TW438797B - Triazine containing anionic compounds useful as antiviral agents - Google Patents

Abstract

This invention provides triazine ring containing anionic compounds, pharmaceutical compositions containing these compounds and methods utilizing these compounds for treating viral infections, particularly infections by respiratory syncitial virus, the compounds having the general structure, and the pharmaceutically acceptable salt thereof.

Description

Printed by the Central Consumers Cooperative of the Ministry of Economic Affairs 1 ^ 43 8 7 9 7 a? B7 V. Description of the invention (') The present invention is about a new triad ring containing anionic compounds, which is effective for treating viruses. Not the human respiratory syncytial virus [HUSV]. The present invention also guarantees methods for treating viral infections and thus vulnerabilities to pharmaceutical compositions. Flfl background Human respiratory syncytial virus (HRSV) was first discovered and distributed in lg56 in the Golden World. It is an important cause of babies and young children suffering from upper and lower respiratory tract diseases. It causes about 100, 000 (j inpatients and 5, 0 [q]) deaths each year in the United States (Chanock, R.H., KU , η. k., Brandt, c. d, and Parrott 'R. Η. 1982. Respiratory syncytial virus, pp 4 7 1-4 8 9, in Viral Infections of flufflans, Second Edition, AS Evans, editor (Plenuia Press, NY).

G 1 ezen, WP ·, T aber, L · H., F rank, A · L., And K ase 1, J. A ·, 1 9 86, Risk of primary infecti〇nfti < einfecti〇n with respiratory syncytial virus, A bi. j 〇is 〇hil 14 0; 5 4 3-5 4 6. MacDonald, NE, Hall, c. B Suffin S.C., Alexson. C., Harris, P. j., & Hauning j A 1982 · Respiratory syncytial virus infection in infants with congenital heart disease. New England Journal of Medicine 3 0 7; 397-400) 0 About 30% of young children hospitalized for acute respiratory diseases have respiratory syncytial virus infection. For older children and adults, the disease is less severe. HRSV is obviously also the main cause of illness and death in the elderly (equivalent to influenza) (Fleming, β. M. and Cross, K, if. 199 3. -3- This paper standard applies Chinese National Standard (CNS) A4 Specifications (210X297 mm) (Please read the notes on the back before filling out this page) 袈. Order A7 B7 Printed by the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (>) 1 1 Re SP irat 〇rysyncytia 1 V ir υ S 0 Γ i R f 1 ue η 2 a 9 Lancet 1 1 3 4 2; 1 50 7-15 10) 0 Respiratory syncytial virus can reach sections of respiratory tract 1 > usually accompanied by fever » Cough »Runny nose and tiredness > And in the immediate 1st 1 bed t diagnosed with bronchitis bronchiolitis 3 persimmon 1 roar or virus reading on the back 1 infection 0 for older children and adults 病毒 The virus is usually limited to Upper respiratory tract I-1 is replicated. When the umulus tract expands to the lungs, the infant is more beta. Severely drawn attention I 0 Lung injury can be permanent 0 Matter 1 I The first infection of re-respiratory syncytial virus occurs early in life and is usually caused by this virus in Q children who are 4 years old Tends per page— > 1 year at least once in I »Sudden period of several months of holding mines 0 Epidemics are usually limited to 3 to 5 months Month 0 Family studies Middle and lower grade school children often introduce virus 1 I into homes 9 Heavier dyed mussels in the family spine are heavier than their younger ones. The clinical results of infection in the family are the heaviest when they are infected for the first time, and 1) they have undergone immune changes in the growing carcass. To mitigate the effects of 0 t I respiratory syncytial virus from non-dominant to severe pneumonia1 | and death In the case of 1 1 in 1 to 3 weeks of insertion due to the production of antibody UkC- (significantly remained in m-TF- life 1) and complete recovery 0 in the United States J about 30% of one-year-old infants with 1 1 1 95% of five-year-old children sdc. Respiratory syncytial virus antibodies with rtnr loops in 0 0 1 1 Larger babies with antibodies' Most infected children and adults develop reinfection. I fsi m Relief of upper respiratory diseases For infants and young children Ϊ disease is treated with the antiviral agent dioxazole riboside (Γ ibavivi η) which is widely used. The use of this chemical compound is restricted due to its toxicity. Therefore, a new therapeutic agent for the treatment of 1 IHRSV infection is urgently needed. 0 1 1 -4 1 1 ii This paper is in accordance with Chinese National Standard (CNS) A4 (210X29? Mm) NM3 87 9 7 A7 B7 V. Description of the invention (5) US Patent No. 5,359,131 teaches stilbene sulphonate, 15 of which is hindered by herpes simplex virus (HSV), human immunodeficiency virus (HIV) ) And cytomegalovirus (CMV) -induced cellular infections. The present invention relates to a novel triple well ring anionic compound, which exhibits antiviral activity, especially human respiratory syncytial virus [HiiSV] activity. The present invention is based on a novel compound selected from the general formula I: X jh \,, / ~ \ N — A— B ′ — ^ N BU N = {/ = \ Formula ^^^ 1 ^^^^ 1 ^^^^ 1 n ^ n HH--B ^ ϋ ^^^^ 1 ^^^^ 1 nfl ^ ^^^^ 1 ". (Please read the notes on the back before filling this page) Among them: Economy Printed by the Central Standard of the Ministry of Education

A is a group 遘

anti-

C 'C, ▲. Each -5 paper size applies Chinese National Standard (CNS) A4 specification (210X 297 mm_) PA 3 A7 B7 V. Description of the invention (4) C 'is selected from -S〇3H, -OSO 3 Η, -OH , Or -C00H; B · is -N IK-Ο 1 or 0; R1 is selected from Η, straight 鐽 or lower alkyl, wherein the carbon atom may be substituted by WC1, Br, F, 0H or CN as appropriate; X is Cb F , Or a group of the formula

U'W '' is selected from -S〇2, -CO, -NC (0), or -NC (S);

• Stems from the following groups Z Y *

Z

-N Y,

Z

/ (-N ^ CH2) r Z or f == ^ N ^ (CH2)-—---—-^^^ 1 — ^ n. ^^^ 1 I 1 ^ 1 ^ 1 ^^^ 1 \ ~ ^ (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs Y is-(CH 2) n-; η is 0 to 6; a is 0 to 2; Z select From H, CH3, CF3, -CH2- (halogen), where halogen is C1, Br, F, or I, -CH2 0H, -C00H, -COO (Ci-Cs) straight R2 / 鐽 or branch low Carboalkyl, -CONR 2 R 2, CN or _CH \; and OH R2 are each selected from H or (Ci -Ce) lower alkyl; It can be understood that when m is 0, W 'can be a 5-membered ring. The permissive salts of the compounds of the present invention are their cations, which are applicable to the national standard (CNS) Λ4 specification (210X 297 mm) of the paper when the paper size reaches ~ 6 ~. Preparation A7 B7 V. Description of the invention (5) The desired effect without any significant pharmacological activity is essentially non-toxic at a dosage. By way of illustration, these salts include their alkali metals such as Na or K; soil testing gold such as Ca or Mg; included Ha group light gold tincture; and organic grade, dihydrazone with dioxamine or ammonia, Sodium salt is preferred. The detailed description clearly shows that among the group of compounds defined by formula I, compounds of a specific subgroup are generally preferred. Generally preferred are their compounds, or their peony allowable salts, where A is C,

Particularly preferred are compounds, where C '= -S〇3H, B' = -NH, Y = -CH2-, Z = -CH2〇H. The best are compounds, where C = -S〇3H, B ' = -NH, Y = -CH2CH2-, Z = -CONH2 The most highly preferred compound is, where A is

And C '= -S〇3H, B = -NH, Y = -CH2CH2-, Z = -C0NH2 The novel compounds of the present invention can be prepared according to the following outline. Referring to sketch I, intermediate 1 is obtained by condensing with a triple well (where X is Cl, F or Br) of structure 2_ at about ου and pH of about 6.5 to about 7.2 (where A and L are as defined above). Further at a temperature of about 451 to about 5510 and 0 «6.5-7.2-7-This paper size applies the Chinese National Standard (CNS) A4 specification (2! 0X 297 mm) ^^^ 1 I ^^^ 1 HH ^ — ^^ 1 ^^^^ 1 In ml lJ ws., Va (Please read the precautions on the back before filling in this page) ^ -43 87 9 7 A7 B7 V. Description of the invention (

The compound of formula 4_ is reacted with the compound of formula L (where (Γ, B 'and 1T are as defined above), and then the desired product of formula I above is obtained at pH 6.5-7.2 and 100-120t: For L. tick_ I 2

χγΝγ ΝγΝ X

X 0 * C; pH 6.5-7.2 (Please read the precautions on the back before filling this page) 袈. 11 Α

Χ N = (B- (x N

X order 4 2 / = \ hbhQ, U'W'5 i 45-55'C; pH 6.5-7.2 ii 100-120 * C; pH 6.5-7.2 Employees' cooperation with the Central Standards Bureau of the Ministry of Economic Affairs Du printed manufacturing type I The alternative route of the compound, as shown in sketch I, is to make the triple well (where X is Π, Br or F) at about -5_ to about 5t: and pH6.5-7.2 -8-This paper size applies Chinese national standards ( CNS) A4 specification (210 X 297 mm) > V. Description of the invention (Α7 Β7 reacts with the compound (where B 'and ST are as defined above) to obtain the condensation product. At about 45 ^ to about 55 = 0 and "about 6.5 6_ (wherein 8 ′ and ST are defined as above and X is Cl, Br or F) at 1 to 7.2 (wherein A and B ′ are defined as above), then at about 100T: to about 120t and pH 6.5-7.2 Heating to get ί. Qi_ Π hb, hQx5 UW, 丫 丫 -5 -5 * C, pH 6.5-7.2 n · nn * nn — ^ ϋ m ^ J. (Please read the precautions on the back before filling this page) A-

B'-H U'W '6 2

i 45-55'C; ii 100-120 * C Economy. The Central Standards Bureau of the Ministry of Standards printed the starting compound L (shown in sketch I) and & _ (shown in sketch I) with- 9- This paper size is in accordance with Chinese National Standard (CMS) A4 specification (2 丨 0X 297 male f) V. Description of the invention (8 A7 B7 Trihydrazine 1 (where X is Cl, Br Or F) The stepwise condensation is similarly reacted in an aqueous or organic-aqueous medium in the presence of a suitable base such as sodium or potassium hydroxide, carbonate, phosphate or bicarbonate. Phosphate phosphate solution at pH 7.0 is preferred. The first step of condensation is carried out at a pH of about 4 to about 8, preferably a pH of about 6.5 to about 7.2, and a temperature of about -10T to about 30 °, preferably about -5C to 51. The third well derivative The exchange of three halogen atoms is achieved at the same pH range and about 10 C to about 7 0 υ, preferably at a temperature of about 45 υ to about 5 5 Γ. The exchange system of the third halogen atom of the triple well derivative is the same The pH range and temperature is about 80t to about 150T !, preferably from 100o to 120T: Formula 6_ (schema I) The exchange of the second or third halogen atom of the triple-well derivative is also performed in organic tritium. Such as trialkylamine (including triethylamine, diisopropylethylamine or N- (lower carbon> alkyl hexahydropyridine) in the presence of organic media. Used to outline the general outline of Σ and Ε The starting materials in the synthesis procedure can be obtained from the market or can be obtained according to H. Adkins, EF Steinbring, E. Pickering. J. A mer. Chem. So c., V. 46, p. 1917 (1924), Synthesized in British Patent No. 1,194,388 (June 10, 1970) and U.S. Patent No. 5,359,131 (October 25, 1994). The starting compound of Formula 2 (where B 'is oxygen) can be as shown in Fig. A Prepared from a substituted compound of formula 2 (B '=-NH2).

aM HNO, slightly 圔 Ba [n + = n] 4 1 _ i ο _ _ This paper size applies the Chinese National Standard (C: NS) Λ4 specification ('2I0X 297 mm) —ϋ ^^^^ 1 ^^^^ 1 One OJ (Please read the notes on the back before filling this page) h3o

A Μ M3 87 9 A7 B7 V. Description of the invention (9 Primary aromatic amines! (Where A is as defined above) and nitrous acid or other chemical reagents that diazotize primary amines with Μ (such as organic nitrite esters) The reaction produces a diazonium salt which is hydrolyzed to a compound of formula 9_ containing phenolic groups. Well Figure IV c

X

X

X C > ν

11 X X U'W '

Hr n ^ i ^^^^ 1 ^^^^ 1 fm nn ^ 11 4 ^^^^ 1-1J Wear τβ (Please read the precautions on the back before filling this page) Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Refer to the slightly round IV, stilbene series of compounds (丄 can be converted to bisbenzyl compounds by catalysis, conditions (hydrogen-Pd / C) or by known in the industry using M The phase M1 is transformed into the compound of dibenzyl hydrazone in the original condition (11) t H uang ~ M i η 1 ο n, J. Aner. Cheat. Soc. (1 948) 70, 280 2]. Z = _C00H丄 Compounds (U and U) can be used at f > H from 7_5 to 10.0, preferably from 8.0 to 8.5 and from 80 to 150 ^ ', preferably from 100 to 1201 〇 By the base -11 _ This paper size applies Chinese national standards (CNS) A4 specification (210X 297 mm) (ί = ^ 3 6/97 Α7 Β7 V. Description of the invention (10 hydrolysed to make compound (J_i) (略 _ V >:

RNVV Sight_ V C '

R

R C '

R '

12: R1 = HN

so2n, CH2CH2C〇NH2,

CH2CH2COOH

R = HN fly times ^ CH2CH2COOH so2n ch2ch2cooh 1 ^ 1 n ^ i- ........ I ^^^ 1 mu _ ^ ϋ ^^^ 1-----aJ. (Please read the first Note: Please fill in this page again.] R = printed by so2n (ch2ch2conh2) 2 m-aminobenzylamine u (where U 'is -so2 or -CO, Y and z are as defined above) Thumbnail VI synthesis. This paper size applies the Chinese National Standard (CNS) Λ4 specification (2 丨 0X297 mm) 5. Description of the invention (11) A7 B7

Circle VI

ν > υΛ a z

Hj / Pd o2isi / ^ ν / γ_ζ \ _ / ~ ΌΛν_ζ η2ν ~

In ^^^^ 1 — ^ n R ^^ — 1 m «H ^ I ^^^^ 1-mr ^^^^ 1 — ^ ϋ n ^ i-OJ (Please read the notes on the back before filling (This page) Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs, Interim Amine or Toluene Sulfonation (T. W. Greene, P. G. Η. Wilts, Protective Groups in Organic Chemistry, John Wiley & Sons, New York 1991, pp. 349-379) is transformed into m-nitrosulfonate 丄 I. The nitro compound li is then converted to an amine-compound 1-7 by a catalytic hydrogenation reaction (hydrogen-Pd / C). The hexahydrofluorene derivative n, 0 (wherein Z is -C00H or -C0NH2) was synthesized from 3,5-dihydropyridinedicarboxylic acid U according to the sketch V0. The reduction of the aromatic ring and the nitrotolyl sulfonation between the hexahydropyridine derivative D yields compound 20, which is a carboxyl-containing compound 21 or is converted to a carbamate-containing compound by esterification and ammonolysis. twenty two. -13- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 143 87 9 7 A7 B7 V. Description of the invention (12 HOOC ^^^ JCOOH-

