a) 7-bromo-5-hydroxy Methyl-2,3-dimethoxy-stilbeneline At 20 ° C, 11.5 g (31.85 mmol) of 7-bromo-5-bromomethyldimethoxy-quinaline were suspended in 100 ml of dioxane in. Then a solution of 16? G (164 mmol) of calcium carbonate in 100 ml of water was added, and the mixture was heated under reflux for 24 hours. Dioxane was concentrated by evaporation and 300 ml of dichloromethane was added. The salt was filtered off, and the organic phase was washed with brine and concentrated by evaporation. The residue was chromatographed on silica gel with ethyl acetate and hexane (1_1). W-NMR (250 DMSO-D6) δ 7.78, 7.68 (2 doublet, 2Η), 5.40 (triple, OH), 4.96 (doublet, 2Η), 4.02 (single, 2Me). Example 15: 7-bromo-2,3-dioxo-5-methyl-1,2,3,4-tetrahydroquinazoline 450 mg (1.5 mmol) 7-bromo-5-hydroxymethyl -2,3-Dimethoxy-quinoxaline was dissolved in 30 ml of acetic acid and 10 ml of 2N hydrochloric acid, the solution was heated under reflux for 2 hours, and cooled to 20 ° C. The solid was filtered off, washed with water and dried. W-NMR (250 MHz, DMSO-D6) δ 7.28, 7.19 (2 doublet, 2H), 5.5 (broad, OH), 4.62 (single peak, 2Η). MS: 270 (IVT). Melting point &gt; 250 ° C. Example 16: Ethyl 7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinone-5-ylmethoxyacetate 450 mg (1.37 mmol) 7-bromo- 2,3-Dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethoxyacetic acid was suspended in 20 ml of ethanol. 0.5 ml of sulfuric acid was added, and the mixture was heated under reflux for 2 hours under nitrogen. After cooling to 20 ° C, 80 ml of ether was added, and the solid was filtered off, washed with ether and dried. W-NMR (250 DMSO-D6) δ 12.0, 11.1 (2 singlet, 2NH), 7.28, 7_26 (2 doublet, 2Η), 4_63 (single, 2Η), 4.23 (single, 2 ，) , 4.20 (quartet, 2Η), 1.22 (triple, 3H). MS: 356 (NT). Melting point = 250-252 ° C. A7 B7 (Please read the precautions on the back before clicking this page) Binding. The paper size of the booklet applies the Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) -78- B7 V. Description of the invention () Examples 17: (7 :: Mo-2,3-dioxo-1,2,3,4-tetrahypnosis_5 · A certain methyl argon VN-phenylethyl hydrazone m The title compound is similar to that used in Example 7 Prepared as described, but with 7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline methoxyacetic acid instead of N- (7-bromo-2,3- Dioxo-1,2,3,4 ~ tetrahydroquinoline-5-ylmethyl) -hexahydropyridine · 3 acetic acid as the starting material. Melting point> 250 ° C. Example 18: 7-Bromo · 2,3-Dioxo-1,2,3,4-Dihydrodihydropyridine-5-Ethyl Acetate Cocoon Ethyl Acetate Under Nitrogen Dissolve 1.5ml (4mmol) 21% Sodium Ethanol Sodium The solution in ethanol was diluted with 10 ml of ethanol. At 0 ° C, 601 mg (5 mmol) of ethyl thioglycolate was added, and the mixture was heated to 20 ° C. After one hour, 1.09 g (3 Mmol) 7-bromo · 5 · bromomethyl-2,3-dimethoxy-tetrahydroquinoline, 10 ml of ethanol and 10 ml of tetrahydrofuran. The mixture was stirred for 18 hours, and 2 ml of 2N Acidified by hydrochloric acid and concentrated by evaporation. The residue was extracted with ethyl acetate and 0.1N hydrochloric acid, and the collected organic phase was washed with 10% sodium carbonate solution and brine, dried over magnesium sulfate and concentrated by evaporation. The residue was dissolved in 20 ml Of 33% hydrogen bromide was dissolved in a solution of acetic acid, and the solution was heated at 130 ° C for 20 minutes 'and cooled to about 80 ° C. 20 ml of ethanol was added with stirring and at 5 ° C' The solution was left to stand for 18 hours. The crystals were filtered, washed with cold ethanol and dried. Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Consumers Cooperative, lH-NMR (250 MHz, DMSOD6) δ 12 · 02, 11.42 (2 single bees , 2NH), 7.22, 7.15 (2 doublet, 2Η), "Ο (multiplet, 4Η), 3.22 (single peak, 2Η), US (triple, Me). MS: 372 (JVT)» Melting point = 251-253 ° C. Example 19: 7-Mo-2.3-dioxo-1,2,3,4-tetrahydropyrene to make -5 mesosulfonic acid-500 mg (1.34 mmol) ) 7-Bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethanesulfonate ethyl acetate is suspended in 20 ml of tetrahydrofuran and 10 ml of water ' Applicable to China National Standards (CNS) 厶 4 specifications 2mx29T ^ PCT) • 79- A7 B7 43878 Five slits, the invention described () was added 225 mg (4 equivalents) of lithium hydroxide hydrate at 20 ° C, the solution was stirred for 48 hours. Tetrahydrofuran was evaporated and concentrated, 60 ml of water was added, and the solution was acidified with 1N hydrochloric acid. The solid was filtered off, washed with water and dried. iH-NMR (250 MHz, DMSO-D6) δ 12.7 (broad, COOH), 12.03, 1ί · 48 (2 singlet, 2NΗ), 7.22, 7,18 (2 doublet, 2Η), 3.98 (single peak , 2Η), 3.17 (single peak, 2Η). MS: 344 (Μ &quot;). Melting point &gt; 250 ° C. Example 20: (7-Zun-2 digas-U, 3,4-tetrahydroquinamidin-5-ylmethanesulfonium VN-phenethylhydrazine The title compound was prepared by a method similar to that described in Example 7. But, (7-bromo-2,3 · dioxo-1,2,3,4-tetrahydroquinolinline-5-ylmethanesulfonyl) -acetic acid was used instead of N- (7- Mo-2 1,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -hexahydropyridine-3-residual acid as starting material ^ H-NMR (250 MHz, DMSO-D6 ) δ 12.02, 11.52 (2 singlet, 2NH), 10.1 (single peak, ΝΗ), 7.58 (doublet, 2Η), 7.32 (multiplet, 2Η), 7.28, 7.20 (2 doublet, 2Η) ), 7.08 (Santong peak, 1H), 4.05 (single peak, 2H), 3.22 (single peak, 2H) »MS: 419 (MV melting point> 250 ° C. Example 21: Hydrogen bromide Ethyl 2-amine-3- (7-mo-2,3-dioxo-1,2,3,4-tetrahydrofluoren-5-yl diacid ethyl ester will be 1.55 g (3.26 mmol) Ethyl 2-amine-3- (7-bromo-2,3-dimethoxy-quinazolin-5-yl) -acetic acid is dissolved in a 33% solution of HBr in acetic acid at 130 The solution was heated for one hour. The mixture was cooled to 200 ° C and diluted with ether. The solid was filtered off and washed with ether. After drying, a white powder was obtained The title compound at the end of the paper. The size of this paper applies to the Chinese National Standard (CNS &gt; A4 size (2 丨 0X297)) (Please read the precautions on the back of til before ^ this page) Order the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs -80-^ ^ δ 7 8 ρ Α7 __ ~~ _ Β7 V. Description of the invention () W-NMR (DMSO-D6) δ = 12.1 (single peak, NH), 8.35 (broad), 7.25, 7.20 ( 2 doublet, 2Η), 4.20-4.03 (multiplet, 3Η), 3.25 (multiplet, case), 1.10 (triple, 3H); MS (FAB): 356 (M + IT ). Melting point> 280 ° C. The starting materials can, for example, be prepared as follows: a) Hemioxalated 2-amine-3- (7-bromo-2,3-dimethoxy-quinoxaline lin-5- (Yl) -ethyl propionate At room temperature and under nitrogen, 2.49 g (18 mmol) of potassium carbonate and 1.6 g (6 mmol of dibenzo-glycine ethyl ester) were added to 1.81 g (5 mmol) ) 7-bromo-5-bromomethyl-2,3-dimethoxy-quinoxaline and 193 mg (0.6 equivalents) of tetra-n-butylammonium bromide in 10 ml of acetonitrile. The reaction mixture was stirred at reflux for 20 minutes. Hours, then cooled to room temperature. The solid was filtered off, washed with acetonitrile, the solvent was concentrated by evaporation, and the residue was dissolved in 1.35 g (15 mmol) of oxalic acid in 25 ml of acetone and 1 ml of water. The solution was stirred at room temperature for 18 hours, and the solid was filtered off, washed with acetone, suspended in water, and stirred for ten minutes. The solid was filtered off, washed with water and acetone and dried. W-NMR (DMSO-D6) δ = 7.87, 7.58 (2 doublet, 2H), 4.33 (triple, 1H), 4.08, 4.〇3 (2 singlet, 2Me), 3.98 (fourfold, 2Η), 3.61, 3.47 (2 double-doublet, 2H), 0.94 (triple-doublet, ffi). Example 22: 2-amine-3-hydrochloride (7-bromo-2,3-dioxo-1,2Λ4-tetrahydroquinolinium glin-5-yl) -C staff of the Central Bureau of Standards of the Ministry of Economy Cooperative printed m Add 368 mg (5 equivalents) of lithium hydroxide hydrate to 767 mg (1.75 mmoles) of 2-amine-3- (7-prepared 2,3-dioxo-1,2,3 , 4-Tetrahydroquinol-5-yl) -propionic acid ethyl ester was dissolved in a solution of tetrahydrofuran / water (2: 1). The reaction mixture was stirred at room temperature for 72 hours. The tetrahydrofuran was evaporated and concentrated, and the solution was acidified with 1N hydrochloric acid. The solid was filtered off, washed with water and dried. This paper size applies to China National Standard (CNS) A4 (210X297 mm) -81-A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs i438782 5. Description of the invention (). W-NMR (D20 + NaOD) δ = 6.88, 6.66 (2 doublet, 2H), 3.19, 2.92, 2.45 (3 doublet, 3H); MS (FD): 327 (1VT). Melting point> 250 ° C. Example 23: Bucket (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -ethyl oxalophanate Dissolve 254 mg (0.79 mmol) of N- (7-bromo-2,3-dimethoxy-quinoxaline-5-ylmethyl) -oxapyronate in about 25% bromide Hydrogen was dissolved in a solution of acetic acid, and the solution was stirred at room temperature for 16 hours. The mixture was diluted with ether and the solid was filtered off and washed with ether. After drying under high vacuum, the title compound was obtained as a beige solid. W-NMR (250 MHz, DMSO-D6 + 5% D20) δ = 7.24, 7.19 (2 doublet, 2H), 4.40 (single peak, 2Η), 4.23 (West doublet ,; 2Η &gt;, 1.27 ( Triplet, identification). Melting point = 192 ° C (decomposition). The starting materials can be prepared, for example, as follows: 〇) &gt;}-(7-bromo-2,3-dimethoxy-quinoxaline-5- Methylmethyl) -ethyl oxapyronate 300 mg (1 mmol) of 5-aminomethyl-7-bromo-2,3-dimethoxyquinoline hydrochloride was suspended in 10 ml of THF, and The suspension was cooled to 0 ° C. Add 0.183 ml (1.3 equivalents) of triethylamine, and then dropwise add 0.123 ml (1.1 equivalents) of monoethyl oxalate chloride over 30 minutes. The mixture was stirred at 0 ° C for 2 hours, then at 20 ° C for 16 hours and evaporated to condense. The residue was stirred in ether, and the solid was filtered off, washed with water and ether and dried. W-NMR (250 MHz ^ CDC13) δ = 8.12 (triple, NH), 7.90, 7.58 (2 doublet, 2Η), 4_81 (doublet, 2 ，), 4.32 (quadruple, 2 峰), 4 · 19, 4.14 (2 singlet, 2Me), 1.38 (triple, 3Η). This paper size is applicable to China National Standard (CNS) A4 (210X297mm) (Please read the precautions on the back before reading this page)

-82- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 3 8 7 β P A7 __ ~ '_ B7 V. Description of the Invention () Example 24: K7-bromo-2,3-dioxo-1,2,3 , 4 · Tetrahydroquinone-5, dimethylformamide) · Methylenediamine. The title compound was prepared by a method similar to that described in Example 23. Melting point &gt; 300 ° C ° Example 25: N- (7-Bromo-2,3-dioxo-1,2,3,4 · Tetrakis-nen-5-ylmethyl) -oxalic acid The methyl ester title compound was prepared using a method similar to that described in Example 21, starting with N- (7-bromo-2,3-dimethoxy-quinoxaline-5-ylformate) &lt; Preparation. Melting point = 265 ° C (decomposition). The starting materials can be prepared, for example, as follows: a. N- (7-bromo-2,3-dimethoxyquinolinline-5-ylmethyl) -oxadiamine 2% mg of N- (7-bromo-2,3-dimethoxy-sialyl-5-ylmethyl) -oxapyronate and 150 mg of potassium carbonate in 2 ml of water and 5 ml of methanol The mixture was stirred for 20 hours and acidified with 1NHC1. The solid was filtered off and washed with methanol and ether. Melting point> 300 ° C. Example 26: N- (7-bromo-2,3 · diox-1 , 2,3,4 ~ tetrahydroquinoline-5-A) -propanediamine The title compound was prepared by a method similar to that described in Example 25. Melting point> 300 ° C. Example 27: ( 7-bromo-2,3-dioxo-1,2,3, 'xiqi sleep 喏 瞅 -5-a methyl V skin -2-carboxamidine M. Will be 310 mg (0,79 ml) (7- Bromo-2,3-dimethoxy-quinoxaline-5-ylmethyl) -furan-2-residue amine 6 ml of Ling 2 mL of about 2S% hydrogen bromide was dissolved in the S acid solution, and the solution was stirred at room temperature for 16 hours. The mixture was diluted with ether, and this paper was scaled to Chinese National Standard (CNS) Λ4 Specifications (2 丨 OX297mm) -83- (Please read the precautions on the back before this page)-Order A? ---- --- B7 V. Description of the invention () '&quot;'-Solid filter Facial washing. Facial _ after &gt; the title compound as a caged taupe solid. Also the leg ⑽ hall, DMS0_D6) deducted 12.〇1, u 42 (2 singlet, 2 post, 9 η (triple peak, _, 7B (doublet peak, 1H), ⑶ (multiple peak, message), ^ 68 (triple peak shoulder = 50 (one doublet, Qiu. MS (FAB): 364 (IVf) »Pei point = Mfc (decomposition) The starting materials can, for example, be prepared as follows: a) Methoxy-quinoxaline_5_ylmethyl) jl guanan-2-carboxamide at 20 ° C will be 300 milligrams (1 millimolar) hydrogen Chloride & Amine_7bromo_23_Dimethoxy-quinoxaline, m mg (U equivalent) furan_2_guinic acid, 212 mg (1 equivalent) hydrochloride N- (3-dimethyl Amine propionate) -N1-Ethyl-Chlorodiimide and 12.2 mg (0 Λ equivalent) of 4-dimethylamine. This pyridine was stirred in dry THF. 20 hours. The mixture was poured into water and the solid was filtered off and washed with water and Qing Fa acetate. After air drying at high Zhen, yield a gray solid of the title compound as a tan. W-NMR (250 MHz, DMSO-D6) 6 = 7.89 (doublet, 1Η), 7.62 (doublet, 1Η) 7.40 (doublet, 1Η), 7.29 (triple, ΝΗ ), 7.13 (doublet, 1Η), 6.49 (triple 1H), 5_01 (doublet, 2H), 4_20, 4.14 (2 singlet, 2Me). Example 28: The following compounds were also prepared using methods similar to those described in Examples 23 to 27: (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5- Dimethyl) -cyclopropylformamidine, soluble at 250eC (decomposition); 2-amine-N- (7-bromo_2,3 · dioxo-1,2,3,4-tetrahydroquinolium hydrobromide Lin-5_ylmethyl) -ethylamine, melting point = 293 ° C (decomposition); N- (7-bromo-2,3-dioxo-1,2,3,4 ~ tetrahydroquinoxaline-5 -Methylmethyl) -3,5-bistrifluoromethyl-benzylamine, melting point &gt; 300 ° C; (Please read the precautions on the back before this page) Pack-* 11 0 Shellfish Consumption, Central Standards Bureau, Ministry of Economic Affairs The paper size printed by the cooperative is applicable to the Chinese National Standard (CNS) A4 (210X 297 mm) -84- Printed by the Consumer Cooperative of the Central Standardization Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () N- (7- Desert -2,3-dioxo-1,2,3,4-tetrahydroquinoline. 5-ylmethyl) -benzylamine, melting point = 20.0t ;. (decomposition). Example 29: N- (7-Mo-2,3-dioxo-1,2,3,4-tetrahydroammon-5-yl group 50 mg (0,19 mmol) hydrochloride 5 -Amine-7-bromo · 2,3-dioxo-tetrahydroquinoline is suspended in 4 ml of Ν, Ν-dimethylformamide, and 0.02 ml (1.2 equiv. ) Acetic anhydride and 0.059 ml (Z2 equivalents) of triethylamine-stir well for 24 hours. The solvent is evaporated and concentrated, and the solid is suspended in ether, and the solid is washed out with methanol and ether. After drying under high vacuum The title compound was obtained as a white solid. W-NMR (250 MHz, DMSO ~ D6) δ = 12.02, 11.48 (2NH), 8.65 (triple peak, NH), 7.22, 7.18 (2 doublet peak, 2Η), 4.35 (Doublet, 2Η), 1.93 (single peak, Me) »MS (ESP) 310 (MM). Melting point> 300 ° C. The following compounds can also be prepared by methods similar to those described in Example 29: N -(7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -trifluoroacetamidamine 'melting point> 300 ° C. Compounds declared below Also prepared using a method similar to that described in Examples 1 to 29: N- (2,3-Z: oxy-7-1,2,3, 'tetrahydroquinoline-5-ylmethyl HL) hydrobromide -Tyrosine, melting point = 264 ° C (decomposition); gas bromide rule- (2,3-dioxo-7,1,2,3,4-tetrahydroquinoline-5-ylformate) Tri-leucine acid 'Melting point = 208 ° C (decomposition); Ammonia-degraded N- (2,3-Zl oxygen · 7fan 1 meaning 3,4-tetrahydroquinoline-5-ylmethyl HL) -proline Amino acid, melting point = 279¾ (decomposition); _ scale applies to China (210X297mm) (please read the precautions on the back before t page) 'Order,-and · -85-A7 B7 Amine sentence 8782 V. Description of the invention () N- (2,3-dioxo-7-nitro-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) hydrobromide-〇 ·· alanine, melting point = 229 ° C (Decomposition); N- (2,3-dioxo-7,1,2,3,4-tetrahydroquinoline-5-ylmethyl) hydrobromide &gt; (D &gt; alanine, melting point = 228 ° C (Decomposition); N- (2,3-diox-7-nitro-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -carnitine hydrobromide, melting point = 280. C (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4 · tetrahydropyridin-5-ylmethyl)-(L) -valinic acid hydrobromide, Melting point = 226 ° C (decomposition); N- (2,3-dioxy * 7mouth-1,2,3,4_tetrahydroquinoline-5-ylmethyl) -methyloxalamidate; N -(2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinolinline-5-ylmethyl) -oxadiamine Acid, melting point = 255 t: (decomposition); 4-[(7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) amine formamidine]- Methyl butyrate, melting point> 250 ° C (decomposition); hydrobromide 1 ^ (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylformate) &gt; ^-Methyl-Glycine, and N · (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl)- N-node-glycine, melting point = 205 ° C (decomposition). Example 32: N- (2,3-dioxo-7-nitro-1,2,3,4 · tetrahydroquinoxaline 5-ylmethylacetamide at 5 ° C, 103 mg (0.34 Millimolar) N- (2,3-dimethoxy-7 gen · sialolin-5-ylmethyl) · acetamidine was stirred in 3 ml of a 25% solution of hydrogen bromide in acetic acid for 24 hours. The reaction mixture was diluted with ether, and the solid was filtered off, washed with ether and dried. Melting point = 269-272 ° C (decomposed). The starting materials can be prepared, for example, as follows: a) N- (2,3- Dimethyl Gas-7H Block Intimidation-5-Base A) Ethylamine This paper size is applicable to China National Standard (CNS) Λ4 specification (2 丨 OX297) 漦 (Please read the precautions on the back before clicking this page) Printed by the Central Standards Bureau of the Ministry of Economic Affairs, printed by the Consumer Cooperatives-86- Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Printed by the Consumers Cooperatives 4 3 8 7 8? A7 ~~ _B7 V. Description of the invention () At room temperature, 111 mg (0.437 mmol) of 5-aminomethyl-2,3-dimethoxy-7-nitro-quinoline (can be prepared by a method similar to that described in Example 9, but with 5- Bromomethyl-2,3-dimethoxy-7-nitrazine as starting material) and 0.046 ml (1.1 equivalent) of acetic acid And 0.073 ml (L2 equivalent) of triethylamine in 5 ml of N, N-dimethylformamidine and stirred for 24 hours. The reaction mixture was diluted with ether, the solid was filtered off, washed with ether and dried. B- NMR (DMSCWDc, 250 MHz): 8.52 (triple, NH), 8.42, 8.16 (2 doublet, 2H), 4.79 (doublet, 2H), 4-15, 4.12 (2 singlet, 2Me), 1.98 ( Unimodal, Me). Example 33: The following compounds can also be prepared by methods similar to those described in Examples 21 to 32: 汴 (7-bromo-2,3-dioxo-1,2,3,4 ~ Tetrahydroquinoxaline-5-ylmethyl) -phenethylamine, melting point> 250 V; N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline -5-ylmethyl) -3-phenyl-propanamidin, melting point = 237V; N &lt; 7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl ) -Thipan-2-chantamine, melting point &gt; 250 ° C; N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylformate &gt; 3-thiophene-acetamidine, melting point &gt; 260 ° C; and N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl ) -3-methoxybenzidine, melting point &gt; 250 ° C. Example 34: Hydrogen bromide N- (2,3-diox-7-nitro-1,2,3,4 • tetrakiquin喏 tf lin-5-yl a) -N- -Benzylamine dissolves 213 mg (0.53 mmol) of N- (2,3-dimethoxy-7-nitro-sleepinline-5-ylmethyl) -N-methyl-benzylamine in about 25 ml of 4 ml % Hydrogen bromide is dissolved in the solution of acetic acid, and the paper size applies the Chinese National Standard (CNS) Λ4 specification (2) 0X297 mm) (please read the note on the back ^^ item one more this page) | I).