Brachial_ Ml HOO

Hypt la

V °° H H U

NH3 / E10H

CH3N3 ^^-so2ci

COOH

COOH

1 '_ nn ί I] _. ^ I _ II n —ϋ T (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs The present invention also includes the treatment of viral infections in mammals The method is preferably a human method, which method comprises administering one or more compounds of the present invention and / or one or more compound S drugs to allow salt to infected mammals. Viral infections that can be treated using the compounds and methods of the present invention include those caused by human respiratory syncytial virus, herpes simplex virus, human giant cell virus, and flu influenza virus, particularly those caused by parainfluenza virus 3 . The compounds of the present invention can be administered to any desired method (including intranasal, axillary, topical, transdermal, intestinal, and intraperitoneal) to the required breastfeeding. 14- This paper applies the Chinese National Standard (CXS ) Λ4 specification (210X297mm) 14 3 8 Γ, 'Α7Β7 Printed by the Consumers' Cooperative of the Standards Bureau of the Ministry of Economic Affairs. 5. Description of invention (15). Can understand the treatment of mammals. It is better for humans to require various compounds of active compounds although various courses of treatment. It depends on various factors, including the age, gender, size, general health status and disease degree of a specific individual. Most with therapy. The antiviral effective amount of the compound to be administered here is generally administered daily M—or in multiple doses of about 0.5 mg / kg to about 500 mg / kg based on the weight of the animal. These doses are preferably administered two to four times a day in divided doses or in a sustained release form. For most large mammals, the total daily dose is from about 1 to 100 mg, preferably from about 2 to 80 mg. A dosage form suitable for the internal eye contains about 0.5 to 500 grams of the active compound directly mixed with a solid or liquid drug carrier. This dose of therapy can be adjusted to provide the best therapeutic response. For example, several divided doses may be administered each day or the dose may be proportionally reduced according to the urgent need of the therapeutic situation. The compounds of the invention may be administered with or without other antiviral agents. The present invention also includes a road medicine composition that can be used in these treatment methods. The osmium composition may include one or more compounds of the present invention. Or its κ 容许 allows a, and one or more 槩 槩 allowable carriers, diluents, excipients, fillers, binders, flavoring agents, and the like. For oral and oral administration, compounds containing the composition of the invention include solid or liquid compositions such as capsules, troches, dragees, pills, tablets, powders, cultures, solutions, suspensions and emulsions . The solid form may be encapsulated by hard or soft gelatin capsules and may contain commonly used peony allowable excipients, fillers, adjuvants, diluents, lubricants, disintegrating agents, suspensions or stabilizers and binding agents, including, But not limited to magnesium stearate, sodium lauryl sulfate, microcrystalline cellulose, polyvinylpyrrolidine, gelatin, full acid, arabic-15-i ^ in ^----n I. M · 1 1 —r m3., -0 (Please read the notes on the back before filling in this page) This paper size is applicable to China National Standard (C'NS) A4 specification (2〗 0 '乂 297mm; i) it Λ A7 B7 Printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs. 5. Description of the invention (14) 1 i Gelatin m sodium acid, composite silicic acid m \ calcium carbonate Λ glycine dextrin Λ 1 i I sucrose sorbic acid phosphate Calcium m Dicalcium acid% Calcium sulfate% Sugar Λ 1 1 Kaolin \ Glycol Sugar Alcohol Nanotalc Λ Dry starch (such as corn, please first 1 sweet potato or cassava starch) and gluten flour 0K can also include antioxidants Dimensional reading 1 1 Biotin E > Ascorbic acid BHT and BHA 〇 Such a preparation may contain a back 1 I 1 There are, for example, i from about 0.05 to about 90 ¾ Active ingredient and carrier combination J More preferably 1 I often Between about 5¾ and 60¾ by weight ΰ Matter 1 1 Liquid α Eye m Suitable excipients include diluent such as water t and drunk. Fill in this pack of ethanol benzyl alcohol and polyethylene glycol% with or without Surfactant Λ Suspension page 1 I agent or emulsifier 0 Suspension can be prepared in glycerol Ή liquid polyethylene glycol and its M compound in oil 1 1 Under normal storage and use conditions »These systems 1 1 agent contains a protection agent M to prevent the growth of microorganisms. The compounds of the present invention can also be diluted at physiologically acceptable levels such as sterile liquids or 1 mixtures thereof (including water · »salt water Λ aqueous dextrose and other Hair volume 1 I solution) Fermentation such as acetogenic isopropanol or ten >-Fermentation secondary fermentation such as malonyl m 1 1 or polyethylene glycol glycerol shrinkage such as 2, 2-dimethyl-1,3 _ _ 2. Pentamidine-4- 1 1 Methanol »Ethers such as poly (ethylene glycol) 400 strong drugs allow oils and fats I fatty acids m or glycerol m with or without added sleep drugs to allow surfactants such as I Sodium or acetamated acetylated fatty acid glyceride suspending agent if gum Λ! 1 carb omers, methyl cellulose, hydroxypropyl methyl cellulose or carboxymethyl cellulose I vitamin Λ emulsifier or medicine Adjuvants 〇 In all cases, the I dosage form must be free of 1 I bacteria and must be liquid to make the syringe easy to handle. ○ Stable and manufactured under the condition of 1 1 pieces and must be protected from contamination by microorganisms such as bacteria and fungi 1 I Function 0 1 1 -16- i I 1 1 This paper size is applicable to China National Standard (CNS) Α4 specification (2! 0 X 297 mm) «243 87 97 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Suiji V. Description of invention (15) 1 t m valid for use in the formula 蕖 Allowed oils include their g oil Λ 1 ί I Animals, plants or synthetics * Including peanut oil, soybean oil, sesame oil, t 1 cottonseed oil, olive oil > sunflower oil stone fat and rock oil. Please use 1! Fatty acids include oleic acid, stearic acid and isostearic acid r It is useful for this purpose. 1 Anti-acid m includes ethyl oleate and isopropyl myristate. Soaps used include 1 i 1 fatty acid alkali ammonium ammonium and triethanolamine salts. Acceptable cleaning Agents include Xuan I cationic detergent% such as dimethyl diammonium ammonium halide and aminyl pyridine. | Halides and amine acetates and anionic detergents such as alkylaryl and olefins. Sulfonic Acids »Alkyl Hydrocarbons, Ethers and Monoglycerides Youku sulphate and sulfonate, _- · 1 i succinic acid m 0 useful non-anionic cleansing agents may include fatty amine oxides \ il > fatty acid alkalase fermentation amines and polyoxyethylene polypropylene copolymerization Item 0 Amphoteric 1! Detergents may include alkyl-β-amino propionate and 2-alkylimidazoline quaternary salts and mixtures thereof. The parenteral composition of the present invention preferably contains about 0.5. To about 2 5¾ weight ratio 1 1 of the illustrated compound in solution 0 sterile injectable solution or suspension form 1 The parenteral formula of formula I contains about 0.052 to about 5¾ suspension agent in isotonic media 1 1 Medium is also better. Yuanyuan solution and M-retaining agent can be added. Suitable surfactants can also be added. These surfactants can include polyethylene sorbitan fatty acids as cool as sorbitan monooleic acid m. Polymers of epoxy resin and hydrophobic base i 1 The adducts are formed by the condensation of glycerol and malonase. The peony compositions of the present invention also include their use for topical and transdermal administration. I. These formulations may include compounds of the present invention in Dermal administration in a solvent system that enhances transdermal absorption 1 1 (including acetic acid or dimethylarylene f with or without other excipients 1 | vehicle) 0 is preferably a topical and transdermal composition here Package 1 I -1 7- 1 1 1 1 This paper size applies the Chinese National Standard (CTNS) Λ4 specification (210X29 * 7 mm) B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (ib) I 1 Contains the compound of the present invention added to the tank and porous membrane type cloth or 1 1 solid matrix type of patch 0 These types of transdermal patches are described in the United States 1 | National Patent Case 3, 7 4 2 , 9 5 1 '3, 7 9 7, 4 94 3, 9 9 6, 93 4, 4, 〇3 1, 894 / — »Please 1 I 4, 5 7 3, 996 and 4, 9 5 6, 1 7 1 Read 0 1 Read t 1 The internal formula of the present invention and administration can be in the form of intranasal drops or internal sprays such as 1 on the back 1 Inhalation_administration 0 The formula may include any combination of medicinal permissible ingredients for intraoral administration > including sterile aqueous saline stabilizers such as molecular weight matters 1 I re 1 ranging from about 20G to about 7 5 0 0 Polyethylene glycol or mixtures thereof. It is suggested that the compounds of the present invention can be used to prevent or treat the virus in the form of a virus. The dye can be used for prevention. 5 The compound can be sprayed or sprayed within 1 1 to prevent the virus. RS V exposure. Length of treatment period response 1 I Signs of specific viral agent infection and risk factors that can be expressed by epidemic and pending patients 1 1 〇 Compounds transmitted in these ways at a concentration of 0.1 1 but 1 to 3 Between 0 mg / ml 1 The transferred volume is between 0.1 and 1 ml / 1 I Nostril 0% i The compound tree can be made gold by P administration or intravenous administration 1 1 body pass for treatment * The compound can be delivered locally to the lungs as an aerosol 1 1 or can be delivered systemically by administering or intravenously. Such administration can be performed within the time period required to control virus I iJs infection. 1 The present invention The compound can be further prepared by the following non-limiting example 1 | Example 〇 Propane-2-ol-acetic acid-4¾ ammonia in water (8: 1: 1 Γ | volume / volume) as a solution m by silicon Thin layer chromatography (TLC} 1 1 and reversed-phase high performance liquid chromatography (RP-HP LC) on coagulum [column: V yd ac C 18 II (4.6 mm X 2 5 Cl), 5 ia m 9 mobile phase A-acetonitrile, B- 0.1 M ammonium acetate 1 1 I in water (PH5 • 5) 'C-formazan; gradient: from mixture A -B 1 1 -1 8-1 within 10 minutes 1 1 1 This paper size applies the Chinese National Standard {CNS) A4 (210 X 297 mm) A7 B7 V. Description of the invention (17) -C (20: 6 5: 1 5, volume / volume) to the mixture ABC ( 2 0:55: Please read the precautions of it and then fill in. · Page 2 5, Volume / Volume)] Preparative RF-Η PLC is performed in Rain U gradient Η PLC system, using Vydac C18 呔 / protein Preparative column (10 mb, 2 2 mb X 2 5 cm); mobile phase: A-methanol-0, 1 M acetic acid In water (ΡΗ5.5) (1: 4, v / v) Beta-methanol - acetonitrile (1: 4, v / v); Gradient: 18-32ΧΒ in 10 minutes. Example 1 4.4'- 萼 "4.6-Di" 3-Amine, U-Etc. (2 -Antimethylamidine), Ether, Imine, 1-1.2.5-Tri 11 # -2-Amine 1_ER cage 7, ene-factory; > 'Erqianzhen will be cyanuric chloride (3.87 g ^ 21 millimoles) at -3-0C in the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs The solution of indocyanin (25 ml) was added to a phosphate buffer solution (100 ml, 0.3M, P7), stirred with K, and then 4,4'-diaminodibenzyl ethylene was dissolved in 20 minutes- 2,2'-Disulfonic acid (3.70 g, 10 mmol) was added to a solution of 1Η HaOH (20 ml), and the pH was maintained between 6.5 and 7.2 by adding IN NaOH. The stirring was continued at the same temperature and pH 1 hour, while monitoring the completion of the reaction by analytical HPLC (yield 95¾). The 3-aminophenyl-N, N-bis (2-aminomethylmethylethyl) sulfonylimine (13.20 g, 42 mol) (British Case No. 1,194,388; June 10, 1970) Add dimethyl iodide (DHS0M 100ml) to the solution and raise the temperature to 501C. Following stirring for 2,5 hours, followed by stirring at 100-110 for 40 hours, the pH was adjusted by The addition of IN NaOH is maintained at 6.6_7.2. Once the reaction is determined by analytical HPLC (or TLC), the mixture is cooled to 20C and acidified to pH 2 with 5.6N hydrochloric acid. Ambient Na-19- This paper size applies to China Standard (CNS) Λ4 specification (210X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs * = 43 8 7 9 7 A7 B7 V. Description of the invention (18) (60 ml, 4M) Addition and overdose precipitation products. Redissolved in the smallest volume of water by adding IN NaOH to pH 7, and reprecipitated by adding sodium hydroxide. The precipitate was filtered, cold water (20 ml), propan-2-enzyme (40 ml), and propane SB ( 60 ml) was washed and dried under vacuum and 50 °. Yield 13.0 g (: 72¾), melting point > 250 " C decomposition; UV (water): 273ϋM «Πο8ε 5.11), 350mn (loge4.89); MS (ES) (ra / z): Η * 2 887.9; HW1821.2 〇 Example 2. 4.4 · -zero "[fi- 二 ί3-Anti-cage-HN- 雩 (2-Anti-sugar--7, A) Sulfur 1-1, 3, Fi-triple-2--1, 1-diM 7.ene-2. -Dioxine. Dina a in sealed thick-walled glass house 4 , 4'-diaminodibenzyl-2,2'-disulfonic acid di Sodium salt (1.21 g, 2.92 mmol) and 2-chloro-4,6-di [3-aminophenyl-N, N-bis (2-aminomethylmethylethyl) -sulfonium Imino] -l, 3,5 -triplet (Example 6 M4.47 g, 6,44 mmol) suspended in cyclobutane ftl (70 ml) and diisopropylethylamine (1.5 ml) The solution was warmed to 115C. Following the warm up of 40 hours. Once the reaction was complete by analytical HPLC (or TLC), the mixture was cooled to 30 υ, 1 N Na G a (6.6 mL) was added and the product was precipitated by adding propan-2-ol (200 mL). The precipitate was washed with 溏, washed with acetone (30 ml) and redissolved in the water with the smallest cover, and reprecipitated by adding acetic acid. After washing, the precipitate was washed with ether (30 ml) and dried under vacuum at 50T. Yield: 4.84 g (9U). m · s ^ m ^^^^ 1 I ^^^ 1 ^^^^ 1 1 ^^ [^ 1 In nm ^^^^ 1 ^^^^ 1 ^^^^ 1 1. .¾.- 旮(Please read the precautions on the back before filling out this page) This paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (210X 297 mm) Employees ’Cooperatives of the China National Standards Administration Bureau of the Ministry of Economic Affairs Printing and Printing Co. A7 B7 V. Description of the invention ( 19) g example 3 4.4'-enough "4.6-two" 3-anti-cage->-<. ≫ <-鲹 (? -Cocoonyl-7.some) -1. 3-5-Triple well-2-Some anti- 1-2 cage Zene-2.2 '-Diramie. The disodium title compound was prepared using the general conditions of Example 1, in which 2,4,6-tri Fluoride-1,3,5-triple (304 mg, 2.25 mol) with 4,4'-diaminostilbene-2,2 ~ disulfonic acid (45 5 mg, 1.10 mmol) After 1 hour, it was reacted with 3-aminophenyl-N, N-bis (2-aminomethylmethylethyl) sulfonylimine (1.45 g, 4.62 mmol) after 1 hour (UK Patent No. 1,194,38δ No .; June 10, 1970), followed by purification to obtain the desired compound (1.21 g, 61%). The compounds synthesized by the procedures of Examples 1-3 were the same according to HPLC, UV and mass spectrometry. Rich Example 4 " 4.fi- Two anti-cages-HH-etc. (2-antimethanyl-7-7) Some fluorenimines 1. 3. 5-trioxan-2-ylamino 1_: 1.pen-2 ^ 2 '-Difluorene_dina "The title compound was prepared according to the procedure of Example 2, using 4,4'-diaminobiphenyl-2,2 disulfonic acid dina salt (1.02 g, 2.62 micheles) and 2 -Chloro-4,6-bis [3-aminophenyl-N, N-bis (2-aminomethylethyl) sulfoamidoimino] -1,3,5-triple (Example 6) (4.26 g, 5.76 mmol) in δ0 ml DMS0-cyclobutane (1: 3, v / v) and diisopropylethylamine (1.2 ml). The product was obtained as a colorless solid (3.90 g, 833! ); Melting point > 2 5 0 t: decomposition; UV (water): 2 7 2 nm (10 g ε 4 · 8 6); MS (ES) -21- II.! Ph rp II and clothing staple ( Please read the notes on the back before filling in this page) This paper size is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A 7 B7 V. Invention Description (2) ) (a / z): Μ · 2 874 · 1; HW1794.2. Real examples & 4.4'- 簪 「4.6- 二」 3-Anti-cage->-> -筠 71 基 > A certain sugar, a certain 1-1, a triple well, a certain fat, a 1-two cage, a 7-ene-2.2'-dicarboxylic acid. A dinazine compound was prepared according to the procedure of Example 2, using 4, 4'-Diaminostilbene-2,2_-disulfonic acid (28 mg, 0.075 mmol) and 95 mg (0.15 mmol) 2-chloro-4,6-bis [3- Aminobenzyl-N, N-bis (3-stemethyl) sulfonamidoimino] -1,3,5-triple (Example 6) in cyclobutane (20 mL) and diisopropylbutylamine (35 ml) at UOt for 18 hours. The cooled reaction mixture was mixed with deionized water (40 mL), and a solution of the crude product was purified by preparative RP-HPLC. The dissolved fractions containing the desired product were combined, and the organic solvent was evaporated under vacuum UObbIU) and 301C, and the product was concentrated, except for B and isolated via C18, (cartridgeHSOO mg, taken from Burdick & Jackson). The column was washed with water (30 ml), and the product M formate (50 ml) was re-extracted. Methanol was evaporated to obtain 12 mg (1 U) of the desired product; melting point > 2 50 t decomposition; UV (water): 273nm (loge 4.97), 350nni (loge 4.81); MS (ES) (m / z): Η · 2 7 79, 0; ΜίΠ604. 0.富 例 6 2-氲 4.ft -Di "3-Amine"-NN-Crab (2-Amine form -7-Some) 碏 iS Some sub-defense group 1-1. 3, 5-Tritrap- Add cyanuric chloride (4.2 g, 22.7 mmol) in dioxane (55 ml) dropwise to the phosphate buffer solution (120 binding with 2 ~ 0C and stirring) (Please read the note on the back first) Please fill in this page again for this matter) This paper size applies Chinese National Standard (CNS) Α4 size (210X 297 mm) Printed by the Central Standards Bureau of the Ministry of Economy, Shellfish Consumer Cooperative, 1643 87 9 7 at B7 V. Description of invention (21) ml, 0.3M, PH7) and crushed ice (10 g). 3-aminophenyl-N, N-bis (2-aminomethylethyl) sulfosylimine # U5 within 30 minutes. 0 g, 47.8 moles) (British Patent No. 1.194,388; June 10, 1970) A solution of N, N-dimethylformamide (125 ml) was added dropwise to the resulting fine suspension And the pH was maintained at 6.5-7.2 by adding 1Η KaOH. Stirring was continued for 2.5 hours, only one side was monitored for analytical completeness by analytical 1 ^ 1 ^ (or 7 ^ (:). Once by analytical LPLC (or TLC) The reaction was determined to be complete and the mixture was cooled to Liter) was added and filtered through the product precipitate, washed with cold water (50 liters), acetone (50 liters) and dried under vacuum at 401. Yield 14.5 g (8 6 S;); melting point> 2 5 0 Decomposition: UV (DWSO): 282nm (iose 4.77); MS (CI > (m / z): MH740.1. Dangli 7 4- "4.6-II" 3-Anti-cage-> < .bu < »(2- pickled methyl_some ethyl) 碏 鶄 some sub pickled = well-2-some prevent some 1-4 '-" 4-value-6-"3-proof off even- Κ · Η-_ Hutian 81, 7. 7.) A certain sub-fat-ditrap-2-ylamino 1-di cage 7. 7.-2.2'-difluorene. Di-naline-3 ~ OC A solution of trimeric cyanide (205 mg, 1.12 milliliters) in dipentane U.5 was added with stirring to a phosphoric acid phosphate solution (10 ml, 0.3 Μ, p Η 7). .Add a solution of 4, 4'-diaminostilbene-2, 2'-disulfonic acid di-nano salt (225 g, 0.54 mmol) in a phosphonate buffer solution (3 ml) and The pH was maintained at 6.5-7.2 by the addition of IN HaOH. At the same temperature and pH, the ore was stirred for another 1 hour. On the other hand, the reaction was monitored for completion by analytical HPLC (yield 97¾). Aminophenyl-fluorene, fluorene-bis 2-Aminosylethyl) Sulfoimine (700 -23 ™) This paper size applies to Chinese National Standard (CNS) Λ4 specification (21〇κ297 mm) !. nm 1 i Pack '1τ (please first (Please read the notes on the back and fill in this page again.) A7 B7 printed by the Consumers' Cooperative of the Ministry of Economic Affairs of the Bureau of Standards and Administration of the People's Republic of China. 5. Description of the invention (22) mg, 2.23 mg) in N, N-dimethylformamide ( 10 ml) solution was added and the temperature was raised to 60. After stirring at this temperature for 3 hours and 20 hours at 100-110C, the pH was maintained at 6.6-7.2 by adding IN HaOH. Once the reaction was determined to be complete by analytical HPLC, the mixture was cooled to 20C and M5.6N hydrochloric acid was acidified to pH 2, sodium chloride (5 ml, 4M) was added and the product precipitate was filtered, and washed with cold water (2 ml) And dried under vacuum at 40t. Two portions of the crude product (about 1 g) in deionized water (250 ml) were purified by preparative RP-HPLC. The fractions containing the desired product were combined, the organic solvent was evaporated under vacuum (10 nm H g) and 30 t, and the product was concentrated, desalted and passed through an octadecyl (C18) column (900 mg, from Burdick & Jackson) left alone. The column was washed with water (30 ml) and the product M methanol (50 ml) was re-extracted. Methanol was evaporated to obtain 268 mg (3 2 desired product, melting point> 2 50 t decomposition; UV (water): 2 7 3 nm (logs 4.83), 350nai (] 〇ge4.44); MS (ES) (ra / z): M'2 749.1 5; HW 1 544. 3 ° Cellar Example 8 4.4 "Learning-4- mood-6-". Ί-umbilical cage-NN-ringing (2- anti-send Z) * Ugly certain Asian defense 1-1. 3. 5-Triple well-2-Some defense 1-2 cage 7, ene-2.2 '-diacetic acid. Di-nantamidine will be mixed in ~ 3 ~ 01 and mixed. A solution of polycyanated cyanide (0.91 g, 4.95 mmol) in dibutane (8 ml) was added to the gadolinium phosphate buffer (30 ml, 0.3 team 0 [17). 4,4'-two Amino stilbene-2,2'-disulfonic acid disodium salt (1.00 g, 2.41 mmol) was added to a solution of deionized water (9 ml), and the pH was maintained at 6.5 by adding 1Η NaOH -7.2. At the -24-pack. Order (please read the notes on the back before filling in this page) The paper scale is applicable to China National Standards (CNS) 8-4 specifications (210X297 mm) Central Bureau of Standards, Ministry of Economic Affairs Printed by employee consumer cooperative A7 B7 V. Description of invention (25) Stirring for another hour at the same temperature and pH, on the other hand monitored by analytical HPLC Should it be complete (yield 98¾). 3-Aminobenzyl-N, fluorene-bis (2-aminomethylethyl) sulfoamidoimide (1.57 g, 5.00 mmol) is added to the product within 10 minutes. A solution of Ν, Ν-dimethylformamide (25 ml) was added and the temperature was raised to 50 °. At this temperature, stirring was continued for another 6 hours, and the pH was maintained by adding 1 ((^ 01 {maintained at 6.6-7.2. Once the reaction was judged to be complete by analytical 1 ^ 1 ^ (or TLC), the mixture was cooled to 0 and acidified to pH 2 with 5.6N hydrochloric acid. Sodium chloride (5ml, 4M) was added and the product was filtered. The precipitate was washed with cold water (8 ml), propane (20 ml) and ether (20 ml) and dried under vacuum at 40 t. Yield 2.37 g (80¾), melting point> 3 0 0 1C Decomposition: UV (water ): 2 7 3 nm (10 g ε 4.5 7), 3 50 (10 ge 4, 42); MS (ES) (n / z): M · 2 610.1; MW1266.2. Real. ―Down‖. 4-"4.6- 二" 3-Fang Mo-Ν.Ν-Nie (2-amine methylamine 7, 7,) Aiming at a certain Asian defense 1-1.3.5-Mitsui-2- Something 1-4 夂 4-"3-pickled 茏 -N. H-etc. (2 -Amine 醏 醏 7 ,,) H- (2-Protection of a certain 7. Some) -N'- (3-propionic acid) 1-1.3.5 -Tritrap-2-ylamino 1-stilbene-2, 2 disulfonic acid. Di-naphthalene. And Example 1 0 4-"4.fi- Two "3-antipyridinyl group-NN-2- (2-antipyridine, Z, and so on), a certain imino group, 1-1.3.5, a triple well, a certain amine, and a 1-4 '-" 4- " 3-amine 茏 1. N- 簪 (2- defense application 醮 Z 碥 醸) 碥 醸 Asian defense 1-6- "3- anti-cage-> <. Bu etc. (3-propyl) 1-1.:; .5-trihydrazine-?-Some anti-dioxin-2.2'-dihydrazine. Diazine binding (please read the precautions of ^^ 9 before filling this page) This paper size applies the Chinese National Standard (CNS) Λ4 specification (2! 〇 X 297 mm) Printed by the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 43 87 9 7 A7 B7 V. Description of the invention (24) IN Na0H ( 300 ml) was added a solution of Example 1 (200 mg, 0.11 mmol) in deionized water (20 ml) and the mixture was heated to boiling. The reaction mixture was kept warm for 3 hours, cooled to OC and K5.6N hydrochloric acid was acidified to pH2. Sodium chloride (10 ml, 4 Torr) was added and the product precipitated, filtered, washed with cold water (2 ml) and dried under vacuum at 401C. A solution of the crude product (about 180 mg) in distilled water (125 ml) was purified by preparative RP-HPLC. The dissolved fractions containing the desired product (Example 9) were combined, the organic solvent was evaporated under vacuum (10 OnUg) and 30T: the product was concentrated, desalted and passed through a C18 column (900 mg, from Burdick £ < Jackson ) Single. The column was washed with water (30 ml) and the product M methanol (50 ml) was re-extracted. Evaporate formazan to obtain 24 mg (12¾) of the desired product, melting point> 250 bar decomposition; UV (water): 273nBnoge 5.02), 350nm (loge4.76); MS (ES) (m / z): Μ'2 888.3; MW1822.6 ° The second product (Example 10) was isolated by RP-HPLS- from other solvents containing the desired compound (Example 10), and the same concentration and salt removal as described in Example 9 were used. And the procedure of single detachment through the 18 base (C 18) column. Yield 18 grams (9), melting point > 2 5 0 t decomposition, ϋ V (water) 2 7 3 na (logs 4.9 2), 350 πβ (1 εε 4, 69); HS (ES) ( i / z): Η'2 8 8 9. 2; M \ Π δ 2 4 _ 4. Cellar example η 4.4'-zero "4.6-two" 3-anti-cage-shirt. Section-zero (2-aminomethyl with -7, base) yam gland a certain defense-1. 3. 5-two Trap-2-Even if you have enough knots -2.2'-dioxin. Example 2 (30mg) in the presence of hydrogen in 30ml of water-methanol (1: 1, body, 1H 1) I-cloud (please (Please read the notes on the back before filling this page) This paper size is applicable to Chinese National Standards (CNS) A4 specifications (210X 297 mm) A7 Consumer cooperation of the China Standards Bureau of the Ministry of Economic Affairs, printed B7 V. Invention Description (25) Volume / volume) solution was stirred with palladium / wooden (10 ¾ palladium) for 5 days. The reaction mixture was filtered and the solvent was evaporated. The product was passed through a preparative RP-HPLC single fraction. ) And the organic solvent evaporated at 30 ° C. and the product were separated through an octadecyl (C18) column (300 mg, taken from Burdick & Jackson). The column was washed with water (30 ml) and the product was formazan (50 ml). Re-extract. Evaporate methanol to obtain 16 mg (50 S;) of the desired product; melting point > 2 50 0 1C decomposition; (JV (water): 2 7 4 η IB (loge4.96), MS (ES) ti / z ): Μ'2 889.2 MW1824.4- Fen Case 1 2 4.4, Substitute Γ4.ft- 二 「4-Anti-cage-N.N-Substitute (2-Anti-aminium--7..a.) 碏 瞌 Imine-1.1-1. 3.5-Triwell-2 -ylamine 1-di cage ZY-2.21 -disulfonic acid. The title compound of dinaline salt was prepared according to the procedure used in the synthesis of Example 2, using 4, 4'-diamine dibenzyl. Ethylene-2,2 · -disulfonic acid (48 mg, 0.125 mmol) and 2-chloro-4,6-di [4-aminophenyl-K, N-bis (2-aminemethylethyl) ) Sulfonylimino] -1,3,5-Tritrap (Example 18) (230 mg, 0.310 mmol) in dimethyl sulfoxide (12 ml) and diisopropylethylamine (260 奄Liter). The product was obtained as a colorless solid (173 mg, 77¾); melting point > 2 50 υ decomposition; UV (water): 296 nm (10se 4.94); (10se 4. 5 7); HS (ES) (κι / z): r2 8 8 3. 2; MW 1 8 2 2 _ 4. Case of alfalfa 1.. H 荸 (2-antimethylose-B) 亚 Yaya 1-1U -Three wells-2-Aya-1-Sighting cage-2.2'-Two-Erase. Two-nano binding (please (Please read the notes on the back before filling in this page) Standard (CNS) Λ4 specification (2 〖0Χ 297 mm) A7 B7 Ministry of Economic Affairs Bureau of Standards staff printed consumer cooperatives