•, tT 87-

_ A7 ___ B7___ 5. Description of the invention () Stir the solution for 20 hours at room temperature. The mixture was diluted with ether and then stirred for 10 minutes, and the solid was filtered off and washed with ether and a little water. After drying under high vacuum, the title compound was obtained as a beige solid. (DMSO-D6, 250 MHz): 12.17, 11.8 (2 singlet, 2NH), 9.7 (wide singlet, NH), 7.52 (multiplet, Ph + H), 7.38 (doublet, H), 4.8-4.15 (multiple peak, 4H), 2.5 (single peak, Me); MS (EI): 373 (NT) -Melting point = 208-212 ° C (decomposition). Alternatively, the title compound can be prepared as follows: 213 mg (0.53 mmol) of N- (2,3 · dimethoxy-7-nitro_pyridin-5-ylmethyl) -N-methylamine in 10 ml Heat in refluxing 2N aqueous hydrochloric acid for 18 hours. The reaction mixture was concentrated by evaporation, and the solid was suspended in ether and a small amount of water, filtered off and dried to give the desired compound as a beige solid. The starting materials can be prepared, for example, as follows: a) N- (2,3-Dimethoxy-7-nitro-stilbene-5-ylmethyl VN-methyl-benzylamine 200 mg 5-bromomethyl -2,3-Dimethoxynitrazine-quinoxaline and 0.016 ml (2.2 equivalents) of benzyl-methylamine were dissolved in 10 ml of acetonitrile, and the solution was stirred at reflux for 20 hours. The mixture was evaporated and concentrated, and the residue was dissolved. In ethyl acetate, and rinsed with 5% sodium carbonate aqueous solution and brine. The organic phase was dried over magnesium sulfate, and the solvent was concentrated by evaporation. W-NMR (CDC13, 250 MHz): 7.84, 7.78 (2 doublet peaks, 2Η), 7_Winter 7.2 (multimodal, Ph), 4'13, 4.08 (2 singlet, 2Me), 4.03, 3,65 (2 singlet, 2CH2), 2.26 (single peak, Me). MMM1L1 or less The compound was also prepared by a method similar to that described in Example 34. Hydrobromide 1 ^ (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinaziline-5-yl (A) -Mefranylamine, melting point = 282 ° C (decomposition), · This paper size is applicable to China National Standard (CNS) Λ4 specification (210X297 male Jie) ---------- Cai-- ---- 、 Order ------ ^ J (Please read the notes on the back before f this page) Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs -88- Printed A7 'B7 by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs V. Description of the invention () N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydrobromide) Quinoxaline-5-ylmethyl) -2-morpholine-ethylamine, melting point = 228 ° C (decomposition); N- (2,3-dioxo-7-nitro-1,2,3, hydrobromide, 4-tetrahydroquinazolin-5-ylmethyl) -diethylamine, melting point = 290 ° C (decomposition); N- (2,3-dioxo-7-nitrate) hydrobromide 1,2,3, 4-tetrahydroquinoline-5-ylmethyl &gt; dimethylamine, melting point = 325 ° C (decomposition); N- (2,3-dioxo-7) -1,2,3, diargon bromide 4-tetrahydroquinazolin-5-ylmethyl) -2- (2-% steep) -ethyl-methylamine, melting point = 205 ° C (decomposition); N- (2,3-dioxo-hydrobromide) 7-nitro-1,2,3 + tetrahydroquinoline-5-ylmethyl) -cyclopropylamine, melting point = 268ΐ (decomposition); europium hydrochloride (2,3-dioxo-7-nitro-1, 2,3,4-Tetrahydroquinoline-5-ylmethyl) -diethanolamine, melting point = 251 ° C (decomposition); N- (2,3-dioxo-7-nitro-I, 2, hydrobromide , 3,4-Tetrahydroquinoxaline-5-ylmethyl) -2-amine-2-thiazoline, melting point = 271 ° C (decomposition); N- (2,3-dioxolium dibromide · 7) -Nitro-1,2,3,4-tetrahydroquinoline-5_ylmethyl) -2-amine pyridine, melting point = 183 ° C (decomposition); N- (2,3-dioxohydrobromide) -7- -1,2,3,4-Tetrahydroquinoline-5-ylmethyl> 2-amine thiazole, melting point = 153 ° C (decomposition); N- (2,3-dioxo-7-bromide) Nitra-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -aniline, melting point> 250 ° C; N- (2,3-dioxo-7-nitro-1) hydrobromide, 2,3,4-tetrahydroquinoxaline-5-ylmethyl) -4-fluoroaniline, melting point = 21 generation (decomposition); N- (2,3-dioxo-7-nitro-1) hydrobromide, 2,3,4-Tetrahydroquinoline-5-ylmethyl) -3-aniline, melting point &gt; 250 ° C; This paper size is applicable to Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm). (Please read the notes on the back before reading this page) Pack--89- 8 A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention () Hydrogen bromide N- (2,3-dioxane -7-nitro-1,2,3,4-tetrahydrosialolin-5-ylmethyl) -2 · fluoroaniline, melting point = 222-235 DC; hydrobromination [N- (2,3-dioxo 7 Pain-1,2,3,4-Tetrahydroquinoxaline-5-ylmethyl &gt; 2-Aminobenthiazole] -Ethyl acetate, melting point = 258 ° C (decomposition); Hydrobromination [N- (7-bromo-2,3-dioxo-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -2-aminobutiazole] -ethyl acetate, MS (EI): 438 ( M &quot;). Example 36: Gas chloride [N- (2,3-dioxo-7man-1,2,3,4-tetrahydroquinamidin-5-ylmethyl) -2-amine-4-oxazole 1 -Acetic acid hydrobromide [N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5- Dimethyl a) -2.aminobenthiazole] -ethyl acetate was stirred in 2 ml of a 2N sodium hydroxide solution for 16 hours. The mixture was acidified with 3NHC1 and the resulting solid was filtered off and washed with a small amount of water and 2 x 20 ml of ether. After drying, the title compound was obtained as a yellow solid. iH-NMR (DMSO, D6, 250 MHz): 12.4, 12.3 (2 single peaks, 2ΝΗχ 9.0 (single bee, ΝΗ)), 8.〇9, 9. · 02 (2 double peaks, 2H), 6.75 (Single peak, H), 4.8 (broad singlet, 2H), U (single peak ϊ 2H); melting point = 284 ° C (decomposition). Example 37: Two-gas gasification N- (2,3 · dioxygen -7-Nitro-1,2,3,4-tetrahydroquinol-5-ylmethyl) -N- (2-n than pyridylmethylglycine at 49 ° C, 49 mg (0.1 mmol) Moore) N- (2,3-dimethoxy chloride) dihydrochloride> 7-Nitro-quinoline-5-ylmethyl) -N- (2-pyridylmethyl) · Glycine in 2 ml of 48 A solution of% hydrogen bromide in acetic acid was stirred for 18 hours. The mixture was diluted with ether and the solid was filtered off, washed with ether and dried to give the title compound as a yellow solid. Please smell first

Note on I side

Page ordering This paper applies Chinese National Standards (CNS) standard (210X297 mm)

Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (). W-NMR (DMSO-Ds, 250 MHz): 12.3 (single peak, 2NH), 8.8 8.25, 7.72, 7.68 (4 multiplet, Py) (2 doublet, 2H), 7,92, 7. 4.1 (multiple peak, 2H), 3.6 (single peak, 2H); MS (FAB +) 386 (M + H); melting point> 280 ° C. The starting materials can, for example, be prepared as follows: a) N- (2,3-Dimethoxy-7-nitrate-darkin-5-ylmethyl VN- (2-pyridinyl V-glycine) ethyl ester 150 Ml (0.46 mmol) of 5-bromomethyl-2,3-dimethoxy-7-quinolinoline, 98 mg (U equivalent) of N- (2-l this pyrimidine) -glycine ethyl ester and 0.076 ml (1.2 eq) of triethylamine was stirred at reflux in 5 ml of acetam for 20 hours. The mixture was evaporated and concentrated, and the residue was suspended in ether and filtered. After drying, the title compound was obtained as a white powder. IH-NMR (DMSOD6, 250 MHz): 8.45, 8.37 (2 doublet, 2H), M5, 7.72, 7.43, 7.22 (4 multiplet, Py), 4_39 (single peak, M), 4.〇5 (multiple Peak, 2MΘ2Η), 4.0 · (single peak, 2Η), 3.63 (single peak, 2Η), 1.18 (triple peak, Me) 〇b) Dihydrochlorinated N · (2.3-Dimethoxy-7 ·?) · Sleepy Dora-5 Chrysophyllum VN- (2 ~ 11H: Dipyridine V Glycine at room temperature, 80 mg (0.186 mmol) N- (2,3-Dimethoxy-7-nitrate- Quinoxaline-5 · methylmethyl) -N- (2-pyridylmethyl) -glycolic acid ethyl ester and 51 mg (2 equivalents) potassium carbonate were stirred in 5 ml of methanol and 2 ml of water for 20 hours. The mixture was concentrated, With 2N HC1 acid And concentrated by evaporation. The residue was recrystallized from hot ethyl acetate, filtered, washed with water and ether and dried. Example 38: Gasification of N- (2,3-digas-7-nitro-l, 2 , 3,4-tetrahydropyridine, 5--5-methylmethyl V3-amine-benzoic acid at 20 ° C, 60 mg (0.156 mmol) of N- [2,3-dimethoxy-7 gene- Quinidine_-5-ylformate &gt; 3-amine-benzoic acid in 4 ml of about 24% HBr in acetic acid solution This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) (please first (Notes on the back of the reading are on this page)-Installation. Binding--91-·. 〇Α7 Β7 V. Description of the invention () Stir for 20 hours. The bottle should be mixed _ 乙 _release, and _ body filtered out and used Wash with acetam. Melting point = 275 ° c (decomposition). The starting materials can, for example, be prepared as follows: Methoxy-7-nitrate-Linyl-5-ylmethyl1-3-amine-frame | 350 mg (1.06 millimolar) 5-bromomethyl_2,3_dimethoxysalazine salivaline hydrazone mg (1.05 equivalents) 3-aminobenzoic acid and 0.165 ml (U equivalent) triethylamine dissolved in ml ethyl acetate The mixture was heated under reflux for 24 hours under boiling. The reaction mixture was evaporated and concentrated 'with ethyl acetate and 1NH C1 extraction and rinsing once with brine. The organic phase was collected, dried over magnesium sulfate and concentrated by evaporation. W-NMR (CDC13, 250 MHz): 8.50, 8.27 (2 doublet, 2H), 7.32, 7.15, 7 · 10, 6.75 (4 multiplets, 4Η), 4.85 (single peak, 2Η), 4_13, 4.12 (2 singlet, 2Me). Hydrobromide N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylformyl) -2- (谙 Please read the note on the back and then f This _ Pack. Page) Printed Acryl-g-g at 7 (TC, 180 mg (0.59 mmol) N ~ (2,3-Dimethyloxy-7fan) Quinoxaline-5-ylmethyl) -2-methazine was stirred for 2 hours in a solution of 33 ° / hydrogen in acetic acid. The reaction mixture was diluted with ether, and the solid was filtered off and washed with ether. After drying, the title compound is obtained as a yellow solid. Melting point = 24] eC (decomposition). The starting materials can be prepared, for example, as follows: a) Carbo-7-nitro-quinoline-5-a methyl V2-form Acrylane at room temperature, 200 mg (0.61 mmol) 5-bromomethyl-2,3-dimethoxy-7-nitro-quinoline, 0.086 ml (2 equivalents) of propyleneimine and 0.2¾ ml (0.3 equivalent) of a 40% argon-oxidized tetrabutylammonium hydroxide solution was stirred in 8 ml of dichloromethane for 20 hours. The mixture was evaporated and concentrated, and the residue was extracted with ethyl acetate and 5% sodium carbonate solution. The paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) -92- Printed by Consumer Cooperative A7 ___ B7 V. Description of Invention () Take. The collected organic phase was washed once with brine, dried over magnesium sulfate and evaporated. The solution was concentrated. W-NMR (CDC13, 250 MHz): 8.6 (multiple peak, 2H), 4.18 (multiple bee, 2Me + H), 3.95 (single peak, 2H), 3.38 (multiple peak, 2H), 1.0 (triple peak, Mep Example 40: Hydrogen bromide N- (2,3-dioxo-7fan 1.2,3,4-tetrahydro_pepirin-5-5-a methyl Vtiy butane 'melting point = 265 ° C (decomposition)' can It was prepared using a method similar to that described in Example 39. Example 4L: Hydrobromide N- (2,3-dioxo-7-nitro-1.2 · 3 · 4-tetrahydroquinoxaline-5-ylmethyl M -The title compound of melahydropyridine was prepared using a method similar to that described in Example 39, but with N- (2,3-dimethoxy-7-nitro-quinoline-5-ylformate> 4-form Hexahydropyridine substituted N- (2,3-dimethoxy-7-nitro-quinoline-5-ylformyl) as the starting material. Melting point = 296 ° C (decomposition). From The starting materials can, for example, be prepared as follows: a) N · {2,3 · Dimethoxy-7soul-sleeping-5-ylformate> 4-methylhexahydropyridine 100 mg (0.304 mmol) E.) 5 · bromomethyl-2,3-dimethoxy-7-nitro-quinoline, 0.04 ml (L1 equivalent) of 4-methyl-hexahydropyridine and 0.05 ml (1.2 equivalent) of triethylamine under reflux and stirred for 20 hours The mixture was concentrated by evaporation and the residue was used Extract with ethyl acetate and 5% sodium carbonate solution. The collected organic phase was dried over magnesium sulfate and concentrated by evaporation. W-NMR (CDC13, 250 MHz): 8.58, 8.43 (multiple peak, 2Η), 4.19, 4,17 ( 2 singlet, 2Me), 4.06 (single peak, 2H), 2.97, 2.15, 1.62, 1.40-1.25 (4 multiplets, 9H), 0.93 (doublet, Me). This paper is scaled to the Chinese national standard ( CMS) Λ4 specification (210X Μ? 浼) (Please read the precautions on the back before t this page). Binding · Order -93-Printed by the Central Standards Bureau of the Ministry of Economic Affairs, shoulder workers, consumer cooperatives 5. Description of the invention () Examples 42: The following compounds were prepared using a method similar to that described in Examples 1 to 41: N- (2,3-dioxo-7,14,3,4-tetrahydro_fluorin-5-yl hydrobromide A) -N '-(4-methoxybenzene) -hexahydropyridine trap, melting point = 241 ° C (decomposition); hydrobrominated N- (2,3-dioxo-7 genus -1,2,3, 4. Tetrahydroquinoline-5-ylmethyl) -hexahydropyridine, melting point> 300 ° C; N- (2,3-dioxo-7.-1,2,3,4-tetrahydrobromide) Hydroquineline-5-ylmethyldimethylhexahydropyridine, melting point = 277 ° C (decomposition); hydrobrominated N- (2,3-dioxo-7 rhodium-1, 2, 3, 4 · tetramidine Quinoxaline-5-ylformamidine Melting point> 300 ° C; N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) 4-hexahydropyridone, Melting point = 259 ° C (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylformyl) &gt; hexamethyleneimine, melting point = 298 ° C (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -3-pyrroline hydrobromide, Melting point> 300 ° C; Hydrobrominated N &lt; 2,3-dioxo-7 shoulder-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -thiomorpholine, melting point = 291 ° C (decomposition); N- (2,3-dioxo-7-nitrate-1,2,3,4-xihydroquinoline-5-ylmethylpumaline hydrobromide, melting point &gt; 300 ° C ; Hydrobromide N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -tetrahydrothiazole, melting point = 250 ° C (decomposition) ; N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -pyrbitazidone, melting point = 286 ° C ( (Decomposed); This paper size applies Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) (please read the note on the back before ^ T page) Order -94-% A7 B7 Central Bureau of Standards, Ministry of Economic Affairs Printed by Shelley Consumer Cooperatives V. Description of the invention () N- (2,3-dihydrobromide) Oxy-7-1,2,3,4-tetrahydroquinoline_5_ylformate> N-methyl-hexahydropyridine, melting point = 295 ° C (decomposition); hydrochlorinated N- (2 , 3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -2- (2-Ethyl) -hexahydropyridine, melting point = 298 ° C (decomposition ); Dihydrobromide N · (2,3-dioxo-7soul-1,2,3,4-tetrahydroquinoline_5 scallion)-hexahydropyridine, melting point &gt; 300 ° C; Hydrobromide is called 2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline_-5-ylmethyl) &gt; 3 bicyclo [3.2.2] nonane, melting point = 271 \: (Decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4 · tetrahydroquinoline_-5-ylmethyl) &gt; tetrahydropyridine, melting point = 279 ° C (decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4 ~ tetrahydroquinoline-5-ylformiazole, hydrobromide, melting point = 298 ° C (Decomposition); N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -3-ethoxycarbonyl-pyrazole, Melting point = 195 ° C; Hydrobromide [1- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -111-indane-3 -Yl] -methyl acetate, melting point = 230 ° C; N- (2,3-dioxo-7-nitro-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) hydrobromide -l, 2,3,4-tetrahydroquinoline, melting point = 212-215 ° C. Example 43: N- (7-Mo-2,3-dioxo-1,2,3,4-tetrahydroquinamidine-5-ylmethyl) -methanesulfonamide is 83 mg (0.31 mmol) ) 5-Amino-7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline is suspended in 4 ml of DMF. Add 0.063 ml (1.6 equivalents) of triethylamine and 82 mg (1.4 equivalents) of methanesulfonic anhydride, and stir the solution for 18 hours. The solvent was concentrated by evaporation and the residue was suspended in ether. Filter out the solids, please note first with water and B

The paper size of the I-page edition applies the Chinese national standard (CNS) A4 (210X297 mm) -95-A7 _____________ B7 V. Description of the invention () Ether washing and drying to obtain the title compound as a white powder. Melting point> 300 eC .: (7-Mo-2-3-dioxo-1,2,3,4-tetrahydrofluoran-5-ylmethyl) -1 ^ -methyl-2-phenylacetamide and 2 ml of hydrochloric acid (2N in water) Add 129 mg (0.3 mmol) of (7-Mo-2,3-dimethoxy-quinolylmethyl) -N-methyl-2-phenylacetamide in 3 ml of tetrahydro The solution was heated and refluxed at the boiling point for 16 hours-after cooling in an ice bath, the precipitate was filtered off and rinsed with cold water. The hot DMF was placed in a refrigerator overnight to produce colorless crystals, and The crystals were filtered off and dried under high vacuum. LH-NMR (300 MH ^ DMSO-D6) δ 12.05-11.95 (broad singlet, 1H), 11.51-11.33 (broad singlet, 1Η), 7.38-7.10 (multiple peaks) , 7Η), 4'78 (single peak, 0.2Η), 4.S9 (single peak, 1. New Zealand), 3.82 (single peak, 1.8Η), 3.62 (single peak, 0_2H), 2_ &quot; ( (Single peak, MΗ), 2.82 (single peak, 0.3 ·). MS (FAB): 402 (Nf), melting point &gt; 260 ° C. The raw materials can, for example, be prepared as follows: a &gt; £ 7 ^ 2 &gt;. ~ Methoxy-dark-spent-5-ylmethyl V2-phenylethylamidamine can be prepared using the method described in Example 27 b) () 7 "Mo-2,3-dimethyl argon_Nanjing Zan-5 Zanjia) to -methyl-2-phenylacetamide 208 mg (0.5 millimolar) (7-bromo-2,3- Dimethoxy-quinoxaline-5 · methylmethyl) -2-benzene, acetamidine dissolved in 4 ml of absolute tetrahydrofuran solution, 30.5 mg (0.7 mmol) sodium hydride suspension was added dropwise within 15 minutes to dissolve 3 ml of absolute tetrahydrofuran suspension. After heating under reflux for 90 minutes under boiling, the mixture was cooled in an ice bath. After adding 8S mg (0.6 mmol) of methyl iodide, the suspension was stirred at 0 ° C for 1 hour and at room temperature for another 15 hours. Add 0.9g of silicone, and this paper size is applicable to China National Operation (CNS) A4 specification (210X297mm) (Please read the precautions on the back before ^^ this page) -96- A7 B7 Bu Wuzi 5. Description of the invention () The suspension was concentrated, dried and purified on a silica gel column with dichloromethane / hexane / · ether (8: 4: 1) as the eluent. . After concentration and drying under high vacuum, the title compound was obtained as a substantially colorless honey, which consisted of a cis / trans isomer mixture in a ratio of about 2: 3. W-NMR (300 MHz »CDC13) 7.87 (doublet, IΗζ» 0.4H), 7'83 (dual bee, IΗζ »0.6Η), 7.4-7.15 (multiple peak, 6Η), 5.10 (single peak, 1.2Η), 5.00 (single peak, 0.8Η), 4.15 (single peak, UH), 4.12 (single peak, 1.8Η), 4.09 (single peak, 3Η), 3.82 (single peak, 1.2Η), 3J5 (single Peak, 0.8Η), 3.03 (single peak, 1.2Η), 2.98 (single peak, 1.8Η). Example 45: N- (7-bromo-2,3-dioxo-U, 3,4 ~ tetrakisquinolin-5-ylmethyl) · «-ι Under nitrogen pressure, 255 mg (0.607 mmol) Moore) N- (7-bromo-2,3-dimethoxy-quinoline-5- «methyl) -ct-amine-phosphonic acid dimethyl ester was dissolved in 5 ml of absolute dichloromethane and 0.33 ml (2.55 mmol) of trimethylsilyl bromide was added at room temperature. After stirring at room temperature for 3 hours, 5 ml of ethanol was added, and stirring was continued for another 22 hours at room temperature. The mixture was then concentrated to dryness. 5 ml of ΗΒΓ (33% in glacial acetic acid) was added to the gray-brown foam, and the mixture was stirred at room temperature for 3 hours before being concentrated to dryness again. The beige residue was dissolved in a K2C05 solution (about 1N in water). The pH was adjusted to 6 with dilute hydrochloric acid, and the suspension was filtered while hot. Hot DMF was added to the filtrate, and then a small amount of ethanol was added until the mixture appeared slightly turbid. The title compound was isolated as gray-brown crystals within 3 days. iH-NMR (300 MHz »D20) 7.53 (broad singlet, 1H), 7.47 (broad singlet, IH), 4.57 (broad singlet, 2H), 3.15 (duplex bee, 11.8Hz» 2H); 3IP- NMR 8 ppm; MS (FAB4) 364,366 [M + H +] &quot;, (FAB ·) 362, 364 Melting point> 270 ° C »The starting materials can be, for example, prepared as follows: a) Bromine-2,3-di Methoxy-quinol-5-ylmethyl V three papers This paper size is applicable to the Chinese national plug (CNS M4 specification (2 丨 0X297) 浼 ΊΊΊ .............. f: ;-ς Μ (please read the notes on the back before filling this page) Order printed by the Ministry of Economic Affairs t Central Standard Bureau employee consumer cooperatives Α7 Β7, u printed by the Central Standard Bureau employee consumer cooperatives of the Ministry of Economic Affairs ()-2.98 g (10 mmol) (7-bromo-2,3-dimethoxy-sialoline-5 · ylmethyl) -amine is heated and dissolved in 40 ml of ethanol. After cooling to room temperature 1 ml of formaldehyde aqueous solution (37% in water) was added dropwise to the light yellow solution. After the addition was completed, the product settled out as a colorless precipitate. After stirring for 3 hours, the precipitate was filtered out and β was dried under high airspace To give the title compound as a colorless amorphous mass. W- NMR (300 MHz »CDC13) δ 7.83 (doublet, 2.31¾ 3Η), 7.72 (doublet, 2.3Hz» 3H), 4.24 (single peak, 6H), 4_13 (single peak, 9H), 4.04 (Single peak, 9H), 3.69 (broad single peak, 6H). MS (FAB): 930, 932. 丨 ㈤ 「b) Ν- (7- Mo-2,3-Dimethanyl-Nitride Team-5 -At 0 ° C and nitrogen pressure, 0.23 ml (2.5 mmoles) of dimethyl phosphite, 0383 ml (2.75 mmoles) of triethylamine and 0.476 ml (3.75 mmoles) Trimethylsilyl chloride was dissolved in 25 ml of dichloromethane. After stirring at 0 ° C for 15 minutes, 0.78 g (0.83 mmol) of tri-N &lt; 7-bromo-2,3-dimethoxy was added dropwise. -嗟 喏 琳 _ 5-ylmethyl) triple well dissolved in 25 ml of dichloromethane. After stirring at room temperature for 30 hours, the suspension was poured into ice-cold hydrochloric acid (0JN in water), and 3 parts were added. Diethyl ether. The organic phase was extracted by shaking with a 0.1 N aqueous hydrochloric acid solution. The collected organic phase was adjusted to a pH of 12 to U with K2C03 and extracted 6 times with chloroform. The organic phase was dried and concentrated through magnesium sulfate to obtain a yellow oil. , Which is attached to a silica gel column, using ethyl acetate / two Chloromethane / ethanol 10: 10: 1 was used as the eluent for purification. After concentration and drying under high vacuum, the title compound was obtained as a glassy, light yellow oil. W-NMR (300 MHz ^ CDCl3) 7.88 (doublet, 2.3Hz, 1H), 7.54 (doublet, 2.3Hz, 1H), 4.25 (single peak, 2HX 4.15 (single peak, 狃), 4.14 (single peak) (Peak, 昍), 3.78 (doublet, 10Hz, 6H), 2.95 (doublet, 13.1Hz, 2H), MS (ES +) 422,420 (ΜΗ &quot;). This paper standard applies to China's national standard &lt; CNS} Λ4 specification (2) 0X297 male t) ----------- ./-&lt; Please read the precautions on the back before filling in this page) Order -98- ^ 43 ^ 43 Ministry of Economic Affairs Printed by the Central Bureau of Quasi-Bureau Shellfish Consumer Cooperatives A7 B7 V. Description of the invention () Example 46: 1- (7-nitro-2.3-dioxo-1,2,3,4-tetrahydro A methyl V3-f4-shenylphenylurea title compound was prepared using a method similar to that described in the Examples, but with the name 2,3-Dimethoxy-7-quinolinol-5-ylmethyl) -3. -(4-methoxybenzene) -urea substituted N-〇2,3-monomethoxy-7-nitro-pyridin-5-ylformyl> 2-methyl Ⅲ acetamide as the starting material; faB- MS: Nf = 385; TLC: ethyl acetate / methanol (3: 1) Rp 0.5. The starting materials can, for example, be prepared as follows: a) N- (2,3-Dimethoxy-7-nitro-quino-5-ylmethyl V3- (4-methylargon platinum-fluorene at room temperature ' Add 62 mg (0.416 mmol) of 4-methoxyphenyl isocyanate to 100 mg (0.379 mmol) of 5-aminomethyl-2,3-dimethoxy-7-nitro-quinoxaline in 2 In ml of a suspension of tert-butyl methyl ether, and the mixture was stirred for 3 hours. The suspension was then filtered, and the filter residue was washed with tert-butyl methyl ether and dried under a high vacuum to obtain the title compound as a beige solid. W-NMR (CDC13, 200 MHz): 8.47, 8.26 (2 doublet, 2H), 7.70 (single peak, NH), 7.22 (doublet, 2H), 6.74 (doublet, 2H), 6.15 (Multiple peak, NH), 4.89 (doublet, CH2), 4.11, 4.09 (2 singlet, 2Me), 3,70 (single peak, Me). Example 47: The following compounds are also used similarly to the examples Prepared by the method described in 46: 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -3- (2-methoxybenzene) -Gland, FAB · MS: 1 ^ = 385; TLC: ethyl acetate / methanol (3: 1) R &lt; = 0.5; l- (7 ~ S | -2,3-dioxo-1,2, 3,4-tetrahydroquinoline_5-ylmethyl) -3- (2-ethyl Carbonyl ethyl) π; 1- (7fan 2,3-dioxo-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -3- (2sodium ethyl) · urea 'FAB- MS: NT = 351; TLC: Ethyl acetate / methanol (1: 3) price; This paper size applies Chinese National Standard (CNS) Λ4 specification (2 丨 0X297 mm) -99-

------------ Λ] /-(Please read the precautions on the back before ordering on this page

A7 B7 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention () 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline I-based methyl)- 3-phenyl-urea, FAB-MS :. M- = 355; TLC: ethyl acetate / methanol (3: 1) Rf = 0.70; 1- (7-nitro-2,3-dioxo-1,2, 3,4-tetrahydroquinoline-5 side formazan) &gt; 3_ (4-trifluoromethoxybenzene) -urea, FAB-MS: 1 ^ = 439; TLC: ethyl acetate / methanol (3: 1) RHJ.50. Example 48: The title compound of N- (7-nitro, 2.3-dioxo-U.3,4-tetramethylpyridin-5-ylmethylVpentylamine was used in a manner similar to that described in Example 39, However, N- (2,3-dimethoxy-7-quinolin-5_ylmethyl) -pentamidine is substituted for N- (2,3-dimethoxy-7-nitro-quinolinolyl) ) -2-methazine as starting material; FAB ^ MS: M &quot; = 320; NMR (DMSO-D «,: 200 MHz): 1223, 11.82 (2 singlet, 2NΗ), 8.73 (triple peak, ΝΗ), 7.94, 7.89 (2 doublet, 2H), 4.46 (doublet, CH2), 2.20 (triple, CH2), 1.53 (five-fold, CH2), 1.28 (sixfold, CH2), 0.87 (triple bee, CH3). TLC: ethyl acetate / methanol (+ 2% acetic acid) Rf = 0.80. The starting materials can be, for example, prepared as follows: α) N ^ Z1methoxy-7-quinolin- 5-yl mevalonylamine Add 79 μl (0,567 mmol) triethylamine and 55 μl (0.454 mmol) n-pentyl chloride to 1000 mg (0.378 mmol) of 5-amine Methyl-2,3-dimethoxy-7so-quinoline was dissolved in 2 ml of a suspension of third butyl methyl ether, and the mixture was stirred at room temperature for 16 hours. The mixture was then dissolved in dichloromethane, washed with 1N hydrochloric acid and 1N sodium hydroxide solution, dried over magnesium sulfate and concentrated by evaporation to give the title compound as a yellowish powder. Xuan Mil: The following compounds were also prepared using methods similar to those described in Example 48: 1 ^ 7-nitro-2,3-dioxo1,2,3,4-tetrahydroquinoline-5-ylformate ) -Montamethamine, at the place. 3: M ^ 390; tlc: ethyl acetate / methanol (1: 1 + 2% acetic acid) Rp 0.80; (谙 first read the precautions on the back and then ί this page )-Binding · Binding_ Line 1 This paper size is applicable to China National Standards (CNS) A4 specifications (210 × 297 gigabytes) -100- Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 V. Description of the invention () N- ( 7-Nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) _3,3-dimethyl-butanidine, FAB-MS: M ^ 334; TLC : Ethyl acetate / methanol (1: 1 + 2% acetic acid) RH), 67; N- (7 ~ nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5- Methylmethylacetamidine) -benzylamine; N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5_ylmethyl)-(2-hydroxy) · Benzamidine, ESC1 + -MS: (M + H) + = 357; TLC: ethyl acetate / methanol (1: 1 + 2% acetic acid) R ^ O.33. Oxy-U.3.4 · Tetra argon-5-ylmethyl) -2-methoxy-acetamidine The title compound was prepared using a method similar to that described in Example 39, but with N- (2,3C formazan) Oxygen_7 mouth Mingling Lin_5 cymene in methoxy · acetamidine to replace N_ (2,3 · dimethoxy-7-nitro-quinolinolyl formamide> 2-methylazine as the starting material; FAB-MS: Μ &quot; = 308; TLC: ethyl acetate / methanol (i: i + 2% acetic acid) only cold ribs "» The starting materials can be, for example, prepared as follows: a) Oxygen-7 is painful- 5. The title compound of methylamino V2-methanamine was prepared by a method similar to that described in Example 29a), but with 5-aminomethyl-2,3-dimethoxy-7-nitro-quinoxaline and 2 -Methoxyacetic acid replaced 5-aminomethyl-2,3-dimethoxy-7-nitro-quinoline and furan-2-carboxylic acid as starting materials. Example 5L: The following compounds were also prepared using a method similar to that described in Example 50: Dioxin, hydrazone, 2,3,4, tetrahydroquinoline-5-ylmethyl) _N ,, N · -di Methylglycine, APCiMVIS: (M + H) + = 321; TLC: methanol / acetic acid (9: 1) RHU9; Ν- (7 · ^ 2,3-dioxo-1,2,3,4- Tetrahydroquinoline-5-ylformate> 3,4,5-trimethoxy-benzidineamine, ESCr-MS: (M + H) + = 429; TLC: ethyl acetate / methanol (1: 1 + 2% acetic acid) Rf = 0.30; This paper size is applicable to China National Standard (CNS) A4 size (210X297 mm) (Please read the precautions on the back before t this page) Order -101-Staff of Central Bureau of Standards, Ministry of Economic Affairs Consumption cooperatives printed 4th order 82 A7 _B7_ V. Description of the invention () Called 7-nitro-2,3-dioxo_U, 3,4-tetrahydroquinoline-5-ylmethyl) -3,5 -Dimethoxy-4-hydroxy-benzylamine, FAB-MS: NT = 416; TLC: ethyl acetate / methanol (1: 1 + 2% acetic acid) Rf = 0.90; N ~ (7-nitro-2, 3-dioxo-1,2,3,4 ~ tetrahydroquinoxaline-5-ylmethyl) -N · -acetamidine-glycinamine,? Can-1 ^: 1 ^ = 335; 11 ^ acetic acid Ethyl ester / methanol (1: 1 + 2% acetic acid) 11 cadmium 0_80; Ν- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N · -amine formamidine-glycine 'Amineamine, FAB-MS: ΝΤ = 336; TLC: ethyl acetate / methanol 0: 1 + 2% acetic acid) Rf = 0.60; 4- [ΝΚ7 · NO-2,3-dioxo-1, 2, 3 + tetrahydroquinoline-5-ylmethyl) sulfamonium] -benzylamidine 'ESC1 + -MS: (M + H) + = 420; TLC: methanol / acetic acid (9: 1) Rp0.88; 2 -Amine-3-methyl-1 ^-(7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -butanamine, ESCl'MS: (M + H) + = 336; TLC: methanol / acetic acid (9: 1) RH &gt;.68; 2-amine-3-hydroxy-N · (7-nitro-2,3-dioxo-1,2, 3,4-tetrahydroquinoline-5-ylmethyl) -butyramine, ESC1 + -MS: (M + H) + = 338; TLC: methanol / acetic acid (9: 1) R ^ O.48; 2 -Amine-4-carboxy-N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -butanamine 'FAB-MS: M ^ 365; TLC: methanol / acetic acid (9: 1) Rf = 0.39; hydrobromide 1-7 7 2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N -Acetylamine-tryptamine, FAB-MS: JVf = 464; TLC: methanol / acetic acid (9: 1) R (= 0.25; 2-amine-N- (7-nitro-2,3-dioxol- 1,2,3,4 ~ tetrahydroquinoline-5-ylmethyl) -L-seramine ES'ESC1 + -MS: (M + H) + = 324; TLC: methanol / acetic acid (9: 1) RHU0; 2-amine-N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5_ylmethyl) -D-serine 2-L-amine-3-amine formamidine-N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -propanilamine, FAB-MS: ΐνΓ = 351; TLC: ethyl acetate / methanol (1: 1 + 2% acetic acid) R 0.90; J. (please read the note on the back before reading this page) • Pack. Order- Line-This paper size applies to Chinese National Standard (CNS) A4 specification (2 丨 0 × 297 mm) -102- Ting 438782 Printed by A7 B7, Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs 5. Description of invention () 2-D-amine -3-amine formamidine-N- (7-nitro · 2,3-dioxo-1,2,3,4 ~ tetrahydroquinoline-5-ylmethyl) -propanil. Amine; LN-〇 nitrate -2,3-dioxo-1,2,3,4-tetrahydroquinoxaline. 5-ylmethyl) -histamine amide; DN- (7fan 2,3-dioxo-1,2,3, 4-tetrahydrofluorin-5-ylmethyl) -histamine sulfonamide "Example 52: N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydro dark hydrazone_ _5Jinjia) -Peppervin title compound was prepared by a method similar to that described in Example 39, but with N- (2,3-dimethoxy-7 Amidine substituted N_ (2,3 · Dimethoxy-7-nitro-quinoline-5-ylmethyl) -2-methylacetaline as starting material; FAB-MS: 1VT = 336; TLC: acetic acid Ethyl acetate / methanol (1: 1 + 2% acetic acid ) RpO.48. The starting materials can, for example, be prepared as follows: a) N- (2,3-Dimethoxy-7-nitro-quinazone-5-yl form V Permamine will be 55 microliters (0_397 mmol) Triethylamine and 40 mg (0.397 mmoles) of succinic anhydride were added to 100 mg (0.378 mmoles) of 5-aminomethyl-2,3-dimethoxy-7-quinolinine in 2 ml In a suspension of third butyl methyl ether, the mixture was stirred at room temperature for 3 hours. The mixture was then filtered, and the residue was washed twice with third butyl methyl ether. The residue was filtered on silica gel with dichloromethane Methane / methanol / acetic acid (95: 4.5: 0.5) chromatography gave the title compound as a beige powder. Example 53: The following compounds were also prepared using a method similar to that described in Example 52: -2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) microfluorene; N- (7-nitro-2,3-dioxo-1,2,3 , 4-tetrahydroquinoline, each methyl) -pentanediamine 'FAB-MS: ΐνΤ = 350; TLC: ethyl acetate / methanol (1: 1 + 2% acetic acid); Ν- (7-nitro- 2,3-dioxo-U, 3,4-tetrahydroquinoline-5-ylmethyl) -N-methyl-permamine 'FAB-MS: M &quot; = 350; TLC: dichloromethane / methanol / Acetic acid (8 0: 18: 2) Rf = 0.46. F Please read the precautions on the back before # '% this page} • Install--Order · This paper size applies to China National Standard (CNS) A4 (210X297 mm) -103-f-sentence A7 B7 V. Description of the invention (Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, N- (7-nitro-2,3-digas-U, 3,4 ~ tetrahydroline) _5_ 某 _ The title compound was prepared using a method similar to that described in the Example, but with N · (2'3_dimethylmethoxy-7rhyme_quinoxaline-5-yl A &gt; N · (2-diethylamineethyl), amine-substituted N_ (2,3_dimethoxy-7-nitro-sialylinyl a) &gt; 2-methylazine as starting material; FAB_ MS : M &quot; = 335; tLC: methanol / water (5: 1) Rf = (U6. The starting materials can be, for example, prepared as follows: methoxy_7 魂 _ 晔 喏 雕 _5_ 基 甲 VN_ (2_ 二Ethylamine B) _amine The title compound was prepared in a manner similar to that described in Example 39a), i.e., 5-bromomethyl <2,3_dimethoxy_7_nitro_quinoxaline and Preparation of amine as starting material &lt; The title compound was obtained as a colorless oil. Example il: The following compounds were also prepared by a method similar to that described in Example 54. Preparation: 'Hydrogenated bromide &gt; H7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl &gt;N-methyl-amine; hydrobrominated ( 7-nitro-2,3-dioxo-1,2,3,4-tetrahydrofluorin-5-ylformyl) (1,1-dioxo-2,3,4,5-tetrahydro- Thiophene · 3-yl) -amine, FAB ^ MS: ΐνΤ = 354; TLC: methanol / acetic acid (9: 1) Rf = 0.69; hydrobromide N- (7-nitro · 2,3-dioxo-1, 2,3,4-tetrahydroquinoxaline-5-ylmethyl VN-methyl-N- (2-gen ethyl) -amine; N- (7 · nitro-2,3-dioxo-1,2) hydrobromide , 3,4-tetrahydroquinoline-5-ylmethyl) -N- (3,4-methylenedioxolium) · amine, APC1 + -MS: (M + H) + = 371; TLC: methanol Acetic acid (9: 1) R produces 0.70; N- (7-nitro-2,3-dioxo-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -N-methyl hydrobromide -N-methoxy-amine, ESC1 + -MS: (M + H) + = 281; TLC: methanol / acetic acid (9: 1) Rt = 〇.86; please read the note first

I The size of the bound paper is in accordance with the Chinese National Standard (CNS) A4 (210X297 mm) -104- Central Standards Bureau of the Ministry of Economic Affairs W: Industrial and consumer cooperatives Inju Weng 4 cut 0.. A7 _87_ V. Description of the invention () Hydrogen N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N-isopropyl-amine 'APC1 + -MS: (M + H) + = 279; TLC: methanol / acetic acid (9: 1) R yields 0.53; hydrobromide N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline -5-Methylformate) -N · -Ethylene-Ethylene Diamine, FAB-MS: M &quot; = 321; TLC: Methanol / acetic acid (9: 1) Rf = 〇 * 40; Cis-2 hydrobromide -(7pain-2,3-dioxo-1 »2,3,4-tetrahydroquinoline_5 · methylmethyl) amine] -cyclohex-1-carboxamide, FAB-MS: M &quot; = 359; TLC: methanol / acetic acid (9: 1) Rf = 0.50; hydrobromide N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-yl (A) -N-methyl-taurine, FAB-MS: M &quot; = 357; TLC: methanol / acetic acid (9: 1) Rf = 0.69; cis-3-hydrobromide [N- (7-nitro -2,3-dioxo-i, 2,3,4-tetrahydroquinolinline-5 ~ S methyl) amine] -cyclohex-1-carboxylic acid, FAB-MS: M &quot; = 362; TLC: methanol / Acetic acid (9: 1) Rp.70; 3- [N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinol-5-yl (A) Amine] -3-benzene-propionic acid, ESC1 + -MS: (M + H) + = 385; TLC: methanol / acetic acid (9: 1) RHU4; cis-2-hydrobromide [N- (7 番2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 cypromethamine) -cyclopentane · residual acid; N · &lt;7-yun-2,3-dioxo-1; 2,3,4 · Tetrahydroquinoline-5-ylmethyl) -II-pyrrole-2-one, FAB-MS: Xin 304; TLC; ethyl acetate / methanol (2: 1 + 2% acetic acid) RpO.60; Ν · (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -pyrrolidine ice (4-chlorobenzene) -2- Ketone, FAB-MS: M &quot; = 414; ILC: Methanol / acetic acid (1〇: 1) Ri = 〇.78; N- (7 ~ g | -2,3-dioxo-1,2,3,4 -Tetrahydroquinoline-5-ylsulfonyloxy-2-methyl-propan-2-yl) -amine, FAB-MS: 1 ^ = 350; TLC: methanol / acetic acid (9: 1) RHJ.86 ; Hydrobromide N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N-cyclohexyl-N-methyl-amine, FAB -MS: ΐνΤ = 332; TLC: methanol / acetic acid (9: 1) Rr.70; hydrochloride N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquine Periline-5-ylmethyl) -N- (1,1-dimethyl-2-hydroxy-ethyl) -amine, ESC1 + -MS: (M + H) + = 309; TLC: methanol / acetic acid (9: 1 ) R produces 0.62. This paper size applies Chinese National Standard (CNS) A4 specification (2 丨 0X297 mm) (please read the precautions on the back before ^; # this page) Packing, Ding-105- A7 B7 V. Description of the invention () Example 56: Cis-2-HSM7-nitro-Z3-digas-1,2,3,4-tetrahydroquinoxaline-5-yl-methyl) amine 1-cyclohexanecarboxylic acid Prepared using a method similar to that described in Example 39, but with cis-2- [N- (2,3-dimethoxylnitr-quinoline-5-ylmethyl) amine] -cyclohex-1-carboxyl Acid substituted N · (2,3-dimethoxy-7-nitro-quinoline-5-ylmethyl) -2-methylazine as starting material; melting point = 249-251 ° C; ESC1 MS: (MH ) + = 361; TLC: methanol / acetic acid (9: 1) RHU-0.45. The starting materials can, for example, be prepared as follows: a) 2,3-Dimethoxy-quinaline-5-carbaldehyde 17 ml (188 mmol) 2-nitropropane is added to 3.7 g (163 mmol) Sodium is dissolved in 700 ml of methanol. After stirring for 5 minutes, 35.5 g (125.4 mmol) of solid 2,3-dimethoxymethane-quinoxaline was added. The mixture was heated at reflux for 1 hour to form a homogeneous solution. After cooling, the solution was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and 1NHC1, the phases were separated, and the organic phase was washed with water and brine, dried over magnesium sulfate and concentrated. The title compound was crystallized from ethyl acetate to white crystals. Melting point: 137-140 ° C; TLC (EtOAc / hexane 1: 3): RiN) .45. b) 2,3 · Dimethan-7-fit- 暗 喏 呵 -5-_ Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economics ---------- ¥-η (Please read first Note on the back page again (# page)) 44 ml of 100% nitric acid, 44 ml of 97% sulfuric acid and 44 ml of trifluoroacetic anhydride are continuously added to 22 g (10. 8 mmol) cooled to 0X 2 , 3-Dimethoxy-5-bromomethyl-quinoxaline was dissolved in 88 ml of trifluoroacetic acid. The mixture was kept at 0 ° C for 2 hours and then carefully poured into a mixture of 4NNaOH and ice. The temperature must not exceed 20eC. The mixture was extracted with ethyl acetate. The organic phase was washed with a 1 N aqueous NaOH solution, water and brine, and dried over magnesium sulfate. The paper size of the crude product is applicable to the Chinese National Standard (CNS) A4 specification (2) 0X297 gong) -106- ./¾. A7 B7 V. Description of the invention () 丨 Supplement ') 1 d. + _____________ The title compound is a pale yellow crystal. Melting point: 147-149 ° C; TLC (EtOAc / hexane 1: 3): Rf = 0.25. c) cis-2-fN-g3-dimethyl ¥ -7-nitro-quinazol-5-ylmethyl) amine 1-cyclohexyl · carboxylic acid 105 mg (0.588 mmol) cis_2_ Amine-cyclohexylcarboxylic acid and 82 μl (0.588 mmol) of triethylamine were continuously added to 129 mg (0.490 mmol) of 2,3-dimethoxy-7-nitro-sialylin-5. 1 ml of dichloromethane and 2 ml of ethanol. After stirring at room temperature for 3 hours, 1 g of anhydrous sodium sulfate was added to the suspension, and the mixture was stirred at room temperature for another 20 hours. The concentrated suspension was diluted with 0.5 ml of ethanol and 46 mg (.1.23 mmol) of sodium borohydride was added. After stirring for 3 hours, 0.5 ml of acetone was added, and after 10 minutes, 0.3 ml of acetic acid was added and filtered. The filter residue was washed with ethanol and dichloromethane. The filtrate was chromatographed on silica gel with dichloromethane / ethyl acetate (97: 3) * and then with dichloromethane / methanol / glacial acetic acid (90: 9: 1) to give the title compound as a white powder. Example 57: The following compounds were also prepared using a method similar to that described in Example 56: N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrobromide -5-ylmethyl) amine moiety phosphonic acid 'ES-MS: [Μ-Η] · = 329; ^ -NMR (DMSO-de + DC1): 8.30 (doublet, J = 2 for 1H), 8.17 ( Doublet 'J = 2 for 1H), 4.52 (single peak, 2H), 3_30 (Doublet, J = 15 for 2H); HPLC: CH3CN / H20 + 0.1% CF3C00H, 0 to 3, 5 minutes, 5 : 95 isocratic, 3.5 to 7.5 minutes, gradient change to 100: 0, Rt = 3.7 minutes (MN Nucleosil 100, C18, 5 is called 250 X 4 mm, 1 ml / min); hydrochloride 1 ^-(7-nitrate -2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl &gt; amine ~ (3-methoxybenzene &gt; methylphosphonic acid, FAB-MS: M + = 436; HPLC: bHaCN / KW) 40.1% trifluoroacetic acid 20:80 Rt = 4.2 minutes. (NucieosiHOO. C18, 5 μΜ, 250 X 4.6 mm, 1 ml / minute); This paper scale applies Chinese National Standard (CNS) A4 regulations "Grid (210X297)" (Please read the precautions on the back before filling in this page)