V. Description of the invention (2fci) The title compound was prepared according to the procedure used in the synthesis of Example 2, using 4, 4'-diamino-benzene-2,2'-disulfonic acid, disodium sulfonium (113 mg, 0.33 mmol) ) And 2-chloro-4,6-bis [4-aminophenyl-H, N-bis (2-aminomethylethyl) sulfoamidoimino] -1,3,5-Sanken ( Example 18) (535 mg, 0.72 mmol) in 25 ml of DHSO-cyclobutane fiS (2: 3, v / v) and diisopropylethylamine (350 ml). The product was a colorless solid (450 mg, obtained at 7 6; melting point> 2 50 0 Γ decomposition; UV (water): 2 9 6 nb (丨 〇ge 5.13); MS (ES) (m / z): r2 874.4 MW1794.8. Jiao Li 1 4 2- 氲 -4.β- 二 ('V- 碏 醸 Sulfoamido) -1. 3 5-Triple coax-2 ~ 〇υ and mix down A solution of cyanuric cyanide (2.37 g, 12,9 mmol) in propidium (25 ml) was added dropwise to the ointment solution (60 ml, 0.3M, ρΗ7). Within 20 minutes A solution of p-sulfonamide (4.35 g, 25.3 mils) in acetone (30 ml) was added dropwise to the resulting fine suspension, and the pH was maintained at 6.5-7,20 by addition of IN NaOH, and the mixture was stirred for 30 minutes. Minutes (OP, ρΗ7.0) ^ Raise the temperature to 55C. Stir for another 3 hours, on the other hand monitor the completion of the reaction by analytical HPLC (or TLC). Once determined by analytical HPLC (or TLC) Completely, the mixture was cooled to 01C, water (100 liters) was added and the product Shen Yi was filtered, washed with cold water (50 ml), dried on a dishwasher and dissolved in hot acetone (40 ml), Kbenzene (150 Ml) and purified by precipitation. It was washed with propan-2-enzyme (20 ml) and diethyl ether (30 ml), and dried under vacuum at 30¾. Yield, 3.72 g (6U); melting point > 250 It was decomposed; DV ^^^ 1. ^ ^^ 1 ^^^ 1 ^^^ 1 In ϋ— ntnm nn 1. ^ 1. L " i-39 (Please read the precautions on the reverse side before filling out this page) The paper size applies to the Chinese National Standard (CNS) Specification of Λ4 (210 X 29 7 mm) Printed bag A7 B7 of the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention (W) {N e Ο Η}: 2 7 7 ηι (1 og £ 4.68); CI {ES ) (i / z): MH456.0o Wide plate 丄 5 4, 4 ′-「4,5 -Di「 3-amine M fl Ann (suluhonvlaniido)]-1.3. Amine] -Dimothylene-2. 2'-dioxo .... The dinaline title compound was prepared according to the procedure used in Preparation Example 2 using 4,4'-diaminostilbene-disulfonic acid, di Sodium salt (216 mg, 0.52 mmol) and 2-amino-4,6-bis (3'-amidinoanilide) -1,3,5-triple (Example 1 4) (5 24 mg, U mol) in cyclobutane (15 ml) and diisopropylethylamine (250 ml), and at 4 15 hours at 115 ° C. Cold simmer to 2 (TC, the reaction mixture was diluted with ethyl acetate (10 I) ml) and 1 N MaOH (2.08 ml) was added. After centrifugation, the residue was stirred with propan-2-ol (50 ml) until crystallization was complete. The solid was centrifuged, washed with methanol (2 X .30 mL) and ether (2 X 30 mL), and dried under vacuum at 30 ° C. Yield (570 mg, 923i); melting point > 25Q ° C decomposition; UV (water): 273nm (10 g £ 4.7 6), 350niro (log £ 4.5.2). Example lfi 4,4'- Double "4. 6-bis" 3 ~ amine benzyl chloride sulphnnvlimido l -1,3,5-tristrak-2-ylamino suebenzene-2, disulfonic acid, dinadium lanthanum The title compound was prepared according to the procedure used in Preparation Example 2, using 4, 4'-diaminobiphenyl-2, 2'-disulfonic acid (208 mg, ϋ. 60 mmol) and 2-氱 -4, 6-bis (3′-sulfoamidoanilide) -1,3,5-tritrap (example) 4) (ti (Π mg, 1.3 mmole) in cyclobutane (20 ml ) And diisopropylethylamine (850 ml) and 40 hours at 115 ° C. After cooling to 2 Q ° C, the reaction mixture was diluted with ethyl acetate (50 ml) and 1 NN a 0 fi (2. 4 0 -2 9- This paper size applies to the Chinese National Standard (CNS) Λ4 specification (210X297 mm)-^^^ 1 nt i ^ i ^^^ 1 1 ^ 1 ^^^ 1 ^ ^^ 1 nt (please read the precautions on the back before filling this page) 陛 43 87 9 7 A7 B7 V. Description of the invention (28 ml) added. After centrifugation, the residue was mixed with propan-2-enzyme (50 ml) together Stir Until the crystallization is complete. The solid is washed with Carboxylic Acid (40 ml) and diethyl ether (2 x 20 ml), and dried under vacuum at 30 t: yield (505 mg, 7 2 3; ); Melting point > 2 50 0 Γ decomposition; IH (water): 2 7 6 nm (1se 4. 9 3). G Example 1 7 4.4'-Secondary Moss-2.2'-Dicera A solution of sodium carbonate (8.6 ml, 1.5 M) was added to a suspension of 4,4'-diaminobiphenyl-2,2'-disulfonic acid (4.44 g, 12.9 mF) in water (20 ml) and Warm until a clear solution is obtained. After cooling to 51C, add a solution of sodium nitrite (1.78 g, 12.9 mils) in water (3 ml) to this solution. -5 ~ -21C and mix the resulting solution with stirring A solution of concentrated sulfuric acid (3.8 ml) in water (13 ml) and crushed ice (10 g) were added dropwise. Stirring was continued for 30 minutes and the reaction mixture was warmed to 65TC. The temperature was maintained until nitrogen evolved. The mixture was cooled to IOC and M anhydrous sodium carbonate were neutralized, and the solution was evaporated to a residue. The residue was dried under vacuum at 50, mixed with ethanol (225 ml) and quenched. The mash was evaporated and dried under vacuum at 40 ° F. Yield 3 . 8 8 (8 7 S;). Melting point > 2 5 0 13 Decomposition; UV (0. 0 5 NN a 0 Η): 2 5 0 η Zu (loge 4.16), 311nm (loge 3, 40); MS (ES) (b / z): ( HH) · 1 345,0; MW346.0. Printed and bound by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) Example 1 8 2-Ar-4. 6-Di-4-aminophenyl-N. .Yl.) 1 Temium imine 1-3. 3. The 5-triple title compound was prepared according to the procedure used in Preparation Example 6, using 4-aminophenyl-N, H-bis (aminomethylamidoethyl). ) Sulfoimide (3,3 g, this paper size applies Chinese National Standard (CNS) Λ4 specification (210X 297 mm) 4? 8 7 ρ ^ Α7 Β7 V. Description of the invention (29) 10,5 milligrams Ear) (English_Patent No. 1,194,388; June 10, 1970) and trimeric atmosphere (1.0 g, 5.4 millimolar product 莫 colorless solid (3,5 g, 88! 1! 3;) were obtained; Melting point> 2501 ^ decomposition; 0 (0 »^ 0): 30 3 nm (log e 4.84); MS (CI) (m / z): Μ Η 740 · 1. Rich 锎 1 9 Α" 4.6-two " 3-Amine 茏-MH-訾 (2-Anti-stolen stele-B y) 碏 sugar an imine 1-1.3, 5-trihydrazine-2- a gas group]-Cong Cong-2 .; > , -Difluorene. Di-Nanosalts, 4,4'-Hydroxybenzophenone-2,2 · -dihydroacid (Example 17) (131 mg, 0.34 mmol) and 2 in a sealed thick-walled glass tube -chlorine- 4,6-bis [3-Aminobenzyl-bis (2-aminomethylmethylethyl) sulfonamidoimino] -i, 3,5-triple (Example 6 > (550 mg, 0, 74 mmol) to a suspension of cyclobutane-N, N-dimethylformamidine (15¾ liters, 2: 1 vol / vol) and NaOH (lH, 1.48 ml) was added to 115¾. Keep warming for 50 hours. Department of Printing, Employees Cooperatives, China Standards Bureau, Ministry of Economic Affairs, 1 · ^^^ 1 ^^^ 1 ^^^ 1 ^^^ 1 ^^^ 1 TJ (.Please read the notes on the back first (Fill in this page again) — Once the reaction is judged to be complete by analytical HPLC (or TLC), the mixture is cooled to 20 t: and the product is precipitated by the addition of propan-2-enzyme (70 ml). The yeast (15 ml) was washed and dried under vacuum and 401C. Two solutions of the crude product (about 0-6 g) in deionized water (200 ml) were separately purified by preparative RP-HPLC. The dissociation containing the desired product was combined The organic solvent was evaporated under vacuum (UOanHg) and 30T: and the product was concentrated, removed, and passed through a C18 column (900 g, taken from Burdick & Jackson). The column was separated with water (30橐 liter) washing and product M formase (50 draft) re-extraction 171 mg (28¾) of the product obtained by evaporation of formic acid; melting point > 250,000t: decomposition; UV (water): 272nB (loge4.86); MS (ES) (a / z): Γ 2875, 2; MW1796. 4. This paper size applies Chinese National Standard (CNS) A4 specification (2) 0X297 mm) BO. Ta 12 iS'ii. Annual film ί · ι. Supplementary A7 B7 V. Description of the invention (50) Official example 20 mm -a a · -m 「4.fi-二」 3-Anti-mining HH-Bee (2-m methylphenanthrene-7, some) 碏 captain 1-1 gazing cage-2.V-II碏 酹. Disodium triple well-2-a hydrazone 1- compound was prepared according to the procedure used in Preparation Example 2 using 5,5'-dimethyl-4,4'-diaminobiphenyl-2,2 ' -Disulfonic acid, di-nano salt (206 mg, 0.49 mmol) and 2-chloro-4,6-di [3-aminebenzyl- (1, | {-bis (2-amine formamyl) Ethyl) sulfoimino] -1,3,5-triso (Example 6) (805 mg, 1.08 mmol) in 30 ml DMS0-cyclobutane (1: 1, v / v) and Diisopropylethylamine (200 ml) at U5t: 50 hours. The product after HPLC-purification was a colorless solid (191 mg, obtained; melting point > 25) decomposition; UV (water): 27 4nm (l 〇se5.08); MS (ES) (b / z): Η_288δ3.3; MW1822.6. Example 21 short-4.fi-two "3-anti-cage even -NH-qin (2-1? (7, the base) 碏 瞌 very defensive 1-1. 3 5-three coax in li r ::. L 衣衣 i. Γ li line (please read the note on the back before filling in this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs of the Ministry of Economic Affairs of the People's Republic of China -2 to 013 and stir the polytrichloromethane (135 mg, 0.7 3 mmol) to A solution of dioxane (55 ml) was added dropwise to human phosphate (120 ml, 0.3 M, ρΗ7) and crushed ice (10 g). 3-Aminephenyl-bis (2 -Hydroxyethyl) sulfonyliminomine (365 mg, 1.40 mmol) in N, N-dimethylmethanamine (125 ml) was added dropwise to the resulting fine hydrazone suspension, and the pH was adjusted by adding IN NaOH was maintained at 6.5 to 7.2. The mixture was stirred for 1 hour (0T :, pH7,0) and the temperature was raised to 55 C. The mixture was further stirred for 2.5 hours, and on the other hand, it was analyzed by HPLC (or- 32- This paper standard is applicable to the ten national standards of China (CNS) ΛΊ Regulations (:: 0 credit) Time 43 87 9 7 A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (51) TLC) The reaction was monitored for completeness. Once the reaction was judged to be complete by analytical HPLC (or UC), the mixture was cooled to 01, water (160 ml) was added and the product was precipitated. Cooling water (50 ml) and propan-Si (50 mL) and dried under vacuum cleaning 4 0 t. Yield: 395 mg U 9 35); melting point> 2 50 t decomposition; U V (DM S 0): 2 8 4 n b. When 锎 2 ?. H-Zero "4.R-Di-L3-amine Momo-NN-Zero (2-Zen 7, 荜) 碏 Follow a certain Asian defense 1-1. 3.5-Mitsui-2- a defense A 1-Cage-2.2'-diphosphonic acid. This compound was prepared according to the procedure used in Preparation Example 2 using 4,4'-diaminobiphenyl-2,2'-disulfonic acid (28 (Mg, 0.08 mmol) and 115 mg (0.17 mmol) of 2-chloro-4,6-di [3-aminophenyl-N, N-bis (3-hydroxyethyl) sulfosylimino ] -1,3,5-Triple well (Example 21) in acetidine (10 ml) and diisopropylethylamine (25 ml) at UOt: 18 hours. HPLC-purified product as a colorless solid (16 mg, 13¾) obtained; melting point> 2 50 t: decomposition; UV (water): 2 7 2 nm (10 ε 4 8 8); MS (ES) (b / z): M * 2 776.0ϊ HW1534.0 ° Example 9.9-Dioxo-2.7- 螫 "4.6-Di" 3-Antipyridyl- > <. ≫ < -etc. SI, a certain Asian defense, 1-1. Tris-2-ylamine, 1-Dipyridine, and Prefer-3.fi-Dipyridine, Di-Nitrate. The title compound was prepared according to the procedure used in the preparation example, using trimer chloride. Cyanide (59 mg, 0.32 mmol), 9,9-dioxo-2,7- Diamino-dibenzocarbene-3,6-disulfonic acid (77 mg, 0.16 mmol) and 2- (Please read the precautions on the back before filling this page) The paper size applies to Chinese national standards (CNS) Λ4 specification (210 X 297 mm) Printed by Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (") Ammonia-4, 6-bis [4-aminephenyl-Ν, Ν- Bis (2-Aminomethylethyl) sulfoamidoimino] -1,3,5-tritrap (Example 6) (300 mg, 0.96 mmol) in dioxane (15 ml) and phosphoric acid Solution of salt buffer (2G ml, 0.3M, pH 7) at 1 1 (TC for 18 hours.) PLC-The product was obtained as a colorless solid after purification (64 mg, 1 1 3;); melting point > 2 Decomposed at 50 ° C; HS (ES) (m / ζ): Η 2 9 0 5. 1; MW 1 8 5 8 2 0 Example? 4 H-¥ U-Μ-6 -Di 4-amine -K 1 3 -Amine picking-N. Η -㈧㈧- 跎 甲 醅 一 乙 乙) 醅 醅 a sub 昤 1- 1- 醅 醅 1- 彳 3.! ^ Three coax-?-Very amine 1-Difluorene-2. Dioxane. Di-Na salt compound 稂 Prepared according to the procedure used in Preparation Example 2, using 4, 41-diaminostilbene ~ 2, 2'-disulfonic acid (20 mg, D.054 mmol) and 112 mg (0.12 mmol) of 2,4-digas-6- [4-amino 1 '-[3-aminophenyl-N, N-bis ( 2-Metylaminoethyl) sulfoamidoimino] -benzaldehyde amine] -1,3, 5 -Tritrap (Example 26) in cyclobutadiene (20 ml) and diisopropylethylamine (38 ml ) For 18 hours at UQ ° C. HPLC-purified product was a colorless solid (20 mg, obtained from 235Π; melting point > 250 ° C; UV (water): 2 9 5 nm (1 og ε 4. 5 4), 3 5 0 η in (1 ο £ 4.39); HS (ES) (id / z): M 2 7 2 7. 1; HW 1 4 8 2. 2 0 secret 25 in .4'-bis [4,6- [4-amine忖 '-匕-踣 栄 踣 栄-&^; ^ -bis (2-77,）) alkaloids very imine very 1-ronganamine 1-1. .3.5-triple well j-an amine even 1- Dizhu 7.ene-2.2'-dioxoether. The title compound of dina salt was prepared according to the procedure used in Preparation Example 2, using 4, -3 4-This paper is in accordance with the Chinese National Standard (CNS) A4 standard (210 X 297 mm) (Please read the notes on the back before filling out this page)-= " Printed by the Consumer Cooperatives of the Central Bureau of Standards, Ministry of Economic Affairs, printed kdi > 'A7 B7 V. Invention Description (M) 4'-Diaminodiamine Styrene-2,2, disulfonic acid (20 mg, 0.054 mmol) and 203 mg (0.22 mmol) > 2-chloro-4,6-di [4-amino-N '-[3- Aminophenyl-N, N-bis (2-hydroxyethyl) sulfoimino] -benzenesulfonimide] -1,3,5 -trioxine (Example 27) in cyclobutane (20 ml) And diisopropylethylamine (38 ml 18 hours at 1101. HPLC-purified product was obtained as a colorless solid (30 mg, 2 5 3S); melting point > 2 50 0 Γ decomposition; UV (water): 295na (loge 5.21), 350nai (loge 4.69 ), MS (ES) (a / z): Μ · 2 1 08 9.3; HW22 26. (2-anti-fluorenylethyl) sulfoimino 1-benzyl with amine 1 -1, 3, 5-trioxane-2t: and cyanuric chloride (56 mg, 0.3 mmol) with stirring Ear) in dioxane (U ml) solution was added to acetic acid solution (12 ml, 0.3 Η, Η 7). 