Q Order Printed by the Central Laboratories of the Ministry of Economic Affairs, Printed by Consumer Cooperatives -107- Printed by the Central Laboratories of the Ministry of Economic Affairs, Printed by Consumers Cooperatives of A7 B7 V. Description of Invention () 1 ----------- Hydrobromine [C7-Nitro-2,3-dioxo-1,2Λ4 · Tetrahydroquinoline-5dimethylamine K3-hydroxy-benzene &gt; methyl] -phosphonic acid, FAB-MS: M + = 422; HPLC: CH3CN / H2〇 + 0.1% trifluoroacetic acid for 20 minutes R = 2,9 minutes. (NucleosiLiOO. C18, 5 μΗ 250 X 4.6 mm, 1 ml / min); Hydrochloride N- (7-nitro-2,3 -Dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -N-[(4 · diethoxy-phosphorane &gt; benzyl] • amine, ESCT-MS: (MH) + = 421; DC: methylene chloride / methanol / acetic acid (9: 1) Rf = 0.28; hydrobromide N- (7-nitro-2,3. Dioxo-1,2,3,4 · tetrahydroquine Fluoroline-5-ylmethyl) -3-amine-propanephosphonic acid 'FAB-MS: [M + H] + = 345; HPLC: CH3CN / H20 + 0.1% trifluoroacetic acid 20:80, RT = 3.1 Minutes (NucleosiL100. C18, 5 μM, 250 X 4.6mm, 1 ml / min); Ammonia bromide N- (7-nitro · 2,3-dioxo-1,2,3,4 * tetrahydroquinophylline _5_ylmethyl &gt; 2-amine-2-benzene-acetic acid, ES-MS: [M + H] + = 385; ^ -NMRCDMSO-A + DC1); 8 · 20 (doublet, J = 3¾ 1Η), 8.05 (doublet, J = 3¾ 1Η), 7.7-7 .4 (Multiple Bee '5Η), 4.85 (Multiple Peak, 1H), 4.51, 4.15 (AB, J = 14Hz, 2H), 3.46, 3.03 (AB.d, J = 15Hz, J = 10Hz, 2H); HPLC : CH3CN / H20 + 0.1% CF3COOH, 0 to 6 minutes, gradient: 0_0, RT = 1.2 minutes., Waters Symmetry C18, 3.5 μιη »100 people 50 χ 2.1 mm, 0_5 ml / min; [N &lt; 7-Nitro-2,3 · dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) amine] -cyclopropane · 1 · phosphonic acid, melting point &gt; 340 ° C FAB-MS: [Μ-Η] · = 355; HPLC: CH3CN / H20 + 0.1% CF3COOH, 0 to 6 minutes, gradient: 0 to 100, RT = 4.0 minutes, Waters Symmetry C18, 3.5 called 100 Α »50 x 2.1 series 0.5 ml / min; 4- [N- (7 soul-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) amine] -butyric acid, FAB -MS: M + = 322; DC: methanol / acetic acid (9: 1) RHX30. Example 58: Tritiated N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinazolin-5-yl_methylamine methyl V tetrazole 160 mg (0.461 Millimolar) N- (2,3-Dimethoxy-7-nitrate-rhodolin-5-ylmethylamine methyl) -tetrazole was stirred under reflux in 6 ml of 2NHC1 aqueous solution for 20 hours. The reaction mixture was cooled , And the formed solid was filtered off, washed with ether. Melting point = 230 t (decomposed). The starting materials can be prepared, for example, as follows: This paper is scaled to the Chinese National Standards-(CNS) Λ4 grid (21〇 Χ2ί &gt; 7 gong) (Please read the precautions on the back before filling in this page) I ir ^ '^, order -108- depreciate 438 Printed by the Central Standards Bureau of the Ministry of Economic Affairs Consumer Cooperatives A7 B7 V. Description of the invention () a) N- (2,3-Dimethyl-7-nitro-quinoline-5-ylmethyl) -amine ethyl residue 300 mg (0-914 millimolar) 5-bromomethyl-2,3- Dimethoxy-7-nitrazine-line, 338 mg (4 equivalents) of amine hydrochloride acetonitrile and 0.66 ml (4 equivalents) of huninine (diisopropylethylamine) were refluxed in 10 ml of acetonitrile. Stir for 20 hours. The reaction mixture was evaporated and concentrated, and the residue was extracted with ethyl acetate and about 5% sodium carbonate solution. The collected organic phases were washed once with brine, dried over magnesium sulfate and concentrated by evaporation. The resulting brown oil was chromatographed on silica gel (ethyl acetate / petroleum ether 12, then 1: 1) to give the title compound as a slightly yellow solid "b) N · α3-Dimethyl-7-quinolinol -5 cytaramine A) -tetrazole 140 mg (0.461 mmol) N- (2,3 · Dimethoxy-7-glucosino-2--5-methyla) · Amine, 50 mg ( 0.43 eq.) Stannous oxide and 0.244 ml (4 eq.) Of trimethylsilyl azide were stirred under reflux in 6 ml of toluene for 16 hours. The reaction mixture was cooled and the title compound was filtered off as a brown solid. Example 59: Hydrogen bromide N-f7-nitro-2,3-dioxo-1,2,3,4-tetrahydropyridylmethyl) -2-amine-ethylphosphonic acid 380 mg (0,949 milligrams) Moore) N- (2,3-Dimethoxy-7-quinolinline_5 · methylformate) __ 2-Amine · Ethylphosphonic acid dimethyl ester and 1.23 ml (10 equivalents) bromide trimethylsilyl bromide The solution was dissolved in 20 ml of dichloromethane, and the solution was stirred at room temperature for 90 minutes. The reaction mixture was concentrated by evaporation, and the residue was dissolved in 6 ml of about 33% hydrogen bromide at 40 ° C. The reaction mixture was stirred in acetic acid solution for hr. The reaction mixture was diluted with ether, and the solid was filtered off, washed thoroughly with ether and dried to give the title compound as a yellowish solid. Melting point = 235 ° C (decomposition). Starting material However, for example, the preparation is as follows: am- (2.3-Dimethoxy-74 Kentongsui-5-ylmethyl) -2-amine ethylphosphonic acid dimethyl This paper is in accordance with China National Standard (CNS) A4 specifications ( 210X297 mm) (please read the note on the back and then on this page) Order · = ·, 1 hi: 8 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () Under 〇eC, 0.19 ml (U equivalent) three Amine '0.215 ml (1.5 equivalents) of trimethylchlorosilane and 0.104 ml of dimethyl phosphite were dissolved in dichloromethane' and the solution was stirred for 20 minutes. 329 mg (1.135 mmol) of 2,3-dimethoxy- A solution of 5-ethylene-aminomethyl-7-nitro-quinoxaline in methylene chloride was added to the reaction mixture, and stirred at 0 ° C for 5 hours, and then at room temperature for 12 hours. The solution was diluted with water And extracted three times with dichloromethane. The organic phase was collected, dried over magnesium sulfate and concentrated by evaporation to give the title compound as a yellow solid. B) 2,3-Dimethyl-5-ethyleneamine-7-quinol-quine At a room temperature, 300 mg (1.135 mmol) of 2,3-dimethoxy-5-aminemethyl-7-nitro-quinoxaline, 500 mg (3.7 equivalents) of magnesium sulfate and 200 mg (1.28 (Equivalent) potassium carbonate was suspended in 20 ml of dichloromethane. After 15 minutes, 0.13 ml of acetaldehyde was added, and the reaction mixture was stirred at room temperature for 7 hours, then filtered and concentrated by evaporation. Example 60 · 2- (Z3-dioxo-7per-1,2,3.4-tetrahydroquinone pepper-5-yl methyl chloride) · Acetic acid 27 mg (0.711 mmol) 2- (2 , 3-Dimethoxy-7-nitro-quinazolin-5-yl-methoxy) · Third-butyl acetate dissolved in 6 ml of a solution of about 16% hydrogen bromide in acetic acid, and at room temperature Then, the solution was stirred for 20 hours. The reaction mixture was diluted with diethyl ether, and the solid was filtered off, washed with diethyl ether and dried to give the title compound as a solid (melting point> 300 ° C). The starting materials can be prepared, for example, as follows: a) 2- (2,3-Dimethoxy-7b-quinoxaline ^ 5-shen argon V tert-butyl acetate will be 300 mg (U3 mmol) ) 2,3-Dimethyloxy-5 Lime-7Soul-quinoxaline was added to 8 ml of tetrahydrofuran, and cooled to 0. 0. Add milligrams (1.05 equivalents) of about 55% NaH oil, and at 0 ° Under C, stir the mixed liquid for 30 minutes. Add 0.2

The paper size of the edition applies to the Chinese National Standard (CNS) Λ4 specification (2 丨 〇 &gt; &lt; 297) and -110- ^ 43 8 ^ 8 $ Α7 Β7 V. Description of the invention () ml (1.5 equivalents) bromo-acetic acid Third butyl ester, the ice bath was removed after 20 minutes. The reaction mixture was stirred at room temperature for 20 hours, diluted with water and extracted with ethyl acetate. The collected organic phases were washed once with brine, dried over magnesium sulfate and concentrated by evaporation. The residue was chromatographed (SiO2, ethyl acetate / petroleum ether 1: 3) to give the title compound (20 g) as a solid. b) 2.3-Dimethoxy-5 Zun-7-7-quinazine The title compound was prepared using a method similar to that described in Example 14a), but with 5-bromomethyl-2,3-dimethoxy-7 Glucoxorphyrin is the starting material. Example 61: 2- (7 ^^ 2,3-dioxo1,2,3,4-tetrahydroquinol-5-ylmethoxy V propanoic acid The title compound is similar to that described in Example 60 It was prepared by the method, but the starting material was tert-butyl 2-propionate; melting point = 268 ° C (decomposition). Example 62: Brominated N · (7-nitro-2,3-dioxy · 1 , 2,3,4 · Tetrahydroquinone viscera-5-ylmethyl M-amine-sodium ingots' Printed by Zhengong Consumer Cooperative, Central Ladder Bureau of the Ministry of Economic Affairs Page) At room temperature, 212 mg (0.5 millimolar) of 'amine-1- (2,3-dimethoxy-7-nitro-quinoxaline-5-ylmethylpyridine) in 3 ml of 48% hydrogen bromide was dissolved in a solution of glacial acetic acid and stirred for 18 hours. The slightly brown reaction mixture was diluted with 7 ml of ether and then stirred for 10 minutes. The formed solid was washed out with a small amount of ether and dried to obtain The title compound is a yellow solid with a melting point &gt; 245 ° C (decomposition). The starting materials can be prepared, for example, as follows: a) Bromine 4 · amine-fluorene 2,3 · dimethoxy-7per-quinoxaline- Dissolve 197 mg (0.6 mmol) of 5-bromomethyl-2,3-dimethoxy-7-nitro-quinoxaline at room temperature A solution of 2 ml of dichloromethane was added to 282 mg (3 mmol) of 4-aminopyridine in a suspension of 1 ml of dichloromethane and 3 ml of acetic acid. ) A4 specification (210X297 Gong &gt; -111-printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs A7 __ £ __B7_ V. Description of the invention () The mixture was stirred at temperature for 3.5 hours. The formed precipitate was filtered out Then, it was washed with a small amount of acetonitrile on a filter cloth to obtain the title compound as a colorless powder. Example 63: Brominated N- (7-nitro-2,3-synthesis; -1, 2, 3, 4-tetrahydroquinol-5-ylmethyl) _3_amine · This title compound was prepared using a method similar to that described in Example 62, but using 3-aminopyridine as the starting material; melting point &gt; 248 ° C (decomposition). Example 64: Dibromo bromide-1,2,3,4 · tetrakis-quinolinylmethyl V2-amine-this sharply titled compound was prepared by a method similar to that described in Example 62. Prepared, but using 2-aminopyridine as the starting material; melting point> 350 eC (decomposition). Example 65: 3- (7-chloro-2,3-dioxo-quinolin-lin-5τyl m-1 -Alcohol title compound A method similar to that described in Example 15 was prepared by heating 3- (7-chloro-2,3-dimethoxy-quinazolin-5-yl) · propanol with acetic acid / 2N hydrochloric acid. The starting materials can, for example, be prepared as follows: Chloroquineline 406.9 grams (1.953 moles) of phosphorus pentachloride is added to 195.9 grams (0.93 moles). In a mixture of phosphorus oxychloride, the mixture was refluxed and stirred for 18 hours. At a bath temperature of 15 ° C., excess phosphorus oxychloride was distilled off from the reaction mixture. The residue was poured into 6000 ml of ice water, and the resulting suspension was stirred for 2 hours, filtered with suction filtration, and then Rinse with a large amount of water. At 6 ° C, dry the filter residue dry to obtain 20589 g (894%) of 5_moth-2,3,7 · trigas * phospholine, which is a coarse brown crystal. Further reaction without further purification. This paper size Lai towel 11_County (⑽) Congmi (2 gaps 297 times) (Please read the precautions on the back before you ^^-this page) Order 銶 · -112- Printed by the Employees 'Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs ^ ·-·-·, ^' dp A7 _ 二 _B7 V. Description of the invention () b) 7-Chloro-2,3-dimethoxy-5-iodine- Quinoline at room temperature, add 205 g (0.828 mole) of 5-iodo-2,3,7-trigas r molyxoline to 2255 ml of methanol, and add 46S.9 ml of about 5.4M sodium methoxide Solution dissolved in methanol. Then the reaction mixture was heated under reflux and stirred for 18 hours. «The reaction mixture was cooled to 0 ° C, and the suspension was filtered by suction filtration. Then the filter residue was rinsed with methanol and at 60 ° C. Empty and dry The product was purified by continuous extraction with diethyl ether to give% .4 g (48.8%) of 7-chloro-2,3-dimethoxy-5-iodo-quinoline, with a melting point of 94-96 ° C. 〇 3- (7-Chloro-2,3-dimethoxy-dark-five-5-yl) propan-2-qui-1-ol will be 12.9 g (36_8 mmoles) of 7 · chloro-2,3-dimethoxy 5-Bei-Sialoline, 7.6 ml (128.4 mmol) propargyl alcohol, 2.1 g (3 mmol) of bis (triphenylphosphine) dichloride-palladium, 6.6 ml (47.4 mmol) ) Triethylamine and 0.34 g (1.8 mmol) of cuprous iodide were added to 125 ml of dimethylformamide and heated at a bath temperature of 70 ° C. At this temperature, the reaction mixture was stirred for 3.5 Hours, then cooled to room temperature. Ethyl acetate was added to the reaction mixture and extracted with water, 1N hydrochloric acid and brine. The aqueous phase was washed with ethyl acetate. The organic phase was collected, dried over magnesium sulfate, and filtered with suction Filtration and concentration The crude product was chromatographed on silica gel with hexane / ethyl acetate (3 ·· 1) to give 1.1 g of 3- (7-gas r2,3-dioxo-quinoxaline-5 as brown crystals. -Yl) propan-2 · alkyn-1-ol, melting point 135-140 ° C »d) 3 · (7-ambiol 3-dimethoxy-darkin-5-yl) -propan-1-ol in Under normal pressure, 2.05 g (7.36 mmoles) of 3- (7-chloro-2,3-dioxo-quinazolin-5-yl) prop-2-yn-1-ol in 20 ml of tetrahydrofuran, Hydrogenate with about 0.4 grams of Nickel Nickel until it absorbs twice the Mohr amount of hydrogen. The hydrogenated mixture is passed through the glass fiber. The paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm). _ (Please read the precautions on the back before ## ^ this page) Order-鹧 · -113- fv Printed by A7 _.__ B7_____ of the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () Filter cloth is filtered by suction, and the filtrate is concentrated to obtain 2.04 g (98%) of 3- (7-chloro_ 2,3-dioxo-quinoxaline-5-yl) -propan-1-ol 'has a melting point of 104-105. 〇 Example 66 · 4- (7-Amo-2,3-diargon-1.2.3.4-tetrapyrazine-5-ylbutanol The title compound was prepared in a similar manner to that described in Example 65 via 4- (7 County 2,3-Dimethoxy-1,2,3,4 · tetrahydroquinoline-5-yl) butanol is prepared ', and in step C), a considerable amount of butane- 3-Alkynol replaces propargyl alcohol. Example 67: Hydrogen bromide N- 丨 3-Γ7-chloro-2,3 · dioxo-1,2,3,4-tetrahydroquinone-52.5-l-glycine The title compound was similar to In the method described in Example 1, 5- (3-bromopropyl) -7-chloro-2,3-dimethoxy-sialoline was combined with triethylamine and tertiary butyl glycine hydrochloride and ethyl Triethylamine in hydrazone is reacted and then hydrolyzed. The starting materials can be prepared, for example, as follows: a) 5- (3-Bromopropane) -7 • chloro-2,3-dimethoxy-n-pyreline under nitrogen, 0.5 g (1.77 mmol) of 3 -(7,2,3-Dimethoxy-quinazolin-5-yl) -propan-1-ol and 0.287 g (1.77 mmol) of 1, Γ-pseudoimidazole were added to 5 ml of acetonitrile. Add 0.75 ml of allyl bromide, and stir the mixture at room temperature for 30 minutes and reflux for 2 hours. "The reaction mixture is cooled to room temperature, ether is added, and water, 0.1N hydrochloric acid, a saturated solution of sodium carbonate and Brine extraction. The aqueous phase was then washed with ether. The organic phase was collected, dried over magnesium sulfate, filtered through a layer of silica gel, and concentrated to give 0.438 g (79.9%) of 5- (3-bromopropyl) as a yellow oil. 2,3-Dimethoxy-quinoxaline, which can be further used without further purification &quot; Example 68: Dioxo-1,2.3. Winter tetrahydroquinoline-5-ylmethyl) -N-methyl · Amine paper size applies to Chinese National Standards (CNS &gt; Λ4 specification (2 丨 0X297mm) Please read the precautions before back binding) Line-114- Yan A7-B7 V. Description of the invention () Title compound system Using a method similar to that described in Example 34, N- (7-nitro-2,3-dimethoxy-1,2,3,4-tetrahydroquinoline-5-ylmethylene) -N- Methylamine is prepared by treating 25% hydrogen bromide in acetic acid. The starting materials can, for example, be prepared as follows: 3) hydrazone (7-nitro-2,3-dimethoxy-1,2,3,4-tetrahydroquinolinline_5-ylmethyl)-] ^-form -Amine Boron in ethanol N- (7-nitro-2,3-dimethoxy-1,2,3,4-tetrahydroquinoline-5-ylmethylene) -N-methyl-imine The sodium hydride was reduced to the title compound. b) 7S-5--5-formamidine-2,3-dimethoxy-quinoxaline. Dissolve 1.38 g (60 mmol) of sodium in 200 ml of methanol in portions at 0 ° C and nitrogen. At 0 ° C, 5.S5 ml (65 mmol) 2-nitropropane was added dropwise. Then 18.1 g (50 mmol) of 5- (bromomethyl) 7-bromo-2,3-dimethoxy-quinoxaline was added. The beige suspension was heated under reflux and stirred for 1 hour. The reaction mixture was poured into 600 ml of water, and methanol was distilled off. The residue was extracted twice with ethyl acetate, the organic phase was dried over magnesium sulfate and filtered with suction filtration. After the filtrate was concentrated, the residue was dried under high vacuum. Obtained 7 · Ι-5-formamidine-2,3 · dimethoxy-quinoxaline in the form of gray-brown crystals, with a melting point of 179-182 ° C. C) N- (7H3-Dimethoxy · 1,2, The title compound of 3,4-tetrahydroquinoline glin-5-ylmethylene VN-methyl-imine is a 7-bromo-5-formamidine-2,3-dimethoxy- Fluoroline and methylamine are obtained by condensation. D) N- (7 ~ | f-2,3-dimethoxy-1,2,3,4-tetrahydroquinoline-5-ylmethylene VN-methyl- The amine title compound is N- (7-nitro-2,3-dimethoxy-1,2,3,4-tetrahydroquinoline-5, using conventional methods such as sodium borohydride in tetrahydrofuran. -Base methylene) -N-methyl-imine reduction. This paper size applies Chinese National Standard (CNS) M specifications (2 丨 0 X 2 magic male) (Please read the note on the back first ¾ .. then it is a matter of this page) loaded - Ministry of Economic Affairs Bureau of Standards staff printed consumer cooperatives

Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention () Nitra-2,3-dioxo-1 3.4-tetrahydroquinoxaline-5-ylmethyl VN-triethyl-money Prepared as described in Example 39, but replacing N- (with N- (2,3-Z1methoxy-7-nitro-quinoline IF lin-5-ylmethyl) -N »triethyl-ammonium 2,3-monomethoxy-7-nitro-quinoxaline (Linylmethyl), and 2 · methylazepane as a starting material. ESC1.-MS: (M-H) + = 361; TLC: methanol / acetic acid (9: 1) Rf = 0.1-0.45. The starting materials can, for example, be prepared as follows: a) Dimethoxy-7- ^ quinolin-5-yl a) Jie San 7, -Guan 0.795 g (3'65 mmol) double-third -Butoxychi-amine and 641 μl (4 mmol) triethylamine continuously added 1.0 g (3.05 mmol) 5-bromomethyl-2,3-dimethoxy-7-nitro-quine Darkline was dissolved in 5 ml of dimethylformamide solution. After stirring at 5 ° C for 4 hours, '10 ml of tert-butyl methyl ether was added to the suspension, filtered, and the filter was washed with tert-butyl methyl ether to give the title compound as a white crystal 'which As an unexpected by-product "丄 3- [H2,3-Dimethoxy-74 Shaw Quinaquinol-5-a) Ethylamine acetamate at 250 mbar and 70ec, 0.139 g (0.5 mM) Moore) 1- (2,3-dimethoxy 7-nitro-quinamline-5_yl) _ethyl ketone, panax (0.5 mmol mole) ethyl bupropionate hydrochloride and 0.082 A solution of 0.5 g of (0.5 mmol) sodium acetate in 50 ml of toluene, 2 ml of water and 20 ml of ethanol was concentrated. The product was dissolved in a toluene / ethanol (3: 1) mixture 'and concentrated to dryness by evaporation under reduced pressure. The residue was dissolved in 3 ml of tetrahydrofuran, and 0.023 g (0.6 mmol) of sodium borate and 1 ml of methanol were added. After stirring at 25 ° C for 18 hours, the mixture was acidified with 1NHC1, and after 15 minutes, it was made alkaline with 10% sodium bicarbonate, and the mixture was extracted with ethyl acetate. Rinse the organic phase with brine, and apply the Chinese National Standard (CNS) Α4 size (2) 0 × 297 mm through this paper size (please read the precautions on the back first and then this page) Order Gland--116-

V. Description of the invention () Printed by the Ministry of Economic Affairs _ Central Standards Bureau's Consumer Cooperative Co., Ltd. Dry magnesium sulfate 'and use rotary evaporation to condense to dryness. Chromatography on silica gel using ethyl acetate / hexane (1: 1) as the eluent gave the title compound as an oil that solidified immediately. TLC (EtOAc / hexane 1: 1): Rf = 0.20; iH-NMR (C〇a3): δ 8.57 (doublet, Ν3ΗZ »1H); 8.39 (doublet, JSHz» 1H); 4.73 ( Quartet, J = 7Hz, 1H); 4 two 1 (single peak, 3H); 4.18 turbid peak, 3H); 4.12 (quartet, J = 7Hz, 2H); 2.86-2.62 (multiple peak, 2H) 2.55-2.47 (multiple peak, 2H); 2.0-1.7 (broad, NH); 1.51 (doublet peak, J = 7Hz, 3H); 1.23 (triple peak, take 3H for slice). The starting materials can, for example, be prepared as follows: a) 5-Bromo-7soul · Gamme-2,3-dione Sulfates and hydrates Nad2 solution (under nitrogen pressure, 8.91 g (40 mmol)) Sodium crystals (sodium sulfide content 33-38% by weight) and 1.28 grams (40 millimoles) of sulfur in a mixture of 40 ml of water and 10 milliliters of ethanol were heated under reflux for a short time. E) 2_bromo_4,6_ dinitroaniline and 2.08 g (40 mmol) of ammonium chloride were dissolved in a suspension of 70 ml of ethanol and 40 ml of water. The mixture was stirred at 65 ° C for 30 minutes. Then, 40 ml of 2NNaOH was added dropwise over 30 minutes, and the mixture was stirred for another 15 minutes at 65 ° C. After cooling, the reaction mixture was poured into a mixture of 40 ml of 2N HC1, 100 g of ice and 700 ml of water, stirred for 15 minutes to complete the reaction, and extracted twice with ethyl acetate. The collected organic phase was dried over magnesium sulfate, briefly heated with 3 g of bone charcoal, and filtered through a High-Fow® filter. Concentration using a rotary evaporator yielded reddish-brown 3-bromo-5-nitro-1,2-diamine; TLC: ethyl acetate / hexane (1: 1): Rp 0.40. This paper size applies to Chinese National Standards (CNs) a4 specifications (210X29T). (Please read the precautions on the back before t this page.) --117- Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economy V A7 ___ B7 V. Description of the invention () No further purification required 'The product was heated with 17 g (B5 mmol) of oxalic acid dihydrate and 50 ml of diethyl oxalate in 100 ml of toluene to 1501 (bath temperature). During the reaction, the ethanol and water formed during the reaction were distilled off together with toluene using a short Vigreux column. Then the mixture was heated to i90 ° C until no liquid was distilled off. • Diethyl oxalate in excess Removed in the air. The olive green residue was suspended in 100 ml of acetic acid and heated at reflux for 3 hours. After cooling, it was filtered 'and the grey solid was washed with a large amount of acetic acid, water, ethanol and tert-butyl methyl ether to give the title compound. TLC (EtOAc / HOAc 98: 2): Rf = 0.45, W-NMR (DMSO-D6): δ 12.3 (broad, 1H, NH), 11.6 (broad, 1H, NH), 8.19 (1H, double bee, J = 2.5Hz), λ% (1H, doublet, J = 2.5Hz). b) 2,3-Dimethoxy-5-bromo-7-nitro-quinoxaline 'Using 5-bromo-7-nitro-quinoxaline- by a method similar to that described in Examples 4b2) and 4c2)- 2,3-diketone was used as starting material to obtain the title compound as yellow crystals; melting point = 171-175 t :; W-NMR (CDC13): δ 8,61 (doublet, J = 3Hz, 1H) , 8.58 (doublet, J = 3Hz, 1H), 4.28 (single peak, 3H), 4.20 (single peak, 3H). c) 1 ~ (2,3_Dimethoxy-7 · nitr-stilbene-5-yl V ethyl ketone at 80 ° C 'will be 3.84 g (12.23 mmoles) of 2,3-dimethoxy- 5-bromo-7-nitro-sialyline, 4.41 g (12.23 mmol) tributyl- (1-ethoxy-ethan) -stannane and 0.055 g (0.244 mmol) P &lt; K. The mixture of Ac &gt; 2 dissolved in 50 ml of DMF was stirred for 4 hours. Most of the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate, washed with water and brine, dried, and concentrated by rotary evaporation. In silica gel Chromatography using dichloromethane / Kein (U) as the eluent to produce a pale yellow solid vinyl ether intermediate This paper is sized to the Chinese National Standard (CNS &gt; A4 Specification (210X 297 Public Gift :) (谙 先Read the notes on the back, and then t) this page. Binding. BOOK-118- Printed by A7 B7, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (). At 25 ° C, the substance is in tetrahydrofuran / 1NHC1. Stir for 1 hour. Dilute the mixture with ethyl acetate, rinse three times with brine, dry over magnesium sulfate, and concentrate with rotary evaporation. Use ethyl acetate / hexane to separate the pale yellow needle-like crystals. Compound. Melting point: 155-157 ° C; TLC (EtOAc / hexane 1: 3): Rf = 0.25. Example 71: Hydrochlorination of 3- "l- (7-nitro-2,3-dioxo-1" , 2,3,4-tetrahydroquinoxaline-5-yl) -1-ethylamine 1-propionic acid 0.13 g (0.34 mmol) 3- [1- (2,3-dimethoxy-7) -Nitrate-darkin-5-yl) -ethylamine] propionate in 3 ml of methanol and 2 ml of 2NNaOH suspension at 25 ° C. After 1 hour, adjust the mixture to pH 4 and Extraction with chloroform / ethanol. The collected organic phase was extracted, dried over Na 2 SO 4 and concentrated using rotary evaporation. The residue was boiled with 4NHC1 for 18 hours. The mixture was concentrated to dryness using rotary evaporation. Crystallized from water to give a light beige brown Crystalline title compound, melting point> 300 ° C. W-NMR (DMS0D6): δ 12.4 (single peak, 2H); 8.32 (doublet peak, J = 3Hz, 1H); 8.02 (doublet peak, J = 3Hz, 1H); 5.1-4.95 (broad, 1H); 3.2-2.9 (broad, 2H); 2.67 (triple peak, J = 7liz); 1.57 (doublet peak, J = 7Hz, 3H). MS (ES- ): 321. Example 72: 1- 丨 2- (7 Ridge-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-yl) -ethane1-hexahydropyridine ~ 4-carboxylic acid tertiary-butyl ester title compound Using a method similar to that described in Example 1, (2,3-dioxo-7-quinoxaline-5-yl) -ethyl methanesulfonate and hexahydropyridine-4-carboxylic acid third- Derived from butyl ester acid. This paper size applies the Chinese Standard (CNS) Λ4 specification (210 X 297 mm) (谙 Please read the precautions on the back before #true page) -Packing ·

、 1T -119- Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7---__ 一 B7 V. Description of the invention (, --- The starting materials can be touched, and the system is difficult to make: a) B suspect-sleep Pyridoxine at 100t will 3.14 g (1 mmol) of 5-bromo-2,3-dimethoxy-7-nitro-darkinoline 634 g (2 mmol) of tributylethylenetin , 1.26 g (3 mmol) of lithium chloride and 14 g (0.2 mmol) of bis (triphenylphosphine) chloride> pin (Π) dissolved in 20 ml of dimethylformamide and heated 2 Hours. The mixture was cooled to room temperature and concentrated to dryness by evaporation under reduced pressure. Purification by flash chromatography and the use of toluene as the eluent produced the title compound as a yellowish solid "b) 皤 喏 morph_5 _V7, 醢 The title compound is prepared by the usual hydroboration, for example, by reaction with a dimethylsulfide / borane complex. Methoxy-7-nitro-quinazine-5 · a certain V7 .. ester The title compound was prepared by the conventional reaction with methanesulfonyl chloride. i ^ te_LHg: (7 · nitro-2,3-dioxo-1,2,3,4_tetrahydroquinone viscera-5 side) -B] · hexamidinepyridine · 4-carboxy. The title compound is used Prepared similar to the method described in Example 6, but with fluorene 2- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-yl) -ethyl] -hexa Hydropyridine-4-carboxylic acid Third, butyl ester acid is the starting material. 1 ^^^ ~ 1 ^ 1 [^ 1 (7-Nitro-2,3-trioxo-1,2,3,4 ~ tetrapyrazine-5 titer) ~ Ethylamine diacid methyl ester Prepared by a method similar to that described in Example 72, but starting with methyl alanine. 1 · ^ Βί2 ^ 1 ·? [2 · (7 · NO = g, 3- & oxygen-1,2,3,4-tetrahydropyrazine-5) -ethylamine 1-propionic acid The paper size applies the Chinese National Standard (CNS) Α4 specification (2l0x297). (Read the notes on the back and read this page again), binding-120- / 1 BM consumption by the Central Bureau of Standards of the Ministry of Economic Affairs Co-printed A7 __ B7 V. Description of the invention () The title compound can be prepared by a method similar to that described in Example 22, but with hydrochloride 2- [2- (7glucose-2,3-dioxo-1, 2,3,4-Tetrahydroquinoline-5-yl) -ethylamine] -propionic acid methyl ester was used as a starting material. Example 76: 2-Amine-347H3-dioxo-1,2,3,4 · tetrahydroquinofluoren-5-yl) -propionic acid 0.29 g (0.62 mmol) 2-acetamidin-2 A suspension of-(2,3-dimethoxy-7mandolin-5-ylmethyl) -diethyl malonate dissolved in 6 ml of 6N hydrochloric acid is heated under reflux for 24 hours and then concentrated under reduced pressure to dry. The residue was boiled with water, centrifuged and dried to give the title compound as a yellow powder. h-NMR (DMSO-D6): δ 12.3-11.9 (broad, 2Η), 10.3-9.2 (b), 7.98 (doublet, J = 3Hz, 1Η), 7.90 (doublet, J = 3Hz, 1Η) ), 3.50-3.45 (multiplet, 1Η), 3.40-3.32 (multiplet, IH), 3.06-2.98 (multiplet, 1H) _ (ES +)-MS: [M + Na + NH4] + ° starting material It can be prepared, for example, as follows: a) 2-Acetylamine-2- (2,3-dimethoxy-7-nitridine-5-ylformyl V malonate under argon, 0.2Π g (1 mmol) of diethylacetamide malonate was stirred and added to a solution of 0.026 g (1.2 mmol) of sodium dissolved in 3 ml of ethanol. After 5 minutes, 0.328 g (1 mmol) was added E) 2,3-Dimethoxy-5-bromomethyl-7-nitro-quinoxaline 'and then the mixture was stirred at 25 ° C for 18 hours. The mixture was diluted with ethyl acetate and washed with 1N hydrochloric acid, It was then rinsed with brine, dried over magnesium sulfate, and concentrated using rotary evaporation. Chromatography on silica gel using ethyl acetate / hexane (1: 2) as the solution gave the title compound as a fast-curing oil. TLC (EtOAc / Jiyuan 1: 2): Rf = 0.35 This paper size applies the Zhongguanjia Standard (CNS) A scale (21 () &gt; &lt; 297 Gongkang) First heard the item I and then on this page η) Line A7 ____B7__ 5. Description of the invention () W-NMR (CDC13): δ 8.57 (doublet, J = 3Hz, 1H), 8.01 (doublet, J = 3Hz, 1H), 6.34 (single peak, 1HX 4.36-4.24 (multiple peak, 4H), 4.25 (single peak, 3H), 4.18 (single peak, 3H), 1.85 (single peak, 3H), 1.31 (triple peak, J = 7Hz, 6H) Example 77: 3-Amine bromide, 3 ~ (7per-2,3-digas-1,2,3,4-tetrahydrofluorin-5-yl) -propionic acid At 70 ° C, 0.15 g (0.39 mmol) of 3- (2,3-dimethoxy-7-nitro-quinazolin-5-yl) was dissolved in 3-methoxy terminal amine-propionic acid. 5 ml of a 33% HBr / HOAc solution was heated for 16 hours. After cooling, the gray suspension was diluted with tert-butyl methyl ether and filtered with suction to obtain the title compound as a gray powder. W-NMR (DMSCM & gt 6) δ 12.41 (single peak, 1H), 12.4-11.8 (broad, 1H), 8.7-8.3 (broad, NBA 5.4-5.28 (multimodal, 2H), 3.16-2.96 (multimodal, 2H); FAB-MS: [M + l] + 295. The starting materials can be prepared, for example, as follows: a) Dimethoxy-7-nitrate-dark saga-5-yl V-but-3-ene 1 carbamate SV-2560 Shellfish Consumer Cooperative, Central Standards Bureau, Ministry of Economic Affairs Printed with stirring, add 1.26 ml of BF3OEt2-2.63 g (10 mmoles) of 2,3-dimethoxypyridin_5_carbaldehyde, 0.75 g (10 mmoles) of amine all at once Methyl formate and 1.2 g (10.5 mmol) of allyltrimethylsilane were dissolved in a suspension of 30 ml of acetonitrile. The mixture was stirred at 25 ° C for 30 minutes, then poured into a 10% aqueous sodium hydrogen carbonate solution, and diluted with brine and ethyl acetate. The organic phase was separated &apos; dried and concentrated using rotary evaporation. The crude product was crystallized to give the title compound as almost colorless crystals; melting point = 135-136 ° C. TLC (EtOAc / House 1: 3): Rf = 0.17. .b)} _ (g, 3-Dimethoxy-7.-ramie-5-yl V3-methoxycarbonylamine-propionic acid at 25 ° C, 0.31 g (0.85 mmoles) [1 -(2,3-Dimethoxy-7-nitrate-sialin)-This paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) -122- A7 B7 f438782 5. Description of the invention () (please first Read the notes on the back again. # This page) 5-yl) -But-3-ene] carbamate, 733 g (3.42 mmol) sodium iodate (Na [〇4) and 〇.〇 One gram of ruthenium oxide (Ru02) was dissolved in a mixture of 5 ml of acetonitrile, 5 ml of carbon tetrachloride and 5 ml of water, and stirred vigorously for 4 hours. The mixture was then filtered through a High-FlOW® filter, and then filtered with Rinse with ethyl acetate and water. Rinse the organic phase with 1N hydrochloric acid and brine, dry over magnesium sulfate, and concentrate using rotary evaporation. Residue in 5 ml of water, 5 ml of acetic acid, and 5 ml of carbon tetrachloride. The mixture was again mixed with 0.50 g of sodium iodate and 0.005 g of ruthenium oxide, and stirred vigorously for another hour. The mixture was filtered through a Hi-Flow® filter, and then washed with ethyl acetate and water. The organic phase is separated, Rinse with brine, dry over magnesium sulfate and concentrate using rotary evaporation. The crude product was crystallized from tert-butyl methyl ether to give the title compound TLC (EtOAc / HOAc 98: 2): Rf 20'52 as a gray crystal. H-NMR (CDCI3): δ 8.61 (doublet, J = 3Hz, 1H), 8.32 (doublet, J = 3Hz, 1H), 6.36_6.28 (multiple peak, 1H), 6.〇2 -5.88 (multimodal, 1H), 4.23 (unimodal, shift), 4.19 (unimodal, 3H), 3.68 (unimodal, commit), 3. 丨 8-3.09 (multimodal, 2H). Implementation Example 78 The following compounds can also be prepared by methods similar to those described in Examples 1 to 77: Printing of Hydrobromide N- (2,3-dioxo-7- Nitra-1,2,3,4-tetrahydroquinoline-5-ylmethyl) methyltrifluoromethanepyridine, melting point = 273 ° C (decomposition); N- (2,3-dioxyhydrobromide) -7-nitro-1,2,3,4-tetrahydroquinoline-5-ylformate> 2, amine benzimidazole, melting point> 300 ° C; ammoniated desertification N- (2,3 -Dioxin-1,2,3,4-tetraazepine dark lin-5-ylmethyl) -diisopropylamine, melting point = 284ΐ (decomposition); -123- This paper size applies to China National Standards (CNS ) A4 size (210X297 male %)