4-Amino-fT- [3-aminophenyl-N, N-bis (2 -Amidinoethyl) sulfinoimino] benzamidine (130 mg, 0.3 mmol) in dimethylformamide (2 ml) was added dropwise to the resulting suspension. Maintained at 6.5-7.2 by adding IN NaOH. Hold the ore and stir for 1 hour (0C, PH7.0), add water (20 ml), and immerse the product in cold water (10 ml), acetone (5 Ml) was washed and vacuum dried at 20 ° to obtain 108 mg (62%) of the desired product; melting point > 250C decomposition; UV (DHS0); 285 ηι ° Example 27 2-M -4.fi-two "4-prevent a certain-^-" 3- prevent a certain U-enough (2-筠 7, a certain) fluorenimine benzidine]- 1,3, 5-Tri well-35- binding (please read the precautions on the back before filling this page) This paper size is applicable to Chinese National Standard (CNS) Λ4 specification (210X 297 mm) Central Standard Ministry of Economics staff consumption Cooperative printed A7 B7 V. Description of the invention (34) The title compound was prepared according to the procedure used in Preparation Example 6, using 4-amino-N '-[3-hydroxyethyl > sulfosimimine] benzenesulfonium Amine (125 g, 0.31 mmol) and trimeric cyanide (28 mg, 0.15 mmol). The product 取得 colorless solid U05 mg, 74¾) was obtained; melting point > 25〇υ decomposition; ϋV (DMS0): 298ηπ 〇 window example 28 4. two 硪 -2.2. 2'- two-point cage dimethyl dimethyl sulphate 2 2,2'-diphthalic acid (Aldrich, 50.0 g, 206 mmol) was added to 500 ml of 3: 1 90UN03 / H2S04 to keep the temperature below 10C. Stir the stimulating solution in an ice bath for 1 hour, then carefully quench it on about 750 grams of ice. The white solid was isolated by vacuum filtration, which is an isomer in the 2: 1 ratio shown. This mixture was purified by decantation in a 1.5 kg silica gel mixed in 8: 2 isopropion / ammonium hydroxide and dissolved in the same solvent mixture. The product first dissolves from the tube • It actually flows out with the solvent. The Shauri isomer elutes later from the column (see P.R. 232-11). The product fractions were concentrated on a rotary evaporator. The concentrated solution was acidified with (1: 1 to? 111, and filtered to obtain 31.9 g of 4,4'-dinitro-2,2'-diphenyldicarboxylic acid. 30 (^) ^^ 1 ^ (0 « $ 0 (^): 5 7.55 (1H, d, J = 8.7); 8.45UH, dd, J = 2.5, 8, 7); 8.68UH, d, J = 2.5), · 13 (1Η, br s) ° CHN: Theoretical value: C: 48.60 *! H: 2.77S! H: 3.105i. The calculated theoretical value contains 0,75 moles of water, the measured value: C: 48.68! KH: 2.72! «N: 7.42S :. 4.4 '-Dinitromethane-2.2'-Diisocyanic acid-36- lp ^ i > I · ^^^^ 1 ^^^^ 1 ^^^^ 1 nn -Ί (Please read the precautions on the back first (Fill in this page again.) This paper size applies the Chinese Standard for Storehouse (CNS) Λ4 (210 X 297 mm). The Central Consumers Bureau of the Ministry of Economic Affairs, the Consumer Cooperatives of India, Fan ^ 43 87 9 7 A7 B7 V. Description of Invention (35) 4 , 4'-Dinitro-2,2'-diphthalic acid (Example 28, 10.10 g, 30.1 mmol; PR23 2-9) suspended in 90 ml of water and saturated with NaHCO 3 (NaOH can be used ) Titrate to pH 7. Add 10 ¾ M / C (0.5 g; AJdrich) and mix the mixture at 30 psi H2 for 1 hour. The catalyst is removed by quenching and the filtrate is concentrated to about 20 ml. Carefully remove propyl (40 Ml) It was added to the condensed hydrazone solution to precipitate the product dinadium salt. 9.2 g of 4,4'-dinitro-2,2 · -diphenyldiamine was obtained by vacuum collection and vacuum drying. Formic acid. 300MHz NMR (D2 0): 5 4.70 f-NH 2, s); 6.7H1H, dd, J = 2.4, 8.25); 6.79 (1H, d, * 1 = 2.4); 7.00 (1H, d, J = 8.25) aCHN: Theoretical value: C: 49.64 H: 3.72 N: 8.27 (Calculated with 1.25 moles of water >. Measured value: C: 49.5 5 Η: 3. 72 N: 7. 90 «Fen example 30 14 ' -鳔 -U.6-Zero U-"罅-(2- Armor Knee -7. Even)-Anti-Hair 1-¾ Anti-Three Wells 1-艏 -2.2'-Dibismuth Fat. Di-n-naphthalene in a sealed, thick-walled glass tube contains 4,4'-diamine di-n-phthalic acid di-nano salt (Example 2, 9, 66 mg, 0.19 mil) and 2-chloro-4 , 6-bis [3-Aminophenyl-fluorene, N-bis (2-aminomethylamidoethyl) -sulfoamidoimino] -1,3,5-tritrap (Example 6) (300 mg (0.40 moles) was heated to a suspension of cyclodipene (10 ml) and diisopropylethylamine (0.3 ml) to 115 C. Heating was continued for 50 hours. Once the reaction was judged to be complete by analytical Η PLC (or TL C), the mixture was cooled to 20 t, and the product was precipitated by adding propan-2-ol (70 ml) and placed on a vessel. Cold ethanol (15ml) cleaning and I... ^ I policy I order {Please read the precautions on the back before filling this page) This paper size applies the Chinese National Standard (CNS) Α4 size (210X297 mm) A7 Ministry of Economy Printed on B7 of the Consumers' Cooperatives of China Standards Bureau V. Description of Invention (5b) Vacuum drying at 40C. Two solutions of the crude product (about 0.3 g) in deionized water (200 ml) were purified by preparative RP-HPLC, respectively. The fractions containing the desired product were combined, the organic solvent was evaporated under vacuum (10 hi b H g > and 30 t) and the product was concentrated, deionized and passed through a C18 column (900 mg, from Burdick & Jackson} single isolation. The column was washed with water (20 ml) and the product M formate (40 ml) was re-extracted. Methanol was evaporated to obtain 112 mg (34¾) of the desired product; melting point > 2 5 0 1 decomposition; MS ( ES) b / z: M'2 840.2; MW1 724. 4. Real .. Example _. 3) Anti-cages, etc. (2-Shen Ar, some sugar, -Z, etc.); -Aminosulfenilamide (3 g, 17.4 mmol) was dissolved in nitrobenzyl (55 ml). After simmering, the temperature was reduced to 90 ° C, and acrylic acrylic acid was brewed (5 ml. 55.5 mmol). And 1 ′ ″ 丨 1; 〇 [18 (0.4 ml, 40 »: in HeOH) was added. The reaction vessel was equipped with a strong condenser and allowed to operate for 20 hours. TLC showed the reaction was complete. The HC1 solution (30 ml, 1M in two Diethyl ether) was added to the reaction mixture M to produce a viscous oil. This was dissolved in 50 ¾ ethyl acetate / hexane and loaded onto a silica gel column. The desired product hexane was dissolved out. The solvent was evaporated to obtain 3.9 g (65 ¾). Key product; (m / Z): HH 343.2, melting point 59-60 υ. Example 3 2 3-cage-proof-^-zunjia and anti-methylose-7, etc.) Mix 3-aminobenzyl-H, N-bis (2-methoxycarbonyl-ethyl) sulfonamidoimide (Example 31, 0.5 g, 1.45 mmol) with acetic acid (10 ml with gentle stirring). ) Solution to methylamine solution (10ml, S.03H, 33¾ in ^^^ 1 n ^ T ί,-& (Please read the notes on the back before filling this page) This paper size applies to China Standard (CNS) Λ4 specification (210X297 gong) A7 Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (B7 V. Invention Description) Ethanol). After 24 hours, TLC showed the reaction was complete. Water was added to the reaction and the compound M Extraction and drying on sodium sulfate (50 mg). Yield: 300 mg (60¾); MS (ES) ra / z: 345.2 (M + H > +.) Example 33 (4-LW 蒈-(?- Shen Mou Anti-Diagram -7. Mou)-Amine medulla 1- 茏 Fat Mou -6-Tweezers-Μ.3.5] Mitsuchi -2- Mou 甚-1- (2- Shenmou pickled formazan-Z-m) -Fangmou 1-N-Shenmou-Triose Fang-mia Tripolychloride (550 mg, 2.98 mmol) The solution in dioxane (4 ml) was added to the gallate solution (15 ml, pH = 7). To the milky mixture was added 3-aminophenyl-N, N-bis- (2-methyl Carbaminyl-ethyl) sulfosylimine (Example 32, 2.0 g, 5.84 mmol) in dimethylformamide (25 ml), on the other hand the pH was adjusted by adding 1N sodium hydroxide solution Maintained within the range of 6.5-7.2. After the addition, the temperature rose to 55 υ for 2 hours, at which time HPLC analysis showed that the reaction was complete. The mixture was diluted with M water (100 ml), saturated with sodium chloride and extracted with ethyl acetate (4 × 150 ml). The combined extracts were concentrated to a viscous oil (3.5 g), which was dissolved in acetonitrile (30 ml) and left in the refrigerator overnight. The gummy precipitate was stirred with diethyl ether (20 ml) until all the precipitate turned into a fine powder, which was isolated by filtration. An amber solid was obtained (1.8 g, 78¾ yield); melting point > 25 ° decomposition; HS (ES) ra / z 795.7 (H + H) +. Window example: U 4.4 · _ beep-"4. β_ etc.-" U-"" Tetamine very 3 — Argon, certain amine, 1 amine, 1 sugar, certain cage, 1 anti-1-1. 5 -三 679-2-A certain antifungal 1 "1.1 '-A certain 1-? · 2 Diacetic acid. Disodium m-ί i —c · —- nn IJ ^^^^ 1 ^^^^ 1 ^^^^ 1 ^^^^ 1 ^^^^ 1 1 V (Please read the precautions on the back before filling out this page) This paper size applies to the Chinese National Standard (CNS) Λ4 specification (2 丨 0〆297) (%) Employees' cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China [A7 B7] 5. Description of the invention (W) Under litre, the 3-[[3- (4- {3- [双-(2- 甲Aminomethylamidino-ethyl) -sulfamoyl] -anilinobu 6-gas- [1,3,5] Triswell-2 -ylamino) -benzenesulfonyl]-(2-methyl N-methylaminomethylethyl-ethylaminomethyl N-methyl-propylamine (Example 33, 200 mg, 0.25 mmol), 4, -diaminobiphenyl-2, 2'-disulfonic acid A mixture of dinaline salt (41 mg, tl.il mmol) and diisopropylethylamine (5G ml, 0.28 mmol) was heated in a mixture of dimethyl sublime (4 ml) for 25 hours. Similar to the above Isolation procedure yielded a white solid (40 mg ^ 19%); melting point> 25 (TC Decomposition; MS (ES) ffi / z 9 3 0. 5 (Μ 2); HW 1 9 0 8. 1 0 4.-(4. β-bis-(. Ί-「bis- (2-methylamine Shen Yingji-Ethyl) -Amine Test 11 Ergai. _Amine_. 1- [Hydroxy, 3,51 tris-2-ylamino)-Congben-2, 2'-dicarboxylic acid, two. 1 salt: in 3-Π3- (4- {3-ίbis- {2-methylaminomethylmethyl-ethyl) -sulfamoylphenylaniline) -6-chloro- [1,3, 5] Tritrap-2-ylamino) -benzenesulfonyl]-(2-methylaminomethylmethyl-ethyl) -amino group N-methyl-propylamine (Example 33, 200 mg, 0.25 millimolar), 4,4'-diaminobiphenyl-2,2'-dicarboxylic acid, dinaline (37 mg, 0.12 millimolar) in dimethylene (4 Ml) was added to a solution of phosphate buffered saline (3 ml, pH = 7). The mixture was heated at 1 1 CTC for 24 hours. After cooling, water (10 Cl ml) was added and the mixture was prepared in preparative HP LC Separation by column. Yield: 60 mg (27¾) white solid; melting point> 25 (TC decomposition; MS (ES) m / z 894.5 {Μ 2); MW1836〇0 -4 0-This paper is in accordance with Chinese national standard (CNS ) A4 size (210X297mm) 1--I ii----I ^ ^^^ 1 ^^^ 1 ^^^ 1 ------- (Please read the notes on the reverse side before filling out this page) Yin Ju, Employee Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 43 87 9 7 A7 B7 V. Description of the invention (59) Glycosides H-zero-U.fi- 謦- Plant 1 "_- (?-Aminomethylammonium-7.even) -Aminomaxyl-1-Mofang some-three-trap-?-A certain fat-)-Cage-2.2'-Dicarboxylase.Dimethyl SN put 2-chloro-4,6-di [3-aminebenzyl-Team ((-bis (2-aminomethylethyl) -sulfoamidoimino] -1) at 1101, 3,5-Tri well (Ranunculus case 6, 200 mg, 0.27 mmol), 4,4'-diamino-2,2'-diphthalate 2 (38 mg, 0.13 mmol) Ear) and diisopropylethylamine (55 ml, 0.31 mmol) were heated for 30 hours. After cooling, add isopropion (50 ml). The precipitate was filtered and washed with K isozyme. Dry solid (190 mg) was purified by HPLC to obtain a white solid (53 mg, 2U yield); melting point> 250ΐ: decomposition; MS (ES) b / z 854.8 (M + 2H) 2t; MW 1707.8 ^ Example of window: Ϊ7 3-Nitrogen in a cage-NH-zun (2 -Hydroxypropylamidine) A fatty acid in diisopropanolamine (50.0 g, 75 mmol) in a stirred solution of water (500 ml) -Nitrobenzenesulfonate (57.1 g, 35 mmol) was added. The mixture was vigorously stirred at room temperature for 25 hours. The obtained 懋 float solution was washed with solid K 固体 2 0 (2 × 40 0 ml) and dried. And recrystallization from a mixture of ethyl acetate / hexane to obtain the desired product of white crystals. Yield 65.8 g (88 black); melting point 114-1161 :; 1 [1-} ^ 1? (〇0 (; 13, 300 ΜΗζ) 5 8. 67 (d, J 5.1Hz, 1H), 8.44 (d, 1H), 8.15 (t, J 6.0Hz, 1H), 7.77 (ffi, 1H). 4.78 (st 2H), 4.18 ( m, 2H), 3.10 (0, J 5.9Hz, 4H), 1.16 (dd, 6H); MS (ES) m / z 319. 5 (M + H) + ^ ^^ 1- ^^^ 1 n it In ^^^ 1 f ml ^ Jt .¾-2-5 (Please read the precautions on the back before filling out this page) This paper size applies to Chinese National Standard (CN'S) Λ4 specification (210X 297 mm) A7 B7 η 8 7 9 7 V. Explanation of the invention (ρ) Examination example μ 3-Amine Rong-HN-Etc. (2-Throwing Propionate) 碏 瞌 Chia 踣 on the catalyst (1U Pd / C, 1 gram) Hydrogenation of a solution of 3-nitrophenyl-N, N-bis- (2-hydroxypropyl) sulfonylimine (Example 37, 10.0 g, 31.4 mmol) in methanol UQ (0 ml) 1 5 hours. The resulting mixture was filtered through a Ce] ite pad, the solvent was removed, and the resulting viscous oil was purified by column chromatography on a silica gel, which was then eluted from a 4: 1 mixture of ethyl acetate / hexane. The desired product was obtained as pale yellow crystals. Yield: 8.2 g (90.5¾); NHR (CDC 1 a, 300 M Η ζ) 7. 2 8 (d, 1 Η), 7. 1 3 (m, 1 Η), 6.86 (d, 1Η), 4.20 (ra, lfi), 4.13 (dd, 1H), 3.37 (dd,

1H), 3. 0 2 (d, 2 H), 2. 8 0 (dd, 1H); 1. 16 (dd, 6H); MS (ES) m / z 2 8 9. 5 (M + H ) + 0 Cao Example 39 2 Second atmosphere: -4.6 --- (3- [Bis- (2-Pingxi..yl) -sulfamoylphenylanilide [1,2, .. 51 -tri The compound was prepared according to the procedure of Preparation Example 33 using cyanuric nitride (160 mg, G.87 mmol), 3-aminophenylbis (2-hydroxypropyl) sulfonylimine (7 fl G mg, 2.0 mmol), dipentane (3 ml), phosphate M buffer (10 ml, 0.3 M, ρίΠ), Ν, Ν-dimethylformamide (5 ml), and IN NaOH. The product was precipitated as a viscous amber-yellow oil from the cooled reaction mixture with water, washed with water and dried under high vacuum seven to obtain 64 0 mg (9 3 Si) gas triple trap. Melting point> 2 50 ° C decomposition; MS (ES) m / z 687,7, 689.7 (M + H) +. -4 2-This paper size applies to China National Standard (CNS) A4 specification (210X297 mm)----II-- -*-^^ 1 ^^ 1 -I -I ^^ 1 Wear, v include (please read the precautions on the back before filling this page) The Central Consumer Affairs Bureau of the Ministry of Economic Affairs, the Consumer Cooperatives, printed in the Ministry of Economic Affairs Standard Bureau employee consumer cooperative stamp A7 B7 V. Description of invention (41) Example 40 4.4'- 簪-(4.6-Beep- {3- "Enough- (2-Choose a)) Ϊ́ 「-" 1 .3.M-San coax -2- defend）)-Satoshi--2.2'- Disulfapone. Di Na 锞 2- 2- 氛 -4,6- 双-〖3- [双-(2-Hydroxypropyl) -aminosulfonyl] -aniline}-[3,5] -triple (Example 39,300 mg, 0.44 mmol), 4,4'-diamine Diphenyl-2,2'-disulfonic acid, disodium salt (77 mg, 0.2 mmol), 2 ml DMS 0, 2 ml phosphate buffered spinach (1 Ν, ρ Η 7) and 0.25 ml IN NaOH The mixture was exposed to llOt: microwave heating (PR0LAB0 units, single type) for 2 hours. After cooling, the untreated reaction mixture was subjected to preparative HPLC (water / acetonitrile system) on a Prodigy C18 polymer column. The product was obtained as a colorless solid (170 mg, 50.2%); melting point > 25〇υ decomposition; MS (ES) m / 2 822,3 (M-2H) 2 '; MW1691.9 (MW + 2Ha) ^ 窨Example 4.41-Substitute--wait-U- "bis- (2 -fluorenyl-propanyl) -aminopyridyl] -cage defense 1-" 1.3. 51-trihydrazine-2-protection of a certain target- 2.2'- 二 搿 酹. Two nanometers in the oven 2-Chloro-4,6-bis- (3- [bis- (2-hydroxy, -propyl) -sulfamoylphenylanilide}-[1,3,5] _triple ( Example 39, 178 mg, 0.25 millimolar), 4,4'-diamino-2,2'-diphthalate dihydrochloride (35 mg, 0.11 millimolar), 3 draft DMS0 , A mixture of 0.5 ml of phosphate rhenium (IN, pH 7) and 0.5 ml of 1H NaOH for 18 hours. After aging, apply preparative HPLC to obtain 90 mg (please read the precautions on the back before filling this page). The scale is applicable to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) Β < 3. ΙΟ. 12 A7 B7 Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. The invention product (42) (50, 5¾) is the desired product. Melting point> 250t: Decomposition; MS (ES) B / z 788, l (M + 2H) 2f; MW1619'8 (MW + 2Na). Example 42: Buqi-4.fi-zun-II-bis-fatyl-methyl-amino-sulfanyl-sulfanyl 1-¾and 1-η. 3. s 1-Triple well titled the compound according to the procedure of Example 33 Prepared using tripolymethylene chloride (0.42 g, 2.27 mmol), 3-aminophenyl-fluorene, N-bis-aminomethylmethylmethyl-sulfonylimine (CL55675, 1.43 g, 5.0 mmol) Ginger), Di-I alkane (2 ml). Phosphate solution (10 ml. 0.3K, ρΗ7), Ν, Ν -dimethylformamide (4 ml) and IN NaOH. Reactions throughout the procedure The warm compound is heterogeneous. The resulting pink precipitate is centrifuged, washed several times with water, redissolved in the smallest amount of DKF, and re-precipitated with water. Finally, 0.7 g of U5.U) is obtained as the desired product. ; Melting point> 250 C decomposition; MS (ES) m / z 6 8 3. 7, 685.7 (M + H) + 〇 ^ Example 4 3 Although-M.fi-bis- "3-f 唼 -amine methylpro Some methyl-amine-sulfonyl] -¾ anti-iM.s.pn triple-well anti-a certain hydrazone-wax cage even dihydrazine. The dinawei title compound was prepared according to the procedure of Example 40 using 2-chloro-4 , 6-Bis- (3- [bis-aminomethylamidin-1-aminesulfonamido] -aniline}-[1,3,5] -trioxo (Example 42, 500 mg, 0.73 mmol) ), 4,4 * _diaminobibenzyl-2, 2'-disulfonic acid, dinaline (114 mg, 0.29 mmol), 2.5 ml 0 »50, 2.5 ml phosphoric acid Salt buffer solution (1 »,? 1] 7) and 1.0 ml IN NaOH. Continuous microwave heating at 105¾ (PR0LAB0 units, -44- This paper is sized according to the Chinese National Standard (CNS) Λ4 specification (210x29 〃〃 (please Please read the precautions on the back before filling this page). Install the 'Paperworker's Cooperative Du Duxue of the Central Bureau of Standards of the Ministry of Economy 43 87 9 7 A7 B7 V. Description of the invention (45) Single type) 1 hour. By preparative HPLC, 50 mg (10.2¾) of a pink solid product was obtained: melting point> 250; it decomposes; HS (ES) m / z 818.2 (H-2H) 2-; MW1683.7 (MW + 2Na) 〇Tube Example 44 4. .41-Tie-UR-Tie- "3- (Striking-Ada-Shen Shen-Amine-Amino-1 -Anylamino 1-" 1.3,51 Triple Well-2 ~ Base丨 -Difluorene-2.2 '~ dicarboxyl. The title compound of dinathan was prepared according to the procedure of Example 40 using 2-chloro-4,6-bis- (3- [bis-aminomethylamidomethyl-aminesulfonate Fluorenyl] -benzylamino)-[1,3,5b triple wells (42,500 mg, 0.73 mmol), 4,4 · -diamino-2, 2 ^ United stupid acid, dihydrochloride (100 mg, 0.29 mmol ear Mo) .2.5 ml DMS0,2.5 mL phosphate fines flushing (lH, pH7), and 1.0 mL of IN NaOH. Microwave heating (PR0LAB0 unit, single type) was continued at 105T for 1 hour. The resulting mixture was passed through a preparative ΗPLC to obtain 20 mg (4.3¾) of a product as a pink solid; melting point > 25.0% decomposition; MS (ES) m / Z 784.0 (H + 2H) 2t; HW1619 .8 (MW + 2Na). Official Example 45 1-π-Nitro-¾ 碏 醏 a) Hexamidine u-dicarboxylic acid at 2 2 P si in 1 g of ruthenium catalyst (5 Si ruthenium on alumina powder) in Parr device Hydrogenated 3 · 5-pyridinedicarboxylic acid (3.34 g, 20 mmol) in 50 ml of water and 10 ml of ammonium hydroxide solution for 48 hours. After the catalyst and the solvent were removed, the crude 3, 5-6 Hydropyridine dicarboxylic acid was dissolved in 60 ml of 1N HaOH and treated with 6.6 g (30 mmol) of p-nitrobenzenesulfonyl chloride. The reaction mixture was stirred at room temperature and the pH was maintained at 9, 5 -45 by the addition of IN NaOH. This paper size is applicable to the Chinese Standard (CNS) Λ4 specification (210X297 cm) ---------- ----- 11 ------ ^ (Please read the precautions on the back before filling out this page) i4 3 c '/: / A7 B7 printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 44) until it stops falling. The reaction mixture was stirred for another 1.5 hours, the precipitate formed by filtration and the filtrate was acidified with concentrated HC1 to pH 2-3. A white precipitate was formed by washing, washed with K water and dried under high vacuum overnight to obtain 5.3 g (74¾) of the desired product. 1 H-NMR (DMS 0-ds, 300MΗζ) δ 8.55 (d, 1H), 8.40 (s, 1H), 8.15 (d, 1H), 7.95 (t, 1H), 3.14Cni, 4H), 1.65 (m, 2H), 1.45 (n, 2H); MS (ES) m / z 359 (M + H) + ° Fen example 1- (3 -Nitro- ¾ 碏 sugar a) hexa ffllie pyridine-di hydrazine _ 1- (3-nitro-benzenesulfonyl) was treated with excess diazomethane at 01 A suspension of hexahydropyridine-3,5-dicarboxylic acid (Example 45, 3.6 g, 10 mF) in THF (200 ml), and stirred at this temperature until the suspension turned into a clear, bright yellow solution. The reaction mixture was warmed to room temperature, filtered, evaporated, and purified by column chromatography on a silica gel. The desired product was obtained by dissociation with chloroform to obtain 2.5 g (6U) of colorless crystals. 1 H-NMR (CDCla, 300 ΗΗζ) δ 8.65 (s, 1H), 8.49 (d, 1H), 8.11 id, 1H), 7.81 (t, 1H), 3.73 (s, 6H), 3.40 (m , 4H), 2.9 5 (n, 2 H), 2.05 (t, 2H); MS (ES) b / z 3 8 7 · 2 (M + H) +. IF Example 47 1- (3-Nitro- ¾-Confirmed) Hexa-pyridine-3. 5-Dihydrazidine dihydrazine seal 1_ (3_nitro-benzenesulfonyl) hexahydropyridine_3, A solution of dimethyl 5-dicarboxylate (Example 46, 2.5 g, 6,5 mmol) in 200 ml of formic acid (saturated with ammonia at lower pH) and left at room temperature for 7 days. The resulting yellow solution was concentrated to a volume of 100 ml, and the precipitate formed by 泸 was clarified with nv ^^^^ 1 ^^^^ 1 I mu i ^ i ^ i ^^^^ 1 a ^ m is let-=, (Please read the notes on the back of the book before filling in this page) This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X 297 mm) Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (45 ) Wash and dry to obtain 1.8 g (77.7¾) of light beige colored product. MS (ES) m / z 357.1 (M + H) +. Example 48 1- (3- 硪 a-cage-condensed) hexaS-pyridine-3.5-diphosphonic acid enables 1- (3-nitro-benzylsulfonyl) hexahydropyridine-3,5-at 25 psi A solution of a dicarboxylic acid (Example 45, 2.5 g, 4.2 mmol) in 150 ml of methanol was hydrogenated in a Pa "device at 0.15 g of palladium catalyst (10 palladium on carbon) for 1 hour. The catalyst was filtered and the solvent was removed 1.8 g (79¾) of the desired product was obtained as a white solid. MS (ES) m / z 329.1 (M + H) + Example 49 1-ί 3- 硪 some-¾ 碏 meryl) hexapyridine-3.5- Diammonium diacetate was used to make 1- (3-nitro-benzenesulfonyl) hexahydropyridine-3,5-dicarboxylic acid (Example 47, 1.5 g, 4.2 mmol) in 300 ml of methanol at 25 psi. The solution was hydrogenated in a Parr device at 0.1 g of palladium catalyst (10 palladium on carbon) for 1.5 hours. The catalyst was filtered and the solvent was removed to obtain 1.26 g (92 ¾) of the desired product as a pale gray solid. MS (ES > a / Z 327.1 (Μ + ΗΓ 啻 Example 50 2-Oxygen-4.6- 饕-"3- (3.5-Dimethylformate-hexagonal_pyridine-1-contained sugar) -¾Protect 1-M.3.51 Add a solution of cyanuric chloride (280 mg, 1.5 mmol) in dioxane (5 ml) to the osmium osmium solution with 0-2 and mash. 10 ml, 0.3M, pH = 7). To the resulting suspension was added dropwise human 1- (3-amino-benzenesulfonyl) hexahydropyridine-3,5-dicarboxylic acid dioxamine (Example 49 , 1,0 g, 3.1 mmol) in K, N-dishenylformamide (5 ml), pH by adding ___ 1 -___ ^ __________ T, v '° (Please read the back Note: Please fill in this page again.] This paper's standard is applicable to the Chinese National Standard (C'NS) Λ4 specification (2 丨 0 > < 297 mm) Printed by the Consumer Cooperative of the China Standards Bureau of the Ministry of Economic Affairs 4387 9 7 A7 B7 Description of the invention (puff) Add NaOH to maintain at 6.5-7.2. After the addition is complete, add the reaction mixture to 50-551C and stir at this temperature for 2 hours (until HPLC shows complete back-grinding), and then cool to room temperature. Diluted with water, filtered the product to splash, washed with cold water (10 ml), propane (5 ml), and dried under vacuum at 20 C to obtain 8 4 5 mg (7 4.2; Π desired product; melting point> 2 5 0 t decomposition; MS (ES) b / z 765 · 0 (Μ + Η), MW764.2. Example 2 ~ Xiayi 4.fi_etc.-Spot a certain six gas Sft. Yi 1-indeed with Even) a cage against a 1-M. 3. 5 1 triple well standard The compound was prepared according to the procedure of Example 50 using cyanuric nitride (280 mg, 1.5 mmol), 1- (3-amino-benzenesulfonyl) hexahydropyridine-3,5-dicarboxylic acid (Example 48, 1.0 g, 3.1 mil), dioxane (3 ml), phosphate solution (10 ml, 0.3M, ρΗ7), Ν, Ν-dimethylmethanamine (5 drafts) And IN NaOH. After the reaction was completed, the mixture was cooled to room temperature, diluted with water, acidified to pH 5 with MHC1, and the product precipitated was filtered, washed with cold water (10 ml) and dried under vacuum at 20 ° to obtain 8 4 5 mg (7.4 2 3S) desired product; melting point 2 50 0 1C decomposition; MS (ES) β / ζ 769.0 (Η + Η), HW767. 8 ° 52Example 52 (R) -2,2 'a Π.2-7, 懦 二Radical) bis-equal "3-ΓΓ3.5 — etc. (anti-carbonyl hexafluoropyridyl 1 fluorenyl 1 碏 瞌 1 茏]] anti-tri-trap-2-yl 1 amine〗 cage 碏 醅 1 2 Na Na In a sealed, thick-walled glass tube, 4,4'-diaminostilbene-2,2'-disulfonic acid, dinaline (0.41 g ^ 0.1 mmol) and 2-chloro-4,6 -Double--4 8 ~ ________ ^ ______ ^ 4! 1 i I ί I i, III —, 1Ί (Please read the precautions on the back before filling this page) This paper size applies the Chinese National Standard (CNS) Λ4 specification (2I0X297 mm) A7 B7 printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (47) [3- (3,5 -Diaminomethylpyridinyl-hexahydropyridine-1-sulfonyl) > Aniline Base]-[1, 3,5] Three coaxes (Example 50) (1.62 g, 0.21 mmol) in Tintin (3 ml) and two A suspension of methylformamide (5 ml) was warmed to 115 in the presence of diisopropylethylamine (0.08 ml). The ore was warmed for 40 hours. Once analyzed by HPLC (or TLC) judged that the reaction was complete, the mixture was cooled to 30 C, 1 NN a 0 Η (0.5 ml) was added and the product was precipitated by adding propan-2-enzyme (50 ml). The precipitate was filtered to remove (30 ml) was washed and re-dissolved in the water of the smallest body, and then re-spattered by adding ethanol. After washing, the precipitated ethanol (30 ml) was washed and dried under vacuum at 501. Yield 1,5M (85S!) ; MS (ES) id / z911.7 (M-2H) 2; MW 1 869.9 (2Na) ° tube case 53-(4.6-zero- "3- (3 · 5-dipyrazine pickled some-six gas Pyridine-1- 碏 瞌 -1-cage-proof 1- "1.3.5 1 triple well-2-some-proof" -Cage-2.2'-dihydrazine dinazol The title compound was prepared according to the procedure of Example 52 , Using 4,4'-diaminobibenzyl-2,2'-disulfonic acid, di-nano salt (40 mg, 0.1 mmol) and 2-chloro-4,6-bis- [3- ( 3,5-diamine formamidine-hexahydropyridine-1-sulfonyl) -anilino]-[1,3,5] -triple (Example 50) (176 mg, 0.23 mmol) at 60 ML D MS 0-Cyclidine δ (1: 3, vol / horizontal) and diisopropylethylamine (0.08 ml). The product was obtained as a beige solid (153 g, 83¾); melting point> 250f * W; MS (ES) (m / z) 898.3 (H-2H) 2-; Η ¥ 1843.9 (M + 2Na) 〇 ^^^ ^ 1 ^ — ^^ 1 ν ^ ι ^ ϋ. N ^ i 1 ^^ — «1 ^ 1 ^ 1 nn I a ^ l \, 1 (Please read the precautions on the back before filling this page) This paper size Applicable to the Chinese National Standard (CNS) Λ4 specification (210X 297 mm) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (48) Example 54 1.2'.1 \ 1 ”'-“ (2.2'- Diosmic acid "1.1'- Sighting cage 1-4.4_- Ermou"-< »[Di Fangmou-1.:?.5-Three coaxes-decay.?.4-Sanmou etc. -3.1-Dendrobonic acid, "Hexaerythridine PBidine dicarboxy ether The title compound was prepared according to the procedure of Example 52, using 4, 4'-diaminobiphenyl-2,2'-disulfonic acid, Dinadium salt (270 mg, 0.68 mmol) and 2-chloro-4,6-bis- [3- (3,5-dicarboxy-hexaazapyrimidine-1-sulfonyl} -benzylamino] -Π, 3.5] Triple well (Example 51) (1.1 g, 1.43 mmol) at 60 L DMS0-cyclobutane (1: 1, v / v) with diisopropylethylamine (1.2 ml ). The product passed through the addition of propan-2-enzyme precipitation, M propionate 30 ml), washed, dried, redissolved in a minimum amount of water, and reprecipitated by acidification (HC1) to ρΗΙ-2. The obtained product was obtained as a beige solid (1.0 g, 80¾); melting point > 2501 decomposition; HS (ES) U / z) 90 2 '2 (M-2H) 2—; MW 1 80 7. 8 〇g M SB M-Η · N-_ (2- 掸 7 ′ group) Diethylenzyme (Aldrich; 25.0 g, 0.238 mmol) was dissolved in 55 liters of 9: 1 dichloromethane / THF and cooled to 5 T. 3-nitrobenzyl chloride was made in 10 minutes (Aldrich; 25.0 g, 0.113 mol) was added to a solution of 35 ml of THF. The ice bath was removed, and the reaction was stirred for another 30 minutes. The solvent was then stripped, and the residue was partitioned into water (100 drafts) and ethyl acetate (150 Ml). The aqueous layer was extracted with three 25 ml portions of ethyl acetate. The combined organic layers were dried over MgS04, passed through a pad of silica and concentrated in vacuo. The product crystallized during this evaporation and was filtered Get 17.4g-50 "_____; ______ gen______ D (Please read the precautions on the back before filling this page) This paper size applies to Chinese national standards (CNS > A4 size (210X 297mm) Ministry of Economic Affairs Bureau of Standards staff consumer cooperative printed i43 8/9 (A7 B7 five, description of the invention (49) (53.2SO white needles. Melting point 99-10 °. MS (ES) m / z 291.2 (M + H) 1+. g Liu? ifi Suspended the nitro compound (Example 55, 17.2 g, 59.3 mmol) and 1.72 g of 10¾ Pd / C in 170 ml of acetic acid. The mixture was allowed to stand for 2 hours under 40 psi hydrogen. The solvent was removed by filtration and the transparent colorless solution was evaporated to dryness. 15.4 g (98 »; yield) of the corresponding amine compound was obtained. 》 ^ ($) * / 2 261.0 (H + H) 1+. Example 57: "Zero-(2- 锊 Zsome)-Biebusome 1-Mofang-" 1.3 .5 1-Triple well-2-Fatty]-Aiming cage-2.2 '-Second stroke Ether dinatat at 0 t: a solution of trichlorotritrap (U. 55 g, 8.4 mmol) in 20 ml of dioxane was added to 60 ml of pH 7 Yuan rinse. In the resulting fine suspension fatigue A solution of human 4,4'-diamino-2,2 ~ dibenzyl dicarboxylic acid (PR232-10; 1.55 g, 4.0 mmol) in 10 ml of water was added dropwise, and M1N HaOH was maintained at pH 6, 5-7. 丨. Once the addition is complete and the pH is stable, bring the reaction mixture back to ambient temperature. Diethyl sulfonamide (2.6 g, 10 mmol) is dissolved in 20 liters of dioxane solution and solid carbonic acid. Sodium hydride (0.8 4 g, 10 mmol) was added and the resulting mixture was heated under reflux (92 υ) for 2 days. The clear yellow solution was cooled and the dioxane was stripped. The product was precipitated from the aqueous solution and borrowed. 3.16 g of the desired compound was collected by vacuum filtration. The purity was approximately 65¾ by HPLC, and it was a white amorphous solid. Melting point -51- ^^^ 1 I ^^^ 1 n I n ^^^ 1 ^^^ 1 nn HI— --V wear- 旮 (Please read the precautions on the back before filling this page) Paper size applies to Chinese National Standard (CNS) A4 (210X 297 mm) Printed by the Consumer Cooperatives of the China Standards Bureau of the Ministry of Economic Affairs 4 ^ 8797 A7 B7 V. Description of the invention (50) > 250ΐ: Decomposition; MS (ES) U / z) 732.5 (M + 2H) 2t; MW1507.6 (M + 2Na) Example 58 3-Pickled Moum-etc.-0 Ya Ping Mou) a certain Asian defense under 0TC, nitrogen and stirring will be 3 -Aminophenyl-M, N-bis- (2-methoxycarbonyl-ethyl) sulfonylimine (Example 31, 150 mg, 0,4 mmol) in 5 mL of THIU) and human LiAlH4 (3 ml, 1M in THF). After 45 minutes, TLC showed the reaction was complete. Aqueous ammonium (15 ml, 1H) solution was added to the solution, a white precipitate formed and the solution turned yellow. The yellowed solution was poured by The organic layer was dried over sodium sulfate and rotary evaporated to obtain the desired product as a yellow oil. The yield was 110 mg (95.6 Si), (a / z ): Μ Η 2 8 9. 2. Example 5 9 簪-U.fi-di- “3-anti-cage-H and other wavers and so on)-carbohydrate and ammonium 1-1. 3.5-triple well A certain prevention) ~ Cong Cang-2.2'-diphosphonic acid Prepared using the general conditions of Example 1, in which cyanuric chloride (92 mg, 0.50 mol) and 4,4'-diaminobiphenyl-2,2'-disulfonic acid, dinaline (93 mg , 0.24 mmol)), and then reacted with 3-aminophenyl-N, pyrene-bis (3-hydroxypropyl) sulfonylimine (708 mg, 2,5 mmol) (Example 58) ) Reverse. Once the reaction was judged to be complete by analytical 1 ^ 1 ^ (or 1 ^ (:), the mixture was cooled to 20C, and the product was precipitated by the addition of propan-2-ol (40 ml), and cold propion-2-fermentation was performed on a vessel. (15 ml) was washed and dried under vacuum at 40 t. Two copies of the crude product (about 0.35 g) were removed from 齄 -52- (please read the precautions on the back before filling this page) Packing, ιτ This paper size is applicable to China National Standard (CNS) Λ4 specification (210X297 mm) A7 B7 printed by the Employees' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (51) The solution of water (200 ml) was purified separately by preparative HP-HPLC. The fractions containing the desired product were combined, and the hydrazone solvent, the condensed product, the desalted salt, and the single isolation through a C18 column (900 mg from Burdick 8 < Jackson) were evaporated under vacuum and 301. Column M water (40 ml) was washed and the product M was re-extracted with methanol (60 ml). The formazan was evaporated to obtain 162 mg (40¾) of the desired product; melting point > 30〇υ decomposition; MS (ES > (n / z): M_2 822.4; MV1690 .8. Compounds are stored in diseased animals. The biological activity is determined. Host cells (human foreskin fibroblasts are called HF, and the commonly used African green monkey cell line is called vero, shown in Tables 1 and 1a) are loaded in 96-well plates (0.1 in 4X104 cells / well). Ml / well) in cell growth medium containing 2¾ fetal bovine serum or 2¾ bovine serum and incubated overnight. Compounds were added to the respective wells to obtain a concentration of 50 to 0.1 g / ml in a second concentration step. After 1 hour, the virus was added to humans and held with RSV or CMV for 4 days and HSV for 2 days. At the end of the experiment, the amount of virus growth was quantified and the yield decreased at different concentrations of the compound. This can be estimated The concentration of the compound that produces a 50% reduction in virus growth (IC5D) is shown in Table 1 and 1a (excerpt from biological activity), which summarizes the activity of the compound in the determination of the decrease in virus yield. The ability of the test compound to inhibit the formation of viral plaques. Host cells, as indicated in Tables 1, 1 and 2, K106 cells / wells were loaded in 6-well plates and incubated overnight. One of two methods was performed afterwards. In general (Pre-treatment I (Please read the precautions on the back before filling this page) This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X 297 mm) A7 B7 V. Description of the invention (52) Principle, the cell growth medium Ml ml The medium containing the compound at a specific concentration was replaced. The virus was added after 1 hour (~ 100 plaque formation in 40 microliters). Another 1 hour later, the medium M 4 ml of the medium containing the compound at the test concentration was replaced. The cells are incubated for a sufficient time to form viral plaques. Sometimes, compounds are added only after the onset of infection (after treatment). In this case, the growth medium K1 ml of the medium containing about 100 plaque forming units was replaced. After 1 hour, this was replaced with 2 ml of growth medium. After the period defined in Table 2, 2 ml of the compound was added. In both cases, the number of lysolytic plaques in a series of wells with a range of chemical compounds in the range Ϊ1 was compared to the number of wells without chemical compounds. IC so reduced the number of bacterial plaques by 50 and confirmed that the number of virus The compound Maedo determines ICbo. Tables 1, 1 and 2 summarize the antiviral activity in the plaque assay. It was observed that the title compounds of Examples 1 and 4 were effective against all tested RSV strains at about 0.1-0.7 µg / µl. Activity can also be detected by specific members of other viral genera (in the range of 3-20 μg / ml). These results confirm and extend data from yield reduction assays, showing that these compounds are powerful and specific inhibitors of RSV. ^^^ 1 ^^^^ 1 ^^^^ 1 ^^^^ 1 ^^^^ 1 n ^ i, I ttnn ί,, -'a (Please read the notes on the back before filling this page) Economy Produced by the Central Bureau of Standards for Consumer Consumption Du printed -54 ** This paper size applies to Chinese National Standards (CNS) Λ4 specifications (2) 0X 297 mm) 5. Description of the invention (π) A7 B7 compounds against respiratory syncytial virus, In vitro activity of cytomegalovirus and herpes simplex virus Printed by the Ministry of Economic Affairs, Central Bureau of Labor, Consumer Cooperatives, printed example of 1C 50 u G / biL in growth inhibition, ICso ju G / roL RSV / HF in plaque assay RSV / VERO CMV / HF HSV / HF HSV / VERO RSV / VERO CMV / HF HSV / VERO 11 10 10 > 50 9 < 3 0.4 0.3 10 10 < 3 0.7 6 > 50 > 50 > 50 1 0.3 0.5 0.3 7 8 4 0.1 0.1 35 20 35 0.1 > 30 35 5 0.4 8 7 0.7 1 0.8 10 8 > 50 > 50 > 50 12 8 10 13 8 8 20 10 30 15 7 > 8.3 2 1 16 5 ~ 8 · 3 3 3 17 > 50 > 50 > 50 19 2 3 12 30 ~ 50 20 0.5 40 22 0.15 0,25 4 2 23 8 20 24 50 25 30