V. Description of the invention () N- (2,3-dioxo-7-nitrate-1,2,3,4-tetrahydroquinoline 0-lin-5-ylmethyl M-n-propanehexahydropyridine hydrobromide ， Melting point = 286 ° C; Please read the precautions before reading and then hydrobromide N- (2,3-diox-7-nitro-1,2,3,4-tetrahydroquinoline · 5-yl A &gt; 4-Amine-n-butyronate, MS (ES +): (M + H) + = 373; Hydrogen bromide N- (2,3-dioxo-7-nitro-1,2,3, 4-tetrahydroquinoline-5 · ylmethyl) -N-methyl-4-amine-n-butylphosphonic acid, MS (ES +): (M + H) + = 387; Ν · (2,3-di Oxy-7-nitro-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -N-methyl-12-amine-dodecanoic acid, melting point = 232-238 ° C (decomposition); N &lt; 7-nitro_2,3-dioxo-1,2,3,4 ~ tetrahydroquinoline-5-ylmethyl) -4-hydroxy-3-methoxy-benzylamine, melting point> 270 ° C; argon bromide N- [l- (7-nitro-2,3-dioxo-U, 3,4 ~ tetrahydroquinoline-5-ylmethyl) -hexahydropyridine-4-ylmethyl l · methanesulfonamide, (ES &gt; MS: 410 [MH] ·; hydrobromide N- [1 &lt; 7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinol Phenyl-5-ylmethyl) -hexahydropyridine-4 · methylmethyl] -acetamidamine, (ES &gt; MS: 374 [MH] ·; dihydrobromide N- [H7-nitro-2,3-di O-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -hexahydropyridine-4-ylmethyl] -nicotinamide (ES> MS: 437 [MH; p N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -4- (4-fluoro Benzamidine) -hexahydropyridine, (AF) -MS: 425 [MH] ·; Hydrobromide printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs {3-[(7.-2,3-dioxo-1, 2,3,4-tetrahydroquinoxaline-5-ylmethyl) -amine] -2-oxo-2,3,4,5-tetrahydro-phenylhydrazone [top.] Azepine-1-yl} -Acetic acid, (ES +)-MS: 454 [M + H] +; 4- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -Hexahydropyridin-2-carboxylic acid; N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl)-(3-chloro- Benzene) -Methylamine, melting point> 270 ° C; This paper size is applicable to Chinese National Standard (CNS) Λ4 specification (2I0X297 mm) -124- ^ 3 8 7 82 A7 B7 Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs Printed 5. Description of the invention () N- (7-nitro_2,3 · dioxy, 1,2,3,4-tetrahydroquinoxaline-5-ylmethyl)-(3-residue-benzene) Amidamine, melting point_ &gt; 270 ° C; 4- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydrofluorin-5-ylmethyl) &gt; 4-methyl- 3,5-dioxo-hexahydropyridine trap, (AP &gt; MS: 346 [MH]-; hydrochloride M [(7 番 2,3-dioxo-1Λ3,4-tetrahydroquinoline · 5 · Methylamine] -methyl} -benzylsulfonate Amine, melting point &gt; 270 ° C; N · (7 Lu 2,3-dioxo-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -2-oxo-azepine 3-3-yl-amine, melting point> 270 ° C; hydrochloride 4-{[(7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5- Methyl &gt; Amine] Toluic acid, melting point &gt; 270 ° C; hydrochloride 4-[(7-nitro-2,3-dioxo-I, 2,3,4-tetrahydroquinoxaline- 5-ylmethyl) -amine] -benzoic acid, melting point> 270 ° C; 5-[(7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 · Methyl a) -amine] -3H-imidazolamide, melting point &gt; 270 ° C; N- (7glucose-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrobromide _-5_ylmethyl) -3,5-dimethyl-morpholine, melting point &gt; 300 ° C; europium hydrochloride (7-mouth-2,3-dioxo-1,2,3,4-tetrahydro Quinoxaline-5, Benzene) -4,4-ethylenedioxy-hexahydropyridine, melting point = 290 ° C (decomposition); N- (7-nitro-2,3-dioxo-1) hydrobromide, 2,3, 'tetrahydroquinoline-5-ylmethyl) -3-methyl-hexahydro. Pyridine, melting point &gt; 300 ° C (decomposition); N- (7-nitro-2,3-hydrochloride) Dioxo-1,2,3,4-tetrahydroquinoline-5-ylformate &gt; 4-hydroxy-hexahydropyridine, melting point = 290 ° C (decomposition); hydrochlorinated N &lt; 7-nitro-2 , 3-dioxo-1,2,3,4-tetrahydroquinolinline-5-ylformate> 2-hydroxyl A-η-pyrrolidine, melting point = 247 ° C (decomposition); (Please read the precautions on the back before tiling this page). Packing-The size of the paper is applicable to the Chinese National Standard (CNS) Λ4 specification (210 × 297 mm) -125- 8 8 A7 B7 V. Description of the invention () N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl)- 2-Ethyloxymethyl-pyrrolidine, melting point = 175 ° C (decomposition); N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline hydrochloride 5--5-methylmethyl) -4-pyrrolidine-2-carboxylic acid, melting point = 24t ° C (decomposition); N- (7-nitrodioxy-1,2,3,4-tetrahydrohydrochloride) Quinoxaline-5-ylmethyl &gt; 3-hydroxy-hexahydropyridine, melting point &gt; 300 ° C; hydrochloride 2- (7,2,3-dioxo-1,2,3,4-tetrahydro Quinoxaline-5 · methylmethylamine HLKT acid, melting point = 238 ° C (decomposition); 2- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrobromide) Methyl quinolin-5-ylmethylamine butyrate, melting point = 218 ° C (decomposition); 2- (7-nitro-2,3-dioxo-U, 3, 'tetrahydroquinoline-5, hydrochloride -Methylamine) · isobutyric acid, melting point> 300. . ; Methyl 2- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethylamine) -isobutyrate, melting point = 243 ° C (Decomposition); 1_ (7_nitro_2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethylamine) hydrochloride &gt; cyclopropan-1-carboxylic acid, melting point = 254 ° C (decomposition); hydrochloride N- [N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N- Methyl HL) -alanine, melting point = 277 ° C (decomposition); N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylformate> Leucine; N- (7-nitro-2,3-dioxo-1,2,3,4) hydrobromide &gt; Tetrahydroquinoline-5-ylformate &gt; (L &gt; Thramine = 215 ° C (decomposition); N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline_5_ylmethyl) &gt; 2-methyl-β -Alanine, melting point = 238 ° C (decomposition); This paper size applies to Chinese National Standards (CNS specifications (210x Peng mm)) Please read the notes on the back first before ordering # Printed by the Central Laboratories of the Ministry of Economy -126- 87 82 A7 B7 ΎΓ1Τ Year, month, and month 5. Amendments to the invention () -ϋ Dihydrobromide N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline Porphyrin-5-ylmethyl &gt; 4-methylpyridylamine, melting point = 21 8 ° C (decomposition): N- (7-nitro_2,3-dioxo-1,2,3,4_tetrahydroquinoxaline-5-ylmethyl) -2-methylpyridine Amine, melting point = 229 eC (decomposition): NH- (7 · ^ -2,3-dioxo-1,2,3,4-tetrahydroquinamline-5 sparcaline) -amine acetonitrile, melting point = 275 ° C (decomposition); N- (7 · nitro-y-dihydrazone-1,2,3,4 · tetrahydroquinolinline_5 · methylformate> 4-benzylhexahydropyridine , Melting point = 242 ° C (decomposition); hydrochloride N-C7-nitro-2 &gt; dioxo-I, 2,3,4-tetrahydroquinoline-5-ylformate &gt; 4-phenylhexaoxopyridine Glacial carboxylic acid, melting point> 280 ° C: N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl) -4- Amylase hexahydropyridine, melting point &gt; 300 ° C; N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline, 5-methylformyl) hydrochloride &gt; 3-methyl-β-alanine, melting point = 298 eC (decomposition): hydrobromide 1 ^-(7 genera-2,3-dioxo-1,2,3,4 »tetrahydroquinidine * 5 -Methylformate> 4-benzylmethoxycarbonyl-hexahydropyridine, melting point = 258 ° C (decomposition); hydrochloride N- (7-nitro-2,3-dioxo-1,2Λ4 · tetrahydroquine Pyridin-5-ylformate &gt; imine oxalic acid, melting point = 257 ° C (decomposition); Consumer Cooperative of the Central Standards Bureau of the Ministry of Carp Printed (please read the notes on the back before filling this page) N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-yl hydrobromide A &gt; 1,2,3,4 ~ tetrahydroisoquinoline, melting point = 300 ° C (decomposition); hydrobrominated N-C7-nitro_2,3 · dioxo-I, 2,3,4- Tetrahydroquinoline-5-ylmethyl &gt; 2-aminebenzothiazole, melting point = 272 t (decomposition); 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydro Hydroquinoline-5-ylmethylamine) ethylphosphonic acid, melting point = 246 ° C (decomposition); N_ (7-nitro_2,3-dioxo-1, 3,4-tetrahydroquinoline beer- 5-based methyl) -N-acetamidine- (L) -alanine; This paper size applies to China's national standard (CNS) A4 (210X297 mm) -127- 438 438 Shellfish Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs Printing A7 B7 V. Description of the invention () N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylformate) &gt; 4-benzene hydrobromide -Hexahydro D ratio-pyridine, melting point &gt; 230 ° C; hydrochloride N- (7,2-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 · ylmethyl) -4Metal-hexahydropyridine, melting point = 248t: (decomposition); N- (7glucose-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-yl A &gt; 2 A, hexahydropyridine, melting point = 286 ° C (decomposition); hydrochloride N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinolinline-5scarpentyl) -4- (1-Ethyl) -hexahydropyridine, melting point = 238t ( Decomposition); Hydrogen chloride N-C7-nitr_2,3-dioxo-1,2,3,4 · tetrahydroquinoline · 5 * • methylmethyl-methoxy-hexahydropyridine, melting point & gt 300 ° C; N- (7 genera-2,3-dioxo-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -2-methyl-hexahydropyridine; N- (7 -Nitro-2,3-_oxy-1,2,3,4 · tetraazapyrazine_5-ylmethyl) -4-methoxy-4-methyl-hexammine B ratio is steeper, N- (7- Nitrate-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -4,4-dimethoxy-hexahydropyridine; hydrochloride N- (74 |- 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethanine, melting point = 228 ° C (decomposition); N- (7-nitro-2, hydrobromide, 3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -0-acetazone (10-serine, melting point = 250 ° C (decomposition); N- ( 7-nitro · 2,3-dioxo-1,2,3,4-tetrahydroquinolinline-5-ylmethyl) -azepine-2-one; N- (7-nitro-2,3- Dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -hexahydropyridine-2; 1- (7-nitro-2,3-dioxo-1,2,3 , 4-tetrahydroquinoxaline-5-ylformate> 2-ethyl-4-methyl'imidazole; N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydrofluorene Perylene-5-ylmethyl) Steep-2-carboxylic acid; N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -2 · amine-5-hydrobromide Bromine-pyrimidine, melting point &gt; 274 ° C; This paper size is applicable to Chinese National Standard (CNS) Λ4 specification (210 X 297 mm) (谙 Read the precautions on the back first and then Ϊ this page) • Packing. Order -128- Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 丨 878 A7 B7 V. Description of the invention () N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrobromide Lynn-5-ylmethyl &gt; -5-Amine-2-methoxy-4-pyridine, melting point &gt; 30 (TC; NK7-nitro-2,3-dioxo-1,2,3,4 hydrobromide) -Tetrahydroquinoxaline-5 · methylformate &gt; * 2-aminopyrimidine, melting point &gt;300eC; N- (7-nitro_2,3 · dioxo-I, 2,3,4-tetrahydrobromide Hydroquinol. 5-ylmethyl) -2-amine-fl ratio, melting point> 300 ° C; N- (7-nitro-2,3-dioxo-1,2,3,4-hydrobromide Tetrahydroquinoline-5-ylmethyl) -3-amine-pyridine, melting point = 213 ° C (decomposition); N- (7 genera-2,3-dioxo-1,2,3,4) hydrobromide · Tetrahydroquinoline-5-ylformate> 2-Carbentine, melting point = 200 ° C (decomposition); N- (7-nitro-2 &gt; dioxo-1,2,3,4- Tetrahydroquinoline-5-ylformate> 3-amine-5-tertiary-butisoxazole, melting point = 148-1 50 ° C (decomposition); N- (7-knee 2,3-dioxo-1,2,3,4-tetrahydroquinol.5-ylmethyl) -2-amine · 4,5- Dicyano-pyrimidine, melting point &gt; 300 ° C; bromide N- (7-nitro-2,3_dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N, N, N-triethyl-ammonium; 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -1,2,4 ~ tri Azole-3 picolinic acid; 1- (7-2-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl H, 2,4-trimile-5 picolinic acid; 4- (7 · || -2,3-dioxo-U, 3A tetrahydroquinolinline-5-ylmethyl) -1,2,4-triamidine-3-carboxylic acid; 1- (7_nitro -2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylformate> 1,2,3-triamidine ~ 4,5-dicarboxylic acid; 1 &lt; 7 · nitrate -2,3-dioxo-1,2,3,4-tetrahydroquinoline-5- * methylH, 2,4-triazole; K7fan 2,3-diyi 1,2,3,4 -Tetrahydroquinoxaline-5-ylmethyl) -1,2,4-trimile-5acetate; 2- (7-nitro-2,3-dioxo-1,2,3,4 · Tetrahydroquinol-5-ylmethyl H, 2,3-trimile-4,5-dicarboxylic acid; 1- (7-nitro-2,3-dioxo-1 and 3,4-tetrahydroquine Pyridin-5-ylmethyl) 1,2,3-triazole head 5-dicarboxylic acid dimethyl ester; This paper size is applicable to the national standard (CNS) A4 specification (2 丨 OX297 mm) (please first Read the notes on the back again # -¾ 本) Ding-129 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs ti4387 82 at _B7, invention description () 1_ (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinaline- 5-ylmethyl) -1,2,3-triazolamide; 1- (Ga-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5_ylmethyl) ιι, 2,3-triazole cedaramine; 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydrofluoroline-5 scallion) &gt; 1,2 , 3-tri-mile · 4,5-diundroic acid dimethyl ester, melting point = 173-175 ° C; 2- (7-^-2,3 -_ * oxy-1,2,3,4-tetrachloro Sialin-5-ylmethyl) ~ 1,2,3-diwa-4,5-dicarboxylic acid, melting point = 290 ° C (decomposition); 1- (7 genera-2,3-dioxo-1 , 2,3,4-tetrahydroquinazoline, 5-ylmethyl) -imidazole-2,4,5-tricarboxylic acid; P-fluorene- (7man-2,3-dioxo-1,2, 3,4-tetrahydroquinoline-5-yl &gt; methylphosphonic acid; P-methyl ~ (7 soul-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5- Methyl) phosphonic acid; N- (7 · nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-yl &gt; aminoformamidine methylphosphonic acid; 1- ( 7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylformate> 2-oxo-1,2-dihydropyridine; 2- (7-nitro- 2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -1, 2,3,4-tetrahydroisoquinolin-1-one; 1- (7 -NO- 2,3-dioxo-1,2,3,4 · tetrahydroquinoxaline. 5-ylmethyl) -2,3,4,5-tetrakisbenzophenazine-2-one; N- (7 Genus-2,3-dioxo-I, 2,3,4-tetrahydroquinoline-5-ylmethyl) -2-oxo-3-phenylhexahydropyridine; Ν- (7.-2,3- Dioxo-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -2-oxo-5-benzene-hexahydropyridine; N- (7 soul-2,3-dioxo-1, 2,3,4-tetrahydroquinazolin-5-ylmethyl) -5-oxo-pyrrolidin-2-one; 4- (2-oximidazol-1-yl) -N- (7-nitro- 2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -hexahydropyridine; N- {2- [N- (7-nitro-2,3-dioxo -1,2,3, tetrahydroquinkaline-5-ylmethyl) amine] ethyl} -pyrrolidin-2-one; N- (7-nitro-2,3-dioxo-1,2,3 , 4-tetrahydroquinoline-5-ylmethyl) benzene-pyrrolidin-2-one; This paper size applies to China National Standard (CNS) A4 specification (2 丨 〇 parent 297 mm) (read first read the back (Notes on this page) -130- Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention () N- (7-nitro-2,3-dioxo-1,2,3 + Tetrahydroquinoline-5-ylmethylfluorobenzidine) hexahydropyridine; N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinolinline-5-ylmethyl ) -2-oxo-2-benzene-acetamidamine; N- (7-bromo · 2,3-dioxo-1 2,3,4-tetrahydroquinoline-5-ylmethyl) -2-propan-pentamidine; N- (7 · Mo-2,3-dioxo · 1,2,3,4-tetrahydro Quinazolin-5-ylmethyl)-(4-methylfuran) · 2-carboxamide; N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline -5-ylmethyl) · thiophene-3-carboxamidine, melting point> 250 ° C; N- (7-bromo-2,3-dioxo-1,2,3,4 · tetraarginoquinoline- 5-ylmethyl &gt; imide · 4 benzylamine; bromo 4,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -3- (thiophen-3-yl ) -Acrylamide; N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -3-phenylisobutyramide; heart ( 7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -1-phenylcyclopropylformamidine; N- (7-bromo-2, 3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -2-phenylpropanamide; N- (7-bromo-2,3-dioxo-1,2, 3,4 · Tetrahydroquinoline-5-ylmethyl) -2-phenoxyacetamide; N- (7-Mo-2,3-dioxo-1,2,3,4-tetrahydroquinoline Porphyrin-5-ylformate> (3,4-dimethoxybenzene) -acetamidine, melting point> 280 ° C; N- (7-bromo-2,3-dioxo-1,2,3 + Tetrahydroquinoline-5-ylmethyl)-(4-chlorophenyl) acetamidine; N- (7, bromo-2,3-dioxo-1,2,3,4 · tetrahydroquinoline- 5-ylmethyl &gt; (3-chlorobenzene) ethyl amine; Ν- (7-bromo ~ 2,3- Oxygen-l, 2,3,4-tetrahydroquinoline-5-ylmethyl)-(2-chlorobenzene) acetamide; N- (7-bromo-2,3-dioxo-1,2, 3,4-tetrahydroquinoline-5-ylmethyl &gt; (3-methylthiophene) -2-carboxamide, melting point &gt; 280 ° C; & (7-bromo-2,3-dioxo- 1,2,3,4 ~ tetrahydroquinoline-5_ylmethyl)-(5-methylthiophene) -2-carboxamide, melting point &gt; 280 ° C; This paper size applies Chinese National Standard (CNS) A4 specifications (210X297 mm) (please read the note on the back before reading this page)-Forging 43 8 A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () N- (7- Mo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl)-(1-methylpyrrole &gt; 2-endrimidine, melting point &gt; 280 ° C; hydrogen N- (7-bromo-2,3-dioxo-1,2,3,4 »tetrahydroquinolinline-5-ylmethyl) -sufamide, melting point = 272 t (decomposition): 乂(7-bromo-2,3-dioxo-1,2,3,4 ~ tetrahydroquinoline-5-ylformate) ((4 »nitrophenyl) acetamidine, melting point &gt; 270 ° C; 乂(7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl)-(3-nitrophenyl) acetamidine, melting point &gt; 270 ° C; &gt; ^-(7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) &gt; (2-nitrophenyl) acetamide, melting point &gt; 270 ° C; Ν · &lt; 7-bromo-2,3-dioxo-1,2,3,4 · tetrahydroquinoline-t-methylmethyl3,4-methylenedioxybenzene) -ethyl Amidine, melting point &gt; 270 ° C; Ν-ΟBr_2,3-dioxo-1,2,3,4-tetrahydroquinoxaline "5 · methylformamidine 3-phenoxybenzene) -acetamidine ; Ν- (7-bromo-2,3 · dioxo-12,3,4-tetrahydroquinoxaline-5-pyrazine) -2-pyridamidine; 7-bromo-2,3-dioxo · 1,2,3,4 · Tetrahydroquinoxaline-5-ylmethylamine methylphosphonic acid, melting point &gt; 270 ° C; 1- (7-bromo-2,3-dioxy · 1,2, 3,4-tetrahydro-pyridin-5-ylmethylamine) ethanephosphonic acid, NMR (25 MHz DMSO-4) δ (ρρ; η) = 12.2 (single peak, NH); 7,45, 7.35 (2 doublet, 2 Harom); 4.48, 4.40 (2 doublet, CH2); 3.50 (multiplet, 1H); 1.42 (quartet, Me); N-C7-bromo-2 &gt; dioxo- U, 3,4-tetrahydroquinoxaline-5_ylmethyl) -N-benzyloxycarbonyl-amine-methylphosphonic acid N_ (7.bromo-2 &gt; dioxo-1,2,3,4-tetrahydro Quinaquinol-5-ylmethyl) ethyl benzylcarbamate (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 cyperyl) aniline ethyl ester N -(7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N-phenethylhydrazone-amine-methylphosphonic acid N &lt; 7-bromo- 2,3 · dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylformyl) -N-phenethylhydrazone-glycine Acid; 3-Bromo-1- (7-nitro-2,3-dioxo-1,2,3,4 &gt; tetrahydroquinoxaline-5-ylmethyl) -pyrrole melting point = 225 ° C (Decomposition); -f--_ _If-iE. (Please read the notes on the back before filling in this I "-, π- line; This paper size applies to Chinese national standards (CNS &gt; 8 4 specifications (210X29- / Public cabin) -132- ~ heart Λ7 B7 V. Description of the invention () 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-yl) -Pyrrole-3-carboxylic acid ethyl ester, melting point: 195 ° C (decomposition); N-methan (7_bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline -5-ylmethyl) -phenethylamine, melting point &gt; 260 ° C; N- (7-bromo-2,3-dioxo 4,2,3,4-tetrahydroquinoline-5, hydrobromide · Methylformate> 3-Ethylpyrrolidine, melting point = 246 ° C; N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrochloride- 5-ylformyl> 3 · hydroxypyrrolidine, melting point = 263 ° C; 1- (7nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylformyl) -Pyrrole-3-carboxylic acid; 1- (7-nitro-2,3 · dioxo-1,2,3,4-tetrahydroquinoline-5-ylformyl) -Ubirol_2. Money acid ; 1- (7 | 2,3-Dinyl rl, 2,3,4-tetrahydroquinoxaline-5-ylmethyl) -pyrrole ~ 2-acid third-butyl ester; 1- (7 genera- 2,3-two -1,2,3,4-Cycloquinone-5-ylmethyl) -methyl-3-ylacetic acid; 1- (7-nitro-2,3-dioxo-1,2,3,4 * Tetrahydroquinoxaline-5-ylmethyl) -ethyl ethyl acetate; 1 · (7 gene · 2,3-dioxo-1,2,3,4-tetrahydroquinoline-5- 1- (7Qin2,3dioxo-U, 3,4-tetrahydroquinolinline-5-ylformyl) 41§ 丨 2-Junconic acid Tert-butyl ester; 1- (7shoulder-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylformyl) ^-2-carboxylic acid; hydrobromination 1- (7-Nitro-2,3-dioxy * 1,2,3,4-tetrahydroquinoline-5-ylmethyl) -imidazole 'melting point &gt; 300 ° C; Shellfish, Central Bureau of Standards, Ministry of Economic Affairs Printed by the Consumer Cooperative (please read the note on the back before reading this page) 1_ (7 genera, 2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl M · Hydroxymethyl-imidazole; 1- [Ι- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) imidazolyl] acetic acid; hydrobromination 1- (7 · nitro-2,3-dioxo-1,2,3,4-tetrahydroquinol. 5-ylmethyl) -4-methyl-imidazole 'melting point &gt; 300 ° C; H7 hydrobromide -Nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -2-methyl-imide 'melting point &gt; 300 ° C; This paper size applies to China Standard (CNS) A4 size (210X297 mm & gt Printed and issued by the Shellfish Consumer Cooperative of the Central Bureau of Standards and Quarantine of the Ministry of Economic Affairs on the 43rd 70 A7 B7 V. Description of the invention () Hydrobromide 1- (7-nitro-2,3-dioxy-1,2,3,4 ~ Tetrahydroquinopelinylmethyl) _2_ethyl-imidazolam, melting point> 3009C; hydrobromide 1- (7 番 2,3-dioxo-1,2,3,4 ~ tetrahydroquinaziline-5 _Ylmethyl) n-pyrazole, melting point &gt;3000C; hydrobromide 1 &lt; 7 2,3-dioxo-1,2,3,4 ~ tetrahydroquinaline-5-ylmethyl) -3,5-dioxo-pyrazole, melting point> 30 (TC; 2- (7-nitro-2,3-dioxo-1,2,3, hydrotetrahydroquinolin-5) -Methylformate> 1,2,4 ~ triazole, melting point> 250 ° C; 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 -Ylmethyl) pyridine; H7 belongs to -2,3-dioxo-1,2,3, 'tetrahydroquinoline-5-ylmethyl) -hexahydropyridin-3-one; 1 &lt; 7 | 2 , 3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -Dfazolidin-2-one; 1-C7-nitro_2 &gt; dioxo-1,2,3 , 4-tetrahydroquinoline-5-ylmethyl) 4-methyl-hexahydropyrrol-3,5-dione; 3- (7-nitro-2,3-dioxo-1,2,3, 4-tetrahydroquinoline-5-ylmethyl) -2,3,5,6-tetrahydro ~ 4Η-1,2- ^ tillage; N-(. 7 ~ m-2,3-dioxo-1 , 2,3,4-Tetrahydroquinoxaline-5-ylmethyl) -anthranilide; N- (7-nitro-2,3-dioxo-1,2,3,4-tetra Hydroquinone-5-ylmethyl) -o-aminobenzoic acid methyl ester; Ν- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl &gt; Ethyl o-aminobenzoate; 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -2-acetamidine- Hexahydropyridine; 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -2-benzene 4-acetamido-hexahydropyridine ; {3- (7 番 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5 · methylmethylamine) -2-oxo-1,2,3,4-tetrahydro- Phenylhydrazone [bFTheptene-l-yl} -acetic acid; This paper size applies to Chinese national standard (CNS) Λ4 specification (2 丨 0X297 mm) --------- packing— (Please read the back Note again on this page) Order -134- A7 B7 V. Description of the invention () Qin (7-pass-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-yl) -1 ^ -isopropyl-1 ^ (quinolin-4-ylmethyl) amine; 4 ^ (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 · Methylmethylamine) -5-benzene-pentan-1-can; 2- (7 genera-2,3 · dioxo-1 and 3,4-tetrahydroquinoline-5-ylmethyl) -N- ( 4-nitrophenyl) -acetamidamine; N- [N- (7-nitro-2,3-dioxo-1,2,3,4 plumequinoline-5-ylmethyl) glycinamine] glycine Amino acid; .N- [N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) Glycine 醯] -N-methyl-glycine; 1- [^ 7 番 2,3-dioxo-1,2,3,4-tetrahydroquinolinline-5-ylmethyl) glycine 醯]- Pyrrolidine-2-carboxylic acid; N- [N- (7 番 2 &gt; dioxo-1,2,3 + tetrahydroquinoxaline-5-ylmethyl) glycine 醯] phenylalanine; 2- (7 ~ 5 Ken-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethylamine) -alanine; 3- (7-nitro · 2,3-dioxyhydrochloride) -1,2,3,4 · Tetrahydroquinoline-5-methylmethylamine) · propanol; 3- (7-nitro-2,3-dioxo-1,2,3,4-tetrachloro chloride) Hydroquinoline-5-ylmethylamine) -ethanol; N- (7-nitro-2,3-dioxo-I, 2,3,4-tetrahydroquinoline-5-ylmethyl) -5- Dimethylamine-sulfamethoxamine; Ν- (7 · nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) &gt;2-benzyl-aziridine; 2- [2- (7-nitro · 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline.5-yl) ethylamine] -acetic acid; 1- [2- (7 genera-2 , 3-dioxo-1,2,3,4-tetrahydroquinazolin-5-yl) e] -hexahydropyridine; printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, 2- (7 · nitro-2, 3 · dioxo-1,2,3,4-tetrahydroquinoline Ulin-5-yl) ethyl] -hexahydropyridone; 1- [2- (7 genera-2,3 · dioxy-1 , 2,3,4-tetrahydroquinoline-5-yl) acetamidine-3,3; 1- [2- (7-nitro-2,3-dioxo-1,2,3, 4-tetrahydroquinoxaline. 5- ) B] -Hydroxypyridine-4-junic acid; 1- [2- (7Lu 2,3-dioxo-1,2,3,4-tetrahydroquinazolin-5-yl) e]- 4-acetamidamine · hexahydropyridine; 1- [2- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinolinline-5-yl) ethyl] -pyrrolidine -2,5-dione; 1- [2- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinazolin-5-yl) ethyl] -hexahydropyridine -2,6-dione; 1- [2- (7glucose-2,3-dioxo-1,2,3,4-tetrahydroquinazolin-5-yl) ethyl] -pyrrolidine; this paper Standards are applicable to Chinese national standards (CNS &gt; A4 specifications (210X297 gong)) -135- A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs V. Invention Description () N- {2- [2- (7 番 2, 3-dioxo-U, 3,4-tetrahydroquinoline ^ 5-yl) 2:]}-N-shipper: yl) amine; NR- {2- [2- (7-nitro-2 , 3-dioxo-1,2,3,4 · tetrahydroquinoline-5-yl) ethyl] quinoline-4-carboxamide; [2- (7-nitro-2,3-di Oxygen-1,2,3,4-tetrahydroquinoline-5-yl) ethyl] -methanesulfonamide; Ν- [2- (7 gene · 2,3-dioxo-1,2,3, 4-tetrahydroquinoline_5_yl) ethyl] -benzenesulfonamide; N- [2- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline -5-yl) ethyl] -acetamidamine; N- [2- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 titan) ethyl]-( 4-methoxy)- Amides. Embodiment 79: Lozenges (each containing 50 mg of an active ingredient, such as 7-bromo-2,3-dioxo-1,2,3,4 ~ tetrahydroquinoxaline-5-ylmethoxyacetic acid or a salt thereof) ) Can be prepared as follows: Composition 10,000 tablets) 500.0 g 500.0 g 352.0 g 8.0 g 60.0 g 10.0 g 20.0 g An appropriate amount of active ingredient is mixed with lactic acid and 292 g of potato starch, and the mixture is wetted with a gelatin ethanol solution and passed through The sieve is made into granules. After drying, mix the remaining potatoes, magnesium stearate, talc and silica into it, and press the mixture into lozenges, each weighing 145.0 mg and containing 50.0 mg of active ingredients; if necessary, lozenges can be prepared in splits The dents are thought of as a finer dose. Example Rib: Under heating and aseptic conditions, 20% cyclodextrin co-solvent and 3 mg of 7-bromo-2,3 · dioxo-1,2,3,4-tetrahydroquinoline-5- Methyl methoxyacetic acid or its salt (such as active ingredient lactose potato starch gelatin talc magnesium stearate silicon dioxide (high dispersibility) ethanol ethanol paper size applicable to Chinese national standards (CNS &gt; A4 size (2! 0 × 297 mm) please Read the back item first