Decrease by a small amount ο -0 U1-1, (1 fixed Π) cell system must be described in detail atro long (pve middle VI and 1 text HSF), as shown in (H uses 1ε cell ild to control f mother Suppressing MV dimension (Fiber 50), the A2 of the skin into a vf-type RS human plaque is the strain cytolytic bacteria and the poisonous host-sick

This paper size is applicable to Chinese National Standard (CNS) Λ4 specification (210 × 297 mm) -----: ------ install-(Please read the precautions on the back before filling this page) * · 1Τ IB43 87 9 7 A7 B7 V. Description of the invention (55) Table 2 Effect of Examples 1 and 4 on the formation of h in virus plaque virus virus strain IC5Q (μg / ml) (cell) ------------- ------------ Example 1 Example 4 Front 2 hours ^ ι \ Back 4 Front hours / | \ Back • 2

RSV (VERO) A2 LONG 0.2 3A 9320 2B RSS2 18736 RSV (HF) A2 RSV (SKNSH) A2 RSV (HDBK) A2 HPIV3 (VER0) WASH FLt) (MDCK) Al / FM / 1/47 A2 / HK / 8 / 68 A2 / JPN / 305/57 A / Texas / 36/91 5 A / Beij / 32/92 B / Pana / 45/90 HCHV (HF) Adl69 ^ 15 HSV1 (VERO) Patton HSV2 (VER0) 333 12 MS 3 5 2 1 ο ο ο ο 4 ο 4 ο 4 ο ο ο ο ο 5 5 5 2 > > > 3 0 11 3 Λν 3 ο 4 ο 8 2 ο 3 > 5 3 2 ο 5 8 8 ΙΑ ϋ ο ο ο ο ο 0 6 2 0 (Please read the precautions on the back before filling out this page), policies. .1T Printed by the Consumers' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs-* 57- This paper size applies to Chinese national standards ( CNS) Λ4 specification (210 × 297 mm) A7 B7 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. 5. Description of the invention (56) 1 1 Overflowing cells in the well plate at t 6 in the pretreatment scheme. 1 compound treatment for 1 hour 0 μmin. The virus (~) 00 pfu was added and after 1 I incubation (RS V »C MV and HP IV 3 (human i Sfl influenza virus type 3,-, Please 1 first 1 Washington strain), 5-8 days; Influenza virus and herpes simplex disease 1 virus 1 2 days) Calculate plaque a for post-processing, first infect the cells 1 for 1 hour and replace the medium (Contains unadsorbed virus) 〇 After the end of the infection period, pay attention to I 2 or 24 hours. Add the medium containing various compounds to the human body. 0 Item 1 1 Reuse cells include ve Γ 0 (African green monkey cells) HF ( Human foreskin 纗 Vitamin filling%-Ben m cells) SKHSH (human sympathetic neuroblastoma cells), HDBK pages, · 1 I (Η a 〇i η -D arby bovine kidney cells) and MDCK (Μ adi η-D arby canine gluteal cells). 1 1 Action Ellipse 1 | Increase the time to determine the life cycle of the virus when Example 1 performs its action 1 Add to the understanding of the action mechanism 0 This is done by adding at each time relative to the infection! Adding and removing compounds and evaluating The effect of viral protein synthesis is completed 1 | 0 Infect cells on ice for 1 hour »Remove unadsorbed disease t and incubate infected fine β / τ at 37 1 IV. Serve for 18 hours (virus adsorption occurs on ice 9 1 1 but without fusion until the temperature rises to 18 or higher) ◊ at 37 t: after incubation for 18 hours (when most of the protein synthesis is performed by the virus RN A \ 1 guide) ♦ 5 S-formamylic acid was added for 2 hours »The cells were lysed I i 1 and the labeled protein was analyzed on an SDS-PAGE gel. The virus N, IP and β proteins were then displayed. And the incubation temperature rose to 1 1 37 V. Immediately add 10 μg / ml of the compound of Example 1 to 9 and the disease! 1 toxic protein synthesis is completely prevented 0 However r even cultured at 37 I only [After 5 minutes of incubation Example 1 Compound addition * Production of viral proteins is not [1 -58- 1 1 1 1 This paper size is applicable to Chinese National Standard (CNS) A4 specifications (2! 〇X 297 mm) 絵 43 8 7 9 7 A7 B7 Ministry of Economic Affairs Printed by the Consumer Standards Cooperative of the Central Bureau of Standards 5. Invention Description (57) Obstructed. Therefore, the process of inhibition is the fusion process or the step of a specific close phase, which is required for the later viral gene expression. 0 Known close contact RS V-infected cells will fuse a to form syncytia, and this process depends only on the viral F, SH, and G proteins (H e mi η ν ay BR, Yu \ Tanaka Y, Pe! Γ Γ i η e KG 1 Gu .staf S 0 η E, Β erns; te ί JM T Ga I inski HS. 1 994. A n a 1 y si S of Γ es Pi rat 0 rysync: yt ϊ a 1 v ΐ ru SF, G and SH Ρ Γ 0 teinsi η ce] 1 fusi on • Vi Γ 0 1 〇ε y 200 80 1-80 5) ο syncytia formation should not involve viral function, if it is not covered or transcribed, it-usually occurs after it and it is required for viral gene expression later. 0 To determine whether the compound of the present invention inhibits fusion or post-mine step f test The ability to prevent syncytia formation in cells previously infected with RSV. This was caused by 3 infections of νer. Ttfet cells for 1 hour and 7% to 9% followed by fresh culture medium instead of the original medium. After 6 hours of incubation Add 0 after 24 and 48 hours 1 View the infected cells under a microscope to determine the degree of syncytial formation. 0 The difference in the degree of syncytia formation due to the presence of the compound can be easily confirmed »and the compound can be determined based on this strength Easily sorted. The actual 1C50 determined by this method is approximate. Compounds 16 and 17 are 0.3 and 0.05 micrograms / ml, respectively. The ability of these compounds to inhibit the formation of tUrt cells proves that they are resistant to viruses. The role of the life cycle in the fusion step. Example 1 and 4 characters in the living body to prevent RS V bovine cotton rats infected with RS V followed by small particle spray (SPA) for drug delivery, this is used to evaluate compounds In vivo resistance-RSV potential (Gilbert BE, Wyde PR, Wilson SZ, and Meyerson LR. This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X297 mm) ^^^ 1 · .1 · ^ — — m ^^ t HR ^ i I ^ nn n ^ l — ^^ — t--., -¾ Ί (Please read the notes on the back before filling out this page) A7 B7 Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Description of the invention (58) 1 1 1 99 3. s P -30: smi 1 ρ > art 1 C eaer CSC] t Γ eetmert of 1 1 | ΐ η f U € η 2 a A vi Γ 1 1 S ir fecti () η in aicea η dresf ^ ir 'at 〇ry 1 1 syncytia 1 V ru S ί Γ f € ctic η i η c otto η rats, A rt: viral please 1 first 1 Re sear ch 21 37- 45) D See 1 1 Compounds of the present invention are tested in this system. M Determine whether they can inhibit RS V growth in cotton 1 I 1 cotton rats. Animal 1 in Experiment 1 (see Table 3) Caution 1 RS V A2 (No. 0) Respiratory tract infection caused by internal infection O Azazole and 1 nucleoside 60 mg / ml in water. Used in spray booths and filled in after the infection. I 1 »2 and 3 Dosing twice a day for 2 hours 0 Compound 16M Page 1 1 4 .5 mg / ml (in 25 m VN aHCO 3) used in the spray chamber and \ 4 hours before infection > on the 1st t 2 and 3 each for 8 hours \ 1 〇 placebo The same usage of substance 16 uses water. Animals are sacrificed at the 4th order. The lungs are lavaged and the power of RSV in the lavage fluid is determined. Experiment 2 1 Infected untreated animals and exposed to 25 mM Ν aHCO 3 Spray 1! Used as a compound for Zhao Group 〇 Example 1 and 4 5 mg / ml at 25 1 I 9 Μ N aHCO 3 〇— 'Group 0 Hour before infection Example 1 Compound 1 1 Treatment for 4 hours and 8 hours each at the 12th and 3rd (preventive usage) | hours. One group only at the 1st > 2 and 3th (therapeutic usage) > λ Example 1 Compound 1 each Treatment 8 一 组 0 The last group was at 1 τ 2 and 3 hours (treatment 1 1 therapy) Μ Example 4 Compounds were treated for 8 hours each 〇4 hours 1 | All animals were sacrificed »Lung lavage and Determine the RSV force value in the lavage fluid 1 I 〇 Experiment 3 > Placebo for intranasal delivery of water once per day 0 Example 4 1 1 Compounds were inoculated by vaccination before the inoculation and on the 1st day (on the 0th and the 1st day) 1 I Fu Fu injection * 刖 and the 1st-3rd day on the day M in the canonical transmission m and only 1 1 | " β 0 _ 1 1 1 1 This paper size applies to Chinese National Standards (CNS) A4 specifications (210X297 mm) A7 B7 V. Description of the invention (59) Transmission and administration within Μ 鬓 within 1-3 days after inoculation And experiment. The compounds were also tested by intraperitoneal administration. On the 4th day, all animals were sacrificed, their lungs were lavaged and the RSV force value in the lavage fluid was measured. This was done by measuring the dilution endpoint (producing cytopathic (CPE) on o cells). It was also done by plaque analysis on vero cells. The lungs were also homogenized, and the bark material was removed Divide (1000 Xg, 10 minutes) and use the dilution of the supernatant in the plaque analysis to determine the virus valence in the lungs. It can be seen that the compounds of Examples 1 and 4 inhibit RSV in vivo. ^^ 1 · ^^^ 1 tn ^ m an— m I Jm-In ^^^ 1 V. y (Please read the notes on the back before filling out this page) Printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs " 61 " This paper size applies to China Standard (CNS) Λ4 specification (2I0X 297 mm) H? 43 87 9 7 A7 B7 V. Description of the invention (吣) Table 3 Examples 1 and 4 Effect on cotton rat inner respiratory syncytial virus Average effect Monk experimental plaque treatment Method N sample / analysis loglO / gW SD logT (? 1 H20 spray 2x2h / d 5 lavage / CPE 4.1 0.27 dl, 2,3 triazole core or spray n JU / fflh / 3 ε 2 2 m <, Ο 1 6 2 d 4 perfusate / CPE 3.3 0 0.8 Example 1 Spray 4. δικκ / πιΐ 4h uO 8h dl, 2,3 r perfusate / CPE 2.8 Λ Ο Γ \ J * 00 1.0 Untreated 4 lavage solution / CPE 3,68 0.48 placebo spray 4h dO 8h dl, 2,3 4 lavage solution / CPE 3.43 0.25 0.25 Example 1 spray 5ag / «l 4h dO 8h dl, 2, 3 4 Irrigation fluid / CPE 1.73 1.15 1.95 Example 1 Spray 5ng / is 1 8h dl, 2,3 4 Irrigation fluid / CPE 3.43 0.25 0.25 Example 4 Spray & Blg / ID 1 8h dl, 2,3 4 Irrigation 掖 / CPE 2.05 0.5 1.63 d0,1,2,3 Η 2 0 Intranasal administration example 4 Intranasal administration d0 15ag / k dl 30iBg / k ^^^ 1 II »ml» nn ^^^ 1 ^ ^^ 1 I am i \ 1 '(Please read the notes on the back before filling this page) Example 4 _ * Internal investment for dO 15aig / k dl, 2,3 30mg / k Consumption of employees of the Ministry of Economic Affairs Cooperative printed example 4 #internal administration example 4 intranasal administration 30mg / k dl, 2,3 30iag / k dl, 2,3 4 lavage fluid / CPE lavage fluid / bacteriolytic lung / bacteriolytic plaque 4 lavage Liquid / CPE lavage fluid / bacteriolytic lung / bacteriolytic plaque 4 lavage fluid / CPE lavage fluid / bacteriolytic lung / bacteriolytic plaque 4 irrigation fluid / CPE lavage fluid / bacteriolytic lung / bacteriolytic plaque 4 CPE lavage fluid / bacteriolytic lung / bacteriolytic plaque 5 5 5 0 2 2 2 2 2 6 9 7 6 0 3 13 3 3 4 5 13 12 2 12 0.87 0 0 8 5 9 4 6 0 ο ο 1 5 2 7 2 2 9 ο ο ο 2 3 3 5 0 2 2 2 2 3 4 10 3 2 2 2 2 11 0.09 0.26 This paper size applies to the Chinese National Standard (CNS) Λ4 specification (210X297 mm) -62-

Claims (1)

Difficulty 43 A8 B8! CS D8 Patent Application Range No. 8 6 1 0 1 8 1 8 "The Three Cultivations Containing Anionic Compounds Effectively Used as Antiviral Agents" (Amended in 1990 and 3 years) A Patent Application Range: Extreme Compound of the formula: N -N U'W 'where: X U'Wr (please read the notes on the back before filling out this page) is based on the following: C, C C 'General Q- Anti Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, C 'is selected from -S〇3H or -C00H; B · is -NH or 0; X is Cl, F, or the following formula: The paper size applies the Chinese national standard ( CNS) A4 specification (210 X 297 mm) Fan Li specially applies for ABCD where u · is selected from -so 2; V is selected from the following groups: Ί Y- / -N Υ and Υ are-(CH2) η η is 0 to 6; m is 0 to 2; Z is selected from Η, -CH2 OH, -C00 11, or -COHR2 R2; R 2 is selected separately It is self-hydraulic or (Ci-Ce) low-carbon radical; or its ammonium tolerant salt or (C) -C6) alkyl vinegar. For example, the compound of Shen Yuanli Fan Yuan, where Λ is the following formula @ ^-部 纪 ^ 财 吒 ^ 肖 工 垆 费 合作 合 印 印 ®; -2- is -S 0 3 H; is -NΗ: is the group of the following formula This paper standard applies Chinese National Standard (CNS) Α4 is present ( 210 × Public address) Kai 43 87 9 7 Printed by the Central Standards Bureau of the Ministry of Economy For the Yanwei, Xu Fan Y Rongli X ’槃 bu, 谞 υρφ or as 0 in the middle. The formula for the definition of the term H1-C® C defined by the following formula is as follows: Β 团 group 3; ο Η formula s Ν, 1-the following is c Β V is Shen P Female In the middle of its range. * Gg 物 物 基基 Θ Please alkylate the C-defined term. The radical formula is B. The paper size is applicable to the K-valve valence; f ΓΝί;) A4it grid (2Ι0 × 297); 2. The scope of patent application C 'is -S 0 3 Η; B is -N II; * W' is a group of the formula: / \ ι r -Ur 广 1 Π Π Π. Ϊ (¾-t η Ί U ί1 2-, Z is -CO Ν Η 2; and U ', X, Υ, η, and ιπ are as defined in the scope of patent application; or their medically acceptable salts or (CVC6) alkyl esters. 5. If applied The compound of item 1 of the patent scope, wherein the permissible salt is a dinaline salt. 6. The compound of item 1 of the patent scope, which is 4, 4'-bis [4, 6-di [3-amine Phenyl-fluorene, N-bis (2-aminomethylmethyl-ethyl) sulfonylimino] -1,3, 5-tritriptra-2-ylamino] -dibenzyl-2,2 '-Disulfonic acid or its permissive salt. 7. The compound according to item 1 of the scope of patent application, which is 4, 4'-bis [4,6-bis [3-aminephenyl-N, H -bis (2-Aminomethylamidino-ethyl) sulfoamidoimino] -1,3,5-tritrap-2-ylamino] -biben-2,2'-disulfonic acid or its 61 drugs allow 8. The compound according to item 1 of the patent application, which is 4, 4 to bis [4, 6-bis [3-aminebenzyl-H, N-bis (2-hydroxyethyl) pyridine) Amine] -1,3, 5 -Tritrap-2-ylamino] -dibenzylethylene-2,2'-disulfonic acid or its peony permit IS. This paper is described in China® furniture standard ( CNS) Λ4 is now (2 丨 0X297 mm) (Please read the notes on the back before filling out this page) Order the printed and applied for patent scope of the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs. The compound around item 1, which is 4- [4, 6-bis [3-aminophenyl U-bis (2-aminomethylphenylethyl) sulfonamidoSimino] -1.3,5-tris 2-ylamino] -4 '-[4-chloro-6 ~ [3-aminophenyl1, bubis (2-aminomethylethyl) sulfoamidoimino] -1,3, 5 -Tristrap-2-ylamino] -stilbene-2,2'-disulfonic acid or its permissible salt. 1 0, such as the compound in item 1 of Shenyang Marie, which is Ί , 4'-bis [4-chloro-6- [3-aminophenyl-K, Η-bis (2-aminomethylmethylethyl) sulfoacidylidene] -1,3,5 · * 2-Aminoamino] -dibenzylacetic acid or its edible salt. -1 1. If the compound in the scope of claim B 1 of the application, it is 4-[4, 6-bis [3 -aminobenzyl-Ν, Ν-bis (2 ~ amine methyl ethyl) sulfonyl) Amine] -1,3,5-trigen-2-ylamino] -4 '-[4- [3-aminophenyl- 丨 彳, 1bis (2-aminomethylmethylethyl) sulfonium Imidene] _6- [3-limylbenzyl_! 彳-(2_aminomethylmethylethyl) -K '-(3-propionic acid)]-1,3,5_triswell-2- Aminostilbene stilbene-2,2'-disulfonic acid or its H-tolerant salt. Printed by the Shell Standard Consumer Cooperative of the Central Bureau of Standardization of the Ministry of Economic Affairs (please read the precautions on the back before filling out this page) 12. If you apply for the compound of item 1 in the profit scope, it is 4- [4,6- 二 [3- Aminobenzyl-fluorene, N-bis (2-aminomethyl-ethyl) sulfoamidoimino] -1,3,5-triple-2-ylamino] -4 '-[4- [ 3-aminophenyl-«,«-bis (2-aminomethylmethylethyl) sulfonamidoimino] -6- [3-aminobenzyl-N, fluorene-bis (3-propionic acid)] -1,3,5-Dioxo-2-ylamino] -dibenzyl-2,2'-disulfonic acid or a lightly acceptable salt thereof. 1 3. The compound according to item 1 of the scope of patent application, which is 4, 4'-bis [4, 6-bis [3-aminophenyl-fluorene, K-bis (2-aminemethylmethyl-ethyl) Sulfonylimine group 1,3, 5-triple_2_ylamino] -bisbenzyl-2,2'-disulfonic acid or this paper size applies Chinese National Standard (CNS) A4 (210χ Ｍ7 公 螫) Printed by the ABCD Central Consumers' Bureau of the Ministry of Economic Affairs, Shellfish Consumer Cooperatives. 6. The scope of patent applications for its hydroxyl salt allows. 14. The compound as described in item 1 of Shenyang Patent New Letter, which is 4, 4′-bisμ, G-bis [4-aminebenzyl H-bis (2-amine formaldehyde and even ethyl) sulfolandyl Imine 1-1, 3, 5-triple-trap-2-ylamino] -stilbene-2, 2'-disulfonic acid or a pharmaceutically acceptable salt thereof. 1 5. The compound as claimed in claim 1, which is Ί, 4'-bis 丨 4, 6-bis [4-limbenzyl-N, Ν-bis (2-amine φ acid group-B Sulfonylimine 1-1, 3, 5-trigjf-2-ylamino j-biphenyl-2, 2, disulfonic acid or a pharmaceutically acceptable salt thereof. _ 16. The compound according to item 1 of the scope of patent application, which is 4, 4′-bis [4, 6-bis [3-aminophenylanilide] -l, 3,5 -tris E-aminoamino j-stilbene-2,2_-disulfonic acid or its medicinal salt. ί 7. The compound according to item 1. in the scope of patent application, which is 4,4 1 -bis [4, 6 -bis [3 -aminobenzenesulfonimidoimino 1-1, 3,5-triple well -2-aminoamino] -biphenyl-2,2'-disulfonic acid or a pharmaceutically acceptable salt thereof. 18. The compound according to item 1 of the scope of patent application, which is 4, 4 1-bis [4, 6-di 丨 3-aminebenzyl-N, bis (2-aminoformyl-ethyl) sulfonium Imino i-i, 3, 5 -triple-2 -ylamino] -biphenyl-2,2-disulfonic acid or a pharmaceutically acceptable salt thereof. 1 S. The compound according to item 1 of the scope of patent application, which is 5, 5'-dimethyl-4,4, bis {4,6-bis [3-aminophenyl U-bis (2-amine formamidine) -Ethyl) sulfoamidoimine pad 1-1,3,5-trisamino-2-ylaminobiphenyl-2,2'-disulfonic acid or a pharmaceutically acceptable salt thereof. The ft scale of this paper is applicable to China National Standardization (CNS) Λ4 grid (210X297 mm) Please read the precautions on the back before filling in this page) Order 4 A8 B8 CS D8 1 ^ 43 87 9 7 VI. Patent Application Scope 2 0 . If the compound of claim 1 is applied, it is 4, 4'-bis [4. 6-bis [3-aminebenzyl-N, N-bis (2-hydroxyethyl Ιί)) sulfonimide Phenyl] -1, (please read the precautions before filling this page) 3, 5 -Tripyrido-2 -Hexylamino] -biphenyl-2, 2 '-disulfonic acid salt. 2 1. The compound according to item 1 of the application letter, which is 9, 9-dioxo-2, 7-bis [4, 6-bis [3-aminobenzyl-N, Ν-bis (2 -Aminomethylethyl) sulfamoimino] -1, 3, 5-tritrap-2-ylamino] -dibenzopyridine-3.6-disulfonic acid or its peony permissible salt. 2 2. The compound according to item [1] in the scope of application, which is 4, -4′-bis [4-chloro-6- [4-amino-K ·-[3-aminebenzyl-N, N- Bis (2-aminomethylamidoethyl) sulfoamidoimino] -benzidinemethylamine] -1,3, 5 -Triswell-2 -ylamino] -dibenzylethylene-2,2 '- Disulfonic acid or a pharmaceutically acceptable salt thereof. 2 3. The compound according to item 1 of the scope of patent application, which is 4, 4 bis [4-amino-1T- [3-aminebenzyl-N, H-bis (2-hydroxyethyl) sulfonyl Amine] -1,3,5-Tritrap-2-ylamino] -dibenzyl-2,2'-disulfonic acid or its permissible salt. Printed by the Central Bureau of Standards, the Ministry of Economic Affairs, Shellfish Consumer Cooperative, 11 2 4. If the compound in the scope of patent application for item 1 is 4, 4 '-bis- (4, 6-bis {3- [bis- (2-amine Methyl-ethyl) -aminosulfanyl] -benzylamino) -1,3,5-triswell-2 -ylaminobiphenyl-2,2'-dicarboxylic acid, dinaline IS. 25. The compound according to item 1 of the scope of patent application, which is 4, 4'-bis-([, 4.6 -bis-[[3-[[bis- (3- (methylamine) -3 -oxypropyl [Amino] amino] sulfonyl] phenyl] amino] -1,3,5-trigen-2-yl] amino] bibenzyl] -2. 2'-dicarbonic acid, di-nano salt. 2 6 .If the compound in the scope of the application for the first item of the patent, it is 4, 4 '-double- (4, this paper size is applicable to China National Standards (CNS) Ί Ί 格 (210X297 mm) Central Bureau of Standards of the Ministry of Economics consumption of shellfish Cooperative cooperative policy 4 3 I D8 6. Scope of patent application 6-Bis {3- [bis- (2-methylH-carboxamyl-ethyl) -sulfamoylphenylaniline}-Π, 3, 5 ] Tritrap-2-aminoaminobiphenyl-2, 2'-dicarboxylic acid, di-nano salt. 2 7. The compound according to item 1 of the scope of patent application, which is 4,4 (-bis (4, G -bisU-f 5! — (2-aminomethylamidino-ethyl) -sulfanilbiphenylaniline}-[1, 3, 5 1Sangen-2 -ylaminobiphenyl-2 , 2 1-Dimethyl diacetate or a pharmaceutically acceptable salt thereof = 2 8. As for the compound of the first item of the patent application letter, it is 4, ^ -bis (4, 6-bis {3-丨 bis- ( 2 -Hydroxypropyl) -sulfamoyl] -aniline -[1,3,5] Triple well-2 -ylamino] -biphenyl-2, 2 ^ dicarboxylic acid, disodium salt. 2 9 · The compound according to item [Scope of the patent application], which is 4, 4 '-bis (4, 6 -bis 丨 3-[bis- (2-hydroxypropyl) -aminosulfonyl] -aniline}-[1, 3, 5] tris-2-ylamino] -Biphenyl-2, ^ -diphosphonic acid, disodium salt. 30. The compound according to item 1 of the patent application, which is 4, 4 _-bis {4, 6-bis (3-bis-amine Formamylmethyl-aminosulfonyl) -anilino]-[1, 3, 5] Triple well-2 -ylaminobiphenyl-2, 2 1 -disulfonic acid, disodium salt. 3 1 The compound as claimed in item 1 of the scope of patent application, which is 4,4 1-bis {4, 6-bis (3-bis-aminomethylaminomethyl · sulfamoyl) -aniline]. [1, 3, 5 i triple well-2 -ylaminobiphenyl-2, 2'-dicarboxylic acid, di-nano salt. 3 2. As the compound of the scope of the patent claim 1, it is ^)-2, 2- (1,2-Ethylenedieven) bis [5-[[4,6 -bisΠ 3-[[3, 5 -bis (aminocarbonyl) -1 -hexaaziridinyl i-sulfonyl.pentyl] Phenyl Iamino] -1,3,5-tritrap-2-yljamino] benzenesulfonic acid], disodium salt. According to the standard, China National Standards Corporation (CNS) Λ4 sees the standard (210X 297). (Please read the notes on the back before filling in this philosophy.) Order f ί 6. Application for patent scope 3 3. If you apply for profit化合物 The compound of item 1, which is 4., 4 ~ bi- {4, (¾ Please read the note of * before reading the matter and then M: two copies of this) (5-双-[3-(3 J- Diamine formamidine-hexahydropyridine-1 -sulfonaldehyde) -anisole]-[1,3, 5] Tritrap-2 -ylamine) -bibenzyl-2, 2'-disulfonic acid ， 二 纳 ®. 3 4. The compound of item 1 in the claim range, which is 1, 2 ', 1 ”, 1 ...-[(2, 2'-disulfo [1, 1 ^ biphenyl ] -4, 4 '-diyl) bis [imino-1.3.5-triple-6, 2,4-triylbis (imino-3,1-benzylsulfonyl)]] [3, 5 ~ hexaazapyridine dicarboxylic acid or its superdrug-accepting salt. 3 5. If the compound in the scope of claim 1 is applied, it is 4, 4'-bis- (4, 6-bis- [3- [Bis- (2-Hydroxyethylammoniumsulfonyl) -benzylamino}-[1,3,5] -Tristrak-2-ylamino] biphenyl-2, 2'-bisoteric acid, 2 Na salt. 6. If the compound in the item of the scope of the claim is applied, it is 4, 4 '-bis [4, 6-二 [3 -Aminephenyl-fluorene, N-bis (3-hydroxypropyl) -sulfoamidoimino]-1.3.5 -trioxo-2-ylamino] -biphenyl-2,2, -disulfo 37. —A pharmaceutical composition for treating mammalian viral infections, comprising an effective amount of a compound such as the one in the scope of patent application as the active ingredient, and a pharmaceutically acceptable carrier. Ministry of Wisdom " 4 ^ 3 (industrial-consumer cooperation Du printed 38. For example, the pharmaceutical composition in the 37th scope of the patent application | where the effective amount is a dose from 10 mg / kg to about 500 mg / kg "3 9. The pharmaceutical composition of scope item 37, wherein the viral infection is a respiratory syncytial virus infection. 40. For example, the pharmaceutical composition of scope item 37 of the patent application, wherein the viral infection is herpes simplex virus infection. This paper standard applies to Chinese national standards窣 (CNS) Α4 specification (210 × 297 male, ® 43 87 9 7 8 8 8 8 ABCD Of the 2 to 4 diseases of the medically infected disease, please refer to the first The size of the cells of the Yuanfan disease is a group of medicines that are infected with the poison. 7 Dyed 3 Toxic Diseases ΓΓ Its -7.T Economy Deng Yenghuicai is printed by the Bureau ’s Consumer Cooperatives ο Wood Paper Wave Standard Applicable to China National Standard (CNS) A4 Specification (2l0x 2 < > 7g) ta 12 iS'ii. Annual film ί · ι. Supplement without A7 B7 V. Description of invention (50) Official example 20 mm -a. a · -m 「4.fi-二」 3-Anti-mining HH- Beep (2-m formamyl-7, a certain) cyttriol 1-1 gazing cage-2.V-difluorene. Disodium triple wells 2-some fluorene 1- compounds according to the preparation examples 2 The procedure used was prepared using 5,5'-dimethyl-4,4'-diaminobiphenyl-2,2'-disulfonic acid, di-nano salt (206 mg, 0.49 mmol) and 2-chloro-4,6-di [3-aminebenzyl- (1, | {-bis (2-aminomethylmethylethyl) sulfoamidoimino] -1,3,5 -Sangen ( Example 6) (805 mg, 1.08 mmol) in 30 ml of DMS0-cyclobutane (1: 1, v / v) and diisopropylethylamine (200 ml) at U5t: 50 hours. HPLC- The purified product was a colorless solid (191 mg, obtained; melting point > 25〇υ decomposition; UV (water): 27 4nm (10se5.08); MS (ES) (b / z): Η_288δ3.3; MW1822.6. Real. Example 21 Short-4.f i-二 「3-Fang cage even-NH-Qin (2-1? 7, base) 碏 瞌 亚 Fang Fang 1-1. 3 5-Three coax in li r ::. L 衣衣 i. Γ Order li line (please read the note on the back before filling in this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs of the Ministry of Economic Affairs of the People's Republic of China -2 to 013 and stir the polytrichloromethane (135 mg, 0.7 3 mmol) under stirring. A solution of dioxane (55 ml) was added dropwise to human phosphate (120 ml, 0.3 M, ρΗ7) and crushed ice (10 g). 3-Aminephenyl-bis (2 -Hydroxyethyl) sulfonyliminomine (365 mg, 1.40 mmol) in N, N-dimethylmethanamine (125 ml) was added dropwise to the resulting fine hydrazone suspension, and the pH was adjusted by adding IN NaOH was maintained at 6.5 to 7.2. The mixture was stirred for 1 hour (0T :, pH7,0) and the temperature was raised to 55 C. The mixture was further stirred for 2.5 hours, and on the other hand, it was analyzed by HPLC (or- 32- The size of this paper is applicable to the ten national standards of China (CNS) ΛΊ Regulations (:: 0 credit) Difficulty 43 A8 B8! CS D8 Patent Application No. 8 6 1 0 1 8 1 8 Patent of “Three Cultivations of Poisonous Anionic Compounds” (9 (Revised 0,3 years) A Scope of patent application: Compound of extreme formula: N -N U'W 'where: X U'Wr (please read the notes on the back before filling out this page) is based on the following: C, C C 'General Q- Anti Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economy, C 'is selected from -S〇3H or -C00H; B · is -NH or 0; X is Cl, F, or the following formula: CNS) A4 size (210 X 297 mm)