Page order-136- i43 ^ 782 Λ7 __ B7 V. Description of the invention () Its sterile sodium gelatin solution is a sterile, gelatinized aqueous solution containing phenol as a preservative. If a sterile gelatin solution containing the agent is mixed, 1.0 ml of the solution contains The following composition: 3 mg of gelatin, 150.0 mg, 4.7 mg of distilled water containing 20% cyclodextrin co-solvent, 1.0 mg of MML, for the preparation of sterile dry matter for injection (containing 5 g of 7-bromo-2,3-dioxyl. 1,2,3,4-tetrahydroquinoline-5-ylmethoxyacetic acid or a salt thereof, such as its sodium salt), 5 ml of one of the compounds of formula IX mentioned in the previous example is dissolved as an active ingredient in 1 ml of an aqueous solution containing 20 mg of mannitol and 20% cyclodextrin as a co-solvent. The solution was aseptically filtered, and aseptically filled into 2 ml ampoules' and refrigerated and lyophilized-before use, the lyophilisate was dissolved in 1 ml of distilled water or 1 ml of physiological saline. The solution is for intramuscular or intravenous injection. This composition can also be enclosed in a dual-chamber injection ampoule. Embodiment 82: 10,000 film-coated tablets (each containing 100 mg of 7-bromo-2,3-dioxo-1,2,3,4-tetrahydrolin-5-ylmethoxyacetic acid or a salt thereof, For example, its sodium salt) can be prepared as follows: 1000 grams of active ingredients, printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, corn starch, 680 grams of colloidal silicic acid, 200 grams of magnesium stearate, 20 grams of stearic acid, 50 grams of sodium carboxymethyl starch, and 250 grams. Appropriate amount of water -137- This paper size applies Chinese National Standard (CNS) Λ4 specification (21〇297297 1) Boat 43 8 7 82 A7 87 V. Description of the invention () The formula (I) mentioned in the previous embodiment A mixture of the active ingredient of the compound, 50 grams of corn starch and colloidal silicic acid was processed into wet masses with 250 grams of corn starch and 12 g of mineral water. The wet mass was forced through a 3 mm mesh screen and dried in a fluidized bed dryer at 45 eC for 30 minutes. The dried granules were then pressed through a 1 mm mesh sieve and mixed with 300 g of corn starch, magnesium stearate, stearic acid and sodium hydroxymethyl starch sodium (1 mm) previously sieved, and Squeezed to form two-sided slightly convex lozenges. Example 83: By a method similar to that described in Examples 79 to 82, a pharmaceutical preparation containing different compounds of any one of Examples 1 to 78 can also be prepared. (Please read the precautions on the back before continuing on this page ¾) Order Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs This paper size applies to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) -138-

Claims (1)

‘438782 Patent Application No. 8511〇23〇 Amendment of Patent Application Scope (February 90) 6. Scope of patent application 1 A 2,3-dioxo1,2,3, cardiotetrakis-quinoxaline derivative or a salt thereof of formula (I), (I) (Please read the notes on the back before filling out this page), / -¾. One of the free radicals 1 ^ and 112 in the printed formula (I) of the Central Bureau of Standards, Ministry of Economic Affairs, Consumer Cooperatives is hydrogen, The other is the group of the formula _alk_N (R8) _x_ R7 (Ic), -alk-〇-X-R7 (Ie) or -aIk-SX-R7 (if), one of the radicals I and R4 is hydrogen, Halogen or nitro, the other is halogen or nitro, R · 7 is long group, C1-C4 right coagulation group, unsubstituted or killed 1 _c4 kneel, CrC4 alkoxy, mesogen, halogen and / Or trifluorofluorenyl substituted -C1-C4 alkyloxy group; is carbamate, unsubstituted or CrC4: phenyl, CVC4 alkoxy, mesyl, halogen, nitro, phenyl , Alkoxycarbonyl, phenyl, phenoxy, and / or anisolemethyl substituted with trifluoromethyl; is phosphonate, mono-, di or trialkylphosphonic acid or tetratyl, R8 is hydrogen, Ci-C ^ alkyl, or together with the bond rule 8 and the nitrogen atom of the parent to form Shenbihazyl, Hexahydro-P-Hexyl, or Hexa-H-P-Hexyl radical, this paper size applies China National Standards (CNS) A4 Specification U10X 297 mm Order-M '^ 4 Patent Application Range A8 fi $ C8 D8 alk is a C1-C4 alkyl group, and χ (unless it forms a part of the aforementioned ring system with Han 7 and Chi 8 and the bond center and another nitrogen atom) are direct bonds, C1_cyt alkyl, Alkylene, oxy-CrC4 alkylene (including carbonyl), oxygen_Ci_c4 alkylene, amine_CrC4 alkylene, carboxy_Ci_C4 alkylene, Ci_C4 alkoxycarbonyl_C1_C4 alkylene, 0 alkylene , Or a benzene-Ci-CU subgroup that is unsubstituted or substituted with a prime and / or trifluoromethyl group. 2 · If you apply for a patent, please! 2,3_dioxo · tetrazine_P quinol B-Linyl derivative or its salt of formula (1), which is N- (7-nitro-2,3-dioxo-1,2,3 , 4-tetrahydroquinoline_5-methylmethanamine-methylphosphonic acid or a salt thereof. 3. A type for treating _AMpA receptor, kainic acid receptor and corpus callosum glycine binding site A pharmaceutical composition for blocking the symptoms of the reaction, which comprises the compound or the pharmaceutically acceptable salt thereof in the scope of the patent application [or 2], together with the conventional pharmaceutical excipients and carriers. 4. A preparation formula (I) The method of the compound or its salt, (Please read the precautions on the back before filling this page)-* iMi?, Ministry of Economic Affairs, Central Standards Bureau, Industrial and Consumer Cooperation (I) One of the radicals 1 ^ and 2 is hydrogen, and the other is the formula _alk-N (Rg) _x_ -2-ABCD VI. Patent application scope R &gt; 7 (Ic), -alk-0-X -R7 (Ie) or -alk &gt; SX-R7 (If) one of the radicals R3 and R4 is hydrogen, dentin or nitro, the other is halogen or nitro, R7 is carboxyl, CMC4 alkoxy Carbonyl, unsubstituted or substituted with C ^ -CU fe, CI-C4 alkoxy, benzene-C i -C 4 alkoxycarbonyl substituted with a group, haloyl, and / or trifluorofluorenyl; is carbamate Fluorenyl, unsubstituted or substituted by C1-C4, alkoxy, mesyl, halogen, end group, carboxyl, Ci-CU alkoxycarbonyl, phenyl, phenoxy, and / or trifluoromethyl Substituted aniline methyl group; is a phosphonic acid group, mono-, di- or tri-C 丨 -C 4 alkylphosphonic acid group or tetrazolyl group, R8 is hydrogen, Ci-C4 alkyl group, or together with X and bonding With the nitrogen atom of X to form a benzyl group, a hexahydrophenyl group, or a hexaphenyl group, a phenyl group radical, alk is a Ci-C4 group group, and X (unless it is combined with rule 7 and Re and the nitrogen atom of R8 and X are bonded to form a part of the aforementioned ring system) is a direct bond, ci-c 7 sintered radical, central ladder of the Ministry of Economy f Cooperative printing (please read the notes on the back before filling this page) C!-C 4 alkylene, oxygen-C] -C 4 alkylene (including carbonyl), oxygen _ c 1 _ C4 alkenyl Amine, Cr-C ## yenyl group, ene-C〗 -C4 yetyl group, CJ-C4 oxycarbonyl-CrC # yenyl group, ω-β-α-oxy-alkylene or ω-acryl- α-oxy-C i -C 4 fluorenyl, or a benzene-Ci-C4 subunit that is unsubstituted or substituted with halogen and / or trifluoromethyl; wherein a) is in a compound of formula (II) , -3- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) Printed by the Employees 'Cooperatives of the Central Huahua Bureau of the Ministry of Economic Affairs δ? 82 Α8 m C8 D8' Scope of patent application (Wherein the radicals R and R &quot; are the same or different hydroxyl protecting groups, one of the radicals and R, 2 is hydrogen, and the other ▲ S-aik-ISKRO-X-RSdlc), -aU-〇_x_R ' 7 (iIe) or -alk-SX-R'7 (IIf) group 'where R, 7 is r7 group, protected carboxyl group or protected amine methyl group' and r'8 is R {t group or Amine protecting group, removing the hydroxyl protecting group R1 and / or R "and any amine protecting group r, 8, and from the protected groups R'7 or from the protected carbamoyl group R'7, Releasing any carboxyl or carbamate groups, and / or b) condensing the compounds of formula (III) and (iv) with each other, (ΙΠ) and Y2-X-ri7 (IV) (wherein one of the radicals R_'l and R &quot; 2 is hydrogen, and the other is the radical of the formula _alk · YJIIIa). Hydroxyl, fluorenyl, or HN (R8) groups, the other is a group that can be removed to form a bond, which is -4- this paper uses the Chinese National Standard (CNS) A4 specification (210X297 mm) (please read the back first) (Please note this page and fill in this page again) &quot; r A8 B8 C8 D8 VI. Patent application scope 7 feet, protected carboxyl group or protected amine formyl group and ruler, 8 is r8 group or amine protecting group) ' Removal of any amine protecting group R_8, and release of any carboxyl group or carbamoyl group from the protected carboxyl group R′7 or the protected amine f ′ group R′7, and if appropriate, will form The compound is converted into a different compound of formula (1), and the mixture of isomers obtained according to this method is separated into each component and the preferred isomers are isolated and / or the free compound obtained according to this method is converted into a salt 'Or convert the salt obtained in this way into a comparable free compound. (Please read the precautions on the back before filling in page j) s Standard Λ Befe Cooperative Co., Ltd.% -5- Chinese Standard for Paper Wave Scale Appropriate Angle (CNS &gt; A4 Grid (210X297 mm) Announcement 2.23 Issue '~~ Case No. 85110230 Category (Notes for the above sheds by the Bureau of the Bureau) A4 C4 433782 Amendment—Λ &gt; — ·! »-* ·; Shen Yun 丨 Hu Hu-Change-Patent Specification Chinese Invention 4 ^ Name English name Nationality Residence, residence name (name) 2,3 ~ ''-oxy-1,2,3,4-tetrahydroquinoline P if p linyl derivative 2,3-di〇x〇-i, 2, 3,4-tetrahydro-quinoxalinyl derivatives 1. Perry Akering 2. Hans Alger 3. Wes Oberson 4. Mitchell Boeraz 5. Robert Murray 6. Silvio Ofeno 7. Sim, Jakob Fynstra 1-3. 4. 5. 6. Both Switzerland 7. Netherlands 1. Switzerland 2. Germany 3. Switzerland 4. Switzerland 5. Switzerland 6. Switzerland 7. Switzerland. 4127 Bielsfelden, Stowe 23, No. 23 951 Le Lassie, No. 20, Lexson Road, 4123 Alsway, 7A, Kutzling Street, 4102 Binningen 'Industrial Room 31, 1627 Varuz, Shangte Morey No. 393, 4142 Ming Hingstein, No. 1 Main Street, 4053 Basel, No. 29 Pasing Street, Swiss Commercial Novartis Co., Ltd., Ordering, Printing, Production Line, Employee Cooperative Cooperative, Intellectual Property Bureau, Ministry of Economy, Nationality, Switzerland ) Name of Representative Arthur Kenneth Christopher * Tom No. 215, Schwarzswoolly Road, Basel, Switzerland The national standard (CNS) A4 size (210 X 297 mm) of this paper is applicable ίν Α, Λ · .-h J · ^ 〇 / Η ρ No. 85 丨 1〇23〇 · Chinese Application Manual Correction Page (June 1989) A7 B7, amendment 1 qq year, month and month, personal R R V. Description of the invention () group, ω-Πγ-α-oxy-low-level extension base or ω-x-γ-α-oxy-low-level extension storage base), or react with the formula RVX-C (= 〇)- 0-C (= 0) -X-R7 (IVc) carboxylic anhydride (where X is lower alkylene, lower alkylene or one bond) is reacted. The starting material of formula (m) can be prepared by a method known per se, such as the side chain of a compound of formula (Vffl), RM ,, R ', and R.R. N OR &quot; (VIII) (please first (Please read the notes on the back and fill in this page again.) The Ministry of Economic Affairs, Central Bureau of Standards, Consumer Consumption Cooperative, printed with halogen 1 (such as N-bromosuccinimide in the presence of azo-isobutyronitrile). Into a corresponding compound of formula (VIII) (wherein one of the radicals R and R 2 is a group of formula 4), the other is a R 5 group (wherein halogen, especially bromine), and ΪΤ Is a hydroxy protecting group) and removing the hydroxy protecting group redundantly and "or, if necessary, will form a compound of formula (VIII) (wherein one of the radical ^^ and rule, is a formula -alk-Y, , The other is the R5 group (wherein Yi is halogen) using conventional methods, such as the use of alkaline hydrolysis (such as in the presence of potassium carbonate), to convert into equivalent compounds (m &gt; where the brother is a hydroxyl group), Or react with an alkali metal azide in dimethylformamide (such as sodium azide) and then with triphenyl in tetrahydrofuran Reaction, and in each case removes the hydroxyl protecting groups R1 and R &quot;, and converts them into equivalent compounds of formula (in) (wherein Y is an amine group). Method c) compounds of formula (Π) (wherein the radical R One of the R &quot; 2 is the R5 group, and the other is the protected amine group R'6 in the formula -alk-C (RV) (R'6) -RV (the base of na〇) is, for example , An amine group protected by an amine protecting group mentioned in method a), such as a lower alkylamino group or a lower alkoxycarbonylamino group. Protected carboxyl R'7 This paper uses Chinese national standard (CNS &gt; A4 size (2! 〇 &gt; &lt; 297 mm) -57- 8 2 A7 B7 Printed by the Consumer Cooperative of the Central Government Bureau of the Ministry of Economic Affairs. 5. Description of the invention () lH-NMR (250 MHz, CDCb) δ = 7.88, 7_57 (2 doublet, 2H), 4.20 (single peak, 2Η), 4.15, 4.12 (2 singlet, 2Me), 3.32 (single peak, 2Η), 1.42 (single peak, 9Η). Example 2: The following compounds were also prepared using a method similar to that described in Example 1: Hydrogen bromide N- (7-bromod, 3-dioxo-1,2,3,4-tetrahydroquinoxaline- 5-ylmethyl) -β-alanine, melting point = 271 ° C (decomposition); N- (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrobromide -5-ylmethyl)-(L &gt; glutamic acid, melting point = 220 ° C (decomposition); hydrobromide 1 ^ (7-bromo_2,3-dioxo-1,2,3,4-tetrahydro Quinoxaline-5-ylmethyl)-(L) -phenylalanine, melting point = 249 ° C (decomposition); dihydrobromide &lt; xN- (7-bromo-2,3-dioxo-1,2, 3,4 ~ tetrahydroquinoline-5-ylmethyl)-(L) -lysine, melting point = 256 ° C (decomposition): N- (7-bromo-2,3-dioxo-hydrobromide- 1,2,3,4-Tetrahydroquinoxaline-5-ylmethyl) -hexahydropyridine-2-carboxylic acid ethyl ester, melting point = 240 ° C (decomposition); N- (7-bromohydrobromide) -2 &gt; dioxo-1,2,3,4-tetrahydroquinoline-5 · methylformate &gt; · hexahydropyridine glacial ethyl carboxylate, melting point &gt; 250 ° C; hydrobrominated N- (7 -Bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -hexahydropyridine-3-epiate, melting point &gt; 260 eC; hydrobromination 7-bromo-M5-nitro-benzimidazole-1.ylmethyl) -1,4-dihydro-quinazolidine D-2-2,3-dione, Point = 246t: (decomposition); 7-bromo-5- (6 · nitro-benzimidazine) +1, wood dihydro-quinolinline-2,3-dione, melting point = 278 ° C (decomposed); Chinese National Standard (〇 阳) 8 4 specifications (2 丨 0 \ 297 male dragon) (Please read the precautions on the back before filling this page)-* 68-A7! ----- B7 iT date w. 5. Description of the invention () Complementing the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, Consumers Association, India Example 3: The following compounds were prepared by a method similar to that described in Example 1, but with 7-bromo, 5-Bromomethyl-2,3-dimethoxy-8-nitro-quinoline is substituted for 7-bromo-5-bromomethyl-2,3-dimethoxy · • xoline as the starting material: dihydrobromo N- (7-bromo-2,3-dioxo-8 · nitro-i, 2,3,4-tetrahydroquinoline-5-ylmethyl) dimethylamine-hexahydropyridine, melting point = 209 t (decomposition); N- (7-bromo-2,3-dioxo-8-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -1,2, 3,4 · Tetrahydroquinoline, melting point = 213 ° C (decomposition); N- (7-bromo · 2,3 · dioxo-8-nitro-1,2,3,4-tetrahydrobromide Quinoxaline-5-ylmethyl) -β-alanine, melting point = 254 ° C (decomposition); dihydrobromide ocN- (7-bromo-2,3-di -8-Nitro-1,2,3,4-tetrahydroquinoline, methylene amine acid, melting point = 180 ° C (decomposition); N_ (7- Mo-2,3 · dioxo-hydrobromide) 8-nitro-1,2,3,4-tetrahydroquinoline-5 · yltoluidine, melting point = 218 ° C (decomposition); N- (7-bromo-2,3-dioxohydrobromide -8-nitro-1,2,3 + tetrahydroquinoline_5_ylmethyl) · glycine, melting point = 238 ° C (decomposition); N- (7-bromo-2,3-hydrobromide) Dioxo-8-nitro-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -hexahydropyridine-4-uronic acid ethyl ester, melting point = 260 (decomposition). The starting materials can, for example, be prepared as follows: a) 7-bromo · 5-momethyl liao 3-dimethylargon-8 · nitrazine 20 ml of sulfuric acid is cooled to 0 ° C, and then 5 g (13-8 ml) Moore) 7-bromo-5-bromomethyl-2,3-dimethoxy-quinoxaline. After another 15 minutes, 1.46 g (1.05 equivalent) of potassium nitrate was added, and the mixture was stirred at 20 ° C for 15 hours. The mixture was poured onto ice, and the solid was filtered off and washed with water to give the title compound as a beige solid. This paper size applies to the Chinese National Ladder (CNS) A4 specification (210 X 邛 7 mm) (Please read the precautions on the back before filling out this page) Order-69- A7 B7 The suspension was concentrated, dried and purified on a silica gel column using dichloromethane / hexane / ether (8: 4: 1) as the eluent. After concentration and drying under high vacuum, the title compound was obtained as a substantially colorless honey, which consisted of a cis / trans isomer mixture in a ratio of about 2: 3. W-NMR (300 MHz »CDC13) 7.87 (doublet, IΗζ» 0.4H), 7'83 (dual bee, IΗζ »0.6Η), 7.4-7.15 (multiple peak, 6Η), 5.10 (single peak, 1.2Η), 5.00 (single peak, 0.8Η), 4.15 (single peak, UH), 4.12 (single peak, 1.8Η), 4.09 (single peak, 3Η), 3.82 (single peak, 1.2Η), 3J5 (single Peak, 0.8Η), 3.03 (single peak, 1.2Η), 2.98 (single peak, 1.8Η). Example 45: N- (7-bromo-2,3-dioxo-U, 3,4 ~ tetrakisquinolin-5-ylmethyl) · «-ι Under nitrogen pressure, 255 mg (0.607 mmol) Moore) N- (7-bromo-2,3-dimethoxy-quinoline-5- «methyl) -ct-amine-phosphonic acid dimethyl ester was dissolved in 5 ml of absolute dichloromethane and 0.33 ml (2.55 mmol) of trimethylsilyl bromide was added at room temperature. After stirring at room temperature for 3 hours, 5 ml of ethanol was added, and stirring was continued for another 22 hours at room temperature. The mixture was then concentrated to dryness. 5 ml of ΗΒΓ (33% in glacial acetic acid) was added to the gray-brown foam, and the mixture was stirred at room temperature for 3 hours before being concentrated to dryness again. The beige residue was dissolved in a K2C05 solution (about 1N in water). The pH was adjusted to 6 with dilute hydrochloric acid, and the suspension was filtered while hot. Hot DMF was added to the filtrate, and then a small amount of ethanol was added until the mixture appeared slightly turbid. The title compound was isolated as gray-brown crystals within 3 days. iH-NMR (300 MHz »D20) 7.53 (broad singlet, 1H), 7.47 (broad singlet, IH), 4.57 (broad singlet, 2H), 3.15 (duplex bee, 11.8Hz» 2H); 3IP- NMR 8 ppm; MS (FAB4) 364,366 [M + H +] &quot;, (FAB ·) 362, 364 Melting point> 270 ° C »The starting materials can be, for example, prepared as follows: a) Bromine-2,3-di Methoxy-quinol-5-ylmethyl V three papers This paper size is applicable to the Chinese national plug (CNS M4 specification (2 丨 0X297) 浼 ΊΊΊ .............. f: ;-ς Μ (please read the notes on the back before filling this page) Order printed by the Ministry of Economic Affairs t Central Standard Bureau employee consumer cooperatives Α7 Β7, u printed by the Central Standard Bureau employee consumer cooperatives of the Ministry of Economic Affairs ()-2.98 g (10 mmol) (7-bromo-2,3-dimethoxy-sialoline-5 · ylmethyl) -amine is heated and dissolved in 40 ml of ethanol. After cooling to room temperature 1 ml of formaldehyde aqueous solution (37% in water) was added dropwise to the light yellow solution. After the addition was completed, the product settled out as a colorless precipitate. After stirring for 3 hours, the precipitate was filtered out and β was dried under high airspace To get the title of colorless amorphous block W-NMR (300 MHz »CDC13) δ 7.83 (doublet, 2.31¾ 3Η), 7.72 (doublet, 2.3Hz» 3H), 4.24 (single peak, 6H), 4_13 (single peak , 9H), 4.04 (single peak, 9H), 3.69 (broad singlet, 6H). MS (FAB): 930, 932. 丨 ㈤ b) Ν- (7- 莫 -2,3-dimethylene- Sleepy Team-5-A methylformate at 0 ° C and nitrogen pressure: 0.23 ml (2.5 mmoles) of dimethyl phosphite, 0383 ml (2.75 mmoles) of triethylamine and 0.476 ml ( 3.75 mmoles of trimethylsilyl chloride in 25 ml of dichloromethane. After stirring at 0 ° C for 15 minutes, 0.78 g (0.83 mmoles) of tri-N &lt; 7-bromo-2, was added dropwise. A solution of 3-dimethoxy-coline_5-ylformate) in three ml of dichloromethane. After stirring at room temperature for 30 hours, the suspension was poured into ice-cold hydrochloric acid (0JN in water). 3 parts of ether were added. The organic phase was extracted by shaking with a 0.1 N aqueous hydrochloric acid solution. The collected organic phase was adjusted to a pH of 12 to U with K2C03, and extracted 6 times with chloroform. The organic phase was dried over magnesium sulfate and concentrated. After that, a yellow oil was obtained, which was tied to a silica gel column and used Acetate / dichloromethane / ethanol 10: 10: 1 was purified to elution. After concentration and drying under high vacuum, the title compound was obtained as a glassy, light yellow oil. W-NMR (300 MHz ^ CDCl3) 7.88 (doublet, 2.3Hz, 1H), 7.54 (doublet, 2.3Hz, 1H), 4.25 (single peak, 2HX 4.15 (single peak, 狃), 4.14 (single peak) (Peak, 昍), 3.78 (doublet, 10Hz, 6H), 2.95 (doublet, 13.1Hz, 2H), MS (ES +) 422,420 (ΜΗ &quot;). This paper standard applies to China's national standard &lt; CNS} Λ4 specification (2) 0X297 male t) ----------- ./-&lt; Please read the notes on the back before filling in this page) Order -98- ./¾. A7 B7 V. Description of the invention () 丨 Supplement ') 1 d. + _____________ Crystallize to give the title compound as pale yellow crystals. Melting point: 147-149 ° C; TLC (EtOAc / hexane 1: 3): Rf = 0.25. c) cis-2-fN-g3-dimethyl ¥ -7-nitro-quinazol-5-ylmethyl) amine 1-cyclohexyl · carboxylic acid 105 mg (0.588 mmol) cis_2_ Amine-cyclohexylcarboxylic acid and 82 μl (0.588 mmol) of triethylamine were continuously added to 129 mg (0.490 mmol) of 2,3-dimethoxy-7-nitro-sialylin-5. 1 ml of dichloromethane and 2 ml of ethanol. After stirring at room temperature for 3 hours, 1 g of anhydrous sodium sulfate was added to the suspension, and the mixture was stirred at room temperature for another 20 hours. The concentrated suspension was diluted with 0.5 ml of ethanol and 46 mg (.1.23 mmol) of sodium borohydride was added. After stirring for 3 hours, 0.5 ml of acetone was added, and after 10 minutes, 0.3 ml of acetic acid was added and filtered. The filter residue was washed with ethanol and dichloromethane. The filtrate was chromatographed on silica gel with dichloromethane / ethyl acetate (97: 3) * and then with dichloromethane / methanol / glacial acetic acid (90: 9: 1) to give the title compound as a white powder. Example 57: The following compounds were also prepared using a method similar to that described in Example 56: N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline hydrobromide -5-ylmethyl) amine moiety phosphonic acid 'ES-MS: [Μ-Η] · = 329; ^ -NMR (DMSO-de + DC1): 8.30 (doublet, J = 2 for 1H), 8.17 ( Doublet 'J = 2 for 1H), 4.52 (single peak, 2H), 3_30 (Doublet, J = 15 for 2H); HPLC: CH3CN / H20 + 0.1% CF3C00H, 0 to 3, 5 minutes, 5 : 95 isocratic, 3.5 to 7.5 minutes, gradient change to 100: 0, Rt = 3.7 minutes (MN Nucleosil 100, C18, 5 is called 250 X 4 mm, 1 ml / min); hydrochloride 1 ^-(7-nitrate -2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-5-ylmethyl &gt; amine ~ (3-methoxybenzene &gt; methylphosphonic acid, FAB-MS: M + = 436; HPLC: bHaCN / KW) 40.1% trifluoroacetic acid 20:80 Rt = 4.2 minutes. (NucieosiHOO. C18, 5 μΜ, 250 X 4.6 mm, 1 ml / minute); This paper scale applies Chinese National Standard (CNS) A4 regulations "Grid (210X297)" (Please read the precautions on the reverse side before filling out this page) Q Order Printed by the Central Laboratories of the Ministry of Economic Affairs, Printed by Consumer Cooperatives -107- Central Laboratories of the Ministry of Economic Affairs, Shellfish Printed by Fei Cooperative A7 B7 V. Description of the invention () 1 ----------- Hydrobromination [C7-nitro-2,3-dioxo-1, 2Λ4 · tetrahydroquinoline-5 Dimethylamine K3-hydroxy-benzene &gt; methyl] -phosphonic acid, FAB-MS: M + = 422; HPLC: CH3CN / H2 + 0.1% trifluoroacetic acid 20 R = 2, 9 minutes. (NucleosiLiOO. C18, 5 μΗ 250 X 4.6 mm, 1 ml / min); N- (7-nitro-2,3-dioxo-1,2,3,4-tetraarginine-5-ylformate)- Ν-[(4 · diethoxy-phosphonium phosphonium> &gt; benzyl] • amine, ESCT-MS: (MH) + = 421; DC: methylene chloride / methanol / acetic acid (9: 1) Rf = 0.28; hydrogen bromine N- (7-nitro-2,3.dioxo-1,2,3,4 · tetrahydroquinoline-5-ylmethyl) -3-amine-propanephosphonic acid 'FAB-MS: [M + H] + = 345; HPLC: CH3CN / H2〇 + 0.1% trifluoroacetic acid 20:80, RT = 3.1 minutes (Nucleosi L100. C18, 5 μM, 250 X 4.6mm, 1 ml / min); Ammonia bromide N -(7-Nitro · 2,3-dioxo-1,2,3,4 * tetrahydroquinophorphyrin_5_ylmethyl &gt; 2-amine-2-benzene-ethylcarboxylic acid, ES-MS: [ M + H] + = 385; ^ -NMRCDMSO-A + DC1); 8.20 (doublet, J = 3¾ 1Η), 8.05 (doublet, J = 3¾ 1Η), 7.7-7.4 (multiple bee ' 5Η), 4.85 (multiple peak, 1H), 4.51, 4.15 (AB, J = 14Hz, 2H), 3.46, 3.03 (AB.d, J = 15Hz, J = 10Hz, 2H); HPLC: CH3CN / H20 + 0.1% CF3COOH, 0 to 6 minutes, gradient: 0_0, RT = 1.2 minutes., Waters Symmetry C18, 3.5 μιη »100 people 50 χ 2.1 mm, 0-5 ml / minute; hydrobromide trans-2- [N &lt; 7-nitro-2,3 · dioxo-1,2,3,4-tetrahydroquinoxaline-5-yl form) Amine] -Cyclopropane · 1 · Phosphonic acid, melting point> 340 ° C; FAB-MS: [Μ-Η] · = 355; HPLC: CH3CN / H20 + 0.1% CF3COOH, 0 to 6 minutes, gradient: 0 to 100, RT = 4.0 minutes, Waters Symmetry C18, 3.5 called 100 Α »50 x 2.1 series 0.5 ml / min; 4- [N- (7 soul-2,3-dioxo-1, 2,3,4-quad Hydroquinoline-5-ylmethyl) amine] -butyric acid, FAB-MS: M + = 322; DC: methanol / acetic acid (9: 1) RHX30. Example 58: Tritiated N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinazolin-5-yl_methylamine methyl V tetrazole 160 mg (0.461 Millimolar) N- (2,3-Dimethoxy-7-nitrate-rhodolin-5-ylmethylamine methyl) -tetrazole was stirred under reflux in 6 ml of 2NHC1 aqueous solution for 20 hours. The reaction mixture was cooled , And the formed solid was filtered off, washed with ether. Melting point = 230 t (decomposed). The starting materials can be prepared, for example, as follows: This paper is scaled to the Chinese National Standards-(CNS) Λ4 grid (21〇 Χ2ί &gt; 7 males) (Please read the precautions on the back before filling in this page) I ir ^ '^, order -108- 87 82 A7 B7 ΎΓ1月年月月修正五 5. Description of invention () -ϋ Dihydrobromide Ν -(7-Nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylformate> 4-methylpyridylamine, melting point = 218 ° C (decomposition): dihydrogen N- (7-nitro_2,3-dioxo-1,2,3,4_tetrahydroquinoxaline-5-ylmethyl) -2-methylpyridineamine, melting point = 229 eC (decomposition) : NH- (7 · ^ -2,3-dioxo-1,2,3,4-tetrahydroquinamline-5 sparcarol) -amine acetonitrile, melting point = 275 ° C (decomposition); hydrogen Brominated N- (7 · NO-I-Dipyridine-1,2,3,4 · Tetrahydroquinoline_5 · methylformate> 4-take benzylhexahydropyridine, melting point = 242 ° C (decomposition); hydrochloride N-C7-nitro-2 &gt; dioxo-I, 2, 3, 4 -Tetrahydroquinoline-5-ylformate> 4-phenylhexaoxopylic acid, melting point> 280 ° C: N- (7-nitro-2,3-dioxo-1,2 hydrobromide) , 3,4-Tetrahydroquinoxaline-5-ylmethyl) -4-aminocarbamate hexahydropyridine, melting point &gt; 300 ° C; N- (7-nitro-2,3-dioxo-hydrochloride) 1,2,3,4-tetrahydroquinoline, 5-methylformate> 3-methyl-β-alanine, melting point = 298 eC (decomposition): hydrobromide 1 ^-(7 genera-2,3 -Dioxo-1,2,3,4 »tetrahydroquinazepam * 5-ylformyl> 4-benzylmethoxycarbonyl-hexahydropyridine, melting point = 258 ° C (decomposition); hydrochloride N- (7-Nitro-2,3-dioxo-1,2Λ4 · tetrahydroquinoline-5-ylformate> imine oxalic acid, melting point = 257 ° C (decomposition); employee of Central Standards Bureau Printed by Consumer Cooperatives (please read the notes on the back before filling this page) Hydrobromide N- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 -Methylformate &gt; 1,2,3,4 ~ tetrahydroisoquinoline, melting point = 300 ° C (decomposition); N-C7-nitro_2,3 · dioxo-I, 2,3, hydrobromide 4-tetrahydroquinoline-5-ylformate &gt; 2-aminebenzothiazole, molten = 272 t (decomposition); 1- (7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethylamine) ethylphosphonic acid, melting point = 246 ° C (Decomposition); N_ (7-nitro_2,3-dioxo-1,3,4-tetrahydroquinone beer-5-ylmethyl) -N-acetamidine- (L) -alanine; this paper Standards are applicable to Chinese national standard (CNS) A4 (210X297 mm) -127- forging 43 8 A7 B7 Printed by the Bayer Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention () N- (7- Desert-2, 3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl)-(1-methylpyrrole &gt; 2-endrimidine, melting point &gt; 280 ° C; hydrochloride N- (7-bromo-2,3-dioxo-1,2,3,4 »tetrahydroquinolinline-5-ylmethyl) -sufatin, melting point = 272 t (decomposition): 乂 (7-bromo -2,3-dioxo-1,2,3,4 ~ tetrahydroquinoline-5-ylformate> (4 »nitrophenyl) acetamidine, melting point> 270 ° C; ； (7-bromo -2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl)-(3-nitrophenyl) acetamidine, melting point &gt; 270 ° C; &gt; ^-( 7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylformate> (2-nitrophenyl) acetamidine, melting point> 270 ° C; Ν · &lt; 7-bromo-2,3-dioxo-1,2,3,4 · tetrahydroquinoline-t-methylmethyl3,4-methylenedioxybenzene) -acetamidine , Melting point &gt; 270 ° C; Ν-ΟBr_2,3-dioxo-1,2,3,4-tetrahydroquinoxaline "5 · methylformamidine 3-phenoxybenzene) -acetamide; Ν -(7-bromo-2,3 · dioxo-12,3,4-tetrahydroquinolinline-5-carboxyl) -2-pyridinecarboxamide; 7-bromo-2,3-dioxo · 1 , 2,3,4 · Tetrahydroquinoxaline-5-ylmethylamine methylphosphonic acid, melting point &gt; 270 ° C; 1- (7-bromo-2,3-dioxo · 1,2,3, 4-tetrahydro-pyridin-5-ylmethylamine) ethanephosphonic acid, NMR (25 MHz DMSO-4) δ (ρρ; η) = 12.2 (single peak, NH); 7,45, 7.35 (2 Doublet, 2 Harom); 4.48, 4.40 (2 doublet, CH2); 3.50 (multiplet, 1H); 1.42 (quartet, Me); N-C7-bromo-2 &gt; dioxo-U, 3,4-tetrahydroquinoxaline-5_ylmethyl) -N-benzyloxycarbonyl-amine-methylphosphonic acid N_ (7.bromo-2 &gt; dioxo-1,2,3,4-tetrahydroquinidine S--5-ylmethyl) Ethyl carbamic acid hydrazone (7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5 cymene) anilide ethyl ester N- ( 7-bromo-2,3-dioxo-1,2,3,4-tetrahydroquinoline-5-ylmethyl) -N-phenethylhydrazone-amine-methylphosphonic acid N &lt; 7-bromo-2, 3 · Dioxo-1,2,3,4-tetrahydroquinolinline-5-ylmethyl) -N-phenethylhydrazone-glycine; Hydrobromide 3-ethyl-1--1- (7-nitro- 2,3-dioxo-1,2,3,4 &gt; tetrahydroquinoxaline-5-ylformyl) -pyrroleMelting point = 225 ° C (decomposition); -f--_ _If-iE. (Please read the notes on the back before filling in this I "-, π- line; This paper size applies to Chinese national standards (CNS &gt; 8 4 specifications (210X29 -/ Cabin) -132- Boat 438782 Revised Chinese Specification for Patent Application No. 85110230 (February 90) IV. Abstract of Chinese Invention (Name of Invention: '2,3-Dioxo-, 2,3,4-Tetrahydro-quinoline Derivatives) 2,3-dioxo-1,2,3,4-tetrahydro-fluorinyl derivatives of formula (I) One of the radicals and 112 in the formula is a dagger group, and the other is the formula "01 (1 ^)-孤 -117 Office), 41 Jean-CH (R«)-R7 (lb) '-alk- N (Rg) -X-R7 (Ic) '-alk-? &R; r (Rg) (R9) -X-R7A · (Id)' -alk-OX-R7 (Ie) or -alk-SX-R7 (If), R3, R4, and K · 5 are each independently hydrogen, lower alkyl, halogen, trifluoromethyl, cyano, or nitro; unsubstituted or lower alkylated and / or Lower alkylated amine group, r7 is hydrogen, aliphatic-, cycloaliphatic, or heterocyclic aliphatic radical, fluorenyl group derived from carbonic acid or half carbonate or hexamethylene carbonate, cyano, and sulfuric acid Or aliphatic- or aromatic sulfonic acid or phosphoric acid or phosphonate-derived fluorenyl, unsubstituted or substituted with aliphatic or araliphatic and / or aliphatic-, araliphatic-, or aromatic fluorene Amine-substituted amine, or aromatic- or heteroaromatic free radicals, r8 is hydrogen, aliphatic- or araliphatic radical, or by aliphatic- or araliphatic carboxylic acid or carbonate half-ester or carbonic acid Aryl aliphatic half-ester-derived fluorenyl groups, or &amp; and 118 together with X 'and bond ^ with another nitrogen atom to form unsubstituted or substituted via nitrogen atom bond Mono- or di-acylcycloalkyl, acryl Ofcycloalkyl, azithiacycloalkyl or selectively oxidized thiacycloalkyl radicals, or unsubstituted or substituted, selectively partially hydrogenated The aryl or heteroaryl radical is free. R9 is an aliphatic- or araliphatic radical, or a chiral 7, &amp; and together with X and bonding Rs, chi9 and another nitrogen atom are formed via a fourth nitrogen An atomically bonded unsubstituted or substituted fourth heteroaryl radical, and A_ is an anion of a protonic acid, alk is a lower alkylene group, and X (unless it is accompanied by &amp; and 118 and bond 118 And another nitrogen atom, or together with the nitrogen atom R8, R9, and X bond to form a part of the aforementioned ring system) is a divalent aliphatic ... cycloaliphatic-or araliphatic radical or direct bond, It and its pharmaceutically acceptable salts can be used to prepare medicines for treating pathological symptoms that block the glycine-binding site of AMPA, kainic acid, and / or NMDA receptors. ‘438782 Patent Application No. 8511〇23〇 Amendment of Patent Application Scope (February 90) 6. Scope of patent application 1 A 2,3-dioxo1,2,3, cardiotetrakis-quinoxaline derivative or a salt thereof of formula (I), (I) (Please read the notes on the back before filling out this page), / -¾. One of the free radicals 1 ^ and 112 in the printed formula (I) of the Central Bureau of Standards, Ministry of Economic Affairs, Consumer Cooperatives is hydrogen, The other is the group of the formula _alk_N (R8) _x_ R7 (Ic), -alk-〇-X-R7 (Ie) or -aIk-SX-R7 (if), one of the radicals I and R4 is hydrogen, Halogen or nitro, the other is halogen or nitro, R · 7 is long group, C1-C4 right coagulation group, unsubstituted or killed 1 _c4 kneel, CrC4 alkoxy, mesogen, halogen and / Or trifluorofluorenyl substituted -C1-C4 alkyloxy group; is carbamate, unsubstituted or CrC4: phenyl, CVC4 alkoxy, mesyl, halogen, nitro, phenyl , Alkoxycarbonyl, phenyl, phenoxy, and / or anisolemethyl substituted with trifluoromethyl; is phosphonate, mono-, di or trialkylphosphonic acid or tetratyl, R8 is hydrogen, Ci-C ^ alkyl, or together with the bond rule 8 and the nitrogen atom of the parent to form Shenbihazyl, Hexahydro-P-Hexyl, or Hexa-H-P-Hexyl radical, this paper size applies China National Standards (CNS) A4 Specification U10X 297 mm Order-M